Debridement of Chronic Wounds - NIHR Journals Library Admin.

The debridement of chronic wounds:a systematic review

M BradleyN CullumT Sheldon

HTAHealth Technology Assessment NHS R&D HTA Programme

Health Technology Assessment 1999; Vol. 3: No. 17 (Pt 1)

Review

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HTA

The debridement of chronic wounds:a systematic review

M Bradley1*

N Cullum2

T Sheldon3

1 NHS Centre for Reviews and Dissemination, University of York, UK2 Centre for Evidenced Based Nursing, University of York, UK3 York Health Policy Group, University of York, UK

*Corresponding author

Competing interests:none declared

Published September 1999

This report should be referenced as follows:

Bradley M, Cullum N, Sheldon T. The debridement of chronic wounds: a systematic review.Health Technol Assess 1999;3(17 Pt 1).

Health Technology Assessment is indexed in Index Medicus/MEDLINE and Excerpta Medica/EMBASE. Copies of the Executive Summaries are available from the NCCHTA web site(see overleaf).

NHS R&D HTA Programme

The overall aim of the NHS R&D Health Technology Assessment (HTA) programme is toensure that high-quality research information on the costs, effectiveness and broader impact

of health technologies is produced in the most efficient way for those who use, manage and workin the NHS. Research is undertaken in those areas where the evidence will lead to the greatestbenefits to patients, either through improved patient outcomes or the most efficient use of NHS resources.

The Standing Group on Health Technology advises on national priorities for health technologyassessment. Six advisory panels assist the Standing Group in identifying and prioritising projects.These priorities are then considered by the HTA Commissioning Board supported by theNational Coordinating Centre for HTA (NCCHTA).

This report is one of a series covering acute care, diagnostics and imaging, methodology,pharmaceuticals, population screening, and primary and community care. It was identified as a priority by the Pharmaceutical Panel and funded as project number 93/29/01.

The views expressed in this publication are those of the authors and not necessarily those of theStanding Group, the Commissioning Board, the Panel members or the Department of Health.The editors wish to emphasise that funding and publication of this research by the NHS shouldnot be taken as implicit support for the recommendations for policy contained herein. Inparticular, policy options in the area of screening will be considered by the National ScreeningCommittee. This Committee, chaired by the Chief Medical Officer, will take into account theviews expressed here, further available evidence and other relevant considerations.

Reviews in Health Technology Assessment are termed ‘systematic’ when the account of the search,appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permitthe replication of the review by others.

Series Editors: Andrew Stevens, Ruairidh Milne and Ken SteinEditorial Assistant: Melanie Corris

The editors have tried to ensure the accuracy of this report but cannot accept responsibility forany errors or omissions. They would like to thank the referees for their constructive commentson the draft document.

ISSN 1366-5278

© Crown copyright 1999

Enquiries relating to copyright should be addressed to the NCCHTA (see address given below).

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List of abbreviations .................................... i

Executive summary ..................................... iii

1 Introduction .................................................. 1Mechanical debridement ............................... 1Non-mechanical debridement ...................... 2

2 Methods ......................................................... 3Literature search ............................................ 3Study selection and data extraction .............. 3Data synthesis ................................................. 3Assessment of outcome measures ................. 3

3 Results ............................................................ 7Debriding agents versus traditional or control therapy ............................................... 7Comparisons between debriding agents ....... 9Cost-effectiveness ............................................ 9

4 Discussion ...................................................... 19

5 Conclusions ................................................... 23Implications for policy ................................... 23Recommendations for research .................... 23

Acknowledgements ...................................... 25

References ..................................................... 27

Appendix 1 MEDLINE search strategy ....... 31

Appendix 2 CINAHL and EMBASE search strategy ................................................. 33

Appendix 3 Additional databases searched .......................................................... 35

Appendix 4 Expert advisory panel .............. 37

Appendix 5 Quality assessment ................... 39

Appendix 6 Summary of studies ................. 41

Health Technology Assessment reportspublished to date .......................................... 71

Health Technology Assessment panel membership ........................................ 75

Contents


i

List of abbreviations

C comparator*

I intervention*

CI confidence interval

CRD Centre for Reviews and Dissemination

ES effect size

F female*

HTA Health Technology Assessment

ITT intention-to-treat

M male*

NS not significant*

OR odds ratio

RCT randomised controlled trial

SD standard deviation*

SEM standard error of the mean*

* Used only in tables and figures


iii

BackgroundA wide variety of debridement methods andproducts are available, all of which have diverseproperties, costs and levels of acceptability. There is currently wide variation in their use and a lack ofconsensus on how to treat specific wound types.

Objectives

• To summarise the evidence for the relativeeffectiveness and cost-effectiveness of differentdebriding agents on wound healing.

• To identify areas for future research.

Methods

Data sourcesA range of electronic databases and several woundcare journals were searched; organisations, manu-facturers, researchers and healthcare professionalsconcerned with wound care were contacted foradditional trials. The reference sections of obtainedstudies were also searched for further trials.

Inclusion criteriaStudies were considered for inclusion if they wererandomised controlled trials (RCTs), published orunpublished, that assessed the effectiveness of arecognised debriding agent as identified by anexpert panel, and assessed patients with chronicnon-healing wounds (pressure sores, leg ulcers,sinuses and surgical wounds healing by secondaryintention). Studies were only included if they used aquantifiable and objective measure of healing rate.

Data synthesisFor each trial an odds ratio and/or effect size was cal-culated for all objective outcomes. Where possible theanalysis was performed on an intention-to-treat basis,and 95% confidence intervals were included when suf-ficient detail to allow their calculation was provided.

Results

Forty-seven reports describing 35 RCTs wereidentified that met the inclusion criteria.

InterventionsThe following interventions were identified asagents that would be used primarily for wounddebridement.

• Dextranomer polysaccharide beads or paste• Cadexomer iodine polysaccharide beads

or paste• Hydrogels• Enzymatic agents• Adhesive zinc oxide tape• Surgery or sharp debridement• Larval (maggot) therapy.

Other interventions that are believed to have adebriding function, such as hydrocolloid dressingsand antibiotics/antiseptics, were not included inthis review as debridement was not the primaryreason for their application.

No RCTs were found that evaluated the effective-ness of surgical debridement, larval therapy, or thatcompared debridement with no debridement.

Dextranomer polysaccharide beads or pasteversus traditional or control treatmentNine trials met the inclusion criteria, five of whichfound a statistically significant difference betweentreatments: three favoured dextranomer poly-saccharide, and two favoured traditional treatment.

Cadexomer iodine polysaccharide versustraditional or control treatmentNine trials met the inclusion criteria, of whichthree had a statistically significant result thatfavoured cadexomer iodine polysaccharide.

Hydrogels versus traditional or control treatmentOnly one trial out of four that compared ahydrogel with a traditional or control treatmentfound a statistically significant difference betweentreatments, which suggested a small benefit from treatment with a hydrogel dressing compared with a hydrocolloid dressing.

Enzymatic agents versus traditional or control treatmentNone of the five trials in this category showed astatistically significant outcome in favour of eithertreatment for wound closure. In fact, one trial

Executive summary

Executive summary

iv

showed an increase in wound size with both theenzyme collagenase and the control treatment;however, the increase was significantly less in theenzyme-treated group.

Adhesive zinc oxide tape versus traditionaltreatmentA single trial meeting the inclusion criteria showed that adhesive zinc oxide tape was moreeffective in eradicating or reducing by more than50% the necrotic area of diabetic foot ulcers than a hydrocolloid dressing.

Cadexomer iodine polysaccharide versus otherdebriding agentsTwo trials were comparisons with dextranomerpolysaccharide and one trial was a comparison with a hydrogel. None of the trials had statisticallysignificant results.

Dextranomer versus other debriding agentsFour RCTs comparing dextranomer polysaccharidewith another debriding agent included two trialswith enzyme formulations, namely collagenase andstreptokinase/streptodornase, and two trials usinga hydrogel as the comparator. Only one of the twocomparisons with a hydrogel showed a statisticallysignificant benefit associated with the hydrogel.

Hydrogel versus hydrogelA single trial was found. There was no statisticallysignificant difference between the two treatments.

Enzymatic agent versus enzymatic agentOne trial that compared the enzyme preparationstreptokinase/streptodornase with the enzymetrypsin was included in the review. No statisticallysignificant difference between the two treatmentswas found.

Cost-effectivenessCost-effectiveness has not been thoroughly assessedin studies of debriding agents. The unit cost foreach treatment is stated in some studies, and a fewcontain further details on other important vari-ables, such as nursing time or number of dressingchanges. However, no study provides sufficientdetail from which a reliable cost-effectivenessanalysis can be constructed.

Conclusions

No studies were found that compared debridementwith no debridement and without these studies it is

unclear whether wound debridement is a beneficialprocess that expedites healing.

There is insufficient evidence to promote the use of one debriding agent over another. There was only a single comparison between twodebriding agents that produced a significant result (hydrogel significantly reduced necroticwound area compared with dextranomerpolysaccharide paste).

Implications for policyThere is little evidence to identify which agents are the most effective. Pending the availability ofimproved data on relative effectiveness, otherconsiderations, such as cost-minimisation, mayreasonably guide decisions on the use of debriding agents.

Recommendations for researchMuch of the research is of poor quality, and direct comparisons are few. In the trials reviewed,sample sizes were rarely sufficient to detectclinically important effects, and poor baselinecomparability frequently confounded outcomemeasures. Several important messages can beidentified for future studies.

• Recruitment numbers should be based on asample size calculation.

• The proportion of wounds healed should beused as an objective outcome measure. Wherehealing rates are based on wound area, both thepercentage and absolute change in area shouldbe given.

• Experimental groups should be comparable at baseline.

• Baseline data and intervention details shouldalways include a thorough description of how the patients were nursed and report the use of concurrent treatments, including secondary dressings.

• Comparisons between debriding agents are required and should use agents that are recommended for wounds of a similar nature.

• Assessment should be blind to treatment.• Survival rate analysis should be adopted for

all studies that assess wound healing.• All RCTs should be published.• Detailed cost-effectiveness analyses should be

seen as a priority for future trials.• The frequent use of surgical debridement

and the increasing interest in larval therapyindicate that RCTs in these areas are needed.


1

Wound healing is an efficient and naturalprocess that normally requires no special

treatment. However, chronic non-healing woundscan occur when there is some underlying factorpreventing healing, and in such cases interventionis considered necessary. For example, pressuresores are initially acute wounds caused by ischaemicdeath of tissue due to excessive pressure and willusually heal readily when pressure is relieved andthe blood supply restored. However, in certainpatients, particularly the elderly and persons withlow mobility, it may not be easy to resolve thesecausative factors and chronic wounds can develop.

A characteristic of most chronic wounds is anaccumulation of devitalised tissue and cellularexudate at the outer surface. These products resultfrom a restriction of nutrients to the damagedepithelium and form either a dry, hard eschar or, as in the case of deep moist wounds, a slough thatfrequently hardens on the outside with exposure to the air. The accumulation of these products in the wound bed is generally regarded, though not experimentally proven, to prevent or delaygranulation and epithelialisation. The removal of this tissue by a process termed debridement istherefore thought to facilitate healing.1

Although the clinical evidence in support ofdebridement is lacking, treatment is regarded as a necessity for patient acceptability and for the prevention of infection:2 moist slough ismalodorous and visually repugnant, and providesan ideal culture medium for pathological organ-isms. The treatment of infection with topicalprophylactic antibiotics is often unsuccessful in sloughy wounds as the active agent is unable to penetrate and diffuse through the necroticdebris. Debridement will remove this barrier and may thereby assist in the treatment of infection.

Although many products used during the treat-ment of a wound may have a debriding function,only a few are commonly used specifically for this purpose. Despite having diverse properties,costs and levels of acceptability, these specificdebriding agents can broadly be classified asmechanical or non-mechanical interventions (Table 1 ).

Mechanical debridementSurgical or sharp debridement has been practisedfor several centuries and is still commonplacetoday. The technique is simple, requiring only the use of sterile scissors or a scalpel, but it doesrequire some degree of skill to avoid aggravatingthe wound. It is considered that sharp debridementis best suited to wounds where there is a cleardistinction between healthy and devitalised tissueand where a patient is unlikely to experiencesignificant pain.2

Bio-surgery, which exploits the feeding behaviourof certain insect larvae, has an equally long medicalhistory and is presently enjoying a resurgence ofinterest.3 Sterile maggots (fly larvae) are consideredideal debriders, having a ferocious appetite fornecrotic material while actively avoiding newlyformed healthy tissue.4 Maggots are placed directlyonto the affected area and held in place by a close-net-dressing.5 These animals may also perform anantimicrobial role that is beneficial for woundhealing, as the antibacterial agent allotoxin isactively excreted from the maggot’s body.2 Evi-dence for clinical effectiveness is restricted to casereports and expert opinion; it remains untested by randomised controlled trials (RCTs).

Wet-to-dry debridement is used infrequently in theUK but is common in many European countriesand the USA. The wound is soaked in saline tomoisten hard material before the application of a moist gauze pad over the affected area. As thedevitalised tissue drys it re-hardens and becomes

Chapter 1

Introduction

TABLE 1 Classification of debriding agents2

Mechanical Non-mechanical debridement debridement

Surgery (scalpel) Polysaccharide beads or paste (dextranomer,

Wet-to-dry dressings cadexomer iodine)(saline gauze)

Enzymatic agents Bio-surgery (maggot larvae) (streptokinase/

streptodornase,trypsin, collagenase)

Hydrogels

Introduction

2

attached to the gauze, when the dressing ischanged the adhered material is pulled free.6

This method is less discriminating than thosepreviously discussed, removing both healthy andgranulating tissue from the wound bed. Patients are known to experience pain, and newly formedepithelial tissue may be significantly damaged.7

Non-mechanical debridement

Non-mechanical techniques have becomeincreasingly popular for wound cleansing. Thesetreatments are usually easy to apply and may haveadditional properties that are beneficial for woundhealing. Such interventions include enzymes,hydrogels and specific chemical formulations, such as cadexomer iodine and dextranomer.

Several different enzyme preparations are available that digest slough and necrotic tissue. In the UK, only the formulation containingstreptokinase and streptodornase (VaridaseTopical®, Wyeth Laboratories) is licensed for use.8 This enzyme aggressively digests the proteinsfibrin, collagen and elastin which are commonlyfound in the necrotic exudate of a wound.9

Other enzymatic debriding agents are available and used internationally; these include trypsin and collagenase.

Dextranomer polysaccharide is supplied asanhydrous, porous beads with a diameter of 0.1–0.3 mm or as a paste. The beads are highlyhydrophilic and rapidly absorb exudate from anecrotic sloughy mass. Prostaglandins, hormonesand other relatively small molecules enter thematrix of the beads, while larger particles such asbacteria and wound debris become concentrated at the surface of the dextranomer layer. When the beads are changed by washing with saline the absorbed and trapped necrotic material is removed.10

Cadexomer iodine is similar to dextranomer,consisting of small spherical beads that are

hydrophilic in nature. The beads are made from amodified starch infused with iodine at a concentra-tion of 0.9%. Absorption of fluid from the woundresults in a slow controlled displacement of iodinefrom the matrix, which acts as a bactericidal agent.10

The slow and consistent release of iodine overcomesthe problem of iodine inactivation by protein ab-sorption in the wound. The antibacterial property,biodegradability and high rate of fluid absorptiondistinguish cadexomer iodine from dextranomer.

Hydrogels are a group of agents that were pri-marily developed as debriding agents. These gelsare biologically inert and have a significant watercontent. They complement the body’s naturaldebriding process by providing an advantageousenvironment for autolysis, while still acting topreserve living healthy tissue.2 The hydrogel isusually applied directly into the wound bed andheld in place by a non-adherent dressing. Once the gel is fully hydrated it is unable to absorb thecopious quantities of exudate that are released bysome wounds. For this reason hydrogels are oftenused in conjunction with a highly absorbent dress-ing. In addition to the amorphous gel, hydrogelsare also available in a sheet form. Several types of hydrogel are available manufactured underdifferent trade names (Intrasite® Gel, Smith &Nephew Healthcare Ltd; Sterigel®, Seton Health-care Group plc; Granugel®, CovaTec UK Ltd).

In clinical practice there is wide variation in the use of debriding agents and no consensus on whichagent is most appropriate for each type of wound.11

As a result, many clinicians combine debridingagents in a dual or triple therapy in an attempt to maximise healing rates, but such measures areuntested and are not endorsed by manufacturers.This review, commissioned by the NHS HealthTechnology Assessment (HTA) Programme,attempts to summarise the evidence to date for the relative effectiveness and cost-effectiveness ofthese different interventions and to identify thegaps in our research knowledge. In this way it ishoped that clinical practice may better reflect the results of scientific research.


3

Literature searchA systematic review of primary research wasundertaken using the NHS Centre for Reviews and Dissemination (CRD) structured guidelines.12

Nineteen electronic databases of medical literaturewere searched up to October 1997 using a sensitivesearch strategy designed in collaboration with aninformation specialist in CRD (appendices 1–3).This was supplemented by a handsearch of fivespecialist wound care journals, twelve conferenceproceedings and systematic reviews held on theNHS CRD Database of Abstracts of Reviews ofEffectiveness (DARE). The bibliographies of allretrieved and relevant publications were searchedfor further studies. Companies with an interest inwound care products were approached for un-reported trials. An advisory panel of experts inwound management, established to comment on the review as it progressed, were also asked toidentify any additional trials (appendix 4). Rele-vant economic studies were identified by addingeconomic-related search terms to those used in thesearch for clinical trials. Authors of trials publishedafter 1985 were contacted and asked to providedetails of any trial-based economic evaluations.

Study selection and data extractionRetrieved studies were assessed by a single reviewerfor relevance to this review, and decisions on finalinclusion were checked by a second reviewer;disagreements were resolved through discussion.Trials, irrespective of date, language and publi-cation status, were included if they were human-based RCTs, which evaluated the efficacy of arecognised debriding agent in relation to woundhealing and had an outcome measure that wasconsidered an objective measure of healing. Where study details were lacking the authors were invited to provide further information.

Many treatments commonly used in woundmanagement may have a debriding function; only a few, however, are specifically used for thispurpose. An expert panel was consulted to identifythose treatments that they believed were primarilyused for debridement. The panel identified

the following interventions as debriding agents:dextranomer polysaccharide, cadexomer iodinepolysaccharide, hydrogels, various enzymaticagents, adhesive zinc oxide tape, surgery and larval therapy. Other interventions such as hydro-colloid dressings and antibiotics/antiseptics werenot considered by the panel to be debriding agentsas debridement may occur only as a secondaryfunction following their application rather thanbeing the primary reason for their use.

Data from included trials were extracted by a single reviewer into data extraction tables and thenchecked independently by a second reviewer.

Data synthesis

For each trial an odds ratio (OR) and/or effect size (ES) was calculated for all objective outcomes.Where possible the analysis was performed on anintention-to-treat (ITT) basis and 95% confidenceintervals (CIs) were included when sufficient detailto allow their calculation was provided. The resultsfrom each study were plotted onto graphs, andindividual study details are presented in structuredtables containing information relevant to studyvalidity. Heterogeneity between studies indicatedthat pooling of results would be inappropriate.Studies varied in duration of follow-up, nature ofthe comparator treatment, wound types, settingand baseline comparability of patient groups.

Assessment of outcome measures

A single standard outcome measure for woundhealing does not exist. Both objective and subjec-tive measures are widely used by researchers butlittle effort has been made to determine the validity of these measurements.

Most subjective outcomes, such as estimates ofoedema, erythema, granulation, pus and debris, are unlikely to be measured consistently betweenwounds. Unless assessment is blinded to treatmentallocation, subjective outcomes are likely to resultin significant biases. For example, in one trialcadexomer iodine was judged by visual assessmentto be more effective than dextranomer, but a later

Chapter 2

Methods

Methods

4

assessment of quantitative planimetric resultsindicated that there was no difference between thetwo treatments.13 This appears to be a characteristicfeature of research in this area; subjective measure-ments almost invariably overestimate the relativeeffectiveness of the experimental treatment com-pared with objective measures in the same trial.

Objective measures of debridement are usuallybased on wound area. Planimetry, often aided bycomputer assessment, is the most frequently usedtool for calculating wound area, though othermethods, such as the measurement of wounddiameter or the weight of a celluloid tracing drawnaround the area of the wound, are also used.

Measurements of wound volume are infrequentlyreported in the literature. These methods are oftencumbersome and their accuracy has not been suffi-ciently demonstrated.14 Computerised image ana-lysis may in the future, as the equipment becomesmore affordable and portable, prove to be a usefultechnique for the assessment of wound volume.15

However, even though objective measures reduceor eliminate subjective biases and reduce randommeasurement errors, they have certain inherentbiases if the patients being compared have woundswith different baseline size.

A change in wound area is often expressed as thepercentage change, which unlike the absolutechange in area, takes into account the initial size of the wound. For two wounds healing at the samelinear rate (as measured by diameter reduction),percentage area calculations will show a largerchange for a small wound than a big wound. Theconverse is true when the absolute change in area is measured, as for any unit reduction in woundradius a bigger area reduction will occur for a largewound. This has important consequences for thevalidity of trial results, where there is poor com-parability in initial wound size at baseline betweenthe treatment groups. This is illustrated in Table 2.

In large trials, random allocation should ensurethat the mean wound size and variance in eachgroup are similar. In a small trial, random allo-cation is unlikely to result in an even distribution of wound sizes. This problem will persist in smalltrials, even when the average wound size appears to be comparable between groups, because thedistribution of wound sizes about the mean is likelyto differ. This is illustrated in Table 3.

In a trial where there is poor comparabilitybetween groups for wound size at baseline, and the

outcome is based on the change in area, the resultcan only be considered valid if it is obtained eitheragainst the anticipated direction of the bias forwound size, or where percentage area change andabsolute area change are in the same direction. Ifbaseline data are not given then it is not possible todetermine the direction of bias and the validity ofthe result cannot be assessed.

The change in area of a wound also assumes alinear rate of healing or at least a predictable rate.However, this may not always be the case, with somewounds enlarging prior to healing while othersinitially decrease rapidly in size before experi-encing a slower rate of healing. For this reasoncomplete healing is seen as the most valuableoutcome in studies of wound healing. Unfortun-ately, to follow all wounds to complete healing canrequire an extended period of follow-up that is notideal for most studies, where financial resourcesand time are limited. For this reason many studies

TABLE 2 Percentage and absolute measures of wound healingcan give different results for relative effectiveness

Group A Group B

Baseline mean area (cm2) 50 60

Follow-up mean area (cm2) 35 43

Mean of % reduction in area 30 28

Mean absolute reduction in area (cm2) 15 17

Using % change, wounds in group A appear to have healedmore rapidly than those in group B. The converse is true whenthe outcome is expressed as absolute change in wound area

TABLE 3 Groups with similar means may have differentdistributions

Group C Group D

Wound size at baseline (cm2) 10, 10, 30, 30 4, 4, 4, 70

Mean area (cm2) 20 20.5

Standard deviation (SD) 11.5 33

Groups C and D have approximately the same mean area. If both groups of wounds heal at the same rate (thetreatments are equally effective) it could be expected that thethree small wounds in group D will heal before those in groupC.Therefore measuring outcome based on the number ofwounds healed within a certain time period will be biased.Similarly, the percentage change in area will appear greater in group D, while the absolute change in area will appeargreater in group C


5

in the literature report changes in wound sizerather than complete healing.

Despite the potential for the objective outcomesdiscussed to be biased by differences in wound

size at baseline or by the variability of healing rate between wounds, they remain the most reliable assessment of wound healing as theyreduce the bias of the assessor, which cannot be estimated.


7

Atotal of 47 RCTs met the review inclusioncriteria. Twelve studies (26%) had a shared

data set with another publication, and of these: two contained interim results later published in full,16,17 three were reproduced as paperspresented at international conferences,18–20 one was presented at an international conference and later published as a drug company bulletin,21

six studies were repeat publications of resultspreviously published in other journals,22–27 two of which22,23 were identical to a previouslypublished paper,28 except for a change in the first author. Where duplication occurred andsufficient detail could not be extracted from asingle publication, the studies were pooled andincorporated to represent a single trial entry. In total, 35 individual trials from the 47 relevant publications were identified for inclusion.

The majority of trials had methodologicalweaknesses (appendix 5, Table 4 ). Fewer than 10% of studies reported an a priori estimate of the number of participants required to havesufficient power to detect a clinically importanteffect as statistically significant. It was rare for a trial to have more than 50 patients in each arm, and typically fewer than 30 wereincluded. Twenty-six per cent reported that the outcome had been assessed by someone blind to treatment allocation. Appropriate patient characteristics were recorded by treatment group in 90% of studies, but ulcer size at baseline was reported in only 62%.Withdrawals occurred in most trials and wererecorded by group and cause in 72% of trials where it was appropriate, but less than one fifth performed an ITT analysis. Seventy-four per cent of trials clearly stated the inclusion criteria for patients to the trial, but informationthat indicated whether or not that participants had been truly randomised to alternativetreatments was given in only 37%.

Figures 1–7 show the OR and/or ES calculated from the results for each of the included studies.Where possible, ITT analysis has been used; where such analysis was inappropriate the sample size used in the calculation is given in parentheses.

Debriding agents versus traditional or control therapy Twenty-eight trials compared a recogniseddebriding agent with a traditional or controltherapy. The definition and nature of traditionaltherapy varied widely between trials. In many trials,a single traditional treatment was not used in thecomparative group, in extreme cases a differenttreatment regimen was used for each patient in the control group. The absence of a singlestandard comparator makes interpretation of the results across studies difficult.

Dextranomer polysaccharide versustraditional or control treatment Nine RCTs met the inclusion criteria (Figure 1;appendix 6, Table 5). Four trials showed astatistically significant result, three of whichfavoured treatment with dextranomer poly-saccharide,29–31 and one which favoured treatment with calcium alginate dressings.32

In an additional trial, the author’s own statis-tical analysis indicated a significant improve-ment for those wounds treated with a collagen sponge dressing when compared withdextranomer.33 However, insufficient data were available to test the analysis further. The remaining four trials had statisticallyinsignificant results.34–37

Trials of dextranomer polysaccharide versustraditional or control treatment can be groupedinto categories which are defined by the nature of the comparative therapy.

Dextranomer polysaccharide versus EusolTwo small studies compared dextranomer poly-saccharide with Eusol; both were unable to detect a statistical difference between the treatments.35,36

The study by Nasar and Morley36 was confoundedby the switching of treatment for three wounds that were considered to be healing slowly from the Eusol group to the dextranomer group. These patients were excluded from the analysisbecause of the bias that was hence introduced. In this same study, the cost of materials for average treatment time was calculated, and showed that Eusol was 1.6 times more costly than dextranomer.

Chapter 3

Results

Results

8

Dextranomer polysaccharide versus saline soaks Saline soaks were evaluated against dextranomerpolysaccharide in two trials, which were bothconducted over a 2-week period.31,34

The trial by Eriksson and co-workers34 found nostatistically significant difference between thetreatments for the percentage of ulcers healed by50% or 25%. The trial by Sawyer and co-workers,31

however, found a statistically significant effect infavour of dextranomer beads for the healing ofvenous leg ulcers. Despite the absence of baselinedata in this latter trial it is unlikely that such a large difference in healing rates between the twotreatments could be explained merely in terms ofpoor group matching at baseline.

Dextranomer polysaccharide versus othertraditional or control therapiesOne study found that dextranomer poly-saccharide beads were significantly more effective than povidone-iodine for the treat-ment of venous leg ulcers.29 However, high dropout rates were reported, which could have introduced a bias. Dextranomer poly-saccharide beads have also been found to be more effective when compared with antiseptic/antibiotic treatments.30 This is in contrast to a small study comparing dextranomer poly-saccharide beads with an air dried combination of sugar and egg white, which did not find astatistically significant difference between the two treatments.37

Dextranomer polysaccharide paste was out-performed by calcium alginate dressings for the healing of pressure sores over an 8-weekperiod.32 These results were statistically signifi-cant despite a bias that favoured the smaller sores in the dextranomer polysaccharide group.

Insufficient data were provided to determine the CIs required to test statistical significance in a study that compared dextranomer beads with a collagen sponge dressing.33 However, theauthor’s own analysis suggested a statisticallysignificant reduction in healing time occurred with the collagen sponge dressings.

Cadexomer iodine polysaccharide versustraditional or control treatment Nine RCTs compared cadexomer iodinepolysaccharide with a traditional or control therapy (Figure 2 ; appendix 6, Table 6 ). Three trials (five papers) had a statistically significantresult favouring treatment with cadexomer

iodine polysaccharide when compared withhydrogen peroxide and zinc paste,38 hydrogenperoxide or potassium permanganate,22,23,28

and mechanical debridement by wet-to-drydressings.39 However, high withdrawal rates22,23,28

and inappropriate movement of some patientsbetween groups during the trial39 may haveintroduced confounding factors, which would have implications for the validity of these results.

In two trials the authors own statistical analysisindicated that cadexomer iodine resulted in a significant reduction in wound size whencompared to traditional dressing regimes.40,41

However, in both studies the papers providedinsufficient information for CIs to be calcu-lated which prevented further analysis in this review.

The remaining trials comparing a traditionaltreatment with cadexomer iodine polysaccharidewere unable to detect a statistically significant effect in favour of either treatment.42–45 This may have been a consequence of small sample size or a reflection of the diversity of traditionaltherapies evaluated in a single trial. In one trial, 12 of the 13 patients in the traditional group were treated with a variant on the basic standard therapy.41

Hydrogels versus traditional or control treatment Four trials were included that compared a hydrogel with a traditional or control treatment(Figure 3; appendix 6, Table 7 ).46–49 Only one ofthese trials showed a statistically significant differ-ence between treatments. In this comparison ahydrogel dressing showed a small improvement in the number of wounds healed when compared with a hydrocolloid dressing.46

Enzyme treatments versus traditional or control treatment Only one of the five trials included in the reviewshowed a statistically significant difference be-tween an enzymatic debriding agent (collagenase) and a control treatment (Figure 4; appendix 6, Table 8 ).50 However, the wounds in this trial actually increased in size and the predicted bias was in the direction of enzymatic treatment.Despite the majority of trials showing a trend infavour of enzyme treatment, statistical significancecould not be demonstrated. All the trials in thiscategory suffered from small sample size;9,37,51,52

only one of the included studies had more than 15 patients in each arm.52


9

Adhesive zinc oxide tape versus traditional treatmentIn a single trial an adhesive zinc oxide tape wascompared with a hydrocolloid dressing for thetreatment of necrotic diabetic foot ulcers (appen-dix 6, Table 9 ).53 The adhesive zinc oxide tape wasmore effective in eradicating or reducing necroticarea than the hydrocolloid dressing (OR = 4.44;95% CI: 1.34, 14.70). Treatment was discontinuedin nine patients (four from the adhesive zinc oxidetape group and five from the hydrocolloid dressinggroup) due to a significant increase in necroticarea (> 100%). Common adverse effects seen in both groups were maceration of skin edges, pain and oedema.

Comparisons between debriding agentsNine trials were identified that directly comparedtwo debriding agents. Seven trials compared eitherdextranomer polysaccharide or cadexomer iodinepolysaccharide with another debriding agent, onetrial compared two enzyme treatments, and afurther trial was a comparison between hydrogels.

Cadexomer iodine polysaccharideversus other debriding agentsThree RCTs were included that comparedcadexomer iodine polysaccharide with anotherdebriding agent (Figure 5; appendix 6, Table 10 ).Dextranomer polysaccharide13,54 was the com-parator in two trials and a hydrogel was used in the third trial.55 None of the trials showed astatistically significant effect, and in two the pointestimate of relative effectiveness was close to the line of no effect.13,55

Dextranomer polysaccharide versusother debriding agents Four RCTs were included that compared dextra-nomer polysaccharide with another debridingagent (Figure 6; appendix 6, Table 11 ). Two trialswere comparisons with enzyme formulations(collagenase or streptokinase/streptodornase), and two were comparisons with a hydrogel.

Both hydrogel trials attempted to recorddebridement directly by employing an outcomemeasure based on wound cleansing (the reductionin area of necrotic tissue covering the woundbed).56,57 The study by Colin and co-workers56

failed to find a statistically significant effect for100% cleansing. However, the smaller study byThomas and Fear57 found a large statistically sig-nificant effect in favour of the hydrogel. Although

the treatments used in both studies appear to have been similar, it is likely that the formulation of Intrasite used by Colin was a modification of that employed by Thomas and Fear. Interestingly,in the latter study, treatment was continued beyondthe 14-day follow-up period in a selected group ofpatients. After 28 days, a further four wounds werefully cleansed in the dextranomer polysaccharidegroup, compared with no additional successes inthe hydrogel group. This may suggest that over alonger period the results in this trial would havereflected those reported by Colin and co-workers.

A non-significant benefit was found in favour of dextranomer polysaccharide when comparedwith the enzyme collagenase, this benefit wasrecorded against the direction of wound size bias.37 In the only other trial to compare dextra-nomer polysaccharide with an enzyme preparation(streptokinase/streptodornase), no differencebetween the treatments was found.58

Hydrogel versus hydrogelOnly one study made a direct comparison be-tween two hydrogels (Intrasite Gel and Granugel) (Figure 7; appendix 6, Table 12 ).59 This trial found no statistically significant difference between thegroups after 21 days treatment. The total cost fortreatment per person from baseline to final assess-ment was calculated to be £43.25 for Granugel and £40.25 for Intrasite, while the average cost per 10 cm2 reduction in area was £8.59 and £13.38,respectively. The data appear to indicate that treat-ment with Granugel may be more cost-effectivethan with Intrasite. However, this is misleading asthe analysis is based on absolute changes in ulcersize. The Granugel group had larger ulcers atbaseline, suggesting that this group was more likelyto experience larger changes in absolute ulcer area.

Enzyme versus enzyme Only one RCT directly compared two enzymaticagents (Figure 8; appendix 6, Table 13 ).60 Nostatistically significant difference was foundbetween wounds treated with streptokinase/streptodornase and those treated with trypsin.

Cost-effectiveness

Cost-effectiveness has not been thoroughly assessedin studies of debriding agents. The unit cost for eachtreatment is stated in some studies, and a few con-tain further details on other important variables,such as nursing time or number of dressing changes.However, no study provides sufficient detail for areliable cost-effectiveness analysis to be constructed.

Results

10

–40 –20 0 20 40

0.01 0.1 1 10 100

Favours alternative Favours Dextranomer

OR(95% CI)ES(95% CI)

Goode et al, 197935

Comparison: Traditional vs. DextranomerMean baseline area (cm2): Not stated Not statedSample size (N): 10 10No. of wounds healed without secondary closure (n/N): 1/10 (10%) 1/10 (10%) 1.00 (0.05, 18.32)

Traditional therapy: EusolWound type: Surgical wounds (bowel or appendicectomy)Follow-up time: Until healed or ready for secondary suture

Nasar and Morley, 198236

Comparison: Traditional vs. DextranomerMean baseline area (cm2): Not stated Not statedSample size (N): 9 9No. of wounds reduced by > 25%,clean and granulating (n/N): 5/9 (56%) 6/9 (67%) 1.6 (0.24, 10.81)

Traditional therapy: Eusol Wound type: Pressure soresFollow-up time: Until wound was clean and granulating

Sawyer et al, 197931

Comparison: Traditional vs. DextranomerMean baseline area (cm2): Not stated Not statedSample size (N): 31 35No. of wounds healed (n/N): 3/19 (16%) 15/18 (83%) 26.70 (4.639, 153.29)

Traditional therapy: Saline soaks, or mechanical debridement where indicatedWound type: Venous leg ulcersFollow-up time: 3 weeks

Eriksson et al, 198434

Comparison: Traditional vs. DextranomerMean baseline area (cm2): Not stated Not statedSample size (N): 27 26No. of wounds reduced by > 50% (n/N): 6/27 (19%) 2/26 (8%) 0.29 (0.05, 1.60)No. of wounds reduced by 25% or more (n/N): 21/27 (78%) 24/26 (92%) 3.43 (0.62, 18.85)

Traditional therapy: Saline soaksWound type: Venous leg ulcersFollow-up time: 2 weeks

Groenewald, 198029

Comparison: Traditional vs. DextranomerBaseline area (cm2): < 6 cm2: 7 ulcers 7 ulcers

6–12 cm2: 21 ulcers 20 ulcers> 12 cm2: 22 ulcers 23 ulcers

Sample size (N): 50 50No. of wounds healed (n/N): 2/50 (4%) 11/50 (22%) 6.77 (1.42, 32.38)No. of wounds reduced by 50–100% (n/N): 7/50 (14%) 24/50 (48%) 5.67 (2.14, 15.00)

Traditional therapy: Povidone-iodine, zinc oxide, and gauzeWound type: Venous leg ulcersFollow-up time: 3 weeks

FIGURE 1 Dextranomer polysaccharide compared with traditional or control treatments. Study results are presented as OR and/or ES enclosed by their 95% CI. An arrow by a trial indicates that the results were biased by poor comparability between groups for woundsize at baseline; the direction of the arrow suggests which intervention was favoured by this bias. Convergent arrows suggest that thegroups were reasonably comparable for wound size, while divergent arrows indicate that the bias could not be determined from the data presented


11

–40 –20 0 20 40

0.01 0.1 1 10 100

Favours alternative Favours Dextranomer


Sayag et al, 199632

Comparison: Traditional vs. DextranomerMean baseline area (cm2): 20.1 (SD 12.9) 16.1 (SD 12.5)Sample size (N): 47 45No. of wounds reduced by 40–100% (n/N): 35/47 (74%) 19/45 (42%) 0.25 (0.10, 0.61)No. of wounds reduced by > 75% (n/N): 15/47 (32%) 6/45 (13%) 0.33 (0.11, 0.94)

Traditional therapy: Calcium alginate dressing Wound type: Pressure soresFollow-up time: Until the wound reached 40% of its original size or on completion

of 8 weeks’ treatment

Garcia et al, 198430

Comparison: Traditional vs. DextranomerMean baseline area (cm2): Not stated Not statedSample size (N): 22 22Mean % reduction in wound area: 85.2 93.1 7.9 (2.27, 15.53)

(SD 10.8; n = 22) (SD 7.4; n = 22)Mean % reduction in wound circumference: 70.1 80.0 9.9 (–2.70, 22.50)

(SD 20.8; n = 22) (SD 20.6; n = 22)

Traditional therapy: Potassium permanganate and hypertonic saline or antibiotic ointments Wound type: Secondary perimalleolar ulcersFollow-up time: 3 weeks

Parish and Collins, 197937

Comparison: Control vs. DextranomerMean baseline area (cm2): 5.76 20.25Sample size (N): 9 14No. of wounds healed (n/N): 0/9 (0%) 6/14 (43%) 14.53 (0.71, 298.23)

Traditional therapy: Sugar and egg white Wound type: Pressure soresFollow-up time: 4 weeks

Palmieri, 199233

Comparison: Traditional vs. DextranomerMean baseline area (cm2): Not stated Not statedSample size (N): 24 24Mean no. of days to healing for leg ulcers: 36 (n = 6) 60 (n = 6) –24Mean no. of days to healing for pressure sores: 20 (n = 6) 47 (n = 6) –27

Traditional therapy: Collagen sponge Wound type: Leg ulcers and pressure soresFollow-up time: Until all wounds had healed

FIGURE 1 contd Dextranomer polysaccharide compared with traditional or control treatments. Study results are presented as OR and/orES enclosed by their 95% CI. An arrow by a trial indicates that the results were biased by poor comparability between groups for wound sizeat baseline; the direction of the arrow suggests which intervention was favoured by this bias. Convergent arrows suggest that the groups werereasonably comparable for wound size, while divergent arrows indicate that the bias could not be determined from the data presented

Results

12

–60 –30 0 30 60

0.01 0.1 1 10 100

Favours alternative Favours cadexomer iodine

OR(95% CI)ES(95% CI)ES (95% CI)–1.0 –0.5 0 0.5 1.0

Apelqvist and Ragnarson-Tennvall, 199642

Comparison: Traditional vs. Cadexomer iodineMean baseline area (cm2): Not stated Not statedSample size (N): 19 22No. of wounds healed (n/N): 2/19 (11%) 5/22 (23%) 2.5 (0.42, 14.72)

Traditional therapy: Gentamicin or streptokinase/streptodornase; dry salineWound type: Diabetic foot ulcersFollow-up time: 12 weeks

Laudanska and Gustavson, 198838

Comparison: Traditional vs. Cadexomer iodineMean baseline area (cm2): 35.2 (SE 8.1) 27.5 (SE 7.0)Sample size (N): 30 30No. of wounds healed (n/N): 7/30 (23%) 16/30 (53%) 3.76 (1.24, 11.39)Mean % reduction in wound area: 54 (n = 30) 71 (n = 30) 17

Traditional therapy: Hydrogen peroxide and zinc paste; or saline dressings, potassium permanganate and gentian violet

Wound type: Chronic venous leg ulcersFollow-up time: 6 weeks

Ormiston et al, 198544

Comparison: Traditional vs. Cadexomer iodineMean baseline area (cm2): 10.2 (SD 8.7) 12.1 (SD 13.9)Sample size (N): 30 31No. of wounds healed (n/N) 7/30 (23%) 12/31 (39%) 2.08 (0.68, 6.32)Mean % reduction in wound area: 61 (n = 30) 83 (n = 30) 22Mean absolute reduction in wound area per week: 0.46 0.89 0.43

(SEM 0.1; n = 30) (SEM 0.1; n = 30)

Traditional therapy: Gentian violet, Polyfax® ointment and a Melolin® padWound type: Chronic venous leg ulcersFollow-up time: 12 weeks

Steele et al, 198645

Comparison: Traditional vs. Cadexomer iodineMean baseline area (cm2): 17.59 (SE 3.97) 12.64 (SE 2.91)Sample size (N): 30 30No. of wounds healed (n/N): 1/30 (3%) 3/30 (10%) 3.22 (0.32, 32.91)Mean % reduction in wound area: 18 (n = 29) 22 (n = 28) 4

Traditional therapy: Antibiotics, antiseptics, hydrophilic agents, bland agents, steroids, dry dressingsWound type: Venous leg ulcersFollow-up time: 6 weeks

Harcup and Saul, 198640

Comparison: Traditional vs. Cadexomer iodineBaseline area (cm2): 9.08 (SD 1.37) 7.74 (SD 1.04)Sample size (N): 31 41Mean absolute reduction in wound area (cm2): 0.9 (n = 31) 2.81 (n = 41) 1.91Mean % reduction in wound area: 9.91 (n = 31) 36.30 (n = 41) 26.39

Traditional therapy: Support bandage, dry dressing and an antiseptic cleanser (i.e. Eusol)Wound type: Chronic leg ulcersFollow-up time: 4 weeks

Lindsay et al, 198641

Comparison: Traditional vs. Cadexomer iodineMean baseline area (cm2): Not stated Not statedSample size (N): 28 patients entered the trial; data available for only 25Mean % reduction in wound area: 4.2 (n = 13) 33.6 (n = 12) 29.4

Traditional therapy: Non-adherent dressings and a support bandage or one of several alternative treatments


Polyfax®, Dominion;Melonin®, Smith & Nephew Healthcare Ltd

FIGURE 2 Cadexomer iodine polysaccharide compared with traditional or control treatments


13

–60 –30 0 30 60

0.01 0.1 1 10 100


OR(95% CI)ES(95% CI)ES(95% CI)–1.0 –0.5 0 0.5 1.0

Moberg et al, 198343

Comparison: Traditional vs. Cadexomer iodineMean baseline area (cm2): 12.4 (SEM 4.3) 9.6 (SEM 1.8)Sample size (N): 19 19Mean absolute reduction in wound area (cm2): 2.5 2.9 0.4 (–3.05, 3.85)

(SEM 1.1; n = 18) (SEM 1.3; n = 16)Mean % reduction in wound area: 9.6 30.9 21 (–5.83, 48.43)

(SD 31; n = 18) (SD 46; n = 16)

Traditional therapy: Saline dressings, enzymatic agents, non-adhesive dressings Wound type: Pressure soresFollow-up time: 3 weeks

Skog et al, 1983;23 Hillström, 1988;22 Troëng et al, 198328

Comparison: Control vs. Cadexomer iodineMean baseline area (cm2): 34.0 (SEM 5.7) 20.1 (SEM 4.4)Sample size (N): 45 50Mean % change in wound area: +5 –34 39 (8.16, 69.84)

(SEM 15; n = 36) (SEM 5; n = 38)

Traditional therapy: Dilute hydrogen peroxide or potassium permanganate and a non-adherent dressing


Holloway et al, 198939

Comparison: Traditional vs. Cadexomer iodineMean baseline area (cm2): 11.2 20.1Median baseline area (cm2): 9.75 (range, 3–37) 10.7 (range, 0.6–136.0)Sample size (N): 37 38 Mean absolute reduction in wound area per week (cm2): 0.41 0.95 0.54 (0.19, 0.90)

(SEM 0.13; n = 27) (SEM 0.12; n = 27)Mean reduction in wound area per week vs. baseline circumference (cm2/wk/cm2): 0.03 0.04 0.01 (–0.02, 0.04)

(SEM 0.01; n = 27) (SEM 0.01; n = 27)

Traditional therapy: Wet-to-dry dressings and saline-soaked gauze Wound type: Venous leg ulcersFollow-up time: 24 weeks

FIGURE 2 contd Cadexomer iodine polysaccharide compared with traditional or control treatments

Results

14

–100 –50 0 50 100

0.01 0.1 1 10 100

Favours alternative Favours hydrogel

OR(95% CI)ES(95% CI)ES(95% CI)10 5 0 5 10

Darkovich et al, 199046

Comparison: Traditional vs. Hydrogel (Biofilm®)Mean baseline area (cm2): 9.2 (range, 0.4–64) 11.0 (range, 0.2–100)Sample size: 63 60No. of wounds healed (n/N): 15/63 (24%) 26/60 (43%) 2.45 (1.13, 5.30)Mean % reduction in wound area: 40 68 28Mean absolute reduction in wound area (cm2): 3.7 (n = 63) 7.5 (n = 60) 3.8

Traditional therapy: DuoDerm®

Wound type: Pressure soresFollow-up time: 60 days

Brown-Etris et al, 199647

Comparison: Traditional vs. Hydrogel (Transorbent®)Mean baseline area (cm2): Not stated Not statedSample size: 63 77No. of wounds healed (n/N)37/63 (59%) 39/77 (51%) 0.72 (0.37, 1.41)Mean absolute reduction in wound area:

stage II sores (2–30 cm2): 2.3 (n = 12) 3.6 (n = 12) 1.3

stage III sores (2–30 cm2): 5.2 (n = 36) 6.3 (n = 42) 1.1

stage III sores (31–80 cm2): 4.3 (n = 2) 24.5 (n = 3) 20.2

Traditional therapy: DuoDermWound type: Pressure soresFollow-up time: 10 weeks

Lum et al, 199648

Comparison: Traditional vs. Hydrogel (Intrasite)Mean baseline area (cm2): 18.6 36.3

(range, 1.0–72.5) (range, 1.5–160)Sample size (patients): 3 5Mean absolute change reduction in wound area (cm2): +1.9 (n = 3) –20.4 (n = 5) 22.3Mean % reduction in wound area: +10 (n = 3) –56 (n = 5) 66

Traditional therapy: Saline alone or with eusol where the wound was infectedWound type: Pressure soresFollow-up time: 8 weeks

Mulder et al, 199349

Comparison: Control vs. Hydrogel (Clearsite®)Mean baseline area (cm2): Not stated Not statedSample size (N): 21 20Mean % reduction in wound area per week (cm2): 5.1 8 2.9 (–6.45, 12.25)

(SD 14.8; n = 21) (SD 14.8; n = 20)Median % reduction in wound area per week (cm2): 7.0 (n = 21) 5.6 (n = 20) –1.4

Control treatment: Saline soaksWound type: Pressure soresFollow-up time: 8 weeks

Comparison: Traditional vs. Hydrogel (Clearsite)Mean baseline area (cm2): Not stated Not statedSample size (N): 20 20Mean % reduction in wound area per week (cm2) 3.3 8 4.7 (–11.55, 20.95)

(SD 32.7; n = 20) (SD 14.8; n = 20) Median % reduction in wound area per week (cm2) 7.4 (n = 20) 5.6 (n = 20) –1.8

Traditional therapy: DuoDermWound type: Pressure soresFollow-up time: 8 weeks

Biofilm®, Braun Biotrol;Transorbent®, Braun Medical;Duoderm®, UK equivalent Granuflex, ConvaTec Ltd;Clearsite®, New Dimensions in Medicine

FIGURE 3 Hydrogels compared with traditional or control treatments


15

–200 –100 0 100 200

0.01 0.1 1 10 100

Favours alternative Favours enzyme


Westerhof et al, 198752

Comparison: Control vs. Enzyme (Elase®)Mean baseline area (cm2): 20.2 (range, 2–48) 25.7 (range, 2–273)Sample size (N): 17 16No. of wounds sucessfully grafted or healed (n/N): 6/17 (35%) 11/16 (69%) 4.03 (0.94, 17.23)

Mean baseline area (cm2): 22.3 (range, 3–48) 14.9 (range, 2–48)Sample size (N): 8 6No. of complex wounds successfully grafted or healed (n/N): 3/8 (38%) 3/6 (50%) 1.67 (0.20, 14.27)

Mean baseline area (cm2): 18.1 (range, 2–40) 36.4 (range, 3–273)Sample size (N): 9 10No. of venous ulcers successfully grafted or healed (n/N): 3/9 (33%) 8/10 (80%) 8.00 (1.00, 64.00)

Control: Placebo (freeze-dried powder, no active ingredients)Wound type: Leg ulcers Follow-up time: Until ulcers ready for grafting

Lee and Ambrus, 197550

Comparison: Control vs. Enzyme (Santyl®)Mean baseline volume (cm3): 1.25 (SD 1.62) 15.44 (SD 19.92)Sample size (N): 11 17Mean % increase in wound volume: 13.14 78.79 65.65 (1.72, 129.58)

(SD 49.8; n = 11) (SD 94.6; n = 17)

Control therapy: Placebo (heat-inactivated enzyme)Wound type: Pressure soresFollow-up time: 4 weeks

Gordon, 197551

Comparison: Control vs. Enzyme (Chymacort®)Mean baseline area (cm2): 14.5 (SD 22.13) 15.82 (SD 19.67)Sample size (N): 9 10No. of wounds healed (n/N): 0/9 (0%) 2/10 (20%) 5.59 (0.23, 133.71)Mean absolute reduction in ulcer area (cm2): 6.1 10.5 4.40 (–9.92, 18.72)

(SD 13.2; n = 8) (SD 15.0; n = 10)Mean % change in wound size +47 –71.8 118.80 (–50.20, 287.50)

(SD 252.8; n = 8) (SD 22.5; n = 10)

Control therapy: Hydrocortisone and neomycin palitateWound type: Leg ulcers Follow-up time: 6 weeks

Ågren and Strömberg, 19859

Comparison: Traditional vs. Enzyme (Varidase) Mean baseline area (cm2): 5.8 4.2

(range, 1.2–26.0) (range, 1.2–18.2)Sample size (N): 14 14Median % change in wound area: –2.4 (n = 14) +18.7 (n = 11) –21.1

Traditional therapy: Zinc oxide dressingWound type: Pressure soresFollow-up time: 8 weeks


Comparison: Traditional vs. Enzyme (Santyl) Mean baseline area (cm2): 5.76 10.24Sample size (n/N): 9 11No. of wounds healed (n/N): 0/9 (0%) 1/11 (9%) 2.71 (0.098, 75.05)

Traditional therapy: Sugar and egg whiteWound type: Pressure soresFollow-up time: 4 weeks

Elase®, manufacturer unknown;Santyl®, Knoll Pharmaceutical Co;Chymacort®, Armour Pharmaceutical Company Ltd

FIGURE 4 Enzymatic agents compared with traditional or control treatments

Results

16

–20 –10 0 10 20

0.1 0.2 1 5 10



for median

for range

Tarvainen, 198854

Comparison: Dextranomer vs. Cadexomer iodineMean baseline area (cm2): Not stated Not statedSample size (N): 13 14No. of wounds healed (n/N): 2/13 (15%) 7/14 (50%) 5.50 (0.88, 34.48)

Wound type: Leg ulcersFollow-up: 8 weeks

Moss et al, 198713

Comparison: Dextranomer vs. Cadexomer iodineMean baseline area (cm2): 25.5 (SD 29.5) 19.7 (SD 19.8)Sample size (N): 21 21Mean % reduction in wound area: 3 (CI: 4, –9; n = 21) 4 (CI: 5, –14; n = 21) 1 (–10.28, 12.28)

Wound type: Venous leg ulcersFollow-up: 6 weeks

Stewart and Leaper, 198755

Comparison: Hydrogel (Scherisorb®) vs. Cadexomer iodineMedian baseline area (cm2): 2.6 2.8

(range, 0.4–74.4) (range, 0.2–50.5)Sample size (N): 49 46No. of wounds healed (n/N): 14/49 (29%) 14/46 (30%) 1.09 (0.45, 2.64)

Wound type: Leg ulcers of mixed aetiologyFollow-up: 10 weeks

Scherisorb®, presently Intrasite Gel

FIGURE 5 Cadexomer iodine polysaccharide compared with other debriding agents


17

–30 –15 0 15 30

0.01 0.1 1 10 100

Favours alternative Favours dextranomer


Colin et al, 199656

Comparison: Hydrogel (Intrasite) vs. DextranomerBaseline area: 4 cm2: 15 ulcers 18 ulcers

4–13 cm2: 25 ulcers 25 ulcers > 13 cm2: 27 ulcers 25 ulcers

Sample size (N): 67 68No. of wounds 100% cleansed (n/N): 13/67 (19%) 14/68 (21%) 1.08 (0.46, 2.51)No. of wounds 75–100% cleansed (n/N): 33/67 (49%) 29/68 (43%) 0.77 (0.39, 1.51)Median % reduction in wound area: 35 7 –28

(range,–185–+91; (range, –340–+98;n = 53) n = 43)

Median % reduction in non-viable tissue: 74 (range, –103–+100; 62 (range, –340–+100; –12

n = 53) n = 43)

Wound type: Pressure soresFollow-up time: 3 weeks

Thomas and Fear, 199357

Comparison: Hydrogel (Intrasite) vs. DextranomerMean baseline (cm2): 22.2 (SD 23.4) 15.6 (SD 16.2)Sample size (N): 21 20 No. of wounds fully cleansed (n/N): 8/20 (40%) 1/20 (5%) 0.08 (0.01, 0.71)



Comparison: Enzyme (Santyl) vs. DextranomerMean baseline (cm2): 10.24 20.25Sample size (N): 11 14 No. of wounds healed (n/N): 1/11 (9%) 6/14 (43%) 7.50 (0.74, 75.72)


Hulkko et al, 198158

Comparison: Enzyme (Varidase) vs. DextranomerMean baseline (mm): Not stated Not statedSample size (N): 13 18Mean % reduction in wound diameter: 11.9 (n = 12) 14.5 (n = 15) 2.6Mean absolute reduction in wound diameter (mm): 9.8 (n = 12) 9.3 (n = 15) 0.5

Wound type: Venous ulcersFollow-up time: 2 weeks

FIGURE 6 Dextranomer polysaccharide compared with other debriding agents

Results

18

–10 –5 0 5 10

0.01 0.1 1 10 100

Favours Intrasite Favours Granugel


Gibson, 199559

Comparison: Hydrogel (Intrasite) vs. Hydrogel (Granugel)Mean baseline area (cm2): 18.7 24.9Sample size (N): 32 30Mean % reduction in wound area after 21 days: 10 (n = 32) 14 (n = 30) 4Mean % reduction in slough area after 21 days: 32 (n = 32) 37 (n = 30) 5Median absolute reduction in wound area (cm2) after 7 days: 0.54 (n = 32) 0.74 (n = 30) 0.2Median absolute reduction in slough area after 7 days (cm2): 1.12 (n = 32) 1.51 (n = 30) 0.4

Wound type: Leg ulcersFollow-up time: 3 weeks

FIGURE 7 Comparison between hydrogels

–10 –5 0 5 10

0.01 0.1 1 10 100

Favours Trypure Favours Varidase


Hellgren, 198360

Comparison: Enzyme (Trypure®) vs. Enzyme (Varidase)Mean baseline area (cm2): Not stated Not statedSample size (N): 19 21No. of wounds fully cleansed (n/N): 5/19 (26%) 13/21 (62%) 3.58 (0.90, 14.16)Mean % granulated area at 14 days: 56 (n = 16) 60 (n = 21) 4

Wound type: Leg ulcersFollow-up time: 3 weeks

Trypure®, Novo Laboratories

FIGURE 8 Comparison between enzyme treatments


19

There are no RCTs comparing debridementwith no debridement. A limited number of

trials have employed an inert or placebo com-parison, but the extent to which even secondarydressings contribute to wound healing is unclear.Given the multi-faceted way that topical debridingagents are thought to work, the obvious study toanswer the question of whether debridement is a necessity for wound healing would be a com-parative evaluation of surgical, or sharpdebridement with no debridement.

The majority of trials investigated debridement of either pressure sores or venous ulcers and forthese wounds the debriding agent generally showeda benefit over traditional or control treatments.However, without conclusive evidence that debride-ment is an important procedure for wound healing,it is not possible to determine whether the benefitover traditional treatment is a true assessment ofeffectiveness, or a consequence of harm induced by the traditional therapies.

Although evidence in the form of RCTs is lacking,many clinicians believe that debridement facilitateswound closure by removing necrotic tissue that actsas a barrier to new tissue growth. This suggests thatif debridement really does aid wound closure thenthe effectiveness of a debriding agent should bemeasured by an outcome based on wound healing.Even though the debriding agent is not necessarilyused throughout the entire healing process anoutcome measure based on healing remains validas long as both comparison groups follow a similarschedule of nursing care after the debridementperiod. In this way, any difference in healing ratesbetween groups can be attributed to the debridingagent used. Some researchers however, haveattempted to estimate the effectiveness of theseagents by measuring the degree of debridementexpressed as the percentage area of wound coveredin necrotic material. This measurement may not be a reliable indication of treatment effect as theextent of debridement does not appear to havebeen scientifically validated as a surrogate or proxy measure of wound healing.

The results reported in many of the includedstudies are biased by a lack of comparabilitybetween the groups for wound size at baseline.

The underlying bias is frequently in the directionof the treatment effect, suggesting that the studyresults should be viewed cautiously. A statisticallysignificant study result favouring one treatmentover another can only be considered valid if it isobtained either: against the anticipated direction of the bias for wound size, or where percentagearea change and absolute area change are in thesame direction. When baseline data are not givenfor wound size it is not possible to estimate thedegree of bias, and in the absence of otherindicators, validity of the trial result should be considered doubtful.

Analysis of studies where patients received atraditional or control therapy in the comparisonarm indicates that the validity of the outcomemeasure, according to baseline comparability, was doubtful in about 70% of the trials. In theremaining 30%, where wound size bias was unlikely to have affected the outcome measure, the OR or ES was in the direction of the debridingagent in over 88% of cases, though only two studiesobtained statistical significance. In other wordsthose studies with the most reliable results indicatethat treatment with a known debriding agent isfavourable to traditional or control therapy.

Analysis by intervention type suggests that bothdextranomer polysaccharide and cadexomer iodinepolysaccharide may improve wound healing whencompared with a traditional or control therapy.However, evidence for the use of hydrogels orenzymatic agents in preference to traditional orcontrol treatment is less convincing as, with theexception of one trial,46 these debriding agents did not show a statistically significant improvementin wound closure. The lack of evidence for theeffectiveness of enzymatic agents suggests thatcareful consideration should be given to thecontinued use of streptokinase/streptodornase,given that its topical application is known to inducethe production of anti-streptokinase antibodies,which could theoretically put patients at risk ifgiven streptokinase immediately following amyocardial infarction.61

In drawing these conclusions on effectiveness it is necessary to bear in mind that many of thetraditional treatments employed as comparators

Chapter 4

Discussion

Discussion

20

are no longer used in clinical practice, and somemay even have a detrimental effect on healing. Thisimplies that relative effectiveness, as recorded inmany of the trials, may be an over-estimate of whatwe might expect to obtain in a similar trial today.

Recently, there have been several non-systematicnarrative reviews in nursing-orientated publi-cations, which have suggested that hydrogels are the non-mechanical debridement agent ofchoice.2,62 In terms of scientific evidence, such a statement can only be supported by trials thatdirectly compare two or more debriding agents;such trials, however, are relatively rare in theliterature and are generally of poor quality. Usingthe criteria previously described, around 40% ofcomparisons between debriding agents had a validresult, but only one trial found a statistically signifi-cant difference between treatments.57 The smallnumber of reliable trials and the diversity of com-parisons implies that there is insufficient evidenceto promote the use of one debriding agent overanother on the basis of effectiveness alone.

In wound care research it is not uncommon for trials to be associated with funding from thepharmaceutical industry. This may in part explainthe lack of direct comparisons between different,commercially important debriding agents. Apharmaceutical company is unlikely to be willing to compare its product with that of a competitor if the product has only shown marginal benefitsover traditional or control treatments.

A pooled estimate of effectiveness for each debrid-ing agent has not been calculated; to do so wouldbe inappropriate considering the heterogeneousnature of the studies and the potential biases due to differences in wound size at baseline. Poolingwould compound these biases and result in an over-estimate of effectiveness, particularly consideringthe likely influence of publication bias favouringpositive outcomes. If similar trials reported bothabsolute and percentage reductions in ulcer sizethen a pooled estimate could be calculated for eachof the outcomes, which would provide a reasonableestimate of effectiveness. Unfortunately, this is rarelythe case and where sufficient details are providedthere are other differences between studies, such as wound type, follow-up time, the presence of other underlying conditions such as ischaemia, and the variability of traditional treatments within a single comparison group which make combiningresults inappropriate.

A multiplicity of traditional therapies are frequentlyemployed in the same trial to act as a comparator

with a single debriding agent. Although it could be argued that this reflects typical clinical practiceit makes interpretation of the results very difficult.It is likely that within such a varied group oftraditional treatments there will be considerablevariation in effectiveness. It is possible also that one of these treatments may be equally, if not more effective, than the debriding agent underevaluation, but that its beneficial effect is maskedby the other less effective treatments within thegroup. It is also possible that treatment care mayvary depending on the care givers familiarity witheach of the traditional treatments employed. This is less likely to be an issue in the application of a homogeneous debriding agent.

Different debriding agents may be more appro-priate for different types of wound because themode of action employed by each agent to facili-tate wound healing differs. For example, twostudies compared the same hydrogel with dextra-nomer polysaccharide for the treatment of pres-sure sores.56,57 Dextranomer polysaccharide isthought to actively absorb water and necroticmaterial from the wound bed, whereas thehydrogel is believed to liquefy the wound andmaintain a moist environment that facilitates auto-debridement.57 Clearly these two agents work in very different ways and their effectiveness is likely to depend on the type of wound to whichthey are applied. Dextranomer polysaccharide isthen recommended for the treatment of moist,yellow sloughy wounds, while a hydrogel, althougha generalist agent, is recommended particularly for dry necrotic wounds.10 Comparisons betweendebriding agents should then take into account the local nature of the wound under examinationwhen assessing effectiveness.

The categories used in this review to groupdebridement interventions could be misleadingbecause they may mask pharmaceutical develop-ments. For example, the formulation of IntrasiteGel has changed over time, and that used in a trialin the late 1980s is unlikely to be the same as thatused in the early 1990s. The vehicle used for atreatment may also vary. For example, dextranomerpolysaccharide can be applied as either beads or asa paste with polyethylene glycol, and the nature ofthis vehicle may have consequences for effective-ness. Considering all dextranomer polysaccharidetrials together does not take into account thesepotential differences. However, only by groupingthese interventions under broad categories can a general overview of effectiveness be gained, andas the data are not statistically pooled erroneousinterpretations are avoided. In addition, both


21

clinicians and patients alike are primarilyconcerned with whether a treatment works rather than its mode of action. If the subtledifferences identified between products in thelaboratory do not translate into improved woundhealing rates in clinical practice, then there is little benefit in discussing differences in product formulation.

Quality assessment indicates that most studiesincluded in the review have methodological flawsthat affect their validity. In general, the RCTs aretoo small to ensure that wounds of different sizesare equally allocated to both experimental groups.This suggests that most trials will be subject to abias at baseline. Most trials had a short follow-up,which mitigates against the outcome of the numberof wounds healed. Studies that employ such anoutcome measure should analyse the data using‘survival analysis’, which takes into account bothwhether and when a wound healed; in this way it isa more efficient method for estimating the rate ofhealing. Many of the studies also excluded sick,debilitated or confused patients and those withdiseases that affect healing, such as diabetes andrheumatoid arthritis. These are the very patientswhose wounds tend to be chronic and are there-fore the most likely to be prescribed debridingagents in practice. In general then, the patientsenrolled into a trial are a highly selected group and are unlikely to be representative of the thoseencountered in clinical practice.

Subjective outcome measures such as degrees of oedema, erythema, granulation, pus and debrisare frequently recorded by authors, but are notconsidered in this review. These outcomes are more susceptible to bias as the assessor may have an unconscious preference for one of the treat-ments. Analysis of subjective outcomes nearlyalways produced a statistically significant result in favour of the experimental treatment. Similarly,other variables that are likely to influence treat-ment choice such as pain, comfort and quality of life issues, are not addressed in this reviewbecause the outcome measures employed had

not been validated and were likely to result inmisleading information.

Larval (maggot) therapy has had a long history,and is enjoying a resurgence of interest in the UK.4 However, evidence for effectiveness remainsrestricted to case reports and anecdotal articles;there is presently no research evidence to supportclaims of effectiveness. Considering the highprofile of this intervention, clinical trials, partic-ularly RCTs, are urgently required.

Publication bias appears to be present in debride-ment studies with the majority of trials favouringthe debriding agent under evaluation. This may bea reflection of commercial interests in many of theincluded trials. Even if a debriding agent was effec-tive, one would expect by chance to get occasionalresults from studies that found in favour of thealternative treatment, particularly because of thesmall sample size of the RCTs, giving moreopportunity for chance variation.

Future trials that assess wound healing need to be larger in terms of patient numbers than themajority of those reviewed here. The design ofsmaller trials could be improved by the use ofmatched or stratified randomisation to ensurecomparability between treatment groups atbaseline: patients should be stratified based onwound type and size at baseline and these group-ings should then be randomised to treatment. Ifpatients have been matched for wound size andtype then matched pairs analysis should be used toanalyse the data. But even with this type of designthe trial still needs to be large enough to ensurecomparability for other features and confoundingfactors, such as age or duration of the wound.

Planned and future studies would also benefit from the inclusion of a detailed cost-effectivenessanalysis. Several reports included in this reviewdetailed the costs incurred during the trial period,but unfortunately none of the studies providedsufficient detail for a reliable cost-effectivenessanalysis to be constructed.


23

There is some, if limited, evidence to suggestthat the use of a specific debriding agent is

beneficial for wound healing when compared with certain traditional or control treatments. In contrast, there is little or no evidence to suggestthat one debriding agent is more effective than any other.

Implications for policy

As the benefits shown over traditional or controltreatments are at best marginal, the choice ofwhich debriding process to adopt should perhapsbe based on the relative cost of the treatments,unless clinical experience suggests otherwise.There is little reliable research evidence to suggest that the more expensive agents should be used in preference to some of the less costlyones. However, this decision should not be basedon the net cost of each treatment as this does nottake into account important variables, such as thenumber of dressing changes required, coverage of the wound area, or nursing time. The financialcost of a treatment can only be determined fromstudies designed specifically to address this issueand this should be seen as a priority for future research.

Recommendations for research

Much of the research into wound debridement is of poor quality and direct comparisons are few.In those trials reviewed, sample sizes were rarelysufficient to detect clinically important effects, and poor baseline comparability frequentlyconfounded outcome measures. Several importantmessages can be identified for future studies.

• Recruitment numbers should be based on an a priori sample size calculation, though this maybe complicated by the lack of trials on which tobase such a calculation.

• The proportion of wounds healed should beused as an objective outcome measure. Wherehealing rates are based on wound area both thepercentage and absolute change in area shouldbe given.

• Experimental groups should be comparable at baseline. In small RCTs, randomisation alonewill not achieve comparability; in such situationspatients should be paired by baseline character-istics and then the individuals of each pair ran-domised to treatment. However, with particularlysmall groups, pairing of patients is still unlikelyto ensure that all risk factors (known and un-known) are distributed equally between thegroups, and hence, large sample size should still be the ultimate goal.

• Baseline data and intervention details shouldalways include a thorough description of how the patients were nursed and the use of concurrent treatments including secondary dressings.

• Comparisons between debriding agents arerequired and should use agents that arerecommended for wounds of a similar nature.

• Assessment should be blind to treatment.• Survival rate analysis should be adopted for

all studies that assess wound healing.• All RCTs should be published.• Detailed cost-effectiveness analyses should be

seen as a priority for future trials.• RCTs of both surgical and larval debridement

have not been performed. The frequent use of surgical debridement and the increasinginterest in the larval therapy indicate that these trials are needed.

Chapter 5

Conclusions


25

This review was commissioned by the NHS R&D HTA programme. The authors are

indebted to Julie Glanville and Alison Fletcher for assistance with the search, location andcollection of literature. We are also grateful

to our expert panel (appendix 4) for their helpful comments on the review protocol and draft report. The report also benefited greatly from comments received from the HTA referees.

Acknowledgements


27

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16. Fear M, Thomas S. Wound cleansing properties of Debrisan and Scherisorb gel: interim results of a clinical trial. Proceedings of the 1st EuropeanConference on Advances in Wound Management.London: Macmillan Ltd, 1992;1:162–4.

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19. Colin D, Kurring PA, Quinlan D, Yvon C. The clinicalinvestigation of an amorphous hydrogel comparedwith a dextranomer paste dressing in the manage-ment of sloughy pressure sores. Proceedings of the5th European Conference on Advances in WoundManagement. London: Macmillan Ltd, 1996;5:151–5.

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23. Skog E, Arnesjö B, Troëng T, Gjöres JE, Bergljung L,Gundersen J, et al. A randomized trial comparingcadexomer iodine and standard treatment in theout-patient management of chronic venous ulcers.Br J Dermatol 1983;109(1):77–83.

24. Eriksson G, Eklund AE, Kallings LO. The clinicalsignificance of bacterial growth in venous leg ulcers.Scand J Infect Dis 1984;16(2):175–80.

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26. Leaper DJ, Stewart AJ. A comparative trial ofScherisorb gel and cadexomer iodine: problems ofcommunity-based trials involving chronic leg ulcers.In: Turner TD, Schmidt RJ, Harding KG, editors.Advances in wound management. Chichester: Wiley, 1986:121–6.

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32. Sayag J, Meaume S, Bohbot S. Healing properties of calcium alginate dressings. J Wound Care1996;5(8):357–62.

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35. Goode AW, Glazer G, Ellis BW. The cost-effectiveness of Dextranomer and Eusol in thetreatment of infected surgical wounds. Br J ClinPract 1979;33:325–8.

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38. Laudanska H, Gustavson B. In-patient treatment ofchronic varicose venous ulcers. A randomized trialof cadexomer iodine versus standard dressings. J Int Med Res 1988;16(6):428–35.

39. Holloway GA, Jr, Johansen KH, Barnes RW, PierceGE. Multicenter trial of cadexomer iodine to treatvenous stasis ulcer. West J Med 1989;151(1):35–8.

40. Harcup JW, Saul PA. A study of the effect ofcadexomer iodine in the treatment of venous leg ulcers. Br J Clin Pract 1986;40(9):360–4.

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42. Apelqvist J, Ragnarson-Tennvall G. Cavity foot ulcers in diabetic patients: a comparative study of cadexomer iodine ointment and standardtreatment. Acta Derm Venereol 1996;76:231–5.

43. Moberg S, Hoffman L, Grennert ML, Holst A. Arandomized trial of cadexomer iodine in decubitusulcers. J Am Geriatr Soc 1983;31(8):462–5.

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47. Brown-Etris M, Fowler E, Papen J, Stanfield J, HarrisA, Tintle T, et al. Comparison and evaluation of theperformance characteristics, usability and effective-ness on wound healing of Transorbent versusDuoDerm CGF. Proceedings of the 5th EuropeanConference on Advances in Wound Management.London: Macmillan Ltd, 1996;5:151–5.

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31

MEDLINE has been searched for RCTs from1966 to October 1997 using a mixture of free

text terms and MEDLINE search headings:

Wound infection Pilonidal cyst Wounds and injuries Wound healing Leg ulcer Varicose ulcer Skin ulcer Decubitus

The MEDLINE search strategy used is as follows:

decubitus ulcer/ or foot ulcer/ leg ulcer/ or varicose ulcer/ pilonidal cyst/ skin ulcer/ diabetic foot/ ((plantar or diabetic or heel or venous or stasis orarterial) adj ulcer$).tw. ((decubitus or foot or diabetic or ischaemic orpressure) adj ulcer$).tw. ((pressure or bed) adj sore$).tw. ((pilonidal adj cyst) or (pilonidal adj sinus) orbedsore$).tw. ((diabetic adj foot) or (cavity adj wound)).tw. ((varicose or leg or skin) adj ulcer$).tw. (decubitus or (chronic adj wound$)).tw. ((sinus adj wound$) or (cavity adj wound$)).tw.

or/1-13

debridement/ or biological dressings/ orbandages/ occlusive dressings/ or clothing/ or woundhealing/ antibiotics/ or growth substances/ or platelet-derived growth factor/ fibroblast growth factor/ or electrical stimulationtherapy.ti,ab,sh. lasers/ or nutrition/ or surgery/ or surgery,plastic/ surgical flaps/ or skin transplantations/ orhomeopathy/ or homeopathic/ acupuncture therapy/ or acupuncture/ oralternative medicine/ alternative medicine/ or massage/ or iloprost/ or alginates/

zinc/ or zinc oxide/ or ointments/ or anti-infective agents/ dermatologic agents/ or colloids/ or cushions/ or wheelchairs/ beds/ or wound dressings/ (debridement or dressing$ or compress$ or cream$ or (growth adj factor$)).tw. (pressure-relie$ or (recombinant adj protein$) or bandag$ or stocking$).tw. (antibiotic$ or (electric adj therapy) or laser$ ornutrition$ or surg$).tw. (homeopath$ or acupunture or massage orreflexology or ultrasound).tw. (iloprost or alginate$ or zinc or paste$ orointment$ or hydrocolloid$).tw. ((compression adj therapy) or (compression adjbandag$) or wrap$).tw. (bed$ or mattress$ or wheelchair$ or (wheel adjchair) or cushion$).tw. ((wound adj dressing$) or vitamin$ or bind$ orgauze$ or heals or healing).tw. (diet or lotion$ or infect$ or reduc$ or (wound adjhealing)).tw. (treat$ or prevent$ or epidemiol$ or aetiol$ oretiol$ or therap$ or prevalence or incidence).tw.

or/15–35 14 and 36

random allocation/ or randomized controlledtrials/ controlled clinical trials/ or clinical trials phase I/or clinical trials phase II/ clinical trials phase III/ or clinical trials phase IV/ or clinical trials overviews/ single-blind method/ or double-blind method/ publication bias/ or review/ or review, academic/ review tutorial/ or meta-analysis/ or systematicreview/ ((random$ adj controlled adj trial$) or(prospective adj random$)).tw. ((random adj allocation) or random$ or (clinicaladj trial$) or control$).tw. ((standard adj treatment) or compar$ or single-blind$ or double-blind$).tw. (blind$ or placebo$ or systematic$ or (systematicadj review)).tw. (randomized controlled trial or clinical trial).pt. orcomparative study.sh.

Appendix 1

MEDLINE search strategy

Appendix 1

32

or/38-48 37 and 49 limit 50 to human

burns/ or wounds, gunshot/ or corneal ulcer/ orexp dentistry/ peptic ulcer/ or duodenal ulcer/ or stomachulcer/

((peptic adj ulcer) or (duodenal adj ulcer) ortraum$).tw. ((aortocaval adj fistula) or (arteriovenous adjfistula)).tw. (bite adj wound$).tw.

or/52–56 51 not 57


33

Other databases that have been searched forRCTs are:

EMBASE [to October 1997] CINAHL (Cumulative Index of Nursing and Allied Health Literature) [to April 1997]

The CINAHL search strategy used is as follows:

pressure ulcer/ or foot ulcer/ or leg ulcer/ or skin ulcer/ diabetic foot/ or diabetic neuropathies/ diabetic angiopathies/ or diabetes mellitus/co pilonidal cyst/ or surgical wound infection/ ((plantar or diabetic or heel or venous or stasis or arterial) adj ulcer$).tw. ((decubitus or foot or diabetic or ischaemic orpressure) adj ulcer$).tw. ((pressure or bed) adj sore$).tw. ((pilonidal adj cyst) or (pilonidal adj sinus) orbedsore).tw. ((diabetic adj foot) or (cavity adj wound)).tw. ((varicose or leg or skin) adj ulcer$).tw. (decubitus or (chronic adj wound$)).tw. ((sinus adj wound$) or (cavity adj wound$)).tw.

or/1–12

debridement/ or biological dressings/ or occlusivedressings/ (bandages.ti,sh,ab,it. and “Bandages andDressings”/) or compression garments/ or antibiotics/ electric stimulation/ or Laser Surgery/ or lasers/thlasers/ or Nutrition Care (Saba HHCC)/ or diettherapy/ or Nutrition Therapy (Iowa NIC)/ surgery, reconstructive/ or surgery, plastic/ orsurgical flaps/ surgical stapling/ or skin transplantation/ oralternative therapies/ acupuncture/ or massage/ or zinc/ or ointments/ antiinfective agents, local/ or antibiotics/ ordermatologic agents/ dermatology nursing/ or colloids/ or beds nadmattresses/ flotation beds/ or wheelchairs/ orpositioning:wheelchair/ or positioning:therapy/ patient positioning/ or positioning/ or woundcare/ or wound healing/

(debridement or dressing$ or compress$ orcream$).tw. ((growth adj factor$) or pressure relie$ or(recombinant adj protein$) or bandag$).tw. (stocking$ or antibiotic$ or (electric adj therapy)or laser$ or nutrition$ or surg$).tw. (iloprost or alginate$ or zinc or paste$ orointment$ or hydrocolloid$).tw. ((compression adj therapy) or (compression adjbandag$) or wrap$).tw. (bed$ or mattress$ or wheelchair$ or (wheel adjchair) or cushion$).tw. ((wound adj dressing$) or vitamin$ or bind$ orgauze$ or heals or healing).tw. (diet or lotion$ or infect$ or reduc$ or etiol$ or(wound adj healing)).tw. (treat$ or prevent$ or epidemiol$ or aetiol$ ortherap$ or prevalence or incidence).tw. “Bandages and dressings”/ or skin transplantation/or homeopathy/ or ointments/ or “beds andmattresses”/

or/14–34 13 and 35

clinical trials/ or single-blind studies/ or double-blind studies/ control group/ or placebos/ or meta analysis/ ((random$ adj clinical adj trial$) or (prospectiveadj random$)).tw. ((random adj allocation) or random$ or controlledclinical trial$ or control).tw. (comparison group$ or (standard adj treatment) orcompar$).tw. (single-blind$ or (single adj blind) or double-blindor (double adj blind)).tw. (blind$ or placebo$ or systematic or (systematic adjreview)).tw. (meta analysis or meta-analysis).tw. or (trials or trialor prospective).tw. (clinical trials).sh. or (comparative studies).sh .

or/37–45 36 and 46

burns/ or wounds, gunshot/ or corneal ulcer/ orexp dentistry/ peptic ulcer/ or duodenal ulcer/ ((peptic adj ulcer) or (duodenal adj ulcer) ortrauma).tw.

Appendix 2

CINAHL and EMBASE search strategy

Appendix 2

34

(burn$ or (gunshot adj wound$) or (corneal adjulcer) or dentist$ or (bite adj wound)).tw. or/48–51

47 not 52


35

ISI Science Citation Index (on BIDS)

BIOSIS (on Silver Platter)

British Diabetic Association Database

CINAHL (on OVID CD-ROM)

CISCOM, the database of the Reseach Council for Complementary Medicine

Cochrane Database of Systematic Reviews (CDSR)

Cochrane Wounds Group Specialised Trials Register

Current Research in Britain (CRIB)

Database of Abstract of Reviews of Effectiveness(DARE)

Dissertation Abstracts

DHSS Data (on Knight-Ridder Datastar)

EconLit

EMBASE (on Knight-Ridder Datastar)

Index to Scientific and Technical Proceedings(searched on BIDS)

MEDLINE (on OVID CD-ROM)

National Research Register (to locate ongoingresearch in NHS)

NHS Economic Evaluation Database (NHS CRD)

Royal College of Nursing Database (CD-ROM)

System for Information on Grey Literature inEurope (SIGLE – on Blaise Line)

Appendix 3

Additional databases searched


37

Dr Mary Bliss, Consultant Geriatrician, Departmentof Medicine for the Elderly, Homerton Hospital,Homerton Row, London E9 6SR, UK.

Professor Nick Bosanquet, Imperial College Schoolof Medicine, Department of General Practice,Norfolk Place, London W2 1PG, UK.

Professor Andrew Boulton, Department ofMedicine, Manchester Royal Infirmary, OxfordRoad, Manchester M13 9WL, UK.

Dr Richard Bull, Department of Dermatology,Homerton Hospital, Homerton Row, London E9 6SR, UK.

Mr Michael Callam, Department of VascularSurgery, Bedford Hospital, South Wing, KempstonRoad, Bedford MK42 9DJ, UK.

Mrs Carol Dealey, Research Fellow, UniversityHospital Birmingham NHS Trust, Department ofNursing, Queen Elizabeth Medical Centre,Edgbaston, Birmingham B15 2TH, UK.

Professor Peter Friedmann, Dermatology Unit,University Medicine, Level F, Centre Block (Mail Point 825), Southampton General Hospital,Tremona Road, Southampton SO16 6YD, UK.

Mr Brian Gilchrist, Department of Nursing Studies,King’s College London, Cornwall House Annexe,Waterloo Road, London SE1 8TX, UK.

Dr Keith Harding, Director, Wound HealingResearch Unit, University of Wales College ofMedicine, University Department of Surgery, Heath Park, Cardiff CF4 4XN, UK.

Deborah Hofman, Dermatology Department,Churchill Hospital, Headington, Oxford OX3 7LJ, UK.

Vanessa Jones, Educational Facilitator, WoundHealing Research Unit, University Department of Surgery, Heath Park, Cardiff CF4 4XN, UK.

Dr Christina Lindholm, Nattarövägen 42, S-132 34 SaltsjöBoo, Sweden.

Dr Raj Mani, Southampton University HospitalsTrust, Medical Physics Department, Level D, Centre Block, Southampton SO9 4XY, UK.

Andrea Nelson, Department of Health Studies,University of York, Heslington, York YO1 5DD, UK.

Dr Steve Thomas, Director, Surgical MaterialsTesting Laboratory, Bridgend General Hospital,Bridgend, Mid Glamorgan, UK.

Dr Ewan Wilkinson, Liverpool Health Authority,Hamilton House, 24 Pall Mall, Liverpool L3 6AL, UK.

Appendix 4

Expert advisory panel


39

Appendix 5

Quality assessment

TABLE 4 Quality assessment of RCTs of debridement

Study Inclusion Total no. A priori Random- Appropriate Blinded Appropriate With- ITT and exclu- of wounds sample size isation baseline outcome outcome drawals† analysission criteria [arms] calculation procedure characteristics assessment measuresstated stated reported*

Ågren and Strömberg, ✗ 28 patients [2] ✗ ✔ ✔c ✗ ✔ ✔a ✗19859

Apelqvist et al, 199053 ✔ 44 patients [2] ✗ ✗ ✔c ✔ ✔ ✔a ✗

Apelqvist and Tennvall, ✔ 41 [2] ✗ ✔ ✗ ✔ ✔ ✔b ✗199642

Brown-Etris et al, ✔ 140 [2] ✗ ✗ ✔ ✔ ✔ ✔b ✗199647

Colin et al, 199656 ✔ 135 [2] ✔ ✗ ✔c ✗ ✔ ✔a ✔

Darkovich et al, 199046 ✔ 123[2] ✗ ✗ ✔c ✗ ✔ ✔a ✗

Eriksson et al, 198434 ✔ 53 [2] ✗ ✗ ✔ ✗ ✔ N/A N/A

Garcia et al, 198430 ✔ 44 [2] ✗ ✗ ✔ ✗ ✔ N/A N/A

Gibson, 199559 ✗ 62 [2] ✗ ✗ ✔c ✗ ✔ ✗ ✗

Goode et al, 197935 ✗ 20 [2] ✗ ✔ ✔ ✗ ✔ N/A N/A

Gordon, 197551 ✗ 19 [2] ✔ ✗ ✔c ✔ ✔ ✔a ✗

Groenewald, 198029 ✗ 100 [2] ✗ ✗ ✔c ✗ ✔ ✔a ✗

Harcup and Saul, 198640 ✔ 72 [2] ✗ ✗ ✔c ✗ ✔ ✔a ✔

Hellgren, 198360 ✔ 40 [2] ✗ ✗ ✔ ✔ ✔ ✔a ✗

Holloway et al, 198939 ✔ 75 [2] ✗ ✗ ✔c ✗ ✔ ✔a ✗

Hulkko et al, 198158 ✗ 31 [2] ✗ ✗ ✔ ✗ ✔ ✔b ✗

Laudanska and Gustavson, 198838 ✔ 60 [2] ✗ ✗ ✔c ✗ ✔ ✔b ✗

Lee and Ambrus, 197550 ✗ 28 [2] ✗ ✗ ✔c ✗ ✔ ✔a ✗

Lindsay et al, 198641 ✔ 28 [2] ✗ ✗ ✔ ✗ ✔ ✔a ✗

Lum et al, 199648 ✔ 20 [2] ✗ ✔ ✔c ✗ ✔ ✔a ✗

Moberg et al, 198343 ✔ 38 patients [2] ✗ ✗ ✔c ✔ ✔ ✔a ✗

Moss et al, 198713 ✔ 42 [2] ✗ ✗ ✔c ✗ ✔ ✔b ✗

Mulder et al, 199349 ✔ 64 patients [3] ✗ ✔ ✔ ✗ ✔ ✔b ✗

Nasar and Morley, 198236 ✔ 18 [2] ✗ ✗ ✗ ✔ ✔ ✔a ✗

✔ = Yes; ✗ = No; N/A = not appropriate (no withdrawals)* Baseline characteristics: ✔ = one or more appropriate characteristics stated (but not initial wound size); ✔c = initial wound size stated† Withdrawals: ✔a = reported by group and with reason; ✔b = withdrawals but not reported by group or reason not given; ✗ = withdrawals not reported

continued

Appendix 5

40

TABLE 4 contd Quality assessment of RCTs of debridement

Study Inclusion Total no. A priori Random- Appropriate Blinded Appropriate With- ITT and exclu- of wounds sample size isation baseline outcome outcome drawals† analysission criteria [arms] calculation procedure characteristics assessment measuresstated stated reported*

Ormiston et al, 198544 ✔ 61 [2] ✗ ✔ ✔c ✔ ✔ ✔a ✔

Palmieri, 199233 ✔ 48 [2] ✗ ✗ ✔ ✗ ✔ N/A N/A

Parish and Collins, ✗ 34 [3] ✗ ✗ ✔c ✗ ✔ N/A N/A197937

Sawyer et al, 197931 ✗ 37 [2] ✗ ✔ ✗ ✗ ✔ N/A N/A

Sayag et al, 199632 ✔ 92 [2] ✔ ✔ ✔c ✗ ✔ ✔a ✔

Skog et al, 1983;23 ✔ 95 [2] ✗ ✗ ✔c ✗ ✔ ✔a ✗Hillström, 1988;22

Troëng et al, 198328

Steele et al, 198645 ✔ 60 [2] ✗ ✔ ✔c ✗ ✔ ✔a ✗

Stewart and Leaper, ✔ 95 [2] ✗ ✔ ✔c ✗ ✔ ✔a ✗198755

Tarvainen, 198854 ✔ 27 [2] ✗ ✔ ✔ ✗ ✔ ✔a ✗

Thomas and Fear, 199357 ✔ 40 patients [2] ✗ ✔ ✔c ✗ ✔ ✔a ✔

Westerhof et al, 198752 ✔ 33 [2] ✗ ✔ ✔c ✔ ✔ ✔b ✗

✔ = Yes; ✗ = No; N/A = not appropriate (no withdrawals)* Baseline characteristics: ✔ = one or more appropriate characteristics stated (but not initial wound size); ✔c = initial wound size stated† Withdrawals: ✔a = reported by group and with reason; ✔b = withdrawals but not reported by group or reason not given; ✗ = withdrawals not reported


41

Appendix 6

Summary of studies

Appendix 6

42 TAB

LE 5

Dex

trano

mer

pol

ysac

char

ide

vers

us tr

aditi

onal

or

cont

rol t

reat

men

ts

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

Deb

risan

®,P

harm

acia

Upj

ohn

cont

inue

d

Erik

sson

et a

l,198

434

Swed

en

Wou

nd ty

pe:

Veno

us le

g ul

cers

.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

e:A

rea

and

volu

me

mea

sure

dby

ste

reop

hoto

gram

met

ricex

amin

atio

n.

Sett

ing

and

leng

th

of tr

eatm

ent:

Trea

ted

over

a

2-w

eek

perio

d.

Incl

usio

n cr

iteria

:O

utpa

tient

s w

ith v

enou

s le

g ul

cers

.

Excl

usio

n cr

iteria

:D

iabe

tes

mel

litus

;man

ifest

arte

rial i

nsuf

ficie

ncy;

clin

ical

pict

ure

of e

rysip

elas

or

cellu

litis.

Befo

re c

omm

ence

men

t th

e ge

nera

l hea

lth o

f all

part

icip

ants

and

the

stat

e of

veno

us a

nd a

rter

ial p

erip

hera

lci

rcul

atio

n w

ere

eval

uate

d.A

pre

ssur

e in

dex

ankl

e/ar

m o

fle

ss th

an 0

.75

was

con

sider

edpa

thol

ogic

al a

nd a

s su

ch a

nex

clus

ion

crite

ria.

Trea

tmen

t:I:

Dex

tran

omer

pol

ysac

char

ide

bead

s (D

ebris

an®) m

ixed

with

ster

ilise

d gly

cero

l and

cov

ered

with

gau

ze.T

he d

ress

ing

was

chan

ged

ever

y da

y fo

r th

e fir

stw

eek

and

ever

y se

cond

day

for

the

seco

nd w

eek,

n =

26.

C:S

teril

ised

gauz

e so

aked

in

0.9%

(w/v

) sod

ium

chl

orid

e in

wat

er.T

he g

auze

was

moi

sten

edre

gula

rly th

roug

h th

e da

y,n

= 27

.

Prio

r to

the

initi

al tr

eatm

ent a

ndat

the

star

t of t

he s

econ

d w

eek

oftr

eatm

ent,

all u

lcer

s w

ere

bath

edfo

r 15

min

in w

ater

con

tain

ing

1 m

l/l o

f 3%

(w/v

) pot

assiu

mpe

rman

gana

te.C

rust

and

deb

risw

ere

rem

oved

.

Mea

n w

ound

are

a (c

m2 ):

Not

sta

ted.

Oth

er c

hara

cter

istic

s:A

ll gr

oups

Mea

n ag

e (y

ears

):70

.1M

:F r

atio

:1:

3.1

Mea

n du

ratio

n (m

onth

s):

No

deta

ils

Both

gro

ups

com

para

ble

for

all

back

grou

nd c

hara

cter

istic

s ex

cept

elev

ated

blo

od g

luco

se le

vels

and

ahi

stor

y of

pre

viou

s th

rom

bosis

(bot

h th

ese

fact

ors

are

nega

tivel

yco

rrel

ated

with

ulc

er h

ealin

g):

Hig

hH

istor

y of

gluc

ose

leve

lsth

rom

bosis

I:8%

16%

C:

30%

38%

Num

ber

of w

ound

s de

crea

sed

in

% a

rea:

> 50

5025

I:2

814

C:

65

10

Num

ber

of w

ound

s in

crea

sed

in

% a

rea:

> 50

5025

I:0

11

C:

03

3

Num

ber

of w

ound

s de

crea

sed

in

% v

olum

e:>

5050

25I:

46

11C

:9

16

Num

ber

of w

ound

s in

crea

sed

in

% v

olum

e:>

5050

25I:

02

3C

:0

56

No

stat

istic

al d

iffer

ence

bet

wee

n th

e tw

o tr

eatm

ents

was

foun

d.

No

with

draw

als.

Pain

as

judg

ed b

y th

e pa

tient

sho

wed

a r

educ

tion

in th

e I (

dext

rano

mer

) gro

up(p

< 0.

05).

Cha

nges

in a

rea

wer

e fo

und

to b

e hi

ghly

cor

rela

ted

with

bac

kgro

und

varia

bles

:el

evat

ed g

luco

se le

vels

resu

lted

in s

low

er h

ealin

g as

did

a h

istor

y of

pre

viou

sth

rom

bosis

.

Bact

eria

l flo

ra r

emai

ned

unch

ange

d th

roug

hout

the

stud

y irr

espe

ctive

of

trea

tmen

t.

Gar

cia

et a

l,198

430

Spai

n

Wou

nd ty

pe:

Seco

ndar

y pe

rimal

leol

arul

cers

.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

e:A

rea

and

circ

umfe

renc

e of

the

wou

nd m

easu

red

by p

lani

met

ry.

Sett

ing

and

leng

th o

ftr

eatm

ent:

Hos

pita

l and

com

mun

ity-b

ased

tria

l ov

er a

3-w

eek

perio

d.

Incl

usio

n cr

iteria

:Pa

tient

s w

ith s

econ

dary

perim

alle

olar

ulc

ers

and

chro

nic

veno

us in

suffi

cien

cy

Excl

usio

n cr

iteria

:Pa

tient

s no

t sub

mitt

ed fo

rsu

rgic

al tr

eatm

ent.

Trea

tmen

t:I:

Dex

tran

omer

pol

ysac

char

ide

bead

s (D

ebris

an),

n =

22.

C:P

otas

sium

per

man

gana

te 1

/500

0an

d hy

pert

onic

sal

ine

or a

ntib

iotic

oint

men

ts,n

= 2

2.

Mea

n w

ound

are

a:N

ot s

tate

d.

Oth

er c

hara

cter

istic

s:A

ll gr

oups

Mea

n ag

e (y

ears

):56

.5M

:F r

atio

:2.

2:1

Mea

n du

ratio

n (m

onth

s):

164

33 p

atie

nts

requ

ired

hosp

italis

atio

nw

hile

the

rem

aini

ng n

ine

coul

d be

tr

eate

d as

out

-pat

ient

s.

% r

educ

tion

in m

ean

area

of w

ound

afte

r 3

wee

ks:

I:93

.1%

(7.4

SD

;n =

22)

C:8

5.2%

(10.

8 SD

;n =

22)

(p<

0.01

;Stu

dent

’s t-t

est)

% r

educ

tion

in m

ean

circ

umfe

renc

eaf

ter

3 w

eeks

:I:

80.0

% (2

0.6

SD;n

= 2

2)C

:70.

1% (2

0.8

SD;n

= 2

2)

(p>

0.05

,NS;

Stud

ent’s

t-te

st)

No

with

draw

als

repo

rted

.I (

dext

rano

mer

) doe

s no

tin

duce

con

tact

der

mat

itis,

ecze

ma

or a

llerg

ic r

eact

ions

.

Stat

istic

al s

igni

fican

ce is

grea

ter

1 an

d 2

wee

ks a

fter

the

initi

atio

n of

trea

tmen

t(fo

r ar

ea p

< 0

.001

;for

circ

umfe

renc

e p

< 0.

05).


43TAB

LE 5

con

td D

extra

nom

er p

olys

acch

arid

e ve

rsus

trad

ition

al o

r co

ntro

l tre

atm

ents

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

cont

inue

d

Goo

de e

t al,1

97935

UK

Wou

nd ty

pe:

Surg

ical

wou

nds.

Met

hod

of r

ando

misa

tion:

Seal

ed e

nvel

opes

.

Obj

ectiv

e ou

tcom

e:Ti

me

to s

econ

dary

wou

ndcl

osur

e.Ea

ch w

ound

was

phot

ogra

phed

at t

he s

tart

,du

ring

and

at th

e en

d of

trea

tmen

t.

Sett

ing

and

leng

th

of tr

eatm

ent:

Hos

pita

lised

sur

gica

lpa

tient

s.Tr

eatm

ent w

asco

ntin

ued

until

it w

asco

nsid

ered

app

ropr

iate

tocl

ose

the

wou

nd.

Incl

usio

n cr

iteria

:Pa

tient

s w

ho d

evel

oped

wou

ndin

fect

ions

afte

r an

app

endi

cec-

tom

y or

bow

el s

urge

ry.

Excl

usio

n cr

iteria

:N

ot s

tate

d.

Trea

tmen

t:I:

Dex

tran

omer

pol

ysac

char

ide

bead

s (D

ebris

an) w

ere

appl

ied

dire

ctly

into

the

wou

nd to

a d

epth

of 0

.5 c

m,fo

llow

ed b

y a

light

pac

k.D

extr

anom

er w

as a

pplie

d tw

ice

daily

,n =

10.

C:E

usol

and

par

affin

soa

ked

ribbo

n ga

uze

dres

sings

cha

nged

twic

e da

ily,n

= 1

0.

All

othe

r nu

rsin

g pr

oced

ures

wer

eid

entic

al fo

r bo

th g

roup

s.

Mea

n w

ound

are

a (c

m2 ):

Not

sta

ted.

Oth

er c

hara

cter

istic

s:I

CM

ean

age

(yea

rs):

52.9

50.9

M:F

rat

io:

1:0.

41:

0.7

Wou

nds:

App

endi

cect

omy

67

Para

med

ian

43

Del

ayed

prim

ary

sutu

re4

6W

ound

abs

cess

64

All

wou

nds

wer

e ei

ther

hea

vily

cont

amin

ated

at o

pera

tion

and

left

open

for

delay

ed p

rimar

y su

ture

(ten

pat

ient

s),o

r th

ose

whi

chw

ere

clos

ed p

rimar

ily a

nd s

ubse

-qu

ently

dev

elop

ed a

n ab

sces

s th

atre

quire

d th

e re

mov

al o

f sut

ures

and

drai

nage

(ten

pat

ient

s).

Num

ber

of w

ound

s he

aled

with

out

seco

ndar

y cl

osur

e:I:

1/10

(10%

)C

:1/1

0 (1

0%)

Mea

n tim

e an

d ra

nge

(day

s) to

seco

ndar

y cl

osur

e:I:

8.1

(ran

ge,5

–28;

n =

10)

C:1

.6 (r

ange

,6–2

2;n

= 10

)(p

< 0.

05;M

ann-

Whi

tney

U-T

est)

Ther

e w

ere

now

ithdr

awal

s.Th

ree

patie

nts

in th

e C

gro

up(E

usol

) con

tinue

d to

hav

ese

rious

disc

harg

es fo

r up

to

5 da

ys a

fter

wou

nd c

losu

re.

This

did

not o

ccur

in th

e I

(dex

tran

omer

) gro

up.

Wou

nd h

ealin

g w

as th

epr

inci

pal f

acto

r pr

even

ting

disc

harg

e fro

m h

ospi

tal;t

hose

trea

ted

with

I ha

d a

shor

ter

hosp

ital s

tay

by a

med

ian

of2.

2 da

ys.

The

auth

or s

tate

s th

at th

ehi

gh c

ost o

f I is

com

pens

ated

by th

e sa

ving

from

sho

rter

hosp

ital s

tay.

Appendix 6

44 TAB

LE 5

con

td D

extra

nom

er p

olys

acch

arid

e ve

rsus

trad

ition

al o

r co

ntro

l tre

atm

ents

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

cont

inue

d

Gro

enew

ald,

1980

29

Sout

h A

fric

a

Wou

nd ty

pe:

Veno

us le

g ul

cers

.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

e:Th

e ci

rcum

fere

nce

of

the

wou

nd w

as m

easu

red

by a

mill

imet

re o

verla

y.A

pho

togr

aph

was

take

n at

eac

h vi

sit.

Sett

ing

and

leng

th

of tr

eatm

ent:

Hos

pita

l clin

ic.P

atie

nts

trea

ted

for

21 d

ays

and

asse

ssed

dai

ly b

y tw

oin

depe

nden

t inv

estig

ator

s.

Incl

usio

n cr

iteria

:O

utpa

tient

s w

ith p

ost-

phle

bitic

stas

is le

g ul

cers

.

Excl

usio

n cr

iteria

:N

ot s

tate

d.

Trea

tmen

t:I:

Dex

tran

omer

pol

ysac

char

ide

(Deb

risan

) bea

ds w

ere

pour

eddi

rect

ly o

nto

the

ulce

r su

rfac

e to

form

a la

yer

at le

ast 2

–3 m

m th

ick.

A m

ultil

ayer

gau

ze p

ad w

as u

sed

to c

over

the

ulce

r an

d ke

pt in

plac

e by

a s

tand

ard

gauz

e ba

ndag

e,n

= 50

.

C:P

ovid

one-

iodi

ne o

intm

ent w

assw

abbe

d on

to th

e ul

cer

and

apr

essu

re b

anda

ge a

pplie

d.Th

ew

hole

foot

and

low

er le

g w

ere

boun

d w

ith a

zin

c ox

ide-

impr

eg-

nate

d ga

uze

band

age,

n =

50.

The

ulce

rs a

nd s

urro

undi

ng

leg

area

in b

oth

grou

ps w

ere

initi

ally

was

hed

with

a s

oft b

rush

ina

povi

done

-iodi

ne s

olut

ion,

befo

rebe

ing

tem

pora

rily

cove

red

with

gauz

e sw

abs

soak

ed in

Eus

olso

lutio

n.

In th

e pr

esen

ce o

f Pse

udom

onas

infe

ctio

n 0.

25%

ace

tic a

cid

solu

tion

was

app

lied.

The

surr

ound

ing

skin

was

pai

nted

with

tinc

ture

of

met

hiol

ate.

In th

e pr

esen

ce o

fco

mm

only

occ

urrin

g fu

ngal

infe

ctio

ns o

f the

sur

roun

ding

ski

nar

ea,a

n ap

prop

riate

ant

ifung

alag

ent w

as a

pplie

d.W

here

the

sur-

roun

ding

ski

n w

as e

czem

atou

s,flu

cino

line

oint

men

t was

app

lied.

Wou

nd s

ize:

IC

< 6

cm:

77

6–12

cm

:20

21>

12 c

m:

2322

Oth

er c

hara

cter

istic

s: IC

Mea

n ag

e (y

ears

):N

ot s

tate

dM

:F r

atio

:1:

3.5

1:4.

6M

ean

dura

tion

(mon

ths)

:N

ot s

tate

d

Dep

th o

f ulc

er:

Shal

low

2029

Dee

p30

21

Raci

al d

istrib

utio

n (%

):W

hite

2322

Col

oure

d26

25Bl

ack

13

The

num

ber

of a

ffect

ed r

ight

and

left

legs

wer

e al

mos

t equ

al in

eac

hof

the

two

grou

ps.

The

sam

ples

wer

e sh

own

to b

ere

pres

enta

tive

of th

e ov

eral

l clin

icpo

pula

tion.

Redu

ctio

n in

wou

nd s

ize a

t 21

days

:I

C0%

:8

2610

%:

21

25%

:1

150

%:

62

75%

:7

310

0%:

112

Mea

n tim

e to

hea

ling:

I:4.

44 w

eeks

(n =

35)

C:5

.32

wee

ks (n

= 35

)(p

< 0.

05)

30 p

atie

nts,

15 in

each

gro

up w

ere

not i

nclu

ded

in th

efin

al a

naly

sis.T

hese

patie

nts

wer

etr

eate

d su

rgic

ally

afte

r th

e w

ound

was

dee

med

to b

ecl

ean

(e.g

.by

skin

graf

ting)

.

Five

add

ition

alpa

tient

s dr

oppe

dou

t of t

he tr

ial a

ndw

ere

repl

aced

toke

ep th

e gr

oup

num

ber

at 5

0.

(Rea

sons

for

thes

ew

ithdr

awal

s ar

e no

tst

ated

.)

Of 3

0 I (

dext

rano

mer

)pa

tient

s co

mpl

aini

ng o

f pai

n,20

sho

wed

impr

ovem

ent

with

in 2

4 hr

,one

afte

r 3

days

and

one

afte

r 10

day

s.In

the

rem

aini

ng e

ight

pat

ient

s th

epa

in in

itial

ly w

orse

ned

befo

reim

prov

ing.

Of t

he 3

5 C

pat

ient

sco

mpl

aini

ng o

f pai

n,se

ven

impr

oved

afte

r 24

hr,

thre

eaf

ter

3 da

ys,a

nd s

ix a

fter

7 da

ys.In

13

the

pain

wor

sene

d be

fore

impr

ovin

g,in

two

patie

nts

the

pain

leve

lre

mai

ned

unch

ange

d,an

d in

four

the

pain

wor

sene

dw

ithou

t im

prov

ing

late

r.


45TAB

LE 5

con

td D

extra

nom

er p

olys

acch

arid

e ve

rsus

trad

ition

al o

r co

ntro

l tre

atm

ents

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

cont

inue

d

Nas

ar a

nd M

orle

y,19

8236

UK

Wou

nd ty

pe:

Pres

sure

sor

es.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

e:W

ound

are

a w

as m

easu

red

usin

g ce

llulo

id s

quar

es a

ndth

e en

tire

wou

ndph

otog

raph

ed.

End

poin

t was

rea

ched

whe

n th

e w

ound

was

cle

anan

d gr

anul

atin

g an

d ap

pear

-ed

to b

e le

ss th

an 2

5% it

sor

igin

al s

ize (=

hea

led)

.

Sett

ing

and

leng

th

of tr

eatm

ent:

Hos

pita

l-bas

ed tr

ial.

Ass

essm

ents

wer

e m

ade

ever

y 3

days

by

an in

de-

pend

ent o

bser

ver

and

aph

otog

raph

take

n on

ce a

wee

k.Tr

eatm

ent w

asco

ntin

ued

until

the

wou

ndre

ache

d th

e en

d po

int,

orfo

r a

max

imum

of 9

4 da

ys.

Incl

usio

n cr

iteria

:Pa

tient

s w

ith d

eep

pres

sure

sore

s of

app

roxi

mat

ely

simila

rsiz

e.

Excl

usio

n cr

iteria

:U

rinar

y tr

act i

nfec

tion.

Trea

tmen

t:I:

Dex

tran

omer

pol

ysac

char

ide

(Deb

risan

) app

lied

as a

stif

f pas

tetw

ice

daily

for

the

first

3 d

ays

and

daily

ther

eafte

r,n

= 9.

C:E

usol

and

par

affin

pac

ks w

ere

appl

ied

to th

e w

ound

and

dres

sings

wer

e ch

ange

d th

ree

times

dai

ly fo

r th

e fir

st 3

day

s an

dth

erea

fter

twic

e da

ily.M

elol

indr

essin

gs w

ere

used

thro

ugho

uthe

ld in

pla

ce b

y m

icro

pore

tape

.Asa

vlon

sac

het w

as u

sed

each

tim

eth

e dr

essin

g w

as c

hang

ed,n

= 9

.

Prio

r to

initi

atio

n of

the

tria

l all

hard

ened

slo

ughs

wer

e cu

t off

and

all p

atie

nts

wer

e nu

rsed

on

a la

rge

cell

rippl

e m

attr

ess.

The

only

con

-cu

rren

t the

rapy

was

ultr

avio

let

light

app

lied

to 1

2 sq

uare

inch

es

of s

kin

to p

rodu

ce fi

rst d

egre

eer

ythe

ma

with

the

sore

mas

ked

from

the

ultr

avio

let r

ays.

Mea

n w

ound

are

a:N

ot s

tate

d.

Oth

er c

hara

cter

istic

s:I

CM

ean

age

(yea

rs):

83.2

77.4

M:F

rat

io:

Not

sta

ted

Mea

n du

ratio

n (m

onth

s):

Not

sta

ted

Ana

emia

,hyp

oalb

umin

aem

ia,

hypo

vita

min

osis,

and

high

blo

odur

ea w

ere

corr

ecte

d if

pres

ent.

Scru

pulo

us c

ontr

ol o

f dia

betic

patie

nts

was

ens

ured

.Pat

ient

s w

ithur

inar

y in

cont

inen

ce w

ere

cath

eter

ised.

Pres

sure

sor

es w

ere

mos

tly o

n th

efo

ot o

r he

el in

bot

h gr

oups

.

Num

ber

of w

ound

s at

tain

ing

the

end

poin

t:I:

6/9

(67%

) C

:5/9

(56%

)

Mea

n tim

e to

rea

ch e

nd p

oint

:I:

39.3

day

sC

:62

days

I:Thr

ee w

ound

s.Tw

o du

e to

pat

ient

deat

h;on

e as

are

sult

of p

atie

ntdi

scom

fort

.

C:F

our

wou

nds.

One

due

to p

atie

ntde

ath;

thre

esw

itche

d to

dext

rano

mer

(tw

oaf

ter

16 d

ays

and

one

afte

r 48

day

s).

Wou

nds

trea

ted

with

C(E

usol

) wer

e ob

serv

ed to

be

asso

ciat

ed w

ith a

rise

inbl

ood

urea

to 1

1 m

mol

/l.

Cos

t of m

ater

ials

calc

ulat

edfo

r ea

ch tr

eatm

ent f

orav

erag

e tr

eatm

ent t

ime

inth

at g

roup

.C tr

eatm

ent w

as1.

6 tim

es m

ore

cost

ly th

an I.

Appendix 6

46 TAB

LE 5

con

td D

extra

nom

er p

olys

acch

arid

e ve

rsus

trad

ition

al o

r co

ntro

l tre

atm

ents

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

cont

inue

d

Palm

ieri,

1992

33

Italy

Wou

nd ty

pe:

Leg

ulce

rs a

nd p

ress

ure

sore

s.

Met

hod

of a

lloca

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

e:Ti

me

to h

ealin

g.

Sett

ing

and

leng

th

of tr

eatm

ent:

Wou

nd c

linic

.Tre

atm

ent

was

con

tinue

d un

til a

llw

ound

s ha

d he

aled

.

Incl

usio

n cr

iteria

:Ve

nous

leg

ulce

rs,p

ress

ure

sore

s,di

abet

ic g

angr

ene,

pres

sure

sor

es,p

ost t

raum

atic

wou

nds,

burn

s an

d ra

dioa

ctive

ulce

rs.N

ote:

Dat

a ar

e gi

ven

here

for

leg

ulce

rs a

nd

pres

sure

sor

es o

nly.

Excl

usio

n cr

iteria

:A

dditi

onal

trea

tmen

ts w

ith

drug

s (w

ith th

e ex

cept

ion

of d

igita

lis).

I:D

extr

anom

er p

olys

acch

arid

ebe

ads

(Deb

risan

) wer

e ap

plie

ddi

rect

ly to

the

wou

nd b

ead

and

repl

aced

dai

ly,n

= 24

.

C:C

olla

gen

spon

ge a

pplie

d di

rect

lyto

the

wou

nd a

fter

salin

e ne

bulis

-at

ion.

The

dres

sing

was

che

cked

ever

y da

y an

d if

the

colla

gen

spon

ge w

as s

wol

len

or p

artia

lly

reab

sorb

ed m

ore

spon

ge w

asap

plie

d w

ithou

t rem

ovin

g th

epr

evio

us o

ne.G

reas

y sp

onge

and

regu

lar

non-

alle

rgen

ic ta

peco

mpl

eted

the

dres

sing,

n =

24.

All

wou

nds

wer

e sh

arp

debr

ided

prio

r to

ran

dom

isatio

n.In

add

ition

all w

ound

s w

ere

trea

ted

to e

nsur

ene

gativ

e ba

cter

ial c

ultu

res

atba

selin

e.

Wou

nd a

rea:

Not

sta

ted.

Oth

er c

hara

cter

istic

s: All

grou

psA

ge r

ange

(yea

rs):

58–7

5M

:F r

atio

:1:

0.6

Mea

n du

ratio

n (m

onth

s):

Not

sta

ted

Wou

nd ty

pe:

Leg

ulce

rs:

12D

iabe

tic g

angr

ene:

12Pr

essu

re s

ores

:12

Post

trau

mat

ic:

12

Mea

n tim

e to

hea

ling

(day

s):

Leg

ulce

rs:

I:60

(n=

6)

C:3

6 (n

= 6)

(p<

0.00

5;St

uden

t’s t-

test

)

Pres

sure

sor

es:

I:47

(n=

6)

C:2

0 (n

= 6)

(p<

0.00

1;St

uden

t’s t-

test

)

No

with

draw

als.

Paris

h an

d C

ollin

s,19

7937

USA

Wou

nd ty

pe:

Pres

sure

sor

es.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

e:N

umbe

r of

ulc

ers

heal

ed.

Sett

ing

and

leng

th

of tr

eatm

ent:

Com

mun

ity (n

ursin

g ho

me)

4-w

eek

tria

l.

Incl

usio

n cr

iteria

:Pa

tient

s w

ith p

ress

ure

sore

s,re

sidin

g in

a n

ursin

g ho

me.

Excl

usio

n cr

iteria

:N

ot s

tate

d.

I:D

extr

anom

er p

olys

acch

arid

ebe

ads

(Deb

risan

) app

lied

to a

dept

h of

at l

east

3 m

m c

over

edw

ith a

dry

dre

ssin

g.C

hang

ed 1

–3tim

es d

aily

dep

endi

ng o

n ex

udat

e,n

= 14

wou

nds

from

sev

enpa

tient

s.

C:S

ugar

and

egg

whi

te a

pplie

daf

ter

a sa

line

was

h.C

hang

ed fo

urtim

es a

day

.Allo

wed

to d

ry a

ndno

t cov

ered

,n =

9 w

ound

s fro

mfiv

e pa

tient

s.

Mea

n w

ound

size

= √

of s

urfa

cear

ea (c

m):

I:4.

5 C

:2.4

No

stat

istic

al d

iffer

ence

bet

wee

nth

e gr

oups

for

ulce

r siz

e

Oth

er c

hara

cter

istic

s: IC

Age

ran

ge

(yea

rs):

29–5

732

–70

M:F

rat

io:

Not

sta

ted

Mea

n du

ratio

n (m

onth

s):

Not

sta

ted

Num

ber

of w

ound

s he

aled

at

4 w

eeks

:I:

6/14

(43%

)C

:0/9

(0%

)(p

< 0.

05;F

isher

’s te

st)

Num

ber

of p

atie

nts

with

hea

led

wou

nds

at 4

wee

ks:

I:4/

7 (5

7%)

C:0

/5 (0

%)

No

with

draw

als.

No

side-

effe

cts

repo

rted

by

patie

nts

with

any

of t

hetr

eatm

ents

.


47TAB

LE 5

con

td D

extra

nom

er p

olys

acch

arid

e ve

rsus

trad

ition

al o

r co

ntro

l tre

atm

ents

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

pHiso

Hex

®;m

anuf

actu

rer u

nkno

wn

cont

inue

d

Saw

yer

et a

l,197

931

USA

Wou

nd ty

pe:

Veno

us le

g ul

cers

.

Met

hod

of r

ando

misa

tion:

Seal

ed e

nvel

opes

.

Obj

ectiv

e ou

tcom

e:%

incr

ease

in e

pith

elise

dar

ea.M

etho

d of

mea

sure

men

t not

sta

ted.

Sett

ing

and

leng

th

of tr

eatm

ent:

Hos

pita

l and

med

ical

ce

ntre

clin

ic.A

sses

smen

tsw

ere

perfo

rmed

a m

inim

umof

onc

e a

wee

k (d

aily

for

hosp

italis

ed p

atie

nts)

for

3 w

eeks

.

Incl

usio

n cr

iteria

:O

utpa

tient

s or

hos

pita

lised

patie

nts

with

cut

aneo

us u

lcer

s of

mix

ed o

rigin

.Not

e:on

ly th

ere

sults

for

veno

us u

lcer

s ar

epr

esen

ted

here

.

Excl

usio

n cr

iteria

:N

ot s

tate

d.

Trea

tmen

t:I:

Dex

tran

omer

pol

ysac

char

ide

bead

s (D

ebris

an) a

pplie

d to

ade

pth

of 2

–3 m

m.F

or c

onve

xw

ound

s th

e be

ads

wer

e m

ixed

with

gly

cero

l to

form

a p

aste

.Fr

esh

dext

rano

mer

app

lied

once

or tw

ice

daily

,unl

ess

heav

yex

udat

e re

quire

d m

ore

frequ

ent

chan

ging

,n =

18.

C:S

oaks

onl

y.Re

peat

ed tw

ice

daily

,n =

19.

Both

trea

tmen

ts w

ere

cove

red

with

gau

ze a

nd a

clin

g ba

ndag

e.Le

gs w

ere

elev

ated

abo

ve th

ehe

art a

s fre

quen

tly a

s po

ssib

le.

All

wou

nds

soak

ed in

pH

iso H

ex®

for

30 m

in p

rior

to tr

eatm

ent.

Mea

n w

ound

are

a:N

ot s

tate

d

Oth

er c

hara

cter

istic

s:M

ean

age

(yea

rs):

Not

sta

ted

M:F

rat

io:

Not

sta

ted

Mea

n du

ratio

n (m

onth

s):

Not

sta

ted

Num

ber

of w

ound

s he

aled

at

3 w

eeks

:I:

15/1

8 (7

7%)

C:3

/19

(16%

) (p

< 0

.05;

chi-s

quar

ed te

st)

I:N

o w

ithdr

awal

s

C:N

o w

ithdr

awal

s.

Pain

from

the

wou

ndim

prov

ed in

31

patie

nts

trea

ted

with

I (d

extr

anom

er)

and

in fi

ve p

atie

nts

trea

ted

with

C (s

alin

e).

The

pain

wor

sene

d in

two

patie

nts

trea

ted

with

I an

d in

14 p

atie

nts

trea

ted

with

C.

Appendix 6

48 TAB

LE 5

con

td D

extra

nom

er p

olys

acch

arid

e ve

rsus

trad

ition

al o

r co

ntro

l tre

atm

ents

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

Algo

steril

®,L

es L

abor

ator

ies B

roth

ier (n

ow m

anuf

actu

red

by B

eiers

dorf

UKLt

d)* Ya

rkon

y GM

,et a

l.Cla

ssific

ation

of p

ress

ure

ulce

rs.A

rch

Der

mat

ol 1

990;

126:

1218

–19.

Saya

g et

al,1

99632

Fran

ce

Wou

nd ty

pe:

Pres

sure

sor

es.

Met

hod

of r

ando

misa

tion:

Seal

ed e

nvel

opes

.

Obj

ectiv

e ou

tcom

e:A

rea

of w

ound

mea

sure

dby

pla

nim

etry

,dig

itise

dtw

ice

and

the

area

cal

cu-

late

d by

com

pute

r.The

mea

n of

the

two

valu

es w

asus

ed to

det

erm

ine

indi

vid-

ual w

ound

are

a.A

pho

to-

grap

h w

as ta

ken

of e

ach

wou

nd a

t eve

ry e

valu

atio

n.

Sett

ing

and

leng

th

of tr

eatm

ent:

A m

ultic

entr

e tr

ial b

ased

at 2

0 ce

ntre

s (1

7 sp

ecia

l-isi

ng in

the

care

of e

lder

lype

ople

and

thre

e in

derm

atol

ogy)

.Ass

ess-

men

ts w

ere

mad

e on

aw

eekl

y ba

sis b

y th

e sa

me

rese

arch

er a

t eac

hce

ntre

.Tre

atm

ent w

aste

rmin

ated

whe

n th

ew

ound

rea

ched

40%

of

the

initi

al a

rea,

or a

fter

am

axim

um o

f 8 w

eeks

.

Incl

usio

n cr

iteria

:Pa

tient

s ag

ed ≥

60 h

ospi

talis

edfo

r ≥

8 w

eeks

,with

a p

ress

ure

sore

gra

ded

III o

r IV

(* Yark

ony’s

clas

sific

atio

n) a

nd s

urfa

ce

area

from

5–1

00 c

m2 .

Excl

usio

n cr

iteria

:M

ore

than

hal

f the

tota

l ulc

erar

ea h

ad g

ranu

latin

g tis

sue;

wou

nd c

over

ed b

y ne

crot

icpl

aque

;act

ive in

fect

ion

requ

iring

loca

l or

syst

emic

ant

ibio

ticth

erap

y;se

vere

ren

al fa

ilure

;hee

lul

cers

whe

n co

mbi

ned

with

end

-st

age

arte

riopa

thy

of th

e lo

wer

limbs

;rec

eivi

ng r

adio

ther

apy

orcy

toto

xic

ther

apy.

Trea

tmen

t:I:

Dex

tran

omer

pol

ysac

char

ide

past

e (D

ebris

an) a

pplie

d to

ade

pth

of 3

mm

ove

r th

e w

ound

surf

ace,

n =

45.

C:C

alci

um a

lgin

ate

dres

sings

(Algo

ster

il®) a

pplie

d di

rect

ly

on to

wou

nd to

cov

er th

e en

tire

area

,n =

47.

In b

oth

grou

ps a

ste

rile

gauz

e w

asap

plie

d as

a s

econ

dary

dre

ssin

g.N

o ot

her

loca

l tre

atm

ents

wer

eus

ed e

xcep

t for

sal

ine

solu

tion

the

use

of w

hich

was

not

res

tric

ted.

Dre

ssin

gs w

ere

insp

ecte

d an

dch

ange

d da

ily o

r at

leas

t eve

ry

4 da

ys d

epen

ding

on

the

degr

ee

of e

xuda

te.

Mea

n w

ound

are

a (c

m2 ):

I:16

.1 (1

2.5

SD)

C:2

0.1

(12.

9 SD

)

Oth

er c

hara

cter

istic

s:I

CM

ean

(SD

) ag

e (y

ears

):80

.4 (9

.1)

81.9

(8.9

)M

:F r

atio

:1:

2.8

1:2.

9M

ean

(SD

) du

ratio

n (m

onth

s):

3.0

(3.2

)3.

5 (3

.8)

Wou

nd g

rade

:III

3033

IV15

14

No

signi

fican

t diff

eren

ce b

etw

een

the

two

grou

ps (S

tude

nt’s

t-tes

t).

Whe

re p

atie

nts

had

mul

tiple

wou

nds

only

one

was

sel

ecte

d fo

r st

udy.

Pres

sure

sor

es w

ere

loca

ted

onth

e sa

crum

,isch

ium

,tro

chan

ter

and

heel

s.

Mea

n w

ound

are

a re

duct

ion

per

wee

k (c

m2 ):

I:0.

27 (3

.21

SD)

C:2

.39

(3.5

4 SD

) (p

= 0.

0001

;Stu

dent

’s t-t

est)

Mea

n w

ound

are

a re

duct

ion

per

wee

k us

ing

the

data

from

onl

y th

ose

patie

nts

reac

hing

≥40

% (c

m2 ):

I:2.

15 (3

.60

SD)

C:3

.55

(2.1

8 SD

) (p

= 0.

0004

;Stu

dent

’s t-t

est)

Num

ber

of w

ound

s w

ith >

75%

redu

ctio

n in

are

a:1:

6/45

(13%

)C

:15/

47 (3

2%)

Num

ber

of p

ress

ure

sore

s w

ith

≥40

% r

educ

tion

in a

rea:

I:19

/45

(42%

)C

:35/

47 (7

4%)

(p=

0.00

2;Fi

sher

’s ex

act t

est)

Cum

ulat

ive c

urve

s of

the

num

ber

of p

atie

nts

reac

hing

40%

red

uctio

ndi

ffere

d sig

nific

antly

(p=

0.00

02Lo

gran

k te

st) b

etw

een

the

grou

ps,

with

a m

edia

n of

4 w

eeks

in C

and

8

wee

ks in

I.

I:22

With

draw

als:

deat

h (n

= 6)

;ad

vers

e ev

ent

(n=

1);

dete

riora

tion

or s

tagn

atio

n of

ulc

er a

fter

4 w

eek

(n=

15).

C:T

en w

ithdr

awal

s:de

ath

(n=

5);

tran

sfer

(n=

2);

dete

riora

tion

ofhe

alth

(n=

1);

dete

riora

tion

or s

tagn

atio

n of

ulce

r af

ter

4 w

eek

(n=

2).

All

wer

e in

clud

ed in

the

analy

sis a

nd fe

ww

ere

cons

ider

ed to

have

impr

oved

at

the

last

eva

luat

ion.

End

poin

t dat

aw

ere

not a

vaila

ble

for

one

patie

nt in

Cdu

e to

adm

issio

n to

a sp

ecia

l car

e un

it.

On

aver

age

the

num

ber

ofdr

essin

g ch

ange

s pe

r w

eek

was

sim

ilar:

4.28

(1.4

9 SD

)fo

r C

and

4.5

2 (1

.42

SD)

for

I.

8% o

f the

C p

atie

nts

and

33%

of I

patie

nts

expe

rienc

edad

vers

e ef

fect

s.


49TAB

LE 6

Cad

exom

er io

dine

pol

ysac

char

ide

vers

us tr

aditi

onal

or

cont

rol t

reat

men

ts

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

Iodo

sorb

®,S

mith

& N

ephe

w H

ealth

care

Ltd

;Jelon

et®,S

mith

& N

ephe

w H

ealth

care

Ltd

* W

agne

r FW

.The

dys

vasc

ular

foot

:a sy

stem

for d

iagn

osis

and

treat

men

t.Fo

ot A

nkle

198

1;2:

64–1

22.

cont

inue

d

Ape

lqvi

st a

nd Te

nnva

ll,19

9642

Swed

en

Wou

nd ty

pe:

Dia

betic

foot

ulc

ers.

Met

hod

of r

ando

misa

tion:

Com

pute

r al

loca

tion.

Stra

ti-fic

atio

n w

as p

erfo

rmed

on

size

and

type

of w

ound

(Wag

ner

grad

e I–

II).

Obj

ectiv

e ou

tcom

e:A

rea

of w

ound

det

erm

ined

by p

hoto

grap

hing

wou

nds

agai

nst a

gra

duat

ed s

cale

.Th

e m

axim

um le

ngth

and

max

imum

wid

th w

ere

mul

-tip

lied

toge

ther

to c

alcu

late

the

area

.In

addi

tion

the

num

ber

of w

ound

s he

aled

was

rec

orde

d.

Sett

ing

and

leng

th

of tr

eatm

ent:

Ope

n co

ntro

lled

tria

l with

blin

ded

phot

o-ev

alua

tion.

Patie

nts

wer

e tr

eate

dei

ther

at h

ome

or o

nvi

sitin

g an

out

patie

nt c

linic

.A

sses

smen

ts w

ere

mad

e at

1,4,

8 an

d 12

wee

ks.

Incl

usio

n cr

iteria

:C

auca

sian

outp

atie

nts

> 40

yea

rs o

ld w

ith p

revi

ously

know

n di

abet

es m

ellit

us.A

llw

ound

s w

ere

exud

atin

g an

dbe

low

the

ankl

e (W

agne

r gr

ade

I–II* ) w

ith a

n ul

cer

area

> 1

cm

2

and

a sy

stol

ic to

e pr

essu

re

> 30

mm

Hg

or a

sys

tolic

ank

lepr

essu

re >

80

mm

Hg.

Excl

usio

n cr

iteria

:W

ound

s >

25 c

m2 ;p

atie

nts

with

a de

ep a

bsce

ss;o

steo

mye

litis

orga

ngre

ne (W

agne

r gr

ade

III–I

V);

patie

nts

unde

rgoi

ng th

yroi

dgl

and

inve

stig

atio

n;pa

tient

sun

likel

y to

adh

ere

to th

e st

udy

prot

ocol

.

In p

atie

nts

with

sev

eral

wou

nds,

only

the

larg

est w

ound

mee

ting

the

sele

ctio

n cr

iteria

was

chos

en.

Trea

tmen

t:I:

Cad

exom

er io

dine

pol

ysac

-ch

arid

e oi

ntm

ent (

Iodo

sorb

®) w

asch

ange

d on

ce d

aily

for

the

first

wee

k an

d th

en d

aily

or

ever

yse

cond

or

third

day

ther

eafte

rac

cord

ing

to th

e de

gree

of

exud

atio

n,n

= 22

.

C:G

enta

mic

in s

olut

ion

(80

mg/

ml)

was

give

n tw

ice

daily

whe

re c

ellu

litis

was

pre

sent

.St

rept

odor

nase

/ str

epto

kina

se(V

arid

ase T

opic

al) w

as u

sed

for

moi

st n

ecro

tic le

sions

and

cha

nged

twic

e da

ily.D

ry s

alin

e ga

uze

was

used

as

an a

bsor

ptive

dre

ssin

g an

dch

ange

d on

ce o

r tw

ice

daily

acco

rdin

g to

exu

datio

n,n

= 19

.

Wou

nds

wer

e cl

eane

d w

ith s

teril

esa

line

prio

r to

dre

ssin

g in

acc

ord-

ance

with

the

man

ufac

ture

rsgu

idel

ines

.Dre

ssin

gs w

ere

appl

ied

by r

egul

ar h

ealth

care

nur

ses.

For

both

trea

tmen

ts w

hen

the

ulce

rs h

ad s

topp

ed e

xuda

ting,

Vase

line

gauz

e (Je

lone

t®) w

as u

sed.

Foot

wea

r of

pat

ient

s w

asco

rrec

ted

or s

peci

al fo

otw

ear

prov

ided

to r

elie

ve p

ress

ure.

Ora

lan

tibio

tics

wer

e gi

ven

in c

ase

ofsig

ns o

f inf

ectio

n.

Mea

n w

ound

are

a (c

m2 ):

Not

sta

ted.

Oth

er c

hara

cter

istic

s:M

ean

age

(yea

rs):

Not

sta

ted

M:F

rat

io:

Not

sta

ted

Mea

n du

ratio

n (m

onth

s):

Not

sta

ted

Num

ber

of w

ound

s he

aled

:I:

5/22

(23%

)C

:2/1

9 (1

1%)

I:Fi

ve w

ithdr

awal

sC

:One

with

draw

al

Two

patie

nts

wer

eex

clud

ed fr

om th

ean

alysis

due

tovi

olat

ion

of in

clu-

sion

crite

ria (s

ize

> 25

cm

2an

d/or

ulce

r ty

pe,W

agne

rIII

).Tw

o pa

tient

sw

ere

excl

uded

beca

use

of h

ospi

tal-

isatio

n (o

ne fo

rm

yoca

rdia

l inf

arc-

tion,

one

beca

me

febr

ile a

nd la

ter

died

),th

ese

hosp

italis

atio

nsw

ere

not a

ssoc

iate

dw

ith tr

eatm

ent.

One

pat

ient

was

excl

uded

for

non-

com

plia

nce

with

trea

tmen

t.O

neot

her

patie

nt w

asex

clud

ed b

ecau

seof

insu

ffici

ent d

ata.

35 p

atie

nts

rem

aine

d fo

rcl

inic

al e

valu

atio

n.

Mea

n w

eekl

y co

st w

as 9

03SE

K fo

r I a

nd 1

421

SEK

for

C,

of w

hich

the

maj

or p

art w

asco

sts

for

staf

f and

tran

spor

tatio

n re

late

d to

frequ

ency

of d

ress

ing

chan

ges.

No

adve

rse

reac

tions

wer

ere

cord

ed w

ith e

ither

trea

tmen

t.

Appendix 6

50 TAB

LE 6

con

td C

adex

omer

iodi

ne p

olys

acch

arid

e ve

rsus

trad

ition

al o

r co

ntro

l tre

atm

ents

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

Elas

tocr

epe,

Smith

& N

ephe

w H

ealth

care

Ltd

;Sof

ra-T

ulle

,Hoe

chst

Mar

ion R

ouss

el

cont

inue

d

Har

cup

and

Saul

,198

640

UK

Wou

nd ty

pe:

Chr

onic

leg

ulce

rs.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

e:A

rea

of w

ound

was

mea

-su

red

by tr

acin

g th

e ou

tline

on to

a p

last

ic s

heet

.

Sett

ing

and

leng

th o

f tre

at-

men

t:Pa

tient

s wer

e tr

eate

dat

hom

e un

der

the

guid

ance

of a

gen

eral

prac

titio

ner.

Patie

nts o

r ca

rers

wer

e re

-sp

onsib

le fo

r ch

angin

g dr

ess-

ings

.Ass

essm

ents

wer

e m

ade

ever

y 2

wee

ks a

nd 4

wee

ks.

Incl

usio

n cr

iteria

:O

ut-p

atie

nts

with

exu

ding

chro

nic

leg

ulce

rs n

otre

spon

ding

to e

xist

ing

trea

tmen

t.

Excl

usio

n cr

iteria

:C

onco

mita

nt,s

erio

us o

r lif

e-th

reat

enin

g di

seas

e;a

susp

ecte

dm

alig

nant

ulc

er;in

sulin

-req

uirin

gdi

abet

es;p

regn

ancy

;iodi

nese

nsiti

vity

;psy

chia

tric

dise

ase;

low

inte

llige

nce;

dem

entia

;or

othe

r co

nditi

ons

likel

y to

affe

ctth

e pa

tient

’s ab

ility

to c

ompl

yw

ith th

e tr

ial.

Trea

tmen

t:I:

Cad

exom

er io

dine

pol

ysac

-ch

arid

e be

ads

(Iodo

sorb

) app

lied

to a

dep

th o

f 3 m

m a

fter

clea

nsin

gw

ith s

teril

e sa

line

swab

s or

age

ntle

str

eam

of w

ater

or

salin

e.C

over

ed w

ith a

dry

ste

rile

dres

sing

and

secu

red

by b

anda

ging

or s

tock

ing.

Cad

exom

er io

dine

was

cha

nged

dai

ly,n

= 41

.

C:P

rimar

ily a

sup

port

ban

dagin

g or

stoc

king

and

a d

ry d

ress

ing.

21 o

fth

e pa

rtic

ipan

ts re

ceive

d a

varia

nton

this

trea

tmen

t whi

ch in

clud

edam

ongs

t oth

ers:

Crê

pe b

anda

ging

(Elas

tocr

epe®

),ab

sorb

ent d

ress

-in

gs (M

elol

in),

topi

cal a

ntib

iotic

s(P

olyf

ax®) a

nd m

edic

ated

dre

ssin

gs(S

ofra

-Tul

le®),

n =

31.

Mea

n ar

ea o

f wou

nd (c

m2 ):

I:7.

74 (1

.04

SD)

C:9

.08

(1.3

7 SD

)

Oth

er c

hara

cter

istic

s:A

ll gr

oups

Mea

n ag

e (y

ears

):67

.8M

:F r

atio

:1:

2.2

Mea

n du

ratio

n (m

onth

s):

16.9

Add

ition

al w

ound

s (%

):26

Mea

n w

ound

are

a at

4 w

eeks

:I:

2.81

(n=

41)

C:0

.90

(n=

31)

% r

educ

tion

in m

ean

area

of w

ound

at 4

wee

ks:

I:36

.30

(n=

41)

C:9

.91

(n=

31)

p <

0.01

I vs

.C

(ana

lysis

of c

ovar

ianc

e)

I:Thr

ee p

atie

nts

wer

e w

ithdr

awn

afte

r 2

wee

ks d

ueto

var

ious

rea

sons

,in

clud

ing

diar

rhoe

a,er

ythe

ma,

oede

ma,

ulce

r irr

itatio

n an

dun

happ

ines

s w

ith tr

eatm

ent.

Thes

e pa

tient

sw

ere

incl

uded

inth

e an

alysis

at

4 w

eeks

.

Dur

ing

the

4-w

eek

trea

tmen

tpe

riod

thos

e pa

tient

sre

ceiv

ing

C r

epor

ted

a 27

%de

crea

se in

pai

n,w

hile

thos

e tr

eate

d w

ith I

repo

rted

a

66%

red

uctio

n.

Hol

low

ay e

t al,1

98939

USA

Wou

nd ty

pe:

Veno

us le

g ul

cers

.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

e:A

rea

of th

e w

ound

was

mea

sure

d by

pla

nim

etry

on

tran

spar

ent t

raci

ngs.

A c

olou

r ph

otog

raph

was

take

n at

eac

h ev

alua

tion.

Sett

ing

and

leng

th o

ftr

eatm

ent:

A m

ultic

entr

etr

ial c

ondu

cted

for

24w

eeks

or

until

the

wou

ndw

as c

onsid

ered

to b

ehe

aled

.Mea

sure

men

ts w

ere

take

n at

2-w

eek

inte

rval

sfo

r th

e fir

st 8

wee

ks a

ndth

en a

t mon

thly

inte

rval

s.

Incl

usio

n cr

iteria

:O

ut-p

atie

nts

with

ven

ous

stas

isul

cers

pre

sent

for

a m

inim

um

of 3

mon

ths

and

othe

rwise

ingo

od h

ealth

.

Excl

usio

n cr

iteria

:In

itial

ly w

ound

s <

2 cm

indi

amet

er;p

rove

n or

sus

pect

edno

n-ve

nous

cau

se o

f wou

nds;

inab

ility

to c

ompl

y w

ith th

etr

eatm

ent;

maj

or m

edic

aldi

sord

ers;

iodi

ne a

llerg

y;cl

inic

ally

sig

nific

ant a

rter

ial

dise

ase.

Trea

tmen

t:I:

Cad

exom

er io

dine

poly

sacc

harid

e po

wde

r (Io

doso

rb)

sprin

kled

ont

o th

e w

ound

afte

rirr

igat

ion

with

sal

ine,

and

cove

red

with

a d

ry g

auze

dre

ssin

g,n

= 38

.

C:W

et-t

o-dr

y dr

essin

gs w

ithsa

line-

soak

ed s

teril

e 4

x 4

inch

gauz

e pa

ds,n

= 3

7.

Patie

nts

in b

oth

grou

ps w

ere

resp

onsib

le fo

r ch

angi

ng th

eir

own

dres

sings

onc

e a

day.

Both

trea

tmen

ts w

ere

cove

red

with

ato

e-to

-kne

e el

astic

com

pres

sion

band

age.

Mea

n w

ound

are

a (c

m2 ):

I:20

.1C

:11.

2

Oth

er c

hara

cter

istic

s: IC

Mea

n ag

e (y

ears

):63

.061

.5M

:F r

atio

:1:

0.8

1:1.

5M

ean

dura

tion

(mon

ths)

:29

.511

.4

No

stat

istic

al d

iffer

ence

s be

twee

n th

e tw

o gr

oups

re

port

ed.A

lthou

gh th

e m

ean

dura

tion

and

initi

al m

ean

area

ar

e gr

eate

r in

the

I gro

up.

Mea

n re

duct

ion

in w

ound

size

per

wee

k af

ter

24 w

eeks

(cm

2 ):I:

0.95

(0.1

2 SE

M;n

= 2

7)C

:0.4

1 (0

.13

SEM

;n =

27)

(p=

0.00

25;a

naly

sis o

f cov

aria

nce)

Mea

n re

duct

ion

in w

ound

size

vs

.bas

elin

e ci

rcum

fere

nce

afte

r 24

wee

ks (c

m2 /w

k/cm

2 ):I:

0.04

(0.0

1 SE

M;n

= 2

7)C

:0.0

3 (0

.01

SEM

;n =

27)

(p=

0.07

20;a

naly

sis o

f cov

aria

nce)

The

redu

ctio

n in

wou

nd a

rea

was

signi

fican

tly d

iffer

ent f

rom

bas

elin

e in

bot

h gr

oups

(p<

0.00

1;an

alysis

of

cov

aria

nce)

.

15 p

atie

nts d

id n

otco

mpl

ete

the

trea

t-m

ent:

four

faile

d to

resp

ond

to tr

eat-

men

t;tw

o di

ed fr

omca

uses

unr

elat

ed to

thei

r ul

cers

;nin

edr

oppe

d ou

t and

faile

d to

retu

rn

for

follo

w-u

p.Si

x pa

tient

s wer

e no

tin

clude

d in

the

ana-

lysis:

two

wer

e fe

lt to

have

bee

n in

appr

o-pr

iatel

y ad

mitt

ed to

the

stud

y be

caus

eth

eir

ulce

rs w

ere

too

small

;four

lack

edad

equa

te fo

llow

-up

info

rmat

ion.

With

draw

als w

ere

in e

quiva

lent

pro

-po

rtio

ns fr

om b

oth

grou

ps.

Six

patie

nts

trea

ted

with

Iex

perie

nced

mild

tran

sient

burn

ing,

pain

,or

itchi

ng.

No

adve

rse

effe

cts

wer

ere

port

ed in

the

C g

roup

.


51TAB

LE 6

con

td C

adex

omer

iodi

ne p

olys

acch

arid

e ve

rsus

trad

ition

al o

r co

ntro

l tre

atm

ents

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

cont

inue

d

Laud

ansk

a an

d G

usta

vson

,19

8838

Pola

nd

Wou

nd ty

pe:

Veno

us le

g ul

cers

.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

es:

The

wou

nd p

erim

eter

was

draw

n on

to a

tran

spar

ency

and

the

area

cal

cula

ted

bypl

anim

etry

.The

num

ber

ofw

ound

s he

aled

was

reco

rded

.

Sett

ing

and

leng

th

of tr

eatm

ent:

6-w

eek

tria

l.Mea

sure

-m

ents

take

n at

0,1

,2,

4 an

d 6

wee

ks.

Incl

usio

n cr

iteria

:H

ospi

talis

ed p

atie

nts

with

chro

nic

veno

us u

lcer

s th

at h

adre

siste

d ou

tpat

ient

trea

tmen

t for

mor

e th

an 3

mon

ths.

Excl

usio

n cr

iteria

:W

ound

s <

2 cm

;iodi

nese

nsiti

vity

;sev

ere

perip

hera

lar

teria

l dise

ase.

Trea

tmen

t:I:

Cad

exom

er io

dine

pow

der

(Iodo

sorb

) app

lied

daily

in a

3–

4 m

m la

yer,

cove

red

with

a li

ght

elas

tic b

anda

ge,n

= 3

0.

C:D

ilute

hyd

roge

n pe

roxi

de a

ndzin

c pa

ste

(in a

dditi

on s

alin

edr

essin

gs,d

ilute

pot

assiu

m p

er-

man

gana

te a

nd G

entia

n vi

olet

wer

e ap

plie

d) c

over

ed w

ith a

ligh

tel

astic

ban

dage

,n =

30.

All

patie

nts

wer

e gi

ven

com

plet

ebe

d re

st fo

r 6

wee

ks.

Mea

n w

ound

are

a (c

m2 ):

I:27

.5 (7

.0 S

E)C

:35.

2 (8

.1 S

E)

(p>

0.05

;Stu

dent

’s t-t

est)

Oth

er c

hara

cter

istic

s: IC

Mea

n ag

e (y

ears

):64

.863

.5M

:F r

atio

:1:

0.8

1:1.

5M

ean

dura

tion

(mon

ths)

:19

.115

.0

No

stat

istic

al d

iffer

ence

bet

wee

nth

e tw

o gr

oups

.

Det

ails

are

only

ava

ilabl

e fo

r 60

of t

he 6

7 pa

rtic

ipan

ts in

itial

lyra

ndom

ised

to tr

eatm

ent.

Mea

n %

red

uctio

n in

wou

nd a

rea

at6

wee

ks:

I:71

% (n

= 30

)C

:54%

(n=

30)

(p<

0.01

;Stu

dent

’s t-t

est)

Both

trea

tmen

ts w

ere

signi

fican

tlydi

ffere

nt fr

om b

asel

ine.

(p<

0.05

;W

ilcox

on m

atch

ed p

airs

)

Num

ber

of u

lcer

s he

aled

or

shal

low

at 6

wee

ks:

I:16

/30

(53%

)C

:7 /

30 (7

%)

Four

with

draw

als

befo

re th

e fir

stas

sess

men

t:th

ree

due

to s

ocia

l rea

s-on

s an

d on

e du

e to

card

iac

failu

re.

Thre

e pa

tient

sw

ere

with

draw

naf

ter

com

plet

ing

the

tria

l.One

inea

ch g

roup

was

excl

uded

due

tola

rge

ulce

r ar

ea(t

en ti

mes

that

of

the

mea

n ul

cer

area

).The

third

patie

nt h

ad r

heu-

mat

oid

arth

ritis

whi

ch in

terfe

red

with

ass

essm

ent.

30 p

atie

nts

in e

ach

grou

p co

mpl

eted

the

tria

l.

App

licat

ion

of I

resu

lted

inm

ore

pain

than

with

C.

Seru

m c

once

ntra

tions

of

prot

ein-

boun

d io

dine

incr

ease

with

I tr

eatm

ent.

But t

here

isno

dist

urba

nce

of th

yroi

dfu

nctio

n.

Five

pat

ient

s on

I co

mpl

aine

dof

stin

ging

.

Appendix 6

52 TAB

LE 6

con

td C

adex

omer

iodi

ne p

olys

acch

arid

e ve

rsus

trad

ition

al o

r co

ntro

l tre

atm

ents

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

cont

inue

d

Lind

say

et a

l,198

641

UK

Wou

nd ty

pe:

Veno

us le

g ul

cers

.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

e:A

rea

of th

e w

ound

was

trac

ed o

nto

a pl

astic

she

etan

d m

easu

red.

Sett

ing

and

leng

th o

ftr

eatm

ent:

Patie

nts

trea

ted

at h

ome

unde

r th

e gu

idan

ceof

a g

ener

al pr

actit

ione

r.Pa

tient

s or

car

ers

wer

ere

spon

sible

for

chan

ging

dres

sings

.Ass

essm

ents

w

ere

mad

e ev

ery

2 w

eeks

for

4 w

eeks

.

Incl

usio

n cr

iteria

:O

ut-p

atie

nts

with

chr

onic

veno

us le

g ul

cers

and

not

resp

ondi

ng to

exi

stin

gtr

eatm

ent.

Excl

usio

n cr

iteria

:C

onco

mita

nt s

erio

us o

r lif

e-th

reat

enin

g di

seas

e,su

spec

ted

mal

igna

nt c

hang

e in

the

ulce

r;in

sulin

-dep

ende

nt d

iabe

tes;

preg

nanc

y;io

dine

sen

sitiv

ity;

psyc

hiat

ric d

iseas

e;ve

ry lo

win

telli

genc

e;de

men

tia;a

ny o

ther

cond

ition

that

mig

ht a

ffect

the

patie

nts

abili

ty to

com

ply

with

the

cond

ition

s of

the

tria

l.

Trea

tmen

t:28

pat

ient

s en

tere

d th

e tr

ial,b

utal

loca

tion

betw

een

the

grou

ps

was

not

sta

ted.

I:C

adex

omer

iodi

ne p

owde

r(Io

doso

rb) a

pplie

d to

a d

epth

of

not l

ess

than

3 m

m a

fter

clea

nsin

gw

ith s

teril

e sa

line

swab

s,or

age

ntle

str

eam

of w

ater

or

salin

e.C

over

ed w

ith a

dry

ste

rile

dres

s-in

g an

d se

cure

d by

ban

dagi

ng o

rst

ocki

ng.T

he d

ress

ing

was

ch

ange

d on

alte

rnat

e da

ys.

C:P

rimar

ily a

non

-adh

eren

tdr

essin

g pl

us s

uppo

rt b

anda

ging

or

sto

ckin

g.Th

e dr

essin

g w

asch

ange

d on

alte

rnat

e da

ys.T

wel

veof

the

part

icip

ants

rec

eive

d a

varia

nt o

n th

is tr

eatm

ent w

hich

incl

uded

am

ongs

t oth

ers:

Crê

peba

ndag

ing

(Ela

stoc

repe

),ab

sorb

ent

dres

sings

(Mel

olin

),Po

vido

neio

dine

and

med

icat

ed d

ress

ings

(Sof

ra-T

ulle

).

Mea

n w

ound

are

a:N

ot s

tate

d.

Oth

er c

hara

cter

istic

s:A

ll gr

oups

Mea

n ag

e (y

ears

):66

.7M

:F r

atio

:A

ll fe

mal

eM

ean

dura

tion

(mon

ths)

:20

.1N

o.of

pat

ient

s w

ithad

ditio

nal u

lcer

s:11

Mea

n %

red

uctio

n in

wou

nd a

rea

at4

wee

ks:

I:33

.6 (n

= 12

)C

:4.2

(n=

13)

(p <

0.0

05 I

vs.C

;ana

lysis

of

varia

nce)

.

I:O

ne p

atie

nt w

asw

ithdr

awn

afte

r 2

wee

ks d

ue to

an

alle

rgic

rea

ctio

n.

C:O

ne p

atie

nt w

asw

ithdr

awn

afte

r 4

wee

ks o

n th

edi

scov

ery

of p

eri-

pher

al v

ascu

lar

dise

ase.

The

resu

lts

are

base

d on

25

patie

nts

sugg

estin

gth

ere

was

a fu

rthe

rw

ithdr

awal

,pro

b-ab

ly in

the

I gro

up.

Mea

n w

ound

dur

atio

n w

as

20 m

onth

s so

a r

educ

tion

of33

% in

onl

y 4

wee

ks o

n I i

sim

pres

sive.

How

ever

,no

data

are

give

n of

oth

er m

easu

res

that

may

hav

e be

en e

mpl

oyed

to r

educ

e w

ound

size

.

Mob

erg

et a

l,198

343

Swed

en

Wou

nd ty

pe:

Pres

sure

sor

es.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

e:Pe

rimet

er o

f the

wou

ndw

as tr

aced

and

the

area

calc

ulat

ed b

y pl

anim

etry

or

mea

sure

men

t of t

helo

nges

t dia

met

er.

Sett

ing

and

leng

th

of tr

eatm

ent:

3-w

eek

tria

l.

Incl

usio

n cr

iteria

:H

ospi

talis

ed p

atie

nts

with

pres

sure

sor

es.

Excl

usio

n cr

iteria

:C

onfir

med

or

susp

ecte

dm

alig

nanc

ies,

mor

ibun

d,io

dine

sens

itivi

ty,p

sych

iatr

ic il

lnes

s,se

vere

pso

riasis

,any

oth

ercr

iteria

that

mig

ht m

ake

apa

tient

uns

uita

ble

for

a cl

inic

al tr

ial o

r un

able

to

give

info

rmed

con

sent

.

Trea

tmen

t:I:

Cad

exom

er io

dine

pol

ysac

-ch

arid

e po

wde

r (Io

doso

rb)

appl

ied

daily

to a

dep

th o

f 3 m

m.

Rem

oved

by

runn

ing

wat

er

salin

e or

wet

sw

ab,n

= 1

9.

C:S

tand

ard

trea

tmen

t was

var

i-ab

le.I

t inc

lude

d:sa

line

dres

sings

,en

zym

e-ba

sed

debr

idin

g ag

ents

,an

d no

n-ad

hesiv

e dr

essin

gs,n

= 1

9.

All

patie

nts

wer

e su

bjec

t to:

atte

ntio

n to

nut

ritio

n;im

prov

e-m

ent o

f hyg

iene

;rem

oval

of

pres

sure

by

usin

g de

cubi

tus

mat

tres

ses,

turn

ing

the

patie

ntev

ery

2 or

3 h

rs,a

nd o

ptim

alm

obili

satio

n.

Mea

n w

ound

are

a (c

m2 ):

I:9.

6 (1

.8 S

EM)

C:1

2.4

(4.3

SEM

)

Oth

er c

hara

cter

istic

s: IC

Mea

n ag

e (y

ears

):72

.680

.1M

:F r

atio

:1:

4.3

1:2.

6M

ean

dura

tion

(mon

ths)

:6.

26.

2

Valu

es a

re o

nly

avai

labl

e fo

r th

epa

tient

s no

t with

draw

n fro

m th

est

udy.

Mea

n de

crea

se in

are

a of

wou

nd

at 3

wee

ks:

I:2.

9 (1

.3 S

EM;n

= 1

6)

C:2

.5 (1

.1 S

EM;n

= 1

8)(p

< 0.

05 fo

r bo

th tr

eatm

ents

whe

nco

mpa

red

with

bas

elin

e;co

rrel

ated

t-tes

t or

Fish

er’s

exac

t tes

t).

% r

educ

tion

in m

ean

area

of

wou

nd a

t 3 w

eeks

:I:

30.9

% (4

6 SD

;n =

16)

C:1

9.6%

(31

SD;n

= 1

8)

(p<

0.02

;cor

rela

ted

t-tes

t or

Fish

er’s

exac

t tes

t)

I:Thr

eew

ithdr

awal

s.Tw

opa

tient

s fe

lt th

eyw

ere

gett

ing

wor

sean

d on

e ha

d sk

inirr

itatio

n an

doe

dem

a ar

ound

asa

cral

ulc

er a

ndch

ose

not t

oco

ntin

ue.

C:O

ne w

ithdr

awal

whe

re th

e w

ound

had

grow

n an

d th

epa

tient

was

mov

edto

ano

ther

hos

pita

l.

I cau

sed

thre

e pa

tient

s to

expe

rienc

e sm

artin

g af

ter

appl

icat

ion,

one

patie

nt h

adm

inor

ski

n irr

itatio

n an

dan

othe

r ha

d an

exa

cerb

atio

nof

pso

riasis

.

Ove

rall

pain

as

a re

sult

of th

ew

ound

was

sig

nific

antly

less

inpa

tient

s tr

eate

d w

ith I.

I was

eas

y to

app

ly a

ndre

mov

e.


53TAB

LE 6

con

td C

adex

omer

iodi

ne p

olys

acch

arid

e ve

rsus

trad

ition

al o

r co

ntro

l tre

atm

ents

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

ABPI

,ank

le br

achi

al p

ress

ure

inde

x

cont

inue

d

Orm

iston

et a

l,198

544

UK

Wou

nd ty

pe:

Veno

us le

g ul

cers

.

Met

hod

of r

ando

misa

tion:

Seal

ed e

nvel

opes

.

Obj

ectiv

e ou

tcom

es:

Perim

eter

of t

he w

ound

was

draw

n on

to a

tran

spar

ency

and

the

area

calc

ulat

ed b

ypl

anim

etry

.The

wou

nd w

asals

o ph

otog

raph

ed.T

henu

mbe

r of

wou

nds h

eale

dw

as re

cord

ed.

Sett

ing

and

leng

th

of tr

eatm

ent:

12-w

eek

tria

l.Pat

ient

s w

ere

asse

ssed

at r

egul

arin

terv

als.

Afte

r 12

wee

kspa

tient

s w

ere

allo

wed

tocr

oss-

over

.

Incl

usio

n cr

iteria

:O

ut-p

atie

nts

with

chr

onic

veno

us le

g ul

cers

per

sistin

g fo

rat

leas

t 3 m

onth

s.

Excl

usio

n cr

iteria

:U

lcer

s of

non

-ven

ous

aetio

logy

,pe

riphe

ral v

ascu

lar

dise

ase

(ABP

I < 0

.7),

poor

com

plia

nce

expe

cted

due

to c

onco

mita

ntph

ysic

al o

r m

enta

l disa

bilit

y,tr

avel

ling

prob

lem

s.

Alm

ost a

ll pa

tient

s se

lect

edw

ere

able

to d

ress

and

ban

dage

thei

r ow

n ul

cers

.

I:C

adex

omer

iodi

nepo

lysa

ccha

ride

pow

der

(Iodo

sorb

),3–

5 m

m d

eep

and

cove

red

with

aga

uze

pad,

n =

31.

C:G

entia

n vi

olet

,follo

wed

by

topi

cal a

ntib

iotic

s (P

olyf

ax) a

pplie

din

a g

ener

ous

layer

,and

cov

ered

with

a n

on-a

dher

ent p

ad (M

elol

in),

n =

30.

Each

dre

ssin

g w

as c

over

ed w

ith a

crêp

e ba

ndag

e an

d a

cott

on c

rêpe

band

age.

Mea

n w

ound

are

a (c

m2 ):

I:12

.1 (1

3.9

SD)

C:1

0.2

(8.7

SD

)

Oth

er c

hara

cter

istic

s: IC

Mea

n ag

e (y

ears

):67

.370

.3M

:F r

atio

:1:

1.3

1:2.

6M

ean

dura

tion

(mon

ths)

:45

.915

.9

Base

line

data

was

onl

y gi

ven

for

30 o

f the

31

patie

nts

trea

ted

with

I (s

ee w

ithdr

awal

s).

% r

educ

tion

in m

ean

area

of w

ound

at 1

2 w

eeks

:I:

83%

(n=

30)

C:6

1% (n

= 30

) (p

< 0.

02;S

tude

nt’s

t-tes

t).

Redu

ctio

n in

mea

n ar

ea p

er w

eek

over

12

wee

ks (c

m2 ):

I:0.

89 (0

.1 S

EM;n

= 3

0)C

:0.4

6 (0

.1 S

EM;n

= 3

0)

(p<

0.00

01;S

tude

nt’s

t-tes

t).

Both

trea

tmen

ts a

re s

tatis

tical

lydi

ffere

nt fr

om b

asel

ine

(p <

0.0

01;

analy

sis o

f cov

aria

nce)

.

Num

ber

of u

lcer

s he

aled

afte

r 12

wee

ks:

I:12

/31

(39%

)C

:7/3

0 (2

3%)

(p>

0.05

;chi

-squ

ared

ana

lysis

)

I:O

ne p

atie

nt w

asad

mitt

ed to

hosp

ital f

or s

urge

ry,

and

had

inap

prop

riate

lydr

esse

d ul

cers

(thi

spa

tient

was

excl

uded

from

the

base

line

data

set)

.Tw

o fu

rthe

rpa

tient

s w

ere

with

draw

n:on

edi

ed o

f a p

erfo

rate

dul

cer

and

the

othe

rha

d di

fficu

lty in

rem

ovin

g I f

rom

the

ulce

r.The

se tw

opa

tient

s w

ere

incl

uded

in th

ean

alysis

.

C:N

o w

ithdr

awal

s.

Patie

nts

wer

e ab

le to

adeq

uate

ly b

anda

ge th

eir

own

wou

nds.

Two

patie

nts

had

diffi

culty

rem

ovin

g I a

nd th

ree

patie

nts

com

plai

ned

of s

tingi

ng a

nditc

hing

.

Pain

was

ass

esse

d on

a s

cale

of 0

–100

by

the

indi

vidu

alpa

tient

.Pai

n w

as p

erce

ived

to b

e sim

ilar

in b

oth

grou

ps.

Two

patie

nts

on C

and

five

on

I dev

elop

ed e

czem

a,pu

ritis

ora

rash

.

Appendix 6

54 TAB

LE 6

con

td C

adex

omer

iodi

ne p

olys

acch

arid

e ve

rsus

trad

ition

al o

r co

ntro

l tre

atm

ents

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

Salvs

trum

pa®,m

anuf

actu

rer u

nkno

wn

cont

inue

d

Skog

et a

l,198

3;23

Hill

strö

m,1

988;

22

Troë

ng e

t al,1

98328

Swed

en

Wou

nd ty

pe:

Leg

ulce

rs.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

e:A

rea

of th

e w

ound

was

mea

sure

d by

plan

imet

ry,o

rby

mea

surin

g th

e gr

eate

stdi

amet

ers.

All

wou

nds

wer

e ph

otog

raph

ed a

gain

sta

rule

r sc

ale a

t eac

has

sess

men

t.

Sett

ing

and

leng

th

of tr

eatm

ent:

A m

ultic

entr

e tr

ial i

n te

nce

ntre

s.A

sses

smen

ts w

ere

mad

e af

ter

1,2,

4 an

d 6

wee

ks a

t whi

ch p

oint

the

tria

l was

term

inat

ed.

Incl

usio

n cr

iteria

:O

ut-p

atie

nts

with

chr

onic

infe

cted

leg

ulce

rs th

at fa

iled

tore

spon

d to

cur

rent

trea

tmen

ts.

Excl

usio

n cr

iteria

:U

lcer

s w

ith d

iam

eter

s sm

alle

rth

an 2

cm

and

are

as le

ss th

an

3 cm

2 ;hist

ory

of io

dine

sens

itivi

ty;p

erip

hera

l ar

teria

l dise

ase.

Trea

tmen

t:I:

Cad

exom

er io

dine

pol

ysac

-ch

arid

e po

wde

r (Io

doso

rb) a

pplie

dto

a d

epth

of a

ppro

x.3

mm

afte

rw

ashi

ng in

run

ning

wat

er,a

ndco

vere

d w

ith a

dry

dre

ssin

g,n

= 50

.

C:E

ach

day

ulce

rs w

ere

clea

ned

with

dilu

te h

ydro

gen

pero

xide

or

dilu

te p

otas

sium

per

man

gana

tean

d no

n-ad

here

nt d

ress

ings

wer

eap

plie

d.Pa

raffi

n-im

preg

nate

ddr

essin

gs w

ere

mos

t com

mon

lyus

ed,b

ut s

alin

e dr

essin

gs a

nd

blan

d oi

ntm

ents

wer

e oc

casio

nally

used

.In

case

of d

iffic

ultie

s th

eph

ysic

ian

was

abl

e to

mod

ify

the

trea

tmen

t.O

ther

ther

apie

sus

ed in

clud

ed:S

alvs

trum

pa®,

mer

brom

ine

and

syst

emic

antib

iotic

s,n

= 45

.

In b

oth

grou

ps d

urin

g th

e fir

st

few

day

s w

hen

exud

ate

was

hea

vyth

e dr

essin

gs c

ould

be

chan

ged

twic

e da

ily,b

ut fo

r th

e re

mai

nder

of th

e tr

ial t

his

was

sel

dom

nece

ssar

y an

d dr

essin

gs w

ere

chan

ged

daily

.

All

patie

nts

wer

e tr

eate

d w

ithco

mpr

essio

n ba

ndag

es a

pplie

d by

a n

urse

eith

er a

t the

clin

ic o

r at

hom

e.So

me

patie

nts

wer

e tr

aine

dto

cha

nge

thei

r ow

n ba

ndag

es

(n-v

alue

s gi

ven

are

for

patie

nts

rem

aini

ng a

fter

with

draw

als)

.

Mea

n w

ound

are

a (c

m2 ):

I:20

.1 (4

.4 S

EM)

C:3

4.0

(5.7

SEM

)

Oth

er c

hara

cter

istic

s:I

CM

ean

(SEM

) age

(y

ears

):68

.1

72.1

(1

.99)

(3.5

4)M

:F r

atio

:1:

2.8

1:3.

5M

ean

(SEM

) du

ratio

n (m

onth

s):

26.5

22.2

(1

8.3)

(1

4.3)

Wou

nd ty

pe:

Veno

us37

30O

ther

16

Dep

th o

f ulc

er:

Dee

p11

12Su

perf

icia

l26

23Ve

ry s

uper

ficia

l1

1

No

signi

fican

t diff

eren

ce b

etw

een

the

two

grou

ps.

Base

line

deta

ils a

re o

nly

avai

labl

efo

r th

e 74

pat

ient

s co

mpl

etin

g th

e tr

ial f

rom

the

orig

inal

95

ran

dom

ised.

Mea

n %

cha

nge

in w

ound

are

a af

ter

6 w

eeks

(cm

2 ):I:

–34%

(5 S

EM;n

= 3

8)C

:+5%

(15

SEM

;n =

36)

(p<

0.02

;Wilc

oxon

mat

ched

pai

rssig

ned-

rank

s te

st,t

wo-

sided

).

I:Fo

ur p

atie

nts

did

not m

eet t

he s

elec

-tio

n cr

iteria

;one

deve

lope

d a

rash

;tw

o to

ok h

olid

ays;

two

had

beta

-ha

emol

ytic

Str

epto

-co

ccus

infe

ctio

n;tw

o ha

d m

issin

gin

form

atio

n;an

don

e ex

perie

nced

recu

rren

ce o

f ul

cer

pain

.

C:T

hree

pat

ient

sdi

d no

t mee

t the

sele

ctio

n cr

iteria

;fo

ur h

ad b

eta-

haem

olyt

ic S

trep

to-

cocc

us in

fect

ion;

one

deve

lope

dsq

uam

ous

cell

carc

inom

a ;a

nd

one

expe

rienc

ed

a dr

amat

ic in

crea

sein

ulc

er s

ize.

One

pat

ient

on

C a

nd fo

uron

I co

mpl

aine

d of

pai

n on

appl

icat

ion

of th

e dr

essin

g.Th

is su

bsid

ed 3

0–60

min

late

r.

One

pat

ient

dev

elop

ed a

ra

sh in

the

I gro

up,b

ut te

sts

show

ed th

at th

is w

as d

ue to

coal

tar

deriv

ative

s an

d no

tth

e tr

eatm

ent.

Ano

ther

patie

nt in

this

grou

p ac

quire

dan

itch

aro

und

the

ulce

rw

hich

sub

sided

afte

r 2

wee

ks.

Thyr

oxin

e,tr

i-iod

othy

roni

ne,

seru

m th

yrox

ine

bind

ing

prot

ein

and

thyr

oid

inde

x di

d no

t cha

nge

signi

fican

tlyov

er th

e st

udy

perio

d.


55TAB

LE 6

con

td C

adex

omer

iodi

ne p

olys

acch

arid

e ve

rsus

trad

ition

al o

r co

ntro

l tre

atm

ents

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

Stee

le e

t al,1

98645

UK

Wou

nd ty

pe:

Veno

us le

g ul

cers

.

Met

hod

of r

ando

misa

tion:

Rand

om n

umbe

r ta

ble.

Obj

ectiv

e ou

tcom

es:

The

wou

nd p

erim

eter

was

draw

n on

to a

tran

spar

ency

and

the

area

cal

cula

ted

byco

mpu

ter

plan

imet

ry.

Num

ber

of w

ound

s he

aled

was

also

rec

orde

d.

Sett

ing

and

leng

th

of tr

eatm

ent:

Patie

nts

recr

uite

d fro

mpr

imar

y ca

re p

ract

ices

.Si

x-w

eek

tria

l.M

easu

rem

ents

take

n at

0,2,

4 an

d 6

wee

ks.

Incl

usio

n cr

iteria

:O

ut-p

atie

nts

with

ven

ous

leg

ulce

rs p

rese

nt fo

r m

ore

than

3

mon

ths,

and

larg

er th

an 2

cm

2 .

Excl

usio

n cr

iteria

:A

rter

ial d

iseas

e,di

abet

es,

rheu

mat

oid

arth

ritis,

neur

o-lo

gica

l dise

ase,

conn

ectiv

e tis

sue

dise

ase,

and

ongo

ing

hosp

ital

trea

tmen

t.

Trea

tmen

t:I:

Cad

exom

er io

dine

pol

y-sa

ccha

ride

pow

der

(Iodo

sorb

),co

vere

d w

ith g

auze

,n =

30.

C:A

var

iety

of a

gent

s w

ere

used

incl

udin

g:an

tibio

tics,

antis

eptic

s,hy

drop

hilic

age

nts,

blan

d ag

ents

,st

eroi

ds a

nd d

ry d

ress

ings

.All

trea

tmen

ts w

ere

cove

red

with

gauz

e,n

= 30

.

Dre

ssin

gs c

hang

ed th

ree

times

aw

eek.

All

patie

nts

wor

e cr

êpe

band

ages

.

Mea

n w

ound

are

a (m

m2 ):

I:12

64 (2

91 S

EM)

C:1

759

(397

SEM

)(p

= 0.

32;s

tatis

tical

met

hod

not s

tate

d).

Oth

er c

hara

cter

istic

s: IC

Mea

n ag

e (y

ears

):69

.573

.4M

:F r

atio

:1:

2.5

1:2.

6M

ean

dura

tion

(mon

ths)

:16

.616

.3

No

stat

istic

al d

iffer

ence

s be

twee

nth

e tw

o gr

oups

.

Dat

a ar

e on

ly a

vaila

ble

for

57 o

fth

e 60

par

ticip

ants

.

% r

educ

tion

in m

ean

area

of w

ound

sat

6 w

eeks

:I:

22%

(n=

28)

C:1

8% (n

= 29

)(p

= 0.

31;c

hi-s

quar

ed a

naly

sis)

Num

ber

of w

ound

s he

aled

at

6 w

eeks

:I:

3/30

(10%

)C

:1/3

0 (3

%)

I:2

C:1

With

draw

als

due

toho

spita

l adm

issio

nan

d la

ck o

fco

oper

atio

n.

Pain

dire

ctly

afte

r ap

plic

atio

nw

as m

ore

com

mon

for

I.

Day

-to-

day

pain

was

sim

ilar

inbo

th g

roup

s af

ter

6 w

eeks

’tr

eatm

ent.

Appendix 6

56 TAB

LE 7

Hyd

roge

l dre

ssin

gs v

ersu

s tra

ditio

nal o

r co

ntro

l tre

atm

ents

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

cont

inue

d

Brow

n-Et

ris e

t al,1

99647

USA

Wou

nd ty

pe:

Pres

sure

sor

es.

Met

hod

of r

ando

misa

tion:

Not

sta

ted;

stra

tific

atio

noc

curr

ed a

ccor

ding

tosu

rfac

e ar

ea a

nd s

tage

.

Obj

ectiv

e ou

tcom

e:A

rea

redu

ctio

n as

sess

ed

by g

ravi

met

ric p

lani

met

ryw

ith w

ound

trac

ing

onto

plas

tic fi

lm a

nd p

hoto

-gr

aphy

.Ind

epen

dent

ana

lysis

by b

iost

atist

ical

ana

lysis

firm

.Cha

nge

in le

vel o

fw

ound

mar

gin

unde

r-m

inin

g as

sess

ed.

Sett

ing

and

leng

th

of tr

eatm

ent:

A m

ultic

entr

e tr

ial.

Part

icip

atio

n w

as u

ntil

10 w

eeks

,or

whe

n tr

eat-

men

t cha

nge

was

indi

cate

dor

the

wou

nd h

eale

d,w

hich

ever

cam

e fir

st.

Incl

usio

n cr

iteria

:Pa

tient

s >

18 y

ears

with

one

or

mor

e pr

essu

re s

ores

.Sta

ge II

,III

or IV

onl

y.W

ound

size

bet

wee

n2

cm a

nd 8

0 cm

2an

d <

1 cm

deep

;clin

ical

ly n

on-in

fect

ed;

esch

ar-fr

ee,w

ith ≥

75%

gra

nu-

latio

n ba

se w

ith fi

xed

wou

ndm

argi

ns;a

dequ

ate

nutr

ition

alin

take

by

mou

th tu

be o

rhy

pera

limen

tatio

n.

Excl

usio

n cr

iteria

:St

age

I sor

es o

r St

age

IV

sore

s w

ith e

xpos

ed te

ndon

or

bone

;wou

nd s

ize <

2 c

m2

or

> 80

cm

2 ,or

> 1

cm d

eep;

wou

nds

cove

red

with

nec

rotic

esch

ar o

r ne

crot

ic w

ound

bas

eco

ntai

ning

> 2

5% s

loug

h;di

agno

sis o

r su

spic

ion

ofos

teom

yelit

is at

stu

dy w

ound

site;

carc

inom

atos

is;or

sig

ns o

rsy

mpt

oms

of w

ound

clin

ical

infe

ctio

n;in

adeq

uate

nut

ritio

nal

inta

ke;s

inus

trac

t,tu

nnel

ling

or >

0.5

cm

of w

ound

mar

gin

unde

rmin

ing.

I:H

ydro

gel d

ress

ing

(Tra

nsor

bent

),n

= 77

.

C:H

ydro

collo

id d

ress

ing

(Duo

derm

CG

F),n

= 6

3.

Eval

uatio

n to

ok p

lace

wee

kly,

dres

sing

chan

ges

occu

rred

eve

ry

7 da

ys o

r m

ore

frequ

ently

.

Mea

n w

ound

are

a:N

ot s

tate

d

Oth

er c

hara

cter

istic

s:A

ll gr

oups

Mea

n ag

e (y

ears

):70

M:F

rat

io1:

1 IC

Dur

atio

n (m

onth

s):

< 1

23%

31%

1–3

38%

49%

4–

6 10

%14

%7–

12

13 %

2%>

12

16%

4%

Loca

tion:

Sacr

um33

%37

%Tr

ocha

nter

17%

26%

Hee

l 16

%18

%Isc

hium

16

%13

%M

alle

olus

10

%4%

Spin

e 6%

2%K

nee

0%2%

Num

ber

of w

ound

s he

aled

at

10

wee

ks:

I:39

/77

(51%

)C

:37/

63 (5

9%)

Redu

ctio

n in

mea

n ar

ea o

f wou

nds

at 1

0 w

eeks

:St

age

II so

res

(2–3

0 cm

2 ):I:

3.6

cm2

(n=

12)

C:2

.3 c

m2

(n=

12) (

NS)

Stag

e II

sore

s (2

–30

cm2 ):

I:6.

3 cm

2(n

= 42

)C

:5.2

cm

2(n

= 36

) (N

S)

Stag

e III

sor

es (3

1–80

cm

2 ):I:

24.5

cm

2(n

= 3)

C:4

.3 c

m2

(n=

2) (N

S)

Insu

ffici

ent d

ata

wer

e av

aila

ble

for

analy

sis o

f the

sub

grou

ping

s:St

age

II (3

1–80

cm

2 ) St

age

IV (2

–30

cm2 )

Stag

e IV

31–

80 c

m2 )

19 r

ando

mise

dpa

tient

s w

ere

not

incl

uded

in th

ean

alysis

as

they

did

not c

ompl

ete

the

first

3 w

eeks

of t

hest

udy,

or m

issed

two

or m

ore

sequ

entia

l wee

kly

visit

s.

No

signi

fican

t diff

eren

ces

incl

inic

al w

ound

infe

ctio

n,od

our,

or d

ress

ing

chan

ges/

wee

k.


57TAB

LE 7

con

td H

ydro

gel d

ress

ings

ver

sus

tradi

tiona

l or

cont

rol t

reat

men

ts

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

cont

inue

d

Dar

kovi

ch e

t al,1

99046

USA

Wou

nd ty

pe:

Pres

sure

sor

es.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

es:

Perim

eter

of t

he w

ound

was

trac

ed a

nd in

som

eca

ses

phot

ogra

phed

tode

term

ine

size.

The

num

ber

of w

ound

s he

aled

was

al

so r

ecor

ded.

Sett

ing

and

leng

th

of tr

eatm

ent:

Max

imum

60-

day

tria

l unl

ess

wou

nd h

eale

d,pa

tient

disc

harg

ed o

r w

ithdr

awn

by c

linic

ian.

Mea

sure

men

tsta

ken

at e

ach

dres

sing

chan

ge o

r at

leas

t wee

kly

inte

rval

s.

Incl

usio

n cr

iteria

:Pa

tient

s in

acu

te c

are

faci

litie

san

d nu

rsin

g ho

mes

with

sta

ge I

or II

pre

ssur

e so

res

ulce

rs

(size

> 2

cm

2 ).

Excl

usio

n cr

iteria

:Rec

eivi

ngra

diat

ion

ther

apy;

infe

ctio

n,sin

us tr

acts

or

fistu

las

in th

ew

ound

;a b

lood

sug

ar le

vel

> 18

0 m

g/dl

;no

impr

oved

nutr

ition

al s

tatu

s.

I:H

ydro

gel d

ress

ing

(Bio

film

),n

= 60

wou

nds.

C:H

ydro

collo

id d

ress

ings

(Duo

derm

),n

= 63

wou

nds.

All

wou

nds

wer

e in

itial

ly c

lean

sed

with

hyd

roge

n pe

roxi

de a

nd s

alin

e.Pa

tient

s w

ith a

n oi

ly s

kin

wer

ede

grea

sed

to a

llow

for

a 1.

25 in

chad

hesio

n be

lt ar

ound

the

wou

nd.

Alth

ough

this

was

not

mai

ntai

ned

whe

re th

e w

ound

was

> 2

0 cm

2 ,in

stea

d ut

ilisin

g 4

x 4

inch

dres

sings

.

Dre

ssin

gs w

ere

usua

lly c

hang

edev

ery

3–4

days

and

was

hed

insa

line

befo

re r

eapp

licat

ion.

All

patie

nts

lay o

n th

e sa

me

type

of

pres

sure

-red

ucin

g m

attr

esse

s.

Mea

n ar

ea o

f pre

ssur

e so

re (c

m2 ):

I:11

.0 (0

.2–1

00 r

ange

)C

:9.2

(0.4

– 64

ran

ge)

Oth

er c

hara

cter

istic

s: All

grou

psM

ean

age

(yea

rs):

75

(ran

ge,3

0–98

)M

:F r

atio

:1:

1.6 I

CRa

tio o

f gra

de

I:II u

lcer

s:1:

1.3

1:1.

6Se

rum

alb

umin

(g

m/d

l):2.

82.

7N

o.of

sta

ge I

wou

nds:

2731

No.

of s

tage

II w

ound

s:35

36

Ther

e w

as a

sig

nific

ant d

iffer

ence

betw

een

the

age

of p

atie

nts

in

the

acut

e ca

re s

ettin

g (6

9 ye

ars)

and

the

exte

nded

car

e fa

cilit

ies

(83

year

s).

Mea

n w

ound

are

a at

60

days

(cm

2 ):I:

3.5

C:5

.5

Mea

n re

duct

ion

in w

ound

are

a at

60

days

(cm

2 ):I:

7.5

(68%

red

uctio

n)C

:3.7

(40%

red

uctio

n)

Num

ber

of w

ound

s he

aled

at

60

days

:I:

26/6

0 (4

3%)

C:1

5/63

(24%

)

Mea

n tr

eatm

ent d

ays:

I:12

C:1

1.3

I:O

ne p

atie

nt w

asex

clud

ed b

ecau

seth

e w

ound

enl

arge

dby

> 1

0% p

er d

ay.

One

pat

ient

was

excl

uded

bec

ause

the

wou

ndde

crea

sed

by

> 25

% p

er d

ay.

C:T

hree

pat

ient

sw

ere

excl

uded

beca

use

thei

rw

ound

s en

larg

ed

by >

10%

per

day

.O

ne p

atie

nt w

asex

clud

ed b

ecau

seth

e w

ound

decr

ease

d by

>

25%

per

day

.

Patie

nts

appe

ared

to p

refe

r I

(hyd

roge

l) be

caus

e of

the

lack

of o

dour

,cus

hion

ing

and

light

ness

.

The

gel l

ayer

in C

(hyd

ro-

collo

id) w

as fo

und

to d

egra

deea

sily

whi

ch n

eces

sitat

edm

echa

nica

l cle

ansin

g of

the

wou

nd,w

hich

dam

aged

the

heal

ing

tissu

e lay

ers.

Appendix 6

58 TAB

LE 7

con

td H

ydro

gel d

ress

ings

ver

sus

tradi

tiona

l or

cont

rol t

reat

men

ts

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

Alle

vyn®

,Sm

ith &

Nep

hew

Hea

lthca

re L

td

cont

inue

d

Lum

et a

l,199

6(u

npub

lishe

d)48

Hon

g Ko

ng

Wou

nd ty

pe:

Pres

sure

sor

es.

Met

hod

of r

ando

misa

tion:

Patie

nts

with

an

odd

adm

issio

n nu

mbe

r w

ere

assig

ned

to th

e co

ntro

lgr

oup,

thos

e w

ith a

n ev

ennu

mbe

r w

ere

assig

ned

toth

e tr

eatm

ent g

roup

.

Obj

ectiv

e ou

tcom

e:W

ound

size

was

mea

sure

d.In

add

ition

the

time

spen

tby

nur

sing

staf

f and

cos

t of

pha

rmac

eutic

als

was

mon

itore

d.

Sett

ing

and

leng

th

of tr

eatm

ent:

Post

-acu

te h

ospi

tal.

Trea

tmen

t pro

gres

sion

was

mon

itore

d w

eekl

y an

d a

final

ass

essm

ent

was

mad

e af

ter

8 w

eeks

,co

mpl

ete

heal

ing,

disc

harg

e or

dea

th.

Incl

usio

n cr

iteria

:H

ospi

talis

ed p

ost a

cute

pat

ient

sag

ed ≥

65 y

ears

with

pre

ssur

eso

res.

Excl

usio

n cr

iteria

:Pr

essu

re s

ores

≤1

cm2 ;g

rade

Iso

res;

patie

nts

cons

ider

ed fo

rsu

ppor

tive

care

onl

y;pa

tient

sre

quiri

ng a

ntim

icro

bial

age

nts

for

man

agem

ent o

f sys

tem

icin

fect

ion

from

pre

ssur

e so

res;

patie

nts

(or

care

rs) d

id n

ot g

iveco

nsen

t for

the

stud

y.

Trea

tmen

t:I:

Hyd

roge

l dre

ssin

g (In

tras

ite

Gel

) cov

ered

with

a h

ydro

phili

cpo

lyur

etha

ne fo

am d

ress

ing

(Alle

vyn®

),n

= 12

wou

nds

from

five

pat

ient

s.

C:T

he s

ore

was

cle

anse

d w

ith a

freq

uenc

y de

pend

ent

on th

e am

ount

of d

ischa

rge

(for

unin

fect

ed s

ores

cle

ansin

g w

aspe

rform

ed b

y sa

line

only

whi

le

for

infe

cted

sor

es c

lean

sing

was

perfo

rmed

with

1 /2Eu

sol f

or a

tm

ost t

hree

tim

es a

day

follo

wed

by

rinsin

g w

ith s

alin

e),n

= 8

wou

nds

from

five

pat

ient

s.

All

patie

nts

rece

ived

the

sam

ege

nera

l tre

atm

ent w

hich

incl

uded

:ba

thin

g at

leas

t on

alte

rnat

e da

ys;

turn

ing

ever

y 2

hrs

(7 a

m–1

1 pm

)an

d ev

ery

3 hr

s (1

1 pm

–7 a

m);

give

n at

leas

t 1.5

litr

es o

f flu

id

per

day

unle

ss c

ontr

aind

icat

ions

exist

ed;n

utrit

iona

l sup

port

and

mon

itorin

g;vi

tam

ins

only

to b

egi

ven

if ev

iden

ce o

f def

icie

ncy;

anti-

mic

robi

al a

gent

s on

ly to

be

give

nw

ith e

vide

nce

of s

yste

mic

sep

sis.

Mea

n w

ound

are

a (c

m2)

:I:

36.3

(ran

ge,1

.5–1

60)

C:1

8.6

(ran

ge,1

.0–7

2.5)

Oth

er c

hara

cter

istic

s:I

CM

ean

age

(yea

rs):

8078

.4M

:F r

atio

:1:

41:

1.5

Mea

n du

ratio

n (m

onth

s):

Not

sta

ted

No

stat

istic

ally

sig

nific

ant

diffe

renc

e be

twee

n th

e tw

o gr

oups

was

rep

orte

d.

Mea

n siz

e of

pre

ssur

e so

re a

t fin

alas

sess

men

t (cm

2 ):I:

15.9

(p=

0.02

)C

:20.

5 (p

= 0.

87)

(p=

0.94

;Wilc

oxon

sig

n te

st o

rM

ann-

Whi

tney

ran

k su

m te

st w

ere

used

for

stat

istic

al a

naly

sis)

Mea

n %

cha

nge

in w

ound

are

a at

final

ass

essm

ent:

I:–5

6%C

:+10

%

Cos

t of l

ocal

trea

tmen

t (H

K$)

:I

CN

ursin

g tim

e:78

516

58Ph

arm

aceu

tical

ite

ms:

1884

280

Trea

tmen

t with

I w

as s

tatis

tical

ly le

ssex

pens

ive th

an tr

eatm

ent w

ith C

.

I:N

o w

ithdr

awal

s.

C:T

wo

patie

nts

died

from

pneu

mon

ia.

Estim

ated

man

pow

erre

quire

d fo

r ge

nera

l car

e w

as5.

8 an

d 2.

72 h

r/da

y/pa

tient

,w

ith le

ss ti

me

used

in th

etr

eatm

ent a

rm (p

= 0.

046)

.

The

aver

age

dura

tion

of s

tay

was

4.8

day

s in

the

I (H

ydro

-ge

l) gr

oup

and

6.4

days

in th

eC

(sta

ndar

d tr

eatm

ent)

gro

up(p

= 0.

15;N

S).


59TAB

LE 7

con

td H

ydro

gel d

ress

ings

ver

sus

tradi

tiona

l or

cont

rol t

reat

men

ts

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

Mul

der

et a

l,199

349

USA

Wou

nd ty

pe:

Pres

sure

sor

es.

Met

hod

of r

ando

misa

tion:

Com

pute

r al

loca

tion.

Obj

ectiv

e ou

tcom

es:

The

wou

nd p

erim

eter

was

trac

ed o

n to

a tr

ansp

aren

cyan

d th

e ar

ea d

eter

min

ed

by c

ompu

ter

analy

sis.I

nad

ditio

n th

e la

rges

t len

gth,

wid

th a

nd d

epth

of e

ach

wou

nd w

as m

easu

red

and

a ph

otog

raph

take

n at

ea

ch a

sses

smen

t.

Sett

ing

and

leng

th

of tr

eatm

ent:

A m

ultic

entr

e tr

ial a

t thr

eein

depe

nden

t site

s.A

sses

s-m

ents

of w

ound

size

wer

em

ade

wee

kly

for

8 w

eeks

or u

ntil

the

wou

nd w

ashe

aled

.Whe

re p

ossib

le,

each

pat

ient

was

eva

luat

edby

the

sam

e in

vest

igat

orth

roug

hout

the

tria

l.Effo

rts

wer

e m

ade

to s

tand

ardi

seob

serv

atio

ns b

etw

een

inve

stig

ator

s.

Incl

usio

n cr

iteria

:In

-pat

ient

s an

d ou

t-pa

tient

s w

ithst

age

II an

d III

pre

ssur

e so

res.

Sore

s ≥

1.5

cm x

0.5

cm

and

≥

10 c

m x

10

cm w

ere

incl

uded

.Pa

tient

s w

ere

≥18

yea

rs a

nd

had

a lif

e ex

pect

ancy

of a

t le

ast 2

mon

ths.

Excl

usio

n cr

iteria

:St

age

IV w

ound

s or

thos

e w

ithte

ndon

,bon

e,ca

psul

e,or

fasc

iaex

posu

re;p

regn

ancy

;che

mo-

ther

apy;

prio

r w

ound

infe

ctio

n;ex

tens

ive u

nder

min

ing

of th

eul

cer

(> 1

cm

);AID

S;pa

tient

sre

ceiv

ing

> 10

mg

ofco

rtic

oste

roid

s.

Trea

tmen

t:I:

Hyd

roge

l dre

ssin

g (C

lear

site)

,ch

ange

d tw

ice

a w

eek,

n =

23.

C1:

Hyd

roco

lloid

dre

ssin

g(D

uoD

erm

),ch

ange

d tw

ice

aw

eek,

n =

20.

C2:

Salin

e so

lutio

n an

d m

oist

ened

gauz

e,ch

ange

d th

ree

times

a d

ay,

n =

21.

Dre

ssin

gs w

ere

chan

ged

eith

er b

yth

e pa

tient

or

the

care

give

r,af

ter

they

had

rec

eive

d ap

prop

riate

inst

ruct

ions

.

67 p

atie

nts

wer

e en

rolle

d in

to

the

tria

l;dat

a w

ere

analy

sed

for

only

64.

Mea

n w

ound

are

a (c

m2 ):

Not

sta

ted.

Oth

er c

hara

cter

istic

s: IC

1C

2

Mea

n ag

e (y

ears

):56

.763

.157

.2M

:F r

atio

:1:

3.6

1:5.

61:

9.5

Wou

nd s

tage

:II:

89

5III

:14

1318

Race

(pat

ient

s):

Blac

k:4

36

Whi

te:

1716

14H

ispan

ic:

11

0

No

stat

istic

ally

sig

nific

ant

diffe

renc

es b

etw

een

the

thre

egr

oups

was

rep

orte

d.

Mea

n %

red

uctio

n in

wou

nd a

rea

per

wee

k:I:

8 (1

4.8

SD)

C1:

3.3

(32.

7 SD

)C

2:5.

1 (1

4.8

SD)

(p>

0.05

;non

-par

amet

ric te

st)

Med

ian

% r

educ

tion

in w

ound

are

ape

r w

eek:

I:5.

6C

1:7.

4C

2:7.

0(p

> 0.

05;n

on-p

aram

etric

test

)

Thre

e pa

tient

sw

ere

not e

valu

able

and

thei

r da

ta a

reno

t pre

sent

ed in

the

base

line

char

acte

ristic

s.

I:Thr

ee p

atie

nts

wer

e om

itted

from

the

final

ana

lysis

.N

o re

ason

s w

ere

give

n fo

r th

ese

with

draw

als.

C1:

No

with

draw

als.

C2:

No

with

draw

als.

One

pat

ient

in th

e C

1tr

eatm

ent g

roup

(hyd

ro-

collo

id) h

ad m

ild ir

ritat

ion,

and

anot

her

had

min

orse

nsiti

vity

to th

e C

1 dr

essin

g.

One

cas

e of

infla

mm

atio

noc

curr

ed in

the

I (hy

drog

el)

grou

p,an

d an

othe

r pa

tient

had

exco

riatio

n w

hich

was

poss

ibly

rela

ted

to I.

Ther

e w

ere

no a

dver

sere

actio

ns to

C2

(sal

ine)

.

Appendix 6

60 TAB

LE 8

Enz

yme

prep

arat

ions

ver

sus

tradi

tiona

l or

cont

rol t

reat

men

ts

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

cont

inue

d

Ågr

en a

nd S

tröm

berg

,19

859

Swed

en

Wou

nd ty

pe:

Pres

sure

sor

es.

Met

hod

of r

ando

misa

tion:

Patie

nts

cons

ecut

ively

mat

ched

in p

airs

(for

wha

tno

t sta

ted)

.Eac

h m

embe

rof

the

pair

was

ran

dom

lyal

loca

ted

to o

ne o

f the

tw

o tr

eatm

ents

.

Obj

ectiv

e ou

tcom

e:W

ound

are

a w

as tr

aced

and

the

size

mea

sure

d by

plan

imet

ry.A

pho

togr

aph

was

take

n at

eac

has

sess

men

t.

Sett

ing

and

leng

th

of tr

eatm

ent:

Sing

le-b

lind

tria

l for

8

wee

ks.O

ne o

f the

auth

ors

was

res

pons

ible

fo

r m

easu

ring

all t

hew

ound

s at

wee

kly

inte

rval

s.A

n in

depe

nden

t sur

geon

from

ano

ther

hos

pita

las

sess

ed th

e ph

otog

raph

s.

Incl

usio

n cr

iteria

:El

derly

in-p

atie

nts

and

out-

patie

nts

with

one

or

mor

ene

crot

ic p

ress

ure

sore

s.

Excl

usio

n cr

iteria

:N

ot s

tate

d.

Trea

tmen

t:I:

Stre

ptok

inas

e/st

rept

odor

nase

enzy

me

prep

arat

ion

(Var

idas

eTo

pica

l) ap

plie

d to

a s

teril

e ga

uze

com

pres

s.D

ress

ings

cha

nged

tw

ice

daily

,n =

14.

C:Z

inc

oxid

e (4

00 m

g Z

nO/c

m2 )

appl

ied

to a

ste

rile

gauz

eco

mpr

ess.

Dre

ssin

gs c

hang

ed

once

dai

ly,n

= 14

.

All

dres

sings

wer

e se

cure

d w

ithpo

rous

acr

ylic

-bas

ed ta

pes.

Whe

rem

ultip

le w

ound

s ex

isted

they

wer

eal

l tre

ated

uni

form

ly,bu

t onl

y th

ela

rges

t was

mon

itore

d.

Prio

r to

trea

tmen

t loo

sely

atta

ched

nec

rotic

mat

eria

l was

rem

oved

,but

no

surg

ical

deb

ride-

men

t was

per

form

ed th

erea

fter.

No

patie

nts

rece

ived

antib

iotic

s.N

ursin

g ca

re fo

llow

ed it

s us

ual

proc

edur

e.

Med

ian

wou

nd a

rea

(cm

2 ):I:

4.2

(ran

ge,1

.2–1

8.2)

C

:5.8

(ran

ge,1

.2–2

6.0)

Oth

er c

hara

cter

istic

s:I

CM

edia

n ag

e (y

ears

):86

81M

:F r

atio

:1:

3.7

1:1.

8D

iabe

tes

mel

litus

(n):

45

% m

edia

n ch

ange

in w

ound

are

a at

final

ass

essm

ent:

I:+1

8.7%

C:–

2.4%

I:Thr

ee p

atie

nts

wer

e w

ithdr

awn

beca

use

ofun

succ

essfu

ltr

eatm

ent.

In o

ne

of th

ese

patie

nts

a sk

in r

eact

ion

occu

rred

on

the

heel

afte

r 3

wee

ksof

trea

tmen

t.In

anot

her

patie

ntne

cros

is de

velo

ped

to 8

x its

orig

inal

size.

In th

e th

irdpa

tient

Pse

udo-

mon

as a

erug

inos

ain

fect

ion

deve

lope

daf

ter

6 w

eeks

.

C:N

o w

ithdr

awal

s

All

with

draw

als

wer

e in

clud

ed in

the

analy

sis.

I (en

zym

e) w

as a

ssoc

iate

dw

ith a

n in

crea

se in

wou

ndsiz

e.Th

is m

ay b

e du

e to

exce

ssive

wou

nd d

ebrid

e-m

ent,

or in

hibi

tion

of ti

ssue

grow

th b

y th

e en

zym

e.


61TAB

LE 8

con

td E

nzym

e pr

epar

atio

ns v

ersu

s tra

ditio

nal o

r co

ntro

l tre

atm

ents

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

cont

inue

d

Gor

don,

1975

51

UK

Wou

nd ty

pe:

Leg

ulce

rs.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

e:W

ound

are

a w

as e

stim

ated

by m

easu

ring

the

two

larg

est d

iam

eter

s an

dm

ultip

lyin

g to

geth

er.E

ach

wou

nd w

as p

hoto

grap

hed.

Sett

ing

and

leng

th o

ftr

eatm

ent:

Patie

nts

atte

nd-

ing

a cl

inic

for

leg

ulce

rtr

eatm

ent.

Ass

essm

ents

wer

e m

ade

at w

eekl

yin

terv

als

for

6 w

eeks

.

Incl

usio

n cr

iteria

:Pa

tient

s w

ith le

g ul

cers

cons

ider

ed to

be

post

-th

rom

botic

.

Excl

usio

n cr

iteria

:N

ot s

tate

d.

Trea

tmen

t:C

:For

mul

atio

n A

–

hydr

ocor

tison

e ac

etat

e an

dne

omyc

in p

alita

te,n

= 9

.

I:Fo

rmul

atio

n B

(Chy

mac

ort)

.Th

is tr

eatm

ent w

as th

e sa

me

asfo

rmul

atio

n A

but

with

the

addi

tion

of th

e pa

ncre

atic

enz

ymes

chym

otry

psin

and

tryp

sin in

the

prop

ortio

n of

1:6

,n=

10.

All

wou

nds

wer

e co

vere

d w

ith a

non-

adhe

rent

dre

ssin

g;a

tube

gauz

e;an

abs

orbe

nt g

auze

dre

ssin

gpa

d ov

er th

e w

ound

are

a;an

dfin

ally

a 4

-inch

crê

pe b

anda

geap

plie

d fro

m th

e to

es to

the

knee

Dre

ssin

gs w

ere

chan

ged

at th

ecl

inic

.Pat

ient

s w

ere

inst

ruct

ed n

otto

inte

rfere

with

dre

ssin

gs a

nd to

rem

ain

fully

am

bula

nt.

App

roxi

mat

e m

ean

wou

nd

area

(cm

2 ):C

:14.

50 (2

2.13

SD

)I:

15.8

2 (1

9.67

SD

)

Oth

er c

hara

cter

istic

s: All

grou

psM

ean

age

(yea

rs):

61M

:F r

atio

:1:

9.5

Ther

e w

as n

o st

atist

ical

diff

eren

cebe

twee

n th

e tw

o gr

oups

with

resp

ect t

o th

e gi

ven

base

line

char

acte

ristic

s.

App

roxi

mat

e m

ean

wou

nd a

rea

at 6

wee

ks:

C:8

.40

(9.7

9 SD

)I:

5.37

(7.8

2 SD

)(C

vs.

base

line,

p<

0.05

;I v

s.ba

selin

e,p

< 0.

01;s

tatis

tical

test

met

hod

not s

tate

d)

Num

ber

of w

ound

s he

aled

afte

r 6

wee

ks:

C:0

/9 (0

%)

I:2/

10 (2

0%)

C:O

ne p

atie

ntde

faul

ted

afte

r th

e fir

st w

eek

oftr

eatm

ent a

nd

was

exc

lude

d fro

mth

e an

alysis

.

I:N

o w

ithdr

awal

s.

Pain

cau

sed

by tr

eatm

ent w

asin

suffi

cien

t to

caus

ew

ithdr

awal

in e

ither

gro

up.

Lee

& A

mbr

us,1

97550

USA

Wou

nd ty

pe:P

ress

ure

sore

s.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

e:Tw

odi

amet

ers o

f the

wou

ndm

easu

red

and

a co

lour

phot

ogra

ph ta

ken.

In a

dditi

ona

volu

me

mou

ld w

as m

ade

with

Jeltr

ate

or K

err

No.

1,an

d th

e vo

lum

e de

term

ined

by w

ater

disp

lacem

ent.

Sett

ing

and

leng

th o

f tre

at-

men

t:Se

ttin

g no

t sta

ted.

Patie

nts

wer

e tr

eate

d fo

r 4

wee

ks o

r un

til c

ompl

ica-

tions

dev

elop

ed o

r th

epa

tient

die

d.M

easu

rem

ents

whe

re ta

ken

wee

kly

and

onco

mpl

etio

n of

the

stud

y.

Incl

usio

n cr

iteria

:Pa

tient

s w

ith a

dvan

ced

pres

sure

sor

es.

Excl

usio

n cr

iteria

:N

ot s

tate

d.

Trea

tmen

t:I:

Col

lage

nase

enz

yme

prep

arat

ion

(San

tyl)

appl

ied

at 2

50 u

nits

per

gram

of w

hite

pet

rola

tum

,n =

17.

C:P

lace

bo (h

eat-

inac

tivat

ed S

anty

l)ap

plie

d in

the

sam

e pr

opor

tions

as

for

I,n

= 11

.

Befo

re a

pplic

atio

n of

eith

ertr

eatm

ent t

he w

ound

was

was

hed

with

ste

rile

salin

e (p

H 7

.5).

Each

appl

icat

ion

was

app

lied

once

da

ily to

eac

h w

ound

unl

ess

mor

efre

quen

t cle

ansin

g w

as r

equi

red

beca

use

of c

onta

min

atio

n fro

min

cont

inen

ce o

f urin

e,fa

eces

or

bot

h.

All

wou

nds

wer

e co

vere

d w

ith a

ster

ile g

auze

pad

.

Mea

n w

ound

are

a (c

m2 ):

Not

sta

ted.

Mea

n w

ound

vol

ume

(cm

3 ):I:

15.4

4 (1

9.92

SD

)C

:1.2

5 (1

.62

SD)

Oth

er c

hara

cter

istic

s:A

ll gr

oups

Mea

n ag

e (y

ears

):67

.6 (1

3.7

SD)

M:F

rat

io:

1:2.

7

Base

line

wou

nd v

olum

e is

signi

fican

tly d

iffer

ent b

etw

een

grou

ps (p

< 0.

01).

11 p

atie

nts

with

28

adva

nced

pres

sure

sor

es w

ere

incl

uded

inth

e st

udy.

All

had

chro

nic

dise

ase

and

wer

e in

poo

r ph

ysic

al c

on-

ditio

n.Fo

ur h

ad n

eopl

astic

dise

ase;

four

had

ath

eros

cler

otic

hea

rtdi

seas

e or

had

a c

ereb

rova

scul

arac

cide

nt,o

r bo

th;t

wo

had

Park

in-

son’s

dise

ase;

and

one

had

afe

mor

al n

eck

frac

ture

.

Mea

n %

cha

nge

in w

ound

vol

ume

at c

ompl

etio

n of

the

tria

l:I:

+13.

14 (5

9.8

SD)

C:+

78.7

9 (9

4.6

SD)

(Pre

ssur

e so

res

in b

oth

grou

psin

crea

sed

in s

ize.)

I:Pa

tient

s w

ere

rem

oved

from

da

y 6

to d

ay 3

0(t

erm

inat

ion

of

the

tria

l).

C:P

atie

nts

wer

ew

ithdr

awn

from

da

y 3

to d

ay 1

0.N

o pa

tient

in th

isgr

oup

cont

inue

d to

be

trea

ted

afte

r10

day

s.

One

wou

nd tr

eate

d w

ith I

(enz

yme)

exp

erie

nced

mild

blee

ding

and

a b

urni

ngse

nsat

ion.

Appendix 6

62 TAB

LE 8

con

td E

nzym

e pr

epar

atio

ns v

ersu

s tra

ditio

nal o

r co

ntro

l tre

atm

ents

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

cont

inue

d

Paris

h an

d C

ollin

s,19

7937

USA

Wou

nd ty

pe:

Pres

sure

sor

es.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

e:N

umbe

r of

ulc

ers

heal

ed.

Sett

ing

and

leng

th o

f tre

at-

men

t:C

omm

unity

(nur

sing

hom

e) 4

-wee

k tr

ial.

Incl

usio

n cr

iteria

:Pa

tient

s w

ith p

ress

ure

sore

sre

sidin

g in

a n

ursin

g ho

me.

Excl

usio

n cr

iteria

:N

ot s

tate

d.

I:C

olla

gena

se e

nzym

e pr

epar

atio

n(S

anty

l) ap

plie

d da

ily a

fter

a sa

line

was

h an

d co

vere

d w

ith a

dry

dres

sing,

n =

11 w

ound

s fro

m fi

vepa

tient

s.

C:S

ugar

and

egg

whi

te a

pplie

daf

ter

a sa

line

was

h.C

hang

ed fo

urtim

es a

day

.Allo

wed

to d

ry a

ndno

t cov

ered

,n =

9 w

ound

s fro

mfiv

e pa

tient

s.

Mea

n w

ound

size

= √

of s

urfa

cear

ea (c

m):

I:3.

2 C

:2.4

No

stat

istic

al d

iffer

ence

bet

wee

nth

e gr

oups

for

ulce

r siz

e.

Oth

er c

hara

cter

istic

s:I

CA

ge r

ange

(yea

rs):

28–5

932

–70

M:F

rat

io:

Not

sta

ted

Mea

n du

ratio

n (m

onth

s):

Not

sta

ted

Num

ber

of w

ound

s he

aled

at

4 w

eeks

:I:

1/11

(9%

)C

:0/9

(0%

)

Num

ber

of p

atie

nts

with

hea

led

ulce

rs a

t 4 w

eeks

:I:

1/5

(20%

)C

:0/5

(0%

)

No

with

draw

als.

No

side-

effe

cts

repo

rted

by

patie

nts

with

any

of t

hetr

eatm

ents

.

Wes

terh

of e

t al,1

98752

The

Net

herla

nds

Wou

nd ty

pe:

Chr

onic

leg

ulce

rs.

Met

hod

of r

ando

misa

tion:

Patie

nts

allo

tted

a c

ode

num

ber,

one

per

leg.

Trea

t-m

ents

wer

e al

so r

ando

m-

ised

and

code

s co

ncea

led

from

the

inve

stig

ator

s.O

bjec

tive

outc

ome:

Num

ber

of w

ound

s he

aled

and

the

num

ber

whe

re s

kin

graf

ting

was

a s

ucce

ss.A

colo

ur p

hoto

grap

h w

asta

ken

by s

tand

ardi

sed

phot

ogra

phy

at e

ach

asse

ssm

ent p

erio

d.Se

ttin

g an

d le

ngth

of t

reat

-m

ent:

Ass

essm

ents

wer

em

ade

twic

e w

eekl

y.Bo

thth

e pa

tient

and

ass

esso

rw

ere

blin

d to

the

trea

tmen

tgi

ven.

Fina

l ass

essm

ent w

asm

ade

by tw

o in

depe

nden

tin

vest

igat

ors.

Trea

tmen

t was

cont

inue

d un

til th

e as

sess

orw

as c

onfid

ent t

o in

itiat

egr

aftin

g.

Incl

usio

n cr

iteria

:Pa

tient

s w

ith c

hron

ic le

g ul

cers

refe

rred

for

skin

gra

fting

.

Excl

usio

n cr

iteria

:Pr

egna

ncy;

hype

rsen

sitiv

ity to

Elas

e;in

abi

lity

to b

e tr

eate

d by

the

usua

l pre

graf

ting

met

hod.

Trea

tmen

t:I:

Enzy

me

prep

arat

ion

(Ela

se;a

freez

e-dr

ied

pow

der

cont

aini

ng

25 U

fibr

inol

ysin

and

15,

000

Ude

soxy

ribon

ucle

ase)

,n =

16.

C:P

lace

bo p

owde

r (fr

eeze

-drie

dpo

wde

r w

ithou

t act

ive in

gred

i-en

ts),

n =

17.

Wou

nds

wer

e fir

st c

lean

ed w

ithsa

line.

The

trea

tmen

t and

pla

cebo

pow

ders

wer

e di

ssol

ved

in 3

0 m

lof

sal

ine

and

used

to s

oak

gauz

epa

ds.T

he s

oake

d pa

d w

as a

pplie

dto

the

ulce

r an

d co

vere

d w

ith a

para

ffin

dres

sing

and

band

aged

.

Dre

ssin

gs w

ere

chan

ged

thre

etim

es a

day

by

nurs

es fa

mili

ar

with

the

proc

edur

es.

34 p

atie

nts

wer

e en

rolle

d fo

r th

etr

ial w

ith 3

7 le

g ul

cers

.Pat

ient

allo

catio

n de

tails

are

onl

y av

aila

ble

for

thos

e pa

tient

s co

mpl

etin

g th

e st

udy.

Mea

n w

ound

are

a (c

m2 ):

I:25

.7 (2

,273

ran

ge)

C:2

0.2

(2,4

8 ra

nge)

Oth

er c

hara

cter

istic

s:I

CM

ean

age

(yea

rs):

75.9

73.5

M:F

rat

io:

1:2.

21:

1.3

Mea

n du

ratio

n (m

onth

s):

19.8

13.8

Veno

us s

tasis

ulc

ers:

109

Com

plex

ulc

ers:

68

Base

line

char

acte

ristic

s ar

e on

lyav

aila

ble

for

30 o

f the

34

patie

nts.

% o

f wou

nds

succ

essfu

lly g

rafte

d or

need

ing

no g

rafti

ng:

I:69

(95%

CI:

44,8

6)C

:35

(95%

CI:

17,5

9)

% o

f com

plex

ulc

ers

succ

essfu

llygr

afte

d or

nee

ding

no

graf

ting:

I:50

(95%

CI:

19,8

1)C

:38

(95%

CI:

14,6

9)

% o

f ven

ous

stas

is ul

cers

suc

cess

fully

graf

ted

or n

eedi

ng n

o gr

aftin

g:I:

80 (9

5% C

I:49

,94)

C:3

3 (9

5% C

I:12

,65)

Four

pat

ient

s w

ere

excl

uded

from

the

analy

sisfo

r re

ason

sun

rela

ted

to th

eth

erap

y.Th

ese

with

draw

als

wer

eno

t inc

lude

d in

th

e ba

selin

e da

ta.

The

auth

ors

stat

e th

atde

brid

emen

t with

I (e

nzym

e)he

lped

to m

ake

the

wou

ndre

cept

ive to

ski

n gr

aftin

g.

The

pres

ence

of c

ompl

ex le

gul

cers

may

hav

e ex

tend

ed th

ele

ngth

of t

reat

men

t nee

ded

prio

r to

gra

fting

.


63TAB

LE 9

Zin

c ox

ide

tape

ver

sus

tradi

tiona

l tre

atm

ent

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

MeZ

inc®

,Moln

lycke

Hea

lth C

are

Ape

lqvi

st e

t al,1

99053

Swed

en

Wou

nd ty

pe:

Dia

betic

foot

ulc

ers.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

es:

Are

a of

nec

rotic

tiss

uem

easu

red

and

a co

lour

phot

ogra

ph ta

ken.

Asu

cces

sful o

utco

me

was

whe

n th

e ne

crot

ic a

rea

had

redu

ced

by 5

0% o

r m

ore.

Eval

uatio

ns w

ere

blin

ded.

Sett

ing

and

leng

th o

ftr

eatm

ent:

Out

patie

nt c

linic

.A

sses

smen

ts w

ere

mad

ew

eekl

y fo

r 5

wee

ks.

Incl

usio

n cr

iteria

:Pa

tient

s w

ith n

ecro

tic d

iabe

ticfo

ot u

lcer

s (s

uper

ficia

l ful

lth

ickn

ess

skin

ulc

er b

elow

ank

lean

d w

ith s

ysto

lic to

e pr

essu

reab

ove

45 m

mH

g or

abs

ence

of

cuta

neou

s er

ythe

ma;

ulce

rsbe

twee

n 1–

25 c

m2

in a

rea

with

> 50

% o

f are

a co

vere

d w

ithdr

y/w

et n

ecro

tic ti

ssue

).Whe

reth

ere

was

mor

e th

an o

ne u

lcer

the

larg

est w

as c

hose

n.

Excl

usio

n cr

iteria

:Po

sitive

pat

ch te

st;c

linic

al s

igns

of c

ellu

litis;

ulce

rs w

here

the

appl

icat

ion

of th

ese

dres

sings

was

inap

prop

riate

.

Trea

tmen

t:I:A

dhes

ive z

inc

oxid

e ta

pe(M

eZin

c®),

n =

22.

C:H

ydro

collo

id d

ress

ing

(Duo

Der

m),

n =

22.

All

patie

nts

wer

e of

fere

d th

e sa

me

addi

tiona

l tre

atm

ent:

the

foot

w

ear

was

cor

rect

ed a

nd e

xter

nal

pres

sure

on

the

ulce

r re

lieve

d.U

lcer

s w

ere

clea

ned

with

ste

rile

salin

e an

d dr

esse

d ac

cord

ing

toth

e m

anuf

actu

rers

gui

delin

es.

Dre

ssin

gs w

ere

chan

ged

daily

for

the

first

wee

k an

d ev

ery

3 da

ysaf

terw

ards

.

No

surg

ical

deb

ridem

ent w

asal

low

ed.

Mea

n w

ound

are

a (c

m2 ):

I:2.

2 (1

,10.

5 SD

)C

:2.2

(0.9

,20.

4 SD

)

Mea

n ne

crot

ic a

rea

of w

ound

(cm

2 ):I:

1.5

(0.5

,10.

5 SD

)C

:1.6

(0.9

,19.

2 SD

)

Oth

er c

hara

cter

istic

s:I

CM

ean

age

(yea

rs):

6362

M:F

rat

io:

1:1.

21:

0.5

Mea

n du

ratio

n (y

ears

) of d

iabe

tes:

2219

Insu

lin:

1718

Syst

olic

toe

pres

sure

(mm

Hg)

:66

68Sy

stol

ic a

nkle

pr

essu

re (m

mH

g):

104

114

Num

ber

of w

ound

s re

duce

d by

50

% o

r m

ore

at 5

wee

ks:

I:14

/21

(67%

)C

:6/2

1 (2

9%)

Mea

n %

cha

nge

in w

ound

are

a at

5 w

eeks

:I:

60%

red

uctio

n (n

= 18

)C

:5%

incr

ease

(n=

17)

I:Fo

ur p

atie

nts

beca

use

of >

50%

incr

ease

in a

rea

ofne

crot

ic ti

ssue

,as

soci

ated

pai

n an

doe

dem

a or

sig

ns o

fce

llulit

is.

C:F

ive p

atie

nts

beca

use

of >

50%

incr

ease

in a

rea

ofne

crot

ic ti

ssue

,as

soci

ated

pai

n an

doe

dem

a or

sig

ns o

fce

llulit

is.

Com

mon

adv

erse

effe

cts

wer

e se

en in

bot

h gr

oups

whi

ch w

ere

usua

lly m

acer

-at

ion

of th

e sk

in e

dges

.

The

com

plia

nce

of p

atie

nts

was

rep

orte

d as

exc

elle

nt.

Appendix 6

64 TAB

LE 1

0 C

adex

omer

iodi

ne p

olys

acch

arid

e ve

rsus

oth

er d

ebrid

ing

agen

ts

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

cont

inue

d

Mos

s et

al,1

98713

UK

Wou

nd ty

pe:

Veno

us le

g ul

cers

.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

es:

The

wou

nd p

erim

eter

w

as d

raw

n on

to p

oly-

then

e sq

uare

s an

d th

e ar

ea c

alcu

late

d by

com

pute

r pl

anim

etry

.Th

e nu

mbe

r of

wou

nds

heal

ed w

as a

lso r

ecor

ded.

Sett

ing

and

leng

th

of tr

eatm

ent:

6-w

eek

tria

l.Mea

sure

-m

ents

take

n at

0,2

,4

and

6 w

eeks

.Afte

r 6

wee

kspa

tient

s w

ere

allo

wed

to

cro

ss-o

ver.

Incl

usio

n cr

iteria

:O

ut-p

atie

nts

with

unr

espo

nsive

veno

us le

g ul

cers

for

> 3

mon

ths.

Patie

nts

with

ischa

emic

ven

ous

insu

ffici

ency

wer

e in

clud

ed.

Excl

usio

n cr

iteria

:N

ot s

tate

d

56 p

atie

nts

wer

e re

crui

ted

and

obse

rved

on

a va

riety

of

stan

dard

trea

tmen

ts.T

hose

not

impr

ovin

g af

ter

6 w

eeks

wer

ead

mitt

ed to

the

tria

l (n

= 43

).

I:C

adex

omer

iodi

nepo

lysa

ccha

ride

pow

der

(Iodo

sorb

),n

= 21

.

C:D

extr

anom

er p

olys

acch

arid

ebe

ads

(Deb

risan

),n

= 21

.

Both

age

nts

wer

e co

vere

d w

ith a

non-

adhe

sive

pad,

cott

on-w

ool

wad

ding

,sto

ckin

ette

and

a fi

rmel

astic

ban

dage

.

If ba

cter

ial i

nfec

tion

occu

rred

a

2-w

eek

cour

se o

f ora

l ant

ibio

tics

was

allo

wed

.

Med

ian

wou

nd a

rea

(cm

2 ):I:

19.7

(19.

8 SD

)C

:25.

5 (2

9.5

SD)

Oth

er c

hara

cter

istic

s:I

CM

edia

n ag

e (y

ears

):70

68M

:F r

atio

:1:

3.5

1:4.

2M

edia

n du

ratio

n (m

onth

s):

7561

Ischa

emia

:6

5

No

stat

istic

al d

iffer

ence

s be

twee

nth

e tw

o gr

oups

.Dat

a ar

e on

lyav

aila

ble

for

42 o

f the

43

patie

nts.

% r

educ

tion

in m

ean

wou

nd a

rea

at 6

wee

ks:

I:4

(95%

CI:

5,–1

4)C

:3 (9

5% C

I:4,

–9)

(p>

0.05

;tw

o sa

mpl

e t-t

est)

No

signi

fican

t cha

nge

in w

ound

siz

e fro

m b

asel

ine

over

6 w

eeks

(pai

red

t-tes

t).

Num

ber

of w

ound

s he

aled

at

6 w

eeks

:I:

0/21

(0%

)C

:0/2

1 (0

%)

One

pat

ient

was

with

draw

n fro

m

the

tria

l at w

eek

4be

caus

e of

poo

rco

mpl

ianc

e.D

ata

are

only

ava

ilabl

efo

r th

e 42

pat

ient

sre

mai

ning

for

the

6-w

eek

trea

tmen

tpe

riod.

The

antib

acte

rial p

rope

rtie

sof

I (c

adex

omer

pol

ysac

-ch

arid

e) w

ere

of li

ttle

adva

ntag

e in

the

trea

tmen

t of

res

istan

t chr

onic

leg

ulce

rs.

Stew

art a

nd L

eape

r,19

8755

UK

Wou

nd ty

pe:

Leg

ulce

rs.

Met

hod

of r

ando

misa

tion:

Com

pute

r al

loca

tion.

Obj

ectiv

e ou

tcom

e:N

umbe

r of

wou

nds

heal

ed.

Sett

ing

and

leng

th

of tr

eatm

ent:

10-w

eek

tria

l.Mea

sure

-m

ents

take

n w

eekl

y fo

r 6

wee

ks a

nd th

en o

nce

at 8

and

10

wee

ksth

erea

fter.

Incl

usio

n cr

iteria

:O

ut-p

atie

nts

with

leg

ulce

rs o

fva

rious

aet

iolo

gies

.

Excl

usio

n cr

iteria

:rec

eivi

ngst

eroi

ds,c

ytot

oxic

s,or

antib

iotic

s;po

or n

utrit

iona

lst

atus

;abn

orm

al th

yroi

dfu

nctio

n;un

able

to g

ive

info

rmed

con

sent

.

I:C

adex

omer

iodi

nepo

lysa

ccha

ride

pow

der

(Iodo

sorb

)ap

plie

d to

a d

epth

of 3

mm

,n =

46.

C:H

ydro

gel d

ress

ing

(Sch

eriso

rb/In

tras

ite) a

pplie

d to

a d

epth

of 5

mm

,n =

49.

Both

trea

tmen

ts w

ere

cove

red

with

gau

ze,a

non

-adh

eren

t dre

ss-

ing

and

padd

ing.

A c

rêpe

ban

dage

,or

for

thos

e w

ith a

ven

ous

ulce

r a

Tubi

grip

sto

ckin

g w

ere

supp

lied

ifth

e pa

tient

agr

eed

to w

ear

them

.

Med

ian

wou

nd a

rea

(cm

2 ):I:

2.8

(ran

ge,0

.2–5

0.5)

C:2

.6 (r

ange

,0.4

–74.

4)(p

> 0.

05;M

ann-

Whi

tney

U te

st).

Oth

er c

hara

cter

istic

s:I

CM

ean

age

(yea

rs):

7077

M:F

rat

io:

1:1.

41:

2.8

Mea

n du

ratio

n (m

onth

s):

12.0

24.0

No

stat

istic

al d

iffer

ence

s be

twee

nth

e gr

oups

with

the

exce

ptio

n of

age

(p<

0.01

;Man

n-W

hitn

ey

U te

st).

Num

ber

of w

ound

s he

aled

at

10

wee

ks:

I:14

/46

(30%

)C

:14/

49 (2

9%)

(p>

0.05

;chi

-squ

ared

ana

lysis

).

I:13

pat

ient

s.

C:1

1 pa

tient

s.

Thre

e pa

tient

s di

ed;

18 w

ere

with

draw

nby

req

uest

;tw

o ha

dal

lerg

ies;

one

was

lost

to fo

llow

-up.

Both

age

nts

wer

e sim

ilar

for

dres

sing

time

and

pain

expe

rienc

ed b

y th

e pa

tient

.

Cos

t for

one

wee

k of

trea

tmen

t per

per

son:

I:£4

.68

C:£

3.33


65TAB

LE 1

0 co

ntd

Cad

exom

er io

dine

pol

ysac

char

ide

vers

us o

ther

deb

ridin

g ag

ents

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

Tarv

aine

n,19

8854

Finl

and

Wou

nd ty

pe:

Chr

onic

leg

ulce

rs.

Met

hod

of r

ando

misa

tion:

Seal

ed e

nvel

opes

.

Obj

ectiv

e ou

tcom

e:N

umbe

r of

ulc

ers

heal

ed.

Leng

th o

f tre

atm

ent:

Out

patie

nt c

linic

.8-w

eek

tria

l.Mea

sure

men

ts ta

ken

at 0

,2,5

and

8 w

eeks

.

Incl

usio

n cr

iteria

:O

ut-p

atie

nts

> 18

yea

rs w

ithch

roni

c ex

udin

g le

g ul

cers

pres

entin

g at

one

of t

hree

clin

ics.

Excl

usio

n cr

iteria

:In

sulin

-dep

ende

nt d

iabe

tes

mel

litus

;rhe

umat

oid

arth

ritis

and

othe

r co

nnec

tive

tissu

edi

seas

es;g

oitr

e or

kno

wn

alle

rgy

to io

dine

.

Trea

tmen

t:I:

Cad

exom

er io

dine

poly

sacc

harid

e po

wde

r (Io

doso

rb),

n =

14.

C:D

extr

anom

er p

olys

acch

arid

epo

wde

r (D

ebris

an),

n =

13.

Both

age

nts

appl

ied

to a

dep

th

of 3

mm

and

cov

ered

with

a c

lean

com

pres

s.A

com

pres

sion

band

age

was

app

lied

arou

nd th

e le

g.

Dre

ssin

gs c

hang

ed o

nce

daily

by

soak

ing.

Wou

nds

wer

e cl

eans

edm

echa

nica

lly b

efor

e ap

plyi

ng a

ne

w d

ress

ing.

Mea

n w

ound

are

a:N

ot s

tate

d.

Oth

er c

hara

cter

istic

s:I

CM

ean

age

(yea

rs):

67.7

68.8

M:F

rat

io:

1:2.

51:

3.3

Mea

n du

ratio

n (m

onth

s):

54.8

12.2

Num

ber

of w

ound

s he

aled

at

8 w

eeks

:I:

7/14

(50%

)C

:2/1

3 (1

5%)

I:Thr

ee p

atie

nts

had

bact

eria

l inf

ectio

n;on

e pa

tient

exp

eri-

ence

d pa

in;a

nd in

one

patie

nt th

ew

ound

incr

ease

d in

size

.

C:T

wo

patie

nts

had

bact

eria

l inf

ectio

n;an

d on

e pa

tient

expe

rienc

ed p

ain.

Thre

e pa

tient

s in

the

I gro

up(c

adex

omer

pol

ysac

char

ide)

and

one

in th

e C

gro

up(d

extr

anom

er p

olys

acch

arid

e)co

mpl

aine

d of

pai

n du

ring

the

trea

tmen

t per

iod.

This

pain

was

sev

ere

in tw

o of

the

patie

nts,

one

in e

ach

trea

tmen

t gro

up,a

nd r

esul

ted

in w

ithdr

awal

from

the

stud

y.

Appendix 6

66 TAB

LE 1

1 D

extra

nom

er p

olys

acch

arid

e ve

rsus

oth

er d

ebrid

ing

agen

ts

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

cont

inue

d

Col

in e

t al,1

99656

Fran

ce

Wou

nd ty

pe:

Pres

sure

sor

es.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

e:Pe

rcen

tage

red

uctio

n in

area

of n

on-v

iabl

e tis

sue

(wou

nd a

rea

x (%

yel

low

+

% b

lack

tiss

ue) x

1/1

00).

Phot

ogra

phs

wer

e ta

ken

at th

e in

itial

and

fina

las

sess

men

t.

Sett

ing

and

leng

th

of tr

eatm

ent:

Ope

n,m

ultic

entr

e,m

ulti-

natio

nal,p

aral

lel g

roup

tria

l.Si

x di

ffere

nt c

entr

es w

ere

invo

lved

with

app

roxi

mat

ely

equa

l num

bers

of p

atie

nts

in e

ach

tria

l.Ass

essm

ents

wer

e m

ade

ever

y 7

days

until

the

wou

nd w

ascl

eans

ed o

r on

the

com

plet

ion

of 2

1 da

ys.

Incl

usio

n cr

iteria

:M

ale

and

fem

ale

patie

nts

≥16

yea

rs w

ith p

ress

ure

sore

s pr

esen

t in

any

area

that

need

ed c

lean

sing.

Excl

usio

n cr

iteria

:Pr

egna

ncy,

imm

unod

efic

ienc

y,cl

inic

al in

fect

ion

of th

e w

ound

,ha

rd b

lack

esc

har

cove

ring

mor

eth

an 2

0% o

f the

wou

nd,d

iabe

tes,

inab

ility

to fo

llow

the

dem

ands

of th

e pr

otoc

ol in

for

any

reas

on,n

on-c

onse

ntin

g pa

tient

s.

Trea

tmen

t:I:

Dex

tran

omer

pol

ysac

char

ide

past

e (D

ebris

an),

n =

68.

C:H

ydro

gel d

ress

ing

(Intr

asite

Gel

),n

= 67

.

The

two

inte

rven

tions

wer

eap

plie

d in

acc

orda

nce

with

the

man

ufac

ture

rs’ i

nstr

uctio

ns.A

nab

sorb

ent p

last

ic fi

lm d

ress

ing

(Mel

olin

) was

use

d as

a s

tand

ard-

ised

seco

ndar

y dr

essin

g fo

r bo

thtr

eatm

ents

.

Whe

re a

pat

ient

had

mor

e th

anon

e w

ound

onl

y th

e la

rges

t was

eval

uate

d in

the

tria

l.Oth

erw

ound

s w

ere

trea

ted

with

the

sam

e ra

ndom

ised

dres

sing

if th

isw

as c

onsid

ered

app

ropr

iate

by

the

clin

ical

inve

stig

ator

.

Wou

nd a

rea:

IC

< 4

cm2

1815

4–13

cm

225

25>

13 c

m2

2527

Non

-via

ble

tissu

e ar

ea: I

C<

3 cm

218

153–

9 cm

227

24>

9 cm

223

28

Oth

er c

hara

cter

istic

s:I

CM

edia

n ag

e (y

ears

)81

79M

:F r

atio

1:1

1:1.

4

Sore

dur

atio

n:<

1 m

onth

22

241–

3 m

onth

s35

28>

3 m

onth

s11

15

Sore

gra

de:

11

02

1016

345

384

1213

Aut

hors

sta

te g

roup

s w

ere

wel

lm

atch

ed.A

ll pa

tient

s ga

ve w

ritte

nco

nsen

t and

wer

e ca

pabl

e of

part

icip

atin

g in

the

tria

l.

Med

ian

% r

educ

tion

in w

ound

are

aat

21

days

:I:

7 (–

340,

98%

ran

ge)

C:3

5 (–

185,

91%

ran

ge)

(p=

0.03

;Wilc

oxon

Ran

k Su

m te

st).

Num

ber

of w

ound

s by

deg

ree

ofcl

eans

ing

at 2

1 da

ys:

IC

100%

1413

75–9

9%15

2050

–74%

1312

25–4

9%6

90–

25%

75

Det

erio

rate

d13

8

Ove

rall

med

ian

% r

educ

tion

in

non-

viab

le ti

ssue

at 2

1 da

ys:

I:62

(–34

0,10

0 ra

nge)

C:7

4 (–

103,

100

rang

e)(p

= 0.

20;W

ilcox

on R

ank

Sum

test

)

I:19

lost

to fo

llow

-up

,tw

o di

ed,fo

urad

vers

e re

actio

ns(o

ne r

elat

ed to

pa

in o

n ap

plic

atio

nof

the

agen

t,no

deta

ils o

n th

e ot

her

thre

e).

C:1

1 lo

st to

fo

llow

-up,

two

died

,and

one

adve

rse

reac

tion.

Five

adv

erse

eve

nts

wer

ere

port

ed,o

ne in

the

C g

roup

(hyd

roge

l) an

d fo

ur in

the

Igr

oup

(dex

tran

omer

pol

ysac

-ch

arid

e).T

he o

nly

one

con-

sider

ed to

be

dres

sing

rela

ted

was

pai

n re

port

ed b

y on

epa

tient

in th

e I g

roup

.

C w

as fo

und

to b

e ea

sier

toap

ply

and

rem

ove

than

the

I.C

was

also

foun

d to

be

asso

ciat

ed w

ith le

ss p

ain.


67TAB

LE 1

1 co

ntd

Dex

trano

mer

pol

ysac

char

ide

vers

us o

ther

deb

ridin

g ag

ents

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

cont

inue

d

Hul

kko

et a

l,198

158

Finl

and

Wou

nd ty

pe:

Veno

us le

g ul

cers

.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

e:Lo

nges

t and

sho

rtes

tdi

amet

ers

of e

ach

wou

ndw

ere

mea

sure

d,th

e pr

o-du

ct o

f whi

ch w

as u

sed

as a

mea

sure

of w

ound

siz

e.W

ound

s w

ere

also

phot

ogra

phed

at e

ach

asse

ssm

ent.

Sett

ing

and

leng

th

of tr

eatm

ent:

Hos

pita

l-bas

ed tr

ial.

Ass

essm

ents

wer

e m

ade

at 7

and

14

days

.

Incl

usio

n cr

iteria

:In

-pat

ient

s w

ith v

enou

s le

gul

cers

.

Excl

usio

n cr

iteria

:N

ot s

tate

d.

Trea

tmen

t:I:

Dex

tran

omer

pol

ysac

char

ide

bead

s (D

ebris

an) i

n a

glyce

rinpa

ste

(rat

io 4

:1) a

pplie

d to

the

wou

nd in

a la

yer

at le

ast 3

mm

thic

k.Th

e w

ound

was

cov

ered

with

a d

ry s

teril

e co

mpr

ess.

Dre

ssin

gs w

ere

rem

oved

by

rinsin

gw

ith w

ater

or

salin

e irr

igat

ion

Dre

ssin

gs w

ere

chan

ged

twic

e a

day

and

dext

rano

mer

was

app

lied

to o

nly

moi

st w

ound

s,n

= 18

.

C:S

trep

toki

nase

/str

epto

dorn

ase

enzy

me

prep

arat

ion

(Var

idas

eTo

pica

l).O

ne a

mpu

le w

as d

ilute

dw

ith 2

0 m

l of p

hysio

logi

cal s

alin

e.Th

e so

lutio

n w

as e

ither

pla

ced

dire

ctly

ont

o th

e w

ound

or

ast

erile

com

pres

s w

as s

oake

d in

the

solu

tion

prio

r to

app

licat

ion.

A w

ater

proo

f she

et w

as p

lace

d on

top

of th

e co

mpr

ess.

App

li-ca

tions

wer

e ch

ange

d tw

ice

daily

,n =

13.

All

hard

nec

rosis

was

exc

ised

from

wou

nds

in b

oth

grou

ps b

efor

eco

mm

ence

men

t of t

he tr

ial.

Mea

n w

ound

size

:N

ot s

tate

d.

Oth

er c

hara

cter

istic

s:I

CM

edia

n ag

e (y

ears

):68

.865

.1M

:F r

atio

Not

sta

ted

Ulc

er d

urat

ion:

< 1

mon

th1

11–

12 m

onth

s8

6>

12 m

onth

s9

6

All

wou

nds

wer

e ex

udin

g an

dm

any

of th

em w

ere

also

nec

rotic

.

Mea

n re

duct

ion

in w

ound

size

at

14

days

(mm

):I:

9.3

C:9

.8

Mea

n %

red

uctio

n in

wou

nd s

ize a

t14

day

s:I:

14.5

C:1

1.9

(NS)

I:Thr

ee p

atie

nts

wer

e w

ithdr

awn,

nore

ason

s gi

ven.

C:T

reat

men

t was

inte

rrup

ted

betw

een

the

day

7an

d da

y 14

in o

nepa

tient

bec

ause

of

pain

.

No

adve

rse

effe

cts

wer

ere

port

ed in

pat

ient

s tr

eate

dw

ith I

(dex

tran

omer

poly

sacc

harid

e).T

wo

patie

nts

in th

e C

gro

up (e

nzym

e)ex

perie

nced

pai

n,an

d in

one

it w

as s

ever

e.

One

wou

nd tr

eate

d w

ith I

incr

ease

d in

size

.The

re w

asno

size

incr

ease

rep

orte

d in

the

C g

roup

.

Paris

h an

d C

ollin

s,19

7937

USA

Wou

nd ty

pe:

Pres

sure

sor

es.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

e:N

umbe

r of

wou

nds

heal

ed.

Sett

ing

and

leng

th

of tr

eatm

ent:

Com

mun

ity (n

ursin

g ho

me)

4-w

eek

tria

l.

Incl

usio

n cr

iteria

:Pa

tient

s w

ith p

ress

ure

sore

s,re

sidin

g in

a n

ursin

g ho

me.

Excl

usio

n cr

iteria

:N

ot s

tate

d

Trea

tmen

t:I:

Dex

tran

omer

pol

ysac

char

ide

bead

s (D

ebris

an) a

pplie

d to

ade

pth

of a

t lea

st 3

mm

cov

ered

with

a d

ry d

ress

ing.

Cha

nged

1–3

times

dai

ly d

epen

ding

on

exud

ate,

n =

14 w

ound

s fro

m s

even

patie

nts.

C:C

olla

gena

se e

nzym

epr

epar

atio

n (S

anty

l) ap

plie

d da

ilyaf

ter

a sa

line

was

h an

d co

vere

dw

ith a

dry

dre

ssin

g,n

= 11

wou

nds

from

five

pat

ient

s.

Mea

n w

ound

size

= √

of s

urfa

cear

ea (c

m):

I:4.

5C

:3.2

No

stat

istic

al d

iffer

ence

bet

wee

nth

e gr

oups

for

wou

nd s

ize.

Oth

er c

hara

cter

istic

s:I

CA

ge r

ange

(yea

rs)

29–5

728

–59

M:F

rat

io:

Not

sta

ted

Mea

n du

ratio

n (m

onth

s):

Not

sta

ted

Num

ber

of w

ound

s he

aled

at

4 w

eeks

:I:

6/14

(43%

)C

:1/1

1 (9

%)

Num

ber

of p

atie

nts

with

hea

led

wou

nds

at 4

wee

ks:

I:4/

7 (5

7%)

C:1

/5 (2

0%)

No

with

draw

als

No

side-

effe

cts

repo

rted

by

patie

nts

with

any

of t

hetr

eatm

ents

.

Appendix 6

68 TAB

LE 1

1 co

ntd

Dex

trano

mer

pol

ysac

char

ide

vers

us o

ther

deb

ridin

g ag

ents

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

Thom

as a

nd F

ear,

1993

57

UK

Wou

nd ty

pe:

Pres

sure

sor

es.

Met

hod

of r

ando

misa

tion:

Com

pute

r-gen

erat

edra

ndom

isatio

n co

de.

Obj

ectiv

e ou

tcom

e:Th

e nu

mbe

r of

wou

nds

fully

cle

anse

d.C

lean

sing

was

det

erm

ined

by

mea

surin

g th

e %

of t

otal

wou

nd a

rea

cove

red

in s

loug

h.

Sett

ing

and

leng

th

of tr

eatm

ent:

2-w

eek

tria

l.Afte

r 14

day

sth

ose

wou

nds

show

ing

no im

prov

emen

t wer

ew

ithdr

awn

whi

le th

ere

mai

ning

wou

nds

wer

efo

llow

ed fo

r a

furt

her

14 d

ays.

Incl

usio

n cr

iteria

:H

ospi

talis

ed p

atie

nts

with

gr

ade

3 or

4 p

ress

ure

sore

s.Th

e w

ound

s ha

d to

be

cove

red

or p

artia

lly c

over

ed w

ithye

llow

/bro

wn

sloug

h.

Excl

usio

n cr

iteria

:A

ge <

16

year

s,in

sulin

-de

pend

ent d

iabe

tes,

imm

uno-

supp

ress

ion,

preg

nanc

y,ce

llulit

isan

d re

dnes

s of

the

surr

ound

ing

tissu

e (in

dica

tive

of in

fect

ion)

.

Trea

tmen

t:I:

Dex

tran

omer

pol

ysac

char

ide

bead

s (D

ebris

an) m

ade

into

apa

ste

with

pol

yeth

ylen

e gly

col 6

00an

d w

ater

.The

pas

te w

as a

pplie

dto

a d

epth

of 1

0 m

m o

ver

a lay

erof

pol

yam

ide

net,

n =

20.

C:H

ydro

gel d

ress

ing

(Intr

asite

Gel

) app

lied

to a

dep

th o

f 5 m

m.

Cov

ered

with

a p

erfo

rate

d pl

astic

film

abs

orbe

nt d

ress

ing

held

inpl

ace

with

tape

or

a ba

ndag

e,n

= 20

.

Dre

ssin

gs w

ere

chan

ged

asre

quire

d,an

d th

e w

ound

cle

anse

dw

ith s

alin

e be

fore

rea

pplic

atio

n.

Mea

n w

ound

are

a (c

m2 ):

I:15

.6 (1

6.2

SD;r

ange

1.5

–68.

9)C

:22.

2 (2

3.4

SD;r

ange

,2.6

–91.

4)

% w

ound

are

a co

vere

d in

slo

ugh:

I:75

.3 (2

2.4

SD;r

ange

,20–

100)

C:7

3.5

(29.

7 SD

;ran

ge,2

0–10

0)

Oth

er c

hara

cter

istic

s:I

C

Mea

n ag

e (y

ears

):81

.083

.5M

:F r

atio

:1:

5.7

1:3.

8Ra

tio o

f gra

de

3:4

ulce

rs5.

7:1

3.8:

1

Valu

es a

re o

nly

give

n fo

r 39

of t

he40

pat

ient

s en

terin

g th

e tr

ial.

Num

ber

of w

ound

s cl

eans

ed

at 1

4 da

ys:

I:1/

20 (5

%)

C:8

/20

(40%

)(p

= 0.

008;

Fisc

her’s

exa

ct te

st)

Afte

r 14

day

s al

l ulc

ers

wer

ere

asse

ssed

.Wou

nds

show

ing

noev

iden

ce o

f deb

ridem

ent w

ere

clas

sed

as fa

ilure

s an

d w

ithdr

awn.

The

rem

aini

ng w

ound

s w

ere

follo

wed

for

anot

her

14 d

ays.

Add

ition

al w

ound

s cl

eans

ed a

fter

follo

w-u

p at

28

days

:I1

:4/2

0 (o

vera

ll –

5/20

;25%

)C

:0/2

0 (o

vera

ll –

8/20

;40%

)

Up

to 1

4 da

ys:

I:th

ree

beca

use

ofdi

fficu

lty in

app

lyin

gth

e dr

essin

g.C

lass

ed a

s fa

ilure

sin

the

resu

lts.

C:o

ne p

atie

ntbe

caus

e th

e ca

sere

port

form

s w

ere

misl

aid.

Up

to 2

8 da

ys:

With

draw

als

occu

rred

ove

r th

efo

llow

-up

perio

dle

avin

g fo

ur p

atie

nts

in th

e C

gro

up a

ndtw

o pa

tient

s in

the

I gro

up.

C (h

ydro

gel)

had

to b

ech

ange

d m

ore

frequ

ently

th

an I

(dex

tran

omer

poly

sacc

harid

e).

How

ever

,eve

n w

ith fr

eque

ntdr

essin

g th

e co

st o

f the

C p

erpa

tient

was

less

than

for

the

I.

Mea

n co

st p

er p

atie

nt:

I:£4

4.70

C:£

22.6

0(N

B.O

nly

succ

esse

s co

sted

not f

ailu

res)


69TAB

LE 1

2 H

ydro

gel d

ress

ings

ver

sus

hydr

ogel

dre

ssin

gs

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

Gib

son,

1995

59

UK

Wou

nd ty

pe:

Leg

ulce

rs.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

es:

Wou

nd a

rea,

and

the

area

of w

ound

cov

ered

inslo

ugh.

Sett

ing

and

leng

th

of tr

eatm

ent:

A m

ultic

entr

e pa

ralle

l tria

lco

nduc

ted

for

21 d

ays

orun

til th

e w

ound

was

cons

ider

ed to

be

clea

nsed

.M

easu

rem

ents

wer

e ta

ken

at 0

,10

and

21 d

ays

orw

hen

the

wou

nd w

as c

lean

.

Incl

usio

n cr

iteria

:Pa

tient

s w

ith s

loug

hy le

g ul

cers

(> 1

0% s

urfa

ce a

rea

of w

ound

cove

red

in s

loug

h).

Excl

usio

n cr

iteria

:N

ot s

tate

d.

Trea

tmen

t:I:

Hyd

roge

l dre

ssin

g (G

ranu

gel),

n =

30.

C:H

ydro

gel d

ress

ing

(Intr

asite

Gel

),n

= 32

.

Both

hyd

roge

ls w

ere

cove

red

with

eith

er a

n ab

sorb

ent p

last

ic fi

lmdr

essin

g (M

elol

in) o

r a

knitt

edvi

scos

e dr

essin

g (T

ricot

ex).

Dre

ssin

gs w

ere

chan

ged

daily

.

Mea

n w

ound

are

a (c

m2 ):

I:24

.9C

:18.

7

Oth

er c

hara

cter

istic

s:I

CM

ean

age

(yea

rs):

7776

M:F

rat

io:

1:2.

31:

3.5

Year

s sin

ce fi

rst

ulce

r:8

4

88%

of p

atie

nts

wer

e tr

eate

d in

the

com

mun

ity.

Med

ian

redu

ctio

n in

wou

nd a

rea

over

a 7

-day

per

iod

(cm

2 ):I:

0.74

4C

:0.5

40(p

= 0.

62;W

ilcox

on R

ank

Sum

test

)

Med

ian

redu

ctio

n in

slo

ugh

over

a

7-da

y pe

riod

(cm

2 ):I:

1.51

1C

:1.1

18(p

= 0.

25;W

ilcox

on R

ank

Sum

test

)

% r

educ

tion

in m

ean

area

of w

ound

afte

r 21

day

s:I:

14C

:10

(p=

0.35

8;W

ilcox

on R

ank

Sum

test

)

% r

educ

tion

in m

ean

area

of u

lcer

cove

red

in s

loug

h af

ter

21 d

ays:

I:37

C:3

2

Not

sta

ted.

Tota

l cos

ts fo

r tr

eatm

ent p

erpe

rson

from

bas

elin

e to

fina

las

sess

men

t are

:£43

.25

for

Ian

d £4

0.25

for

C.

Both

pro

duct

s w

ere

repo

rted

to b

e sa

fe a

nd c

onve

nien

t to

use

.

Appendix 6

70 TAB

LE 1

3 E

nzym

e pr

epar

atio

ns v

ersu

s en

zym

e pr

epar

atio

ns

Stud

y an

d de

sign

Incl

usio

n/ex

clus

ion

crit

eria

Inte

rven

tion

det

ails

Bas

elin

e ch

arac

teri

stic

sR

esul

ts

Wit

hdra

wal

sC

omm

ents

Hel

lgre

n,19

8360

UK

Wou

nd ty

pe:

Leg

ulce

rs.

Met

hod

of r

ando

misa

tion:

Not

sta

ted.

Obj

ectiv

e ou

tcom

es:

Wou

nd a

rea

draw

n on

to a

tran

spar

ency

and

wei

ghed

to g

ive a

n in

dire

ct m

easu

re-

men

t of w

ound

size

.At

each

eva

luat

ion

a ph

oto-

grap

h w

as ta

ken.

Cle

ansin

gw

as a

lso d

eter

min

ed fr

omth

e %

wou

nd a

rea

cove

red

with

gra

nula

ting

tissu

e.

Sett

ing

and

leng

th

of tr

eatm

ent:

A r

ando

mise

d do

uble

-blin

dtr

ial.

Ass

essm

ents

wer

em

ade

at 7

,14

and

21 d

ays.

Both

the

patie

nt a

ndas

sess

or w

ere

blin

d to

the

trea

tmen

t give

n.Tr

eatm

ent

was

onl

y te

rmin

ated

bef

ore

21 d

ays

if th

e ul

cer

was

tota

lly c

lean

,or

if se

rious

side-

effe

cts

occu

rred

.

Incl

usio

n cr

iteria

:Pa

tient

s w

ith le

g ul

cers

cov

ered

with

pus

and

deb

ris.

Excl

usio

n cr

iteria

:W

ound

s <

3 cm

2 ,> 4

00 c

m2

or m

ore

than

6 c

m d

eep.

Trea

tmen

t:I:T

ryps

in e

nzym

e pr

epar

atio

n(T

rypu

re).

One

am

pule

(50

mg)

was

mix

ed w

ith 1

5 m

l of s

alin

e,n

= 19

.

C:S

trep

toki

nase

/str

epto

dorn

ase

enzy

me

prep

arat

ion

(Var

idas

eTo

pica

l).O

ne a

mpu

le(s

trep

toki

nase

-str

epto

dorn

ase

100,

000

U a

nd 2

5,00

0 U

resp

ectiv

ely)

was

mix

ed w

ith

20 m

l of s

alin

e,n

= 21

.

Befo

re a

pplic

atio

n of

the

test

trea

tmen

t,ea

ch u

lcer

was

was

hed

with

dist

illed

wat

er.T

here

afte

r,w

et c

ompr

esse

s im

preg

nate

d w

ith e

nzym

es w

ere

appl

ied

twic

e da

ily.

Mea

n w

ound

are

a:N

ot s

tate

d.

% g

ranu

late

d ar

ea o

f tot

al u

lcer

area

:I:

25%

C:2

2%

Oth

er c

hara

cter

istic

s:I

CM

ean

age

(yea

rs):

68.9

69.7

M:F

rat

io:

1:1.

41:

4.3

Mea

n du

ratio

n (m

onth

s):

Not

sta

ted

Veno

us le

g ul

cers

:14

15A

rter

ial/v

enou

s an

d ar

teria

l leg

ulc

ers:

33

Oth

er le

g ul

cers

,va

sulit

is,de

cubi

tus:

23

Con

com

itant

di

abet

es m

ellit

us

(pat

ient

s):

76

Con

com

itant

trea

tmen

t was

left

unch

ange

d th

roug

hout

the

tria

lpe

riod.

Mea

n w

ound

are

a at

21

days

:Th

ere

was

no

decr

ease

in u

lcer

are

a.

% g

ranu

late

d ar

ea o

f tot

al w

ound

area

at 1

4 da

ys:

I:56

%C

:60%

(p<

0.01

for

both

trea

tmen

tsco

mpa

red

with

bas

elin

e.St

uden

t’s t-

test

)

Num

ber

of w

ound

s fu

lly c

lean

sed

at 2

1 da

ys:

I:5/

19 (2

6%)

C:1

3/21

(62%

)

A c

ompa

rison

of g

ranu

late

d ar

ea a

t21

day

s w

as n

ot m

ade

due

to th

ehi

gh w

ithdr

awal

rat

es.

I:Thr

ee p

atie

nts

beca

use

of p

ain

asso

ciat

ed w

ith th

edr

essin

g.A

noth

erfiv

e pa

tient

s w

ere

with

draw

n du

e to

the

wou

nd b

eing

clea

nsed

.

C:1

3 pa

tient

s w

ere

with

draw

n du

e to

wou

nd c

lean

sing.

13/1

9 pa

tient

s in

the

I gro

up(T

rypu

re),

and

4/21

pat

ient

s in

the

C g

roup

(Var

idas

e)re

port

ed p

ain

asso

ciat

ed

with

the

dres

sing.

Pain

was

repo

rted

a s

ever

e in

four

of

the

I pat

ient

s,w

hile

pai

n w

as r

ecor

ded

as m

ild in

th

e C

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75

Health Technology Assessment panel membership

This report was identified as a priority by the Pharmaceutical Panel.

Professor John Farndon,University of Bristol*

Professor Senga Bond, University of Newcastle-upon-Tyne

Professor Ian Cameron, Southeast Thames Regional Health Authority

Ms Lynne Clemence, Mid-Kent Health Care Trust

Professor Cam Donaldson, University of Aberdeen

Professor Richard Ellis, St James’s University Hospital,Leeds

Mr Ian Hammond, Bedford & Shires Health & Care NHS Trust

Professor Adrian Harris, Churchill Hospital, Oxford

Dr Gwyneth Lewis, Department of Health

Mrs Wilma MacPherson, St Thomas’s & Guy’s Hospitals,London

Dr Chris McCall, General Practitioner, Dorset

Professor Alan McGregor, St Thomas’s Hospital, London

Professor Jon Nicholl, University of Sheffield

Professor John Norman,University of Southampton

Professor Michael Sheppard,Queen Elizabeth Hospital,Birmingham

Professor Gordon Stirrat, St Michael’s Hospital, Bristol

Dr William Tarnow-Mordi,University of Dundee

Professor Kenneth Taylor,Hammersmith Hospital, London

Acute Sector Panel

continued

Past members

Chair: Professor Francis H Creed,University of Manchester

Professor Clifford Bailey,University of Leeds

Ms Tracy Bury, CharteredSociety of Physiotherapy

Professor Collette Clifford,University of Birmingham

Dr Katherine Darton, M.I.N.D.

Mr John Dunning, Papworth Hospital, Cambridge

Mr Jonathan Earnshaw,Gloucester Royal Hospital

Mr Leonard Fenwick, Freeman Group of Hospitals,Newcastle-upon-Tyne

Professor David Field, Leicester Royal Infirmary

Ms Grace Gibbs, West Middlesex UniversityHospital NHS Trust

Dr Neville Goodman, Southmead Hospital Services Trust, Bristol

Professor Mark P Haggard, MRC

Professor Robert Hawkins, University of Manchester

Dr Duncan Keeley, General Practitioner, Thame

Dr Rajan Madhok, East Riding Health Authority

Dr John Pounsford, Frenchay Hospital, Bristol

Dr Mark Sculpher, University of York

Dr Iqbal Sram, NHS Executive,North West Region

Current members

Professor Michael Maisey, Guy’s & St Thomas’s Hospitals,London*

Professor Andrew Adam, Guy’s, King’s & St Thomas’sSchool of Medicine & Dentistry,London

Dr Pat Cooke, RDRD, Trent Regional Health Authority

Ms Julia Davison, St Bartholomew’s Hospital,London

Professor MA Ferguson-Smith,University of Cambridge

Dr Mansel Hacney, University of Manchester

Professor Sean Hilton, St George’s Hospital Medical School, London

Mr John Hutton, MEDTAP International Inc.,London

Professor Donald Jeffries, St Bartholomew’s Hospital,London

Dr Ian Reynolds, Nottingham Health Authority

Professor Colin Roberts, University of Wales College of Medicine

Miss Annette Sergeant, Chase Farm Hospital, Enfield

Professor John Stuart, University of Birmingham

Dr Ala Szczepura, University of Warwick

Mr Stephen Thornton, Cambridge & Huntingdon Health Commission

Dr Jo Walsworth-Bell, South Staffordshire Health Authority

Diagnostics and Imaging Panel

Past members

Chair: Professor Mike Smith,University of Leeds

Dr Philip J Ayres, Leeds Teaching Hospitals NHS Trust

Dr Paul Collinson, Mayday University Hospital,Thornton Heath

Dr Barry Cookson, Public Health LaboratoryService, Colindale

Professor David C Cumberland,University of Sheffield

Professor Adrian Dixon, University of Cambridge

Mr Steve Ebdon-Jackson,Department of Health

Mrs Maggie Fitchett,Association of Cytogeneticists,Oxford

Dr Peter Howlett, Portsmouth Hospitals NHS Trust

Professor Alistair McGuire, City University, London

Dr Andrew Moore, Editor, Bandolier

Dr Peter Moore, Science Writer, Ashtead

Professor Chris Price, London Hospital MedicalSchool

Dr William Rosenberg,University of Southampton

Dr Gillian Vivian, Royal Cornwall Hospitals Trust

Dr Greg Warner, General Practitioner,Hampshire

Current members

* Previous Chair


76

continued

Professor Anthony Culyer,University of York *

Professor Michael Baum, Royal Marsden Hospital

Dr Rory Collins, University of Oxford

Professor George Davey-Smith,University of Bristol

Professor Stephen Frankel,University of Bristol

Mr Philip Hewitson, Leeds FHSA

Mr Nick Mays, King’s Fund, London

Professor Ian Russell, University of York

Dr Maurice Slevin, St Bartholomew’s Hospital,London

Professor Charles Warlow,Western General Hospital,Edinburgh

Methodology Panel

Past members

Chair: Professor Martin Buxton,Brunel University

Professor Doug Altman, Institute of Health Sciences,Oxford

Dr David Armstrong, Guy’s, King’s & St Thomas’sSchool of Medicine & Dentistry, London

Professor Nick Black, London School of Hygiene & Tropical Medicine

Professor Ann Bowling,University College LondonMedical School

Dr Mike Clarke, University of Oxford

Professor Michael Drummond,University of York

Dr Vikki Entwistle, University of Aberdeen

Professor Ewan Ferlie, Imperial College, London

Professor Ray Fitzpatrick,University of Oxford

Professor Jeremy Grimshaw,University of Aberdeen

Dr Stephen Harrison, University of Leeds

Mr John Henderson, Department of Health

Professor Richard Lilford, Regional Director, R&D, West Midlands

Professor Theresa Marteau,Guy’s, King’s & St Thomas’sSchool of Medicine &Dentistry, London

Dr Henry McQuay, University of Oxford

Dr Nick Payne, University of Sheffield

Professor Margaret Pearson,NHS Executive North West

Professor David Sackett, Centre for Evidence BasedMedicine, Oxford

Dr PAG Sandercock, University of Edinburgh

Dr David Spiegelhalter, Institute of Public Health,Cambridge

Professor Joy Townsend,University of Hertfordshire

Current members

Professor Michael Rawlins,University of Newcastle-upon-Tyne*

Dr Colin Bradley, University of Birmingham

Professor AlasdairBreckenridge, RDRD,Northwest Regional Health Authority

Ms Christine Clark, Hope Hospital, Salford

Mrs Julie Dent, Ealing, Hammersmith &Hounslow Health Authority,London

Mr Barrie Dowdeswell, Royal Victoria Infirmary, Newcastle-upon-Tyne

Dr Tim Elliott, Department of Health

Dr Desmond Fitzgerald, Mere, Bucklow Hill, Cheshire

Professor Keith Gull, University of Manchester

Dr Keith Jones, Medicines Control Agency

Dr John Posnett, University of York

Dr Tim van Zwanenberg, Northern Regional Health Authority

Dr Kent Woods, RDRD, Trent RO, Sheffield

Pharmaceutical Panel

Past members

Chair: Professor Tom Walley,University of Liverpool

Dr Felicity Gabbay, Transcrip Ltd

Mr Peter Golightly, Leicester Royal Infirmary

Dr Alastair Gray, Health Economics ResearchUnit, University of Oxford

Professor Rod Griffiths, NHS Executive West Midlands

Mrs Jeanette Howe, Department of Health

Professor Trevor Jones, ABPI, London

Ms Sally Knight, Lister Hospital, Stevenage

Dr Andrew Mortimore,Southampton & SW HantsHealth Authority

Mr Nigel Offen, Essex RiversHealthcare, Colchester

Mrs Marianne Rigge, The College of Health, London

Mr Simon Robbins, Camden & Islington Health Authority, London

Dr Frances Rotblat, Medicines Control Agency

Dr Eamonn Sheridan, St James’s University Hospital,Leeds

Mrs Katrina Simister, Liverpool Health Authority

Dr Ross Taylor, University of Aberdeen

Current members

* Previous Chair


77

Dr Sheila Adam, Department of Health*

Professor George Freeman,Charing Cross & WestminsterMedical School, London

Dr Mike Gill, Brent & HarrowHealth Authority

Dr Anne Ludbrook, University of Aberdeen

Professor Theresa Marteau, Guy’s, King’s & St Thomas’sSchool of Medicine & Dentistry, London

Professor Catherine Peckham,Institute of Child Health,London

Dr Connie Smith, Parkside NHS Trust, London

Ms Polly Toynbee, Journalist

Professor Nick Wald, University of London

Professor Ciaran Woodman,Centre for CancerEpidemiology, Manchester

Population Screening Panel

Past members

Chair: Professor Sir John Grimley Evans, Radcliffe Infirmary, Oxford

Ms Stella Burnside, Altnagelvin Hospitals Trust,Londonderry

Mr John Cairns, University of Aberdeen

Professor Howard Cuckle,University of Leeds

Dr Carol Dezateux, Institute of Child Health,London

Dr Anne Dixon Brown, NHS Executive, Anglia & Oxford

Professor Dian Donnai, St Mary’s Hospital, Manchester

Dr Tom Fahey, University of Bristol

Mrs Gillian Fletcher, National Childbirth Trust

Dr JA Muir Gray, Institute of Health Sciences,Oxford

Professor Alexander Markham, St James’s University Hospital, Leeds

Dr Ann McPherson, General Practitioner, Oxford

Dr Susan Moss, Institute of Cancer Research

Dr Sarah Stewart-Brown, University of Oxford

Current members

Professor Angela Coulter, King’s Fund, London*

Professor Martin Roland,University of Manchester*

Dr Simon Allison, University of Nottingham

Professor Shah Ebrahim, Royal Free Hospital, London

Ms Cathy Gritzner, King’s Fund, London

Professor Andrew Haines, RDRD, North Thames Regional Health Authority

Dr Nicholas Hicks, Oxfordshire Health Authority

Mr Edward Jones, Rochdale FHSA

Professor Roger Jones, Guy’s, King’s & St Thomas’sSchool of Medicine & Dentistry, London

Mr Lionel Joyce, Chief Executive, Newcastle CityHealth NHS Trust

Professor Martin Knapp, London School of Economics & Political Science

Professor Karen Luker, University of Liverpool

Dr Fiona Moss, Thames Postgraduate Medical& Dental Education

Professor Dianne Newham, King’s College London

Professor Gillian Parker, University of Leicester

Dr Mary Renfrew, University of Oxford

Primary and Community Care Panel

Past members

Chair: Dr John Tripp, Royal Devon & ExeterHealthcare NHS Trust

Mr Kevin Barton, East London & City Health Authority

Professor John Bond,University of Newcastle-upon-Tyne

Dr John Brazier, University of Sheffield

Ms Judith Brodie, Age Concern, London

Mr Shaun Brogan, Daventry & South NorthantsPrimary Care Alliance

Mr Joe Corkill, National Association for Patient Participation

Dr Nicky Cullum, University of York

Professor Pam Enderby,University of Sheffield

Mr Andrew Farmer, Institute of Health Sciences,Oxford

Professor Richard Hobbs,University of Birmingham

Professor Allen Hutchinson,University of Sheffield

Dr Phillip Leech, Department of Health

Dr Aidan Macfarlane,Oxfordshire Health Authority

Professor David Mant, Institute of Health Sciences,Oxford

Dr Chris McCall, General Practitioner, Dorset

Dr Robert Peveler, University of Southampton

Professor Jennie Popay,University of Salford

Ms Hilary Scott, Tower Hamlets Healthcare NHS Trust, London

Dr Ken Stein, North & East Devon Health Authority

Current members

continued

* Previous Chair


78

National Coordinating Centre for Health Technology Assessment, Advisory Group

Chair: Professor John Gabbay, Wessex Institute for Health Research & Development

Professor MikeDrummond, Centre for Health Economics, University of York

Ms Lynn Kerridge, Wessex Institute for HealthResearch & Development

Dr Ruairidh Milne, Wessex Institute for HealthResearch & Development

Ms Kay Pattison, Research & DevelopmentDirectorate, NHS Executive

Professor James Raftery, Health Economics Unit, University of Birmingham

Professor Ian Russell,Department of Health Sciences & Clinical Evaluation, University of York

Dr Ken Stein, North & East Devon Health Authority

Professor Andrew Stevens, Department of Public Health & Epidemiology, University of Birmingham

Current members

Dr Paul Roderick, Wessex Institute for HealthResearch & Development

Past member

Professor Ian Russell, Department of Health Sciences & Clinical Evaluation, University of York*

Professor David Cohen, Professor of Health Economics, University of Glamorgan

Mr Barrie Dowdeswell, Chief Executive, Royal Victoria Infirmary,Newcastle-upon-Tyne

Dr Michael Horlington, Head of Corporate Licensing,Smith & Nephew GroupResearch Centre

Professor Martin Knapp, Director, Personal SocialServices Research Unit, London School of Economics & Political Science

Professor Theresa Marteau, Director, Psychology & Genetics Research Group, Guy’s, King’s & St Thomas’s School ofMedicine & Dentistry, London

Professor Sally McIntyre, MRC Medical Sociology Unit,Glasgow

Professor David Sackett, Centre for Evidence Based Medicine, Oxford

Dr David Spiegelhalter, MRC Biostatistics Unit, Institute of Public Health,Cambridge

Professor David Williams, Department of Clinical Engineering, University of Liverpool

Dr Mark Williams, Public Health Physician, Bristol

* Previous Chair

HTA Commissioning Board

Past members

Chair: Professor Charles Florey,Department of Epidemiology &Public Health, NinewellsHospital & Medical School,University of Dundee

Professor Doug Altman, Director of ICRF/NHS Centrefor Statistics in Medicine,Oxford

Professor John Bond,Professor of Health ServicesResearch, University ofNewcastle-upon-Tyne

Mr Peter Bower, Independent Health Advisor, Newcastle-upon-Tyne

Ms Christine Clark, Honorary Research Pharmacist, Hope Hospital, Salford

Professor Shah Ebrahim,Professor of Epidemiology of Ageing, University of Bristol

Professor Martin Eccles, Professor of Clinical Effectiveness, University of Newcastle-upon-Tyne

Dr Mike Gill, Director of Public Health &Health Policy, Brent & HarrowHealth Authority

Dr Alastair Gray, Director, Health EconomicsResearch Centre, University of Oxford

Professor Mark Haggard,MRC Institute of Hearing Research

Dr Jenny Hewison, Senior Lecturer, Department of Psychology,University of Leeds

Professor Sir Miles Irving (Programme Director),Professor of Surgery, University of Manchester, Hope Hospital, Salford

Professor Alison Kitson, Director, Royal College of Nursing Institute

Dr Donna Lamping, Senior Lecturer, Department ofPublic Health, London Schoolof Hygiene & Tropical Medicine

Professor Alan Maynard, Professor of Economics,University of York

Professor Jon Nicholl, Director, Medical Care Research Unit, University of Sheffield

Professor Gillian Parker, Nuffield Professor ofCommunity Care, University of Leicester

Dr Tim Peters, Reader in Medical Statistics,Department of Social Medicine,University of Bristol

Professor Martin Severs, Professor in Elderly Health Care, Portsmouth University

Dr Sarah Stewart-Brown,Director, Institute of Health Sciences, University of Oxford

Professor Ala Szczepura, Director, Centre for Health Services Studies, University of Warwick

Dr Gillian Vivian,Consultant, Royal CornwallHospitals Trust

Professor Graham Watt, Department of General Practice, Woodside Health Centre,Glasgow

Professor Kent Woods,Regional Director of R&D NHS Executive, Trent

Dr Jeremy Wyatt, Senior Fellow, Health & Public Policy, School of PublicPolicy, University College, London

Current members

Copies of this report can be obtained from:

The National Coordinating Centre for Health Technology Assessment,Mailpoint 728, Boldrewood,University of Southampton,Southampton, SO16 7PX, UK.Fax: +44 (0) 1703 595 639 Email: [email protected]://www.hta.nhsweb.nhs.uk ISSN 1366-5278

Health Technology Assessm

ent 1999;Vol.3:No.17 (Pt 1)

Debridem

ent of chronic wounds

Debridement of Chronic Wounds - NIHR Journals Library Admin.

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