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. 2018 Jun 15;6(6):CD012583.
doi: 10.1002/14651858.CD012583.pub2.

Dressings and topical agents for treating venous leg ulcers

Gill Norman  1 , Maggie J Westby, Amber D Rithalia, Nikki Stubbs, Marta O Soares, Jo C Dumville
Affiliations

Dressings and topical agents for treating venous leg ulcers

Gill Norman et al. Cochrane Database Syst Rev. .

Abstract

Background: Venous leg ulcers are open skin wounds on the lower leg which can be slow to heal, and are both painful and costly. The point prevalence of open venous leg ulcers in the UK is about 3 cases per 10,000 people, and many people experience recurrent episodes of prolonged ulceration. First-line treatment for venous leg ulcers is compression therapy, but a wide range of dressings and topical treatments are also used. This diversity of treatments makes evidence-based decision-making challenging, and a clear and current overview of all the evidence is required. This review is a network meta-analysis (NMA) which assesses the probability of complete ulcer healing associated with alternative dressings and topical agents.

Objectives: To assess the effects of (1) dressings and (2) topical agents for healing venous leg ulcers in any care setting and to rank treatments in order of effectiveness, with assessment of uncertainty and evidence quality.

Search methods: In March 2017 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also scanned reference lists of relevant included studies as well as reviews, meta-analyses, guidelines and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. We updated this search in March 2018; as a result several studies are awaiting classification.

Selection criteria: We included published or unpublished randomised controlled trials (RCTs) that enrolled adults with venous leg ulcers and compared the effects of at least one of the following interventions with any other intervention in the treatment of venous leg ulcers: any dressing, or any topical agent applied directly to an open venous leg ulcer and left in situ. We excluded from this review dressings attached to external devices such as negative pressure wound therapies, skin grafts, growth factors and other biological agents, larval therapy and treatments such as laser, heat or ultrasound. Studies were required to report complete wound healing to be eligible.

Data collection and analysis: Two review authors independently performed study selection, 'Risk of bias' assessment and data extraction. We conducted this NMA using frequentist meta-regression methods for the efficacy outcome; the probability of complete healing. We assumed that treatment effects were similar within dressings classes (e.g. hydrocolloid, foam). We present estimates of effect with their 95% confidence intervals (CIs) for individual treatments focusing on comparisons with widely used dressing classes, and we report ranking probabilities for each intervention (probability of being the best, second best, etc treatment). We assessed the certainty (quality) of the body of evidence using GRADE for each network comparison and for the network as whole.

Main results: We included 78 RCTs (7014 participants) in this review. Of these, 59 studies (5156 participants, 25 different interventions) were included in the NMA; resulting in 40 direct contrasts which informed 300 mixed-treatment contrasts.The evidence for the network as a whole was of low certainty. This judgement was based on the sparsity of the network leading to imprecision and the general high risk of bias in the included studies. Sensitivity analyses also demonstrated instability in key aspects of the network and results are reported for the extended sensitivity analysis. Evidence for individual contrasts was mainly judged to be low or very low certainty.The uncertainty was perpetuated when the results were considered by ranking the treatments in terms of the probability that they were the most effective for ulcer healing, with many treatments having similar, low, probabilities of being the best treatment. The two most highly-ranked treatments both had more than 50% probability of being the best (sucralfate and silver dressings). However, the data for sucralfate was from one small study, which means that this finding should be interpreted with caution. When exploring the data for silver and sucralfate compared with widely-used dressing classes, there was some evidence that silver dressings may increase the probability of venous leg ulcer healing, compared with nonadherent dressings: RR 2.43, 95% CI 1.58 to 3.74 (moderate-certainty evidence in the context of a low-certainty network). For all other combinations of these five interventions it was unclear whether the intervention increased the probability of healing; in each case this was low- or very low-certainty evidence as a consequence of one or more of imprecision, risk of bias and inconsistency.

Authors' conclusions: More research is needed to determine whether particular dressings or topical agents improve the probability of healing of venous leg ulcers. However, the NMA is uninformative regarding which interventions might best be included in a large trial, largely because of the low certainty of the whole network and of individual comparisons.The results of this NMA focus exclusively on complete healing; whilst this is of key importance to people living with venous leg ulcers, clinicians may wish to take into account other patient-important outcomes and factors such as patient preference and cost.

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Conflict of interest statement

Gill Norman: my employment at the University of Manchester while completing this work was funded by the NIHR and focused on high‐priority Cochrane reviews in the prevention and treatment of wounds.

Maggie Westby: my employment at the University of Manchester while completing this work was funded by the NIHR and focused on high‐priority Cochrane reviews in the prevention and treatment of wounds.

Amber Rithalia: none known.

Nikki Stubbs: I have received consultancy payments from Cogora, a healthcare marketing agency, and expenses for conference attendance. Funding from pharmaceutical companies supports training and education events in the service and I have received payments for non product‐related educational sessions. These have been unrelated to the subject matter of the systematic review and have never been in support or in pursuit of the promotion of products.

Marta Soares: none known.

Jo Dumville: I received research funding from the NIHR for the production of systematic reviews focusing on high‐priority Cochrane reviews in the prevention and treatment of wounds.

Andrew Jull (peer reviewer): I was lead author of an excluded study. No other conflicts to declare.

Clifford Richardson (peer reviewer): I work at the University of Manchester and know some of the members of the author team, but do not work with them in any capacity.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
3
3
Network diagram ‐ extended network, by risk of bias (3 categories) Key: green = low/unclear; yellow = high; red = very high overall risk of bias for the contrast. The number of studies for each contrast is given in Table 4.
4
4
Rankograms for the extended base‐case showing the probability that each intervention is the best, second best, third best treatment, etc.
5
5
Rankograms for all treatments in the extended base‐case network showing the probability that each intervention is the best, second best, third best treatment, etc.
6
6
Contour‐enhanced funnel plot for the extended base‐case network showing comparison‐specific pooled effect sizes 1=non‐adherent, 2=alginate, 3=blood product, 4=cadexomer iodine, 5=emollient cream, 6=film, 7=foam, 8=gentian violet, 9=growth factor,
 10=hyaluronic acid + povidone iodine, 11=hyaluronic acid, 12=hydrocolloid, 13=hydrofibre, 14=hydrogel, 15=ibuprofen, 16=octenidine,
 17=paste bandage, 18=PMM, 19=PMM silver, 20=povidone iodine, 21=saline gauze, 22=silver, 23=SSD, 24=sucralfate, 25=zinc oxide
7
7
Network diagram for the base‐case, coded by risk of bias (3 categories) Key: green = low/unclear; yellow = high; red = very high overall risk of bias for the contrast. The number of studies for each contrast is given in Table 4
8
8
Rankograms for the base‐case network showing the probability that each intervention is the best, second best, third best treatment, etc.
9
9
Rankograms for all treatments in base‐case network showing the probability that each intervention is the best, second best, third best treatment, etc.
10
10
Rankograms for the narrow sensitivity analysis showing the probability that each intervention is the best, second best, third best treatment, etc.
11
11
Comparisons of alginate with other treatments in the extended base‐case network with risk of bias
12
12
Comparisons of cadexomer iodine with other treatments in the extended base‐case network with risk of bias
13
13
Comparisons of foam with other treatments in the extended base‐case network with risk of bias
14
14
Comparisons of hydrocolloid with other treatments in the extended base‐case network with risk of bias
15
15
Comparisons of hydrofibre with other treatments in the extended base‐case network with risk of bias
16
16
Comparisons of hydrogel with other treatments in the extended base‐case network with risk of bias
17
17
Comparisons of paste bandage with other treatments in the extended base‐case network with risk of bias
18
18
Comparisons of PMM and PMM silver with other treatments in the extended base‐case network with risk of bias
19
19
Comparisons of saline gauze with other treatments in the extended base‐case network with risk of bias
20
20
Comparisons of silver and SSD with other treatments in the extended base‐case network with risk of bias
21
21
Comparisons of nonadherent with other treatments in the extended base‐case network with risk of bias
22
22
Risk of bias contributions to each NMA comparison in the extended base‐case network (vertical scale 0% to 100%)
 red = very high risk of bias, yellow = high risk of bias, green = low risk of bias
1.1
1.1. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 1 Alginate vs nonadherent.
1.2
1.2. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 2 Cadexomer iodine vs nonadherent.
1.3
1.3. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 3 Film vs nonadherent.
1.4
1.4. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 4 Foam vs nonadherent.
1.5
1.5. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 5 Hyaluronic plus povidone vs nonadherent.
1.6
1.6. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 6 Hydrocolloid vs non‐adherent.
1.7
1.7. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 7 Hydrofibre vs nonadherent.
1.8
1.8. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 8 Hydrogel vs nonadherent.
1.9
1.9. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 9 PMM vs nonadherent.
1.10
1.10. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 10 SSD vs nonadherent.
1.11
1.11. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 11 Foam vs alginate.
1.12
1.12. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 12 Hydrocolloid vs alginate.
1.13
1.13. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 13 Hydrofibre vs alginate.
1.14
1.14. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 14 Paste bandage vs alginate.
1.15
1.15. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 15 PMM vs alginate.
1.16
1.16. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 16 Gentian violet vs cadexomer iodine.
1.17
1.17. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 17 Hydrocolloid vs cadexomer iodine.
1.18
1.18. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 18 Hydrocolloid vs foam.
1.19
1.19. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 19 Ibuprofen foam vs foam.
1.20
1.20. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 20 Octenidine vs foam.
1.21
1.21. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 21 Paste bandage vs foam.
1.22
1.22. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 22 PMM vs foam.
1.23
1.23. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 23 PMM silver vs foam.
1.24
1.24. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 24 Silver vs foam.
1.25
1.25. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 25 Saline gauze vs hyaluronic acid.
1.26
1.26. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 26 PMM silver vs hydrocolloid.
1.27
1.27. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 27 Povidone iodine vs hydrocolloid.
1.28
1.28. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 28 Saline gauze vs hydrocolloid.
1.29
1.29. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 29 Silver vs hydrocolloid.
1.30
1.30. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 30 Zinc oxide vs hydrocolloid.
1.31
1.31. Analysis
Comparison 1 Direct evidence ‐ included in base‐case network, Outcome 31 Sucralfate vs hydrogel.
2.1
2.1. Analysis
Comparison 2 Direct evidence ‐ not in base case network, in expanded base case, Outcome 1 Blood product vs emollient.
2.2
2.2. Analysis
Comparison 2 Direct evidence ‐ not in base case network, in expanded base case, Outcome 2 Blood product vs hydrocolloid.
2.3
2.3. Analysis
Comparison 2 Direct evidence ‐ not in base case network, in expanded base case, Outcome 3 Blood product vs hydrogel.
2.4
2.4. Analysis
Comparison 2 Direct evidence ‐ not in base case network, in expanded base case, Outcome 4 Blood product vs saline gauze.
2.5
2.5. Analysis
Comparison 2 Direct evidence ‐ not in base case network, in expanded base case, Outcome 5 Hyaluronic vs emollient cream.
2.6
2.6. Analysis
Comparison 2 Direct evidence ‐ not in base case network, in expanded base case, Outcome 6 Growth factor vs hydrocolloid.
2.7
2.7. Analysis
Comparison 2 Direct evidence ‐ not in base case network, in expanded base case, Outcome 7 Growth factor vs hydrogel.
2.8
2.8. Analysis
Comparison 2 Direct evidence ‐ not in base case network, in expanded base case, Outcome 8 Growth factor vs nonadherent.
2.9
2.9. Analysis
Comparison 2 Direct evidence ‐ not in base case network, in expanded base case, Outcome 9 SSD vs emollient.
3.1
3.1. Analysis
Comparison 3 Direct evidence ‐ not in network, Outcome 1 A. Pichinchensis vs alginate.
3.2
3.2. Analysis
Comparison 3 Direct evidence ‐ not in network, Outcome 2 Non‐adherent vs cellulose.
3.3
3.3. Analysis
Comparison 3 Direct evidence ‐ not in network, Outcome 3 Phenytoin vs no treatment.
3.4
3.4. Analysis
Comparison 3 Direct evidence ‐ not in network, Outcome 4 Cadexomer iodine vs standard treatment.
3.5
3.5. Analysis
Comparison 3 Direct evidence ‐ not in network, Outcome 5 Honey vs standard treatment.
3.6
3.6. Analysis
Comparison 3 Direct evidence ‐ not in network, Outcome 6 Papain vs hydrogel.
3.7
3.7. Analysis
Comparison 3 Direct evidence ‐ not in network, Outcome 7 Shale oil vs hydrogel.
3.8
3.8. Analysis
Comparison 3 Direct evidence ‐ not in network, Outcome 8 Tripeptide copper vs hydrogel.
3.9
3.9. Analysis
Comparison 3 Direct evidence ‐ not in network, Outcome 9 Hydrocolloid vs collagen.
3.10
3.10. Analysis
Comparison 3 Direct evidence ‐ not in network, Outcome 10 Hydrocolloid vs dextranomer.
3.11
3.11. Analysis
Comparison 3 Direct evidence ‐ not in network, Outcome 11 Hydrocolloid vs magnesium sulphate.
3.12
3.12. Analysis
Comparison 3 Direct evidence ‐ not in network, Outcome 12 Hydrocolloid vs nonadherent or iodine.
3.13
3.13. Analysis
Comparison 3 Direct evidence ‐ not in network, Outcome 13 Ozonated oil vs zinc oxide.
3.14
3.14. Analysis
Comparison 3 Direct evidence ‐ not in network, Outcome 14 Cadexomer iodine vs dextranomer.
3.15
3.15. Analysis
Comparison 3 Direct evidence ‐ not in network, Outcome 15 Silica gel fibre vs standard care.
3.16
3.16. Analysis
Comparison 3 Direct evidence ‐ not in network, Outcome 16 Silver vs non‐silver.
3.17
3.17. Analysis
Comparison 3 Direct evidence ‐ not in network, Outcome 17 Sulphadryl vs inactive powder.
3.18
3.18. Analysis
Comparison 3 Direct evidence ‐ not in network, Outcome 18 Tripeptide copper vs emollient cream.
3.19
3.19. Analysis
Comparison 3 Direct evidence ‐ not in network, Outcome 19 Tripeptide copper vs SSD.
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References

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Harding 2001 {published data only}
    1. Harding KG, Price P, Robinson B, Thomas S, Hofman D. Cost and dressing evaluation of hydrofiber and alginate dressings in the management of community‐based patients with chronic leg ulceration. Wounds 2001;13(6):229‐36.
    1. Harding KG, Price P, Robinson B, Thomas S, Holman D. Cost and dressing evaluation of a hydrofiber and alginate dressing in the management of community‐based patients with chronic leg ulceration. Ostomy/Wound Management 2001;47(12):52.
Hokkam 2011 {published data only}
    1. Hokkam E, El‐Labban G, Shams M, Rifaat S, El‐Mezaien M. The use of topical phenytoin for healing of chronic venous ulcerations. International Journal of Surgery 2011;9(4):335‐8. - PubMed
Humbert 2013 {published data only}
    1. Humbert P, Mikosinki J, Benchikhi H, Allaert F‐A. Efficacy and safety of a gauze pad containing hyaluronic acid in treatment of leg ulcers of venous or mixed origin: a double‐blind, randomised, controlled trial. International Wound Journal 2013;10(2):159‐66. - PMC - PubMed
Ivins 2006 {published data only}
    1. Ivins N, Harding KG, Price P, Jørgensen B, Lohmann M, Gottrup F, et al. Safety and efficacy in long‐term use of a sustained silver‐releasing foam dressing: a randomized, controlled trial on venous leg ulcers. Symposium on Advanced Wound Care (SAWC) & Medical Research Forum on Wound Repair; 2006 April 30‐May 3; San Antonio (TX). 2006:Poster 12.
    1. Ivins N, Jørgensen B, Lohmann M, Harding KG, Price P, Gottrup F, et al. Safety and efficacy in long term use of a sustained silver‐releasing foam dressing: a randomised, controlled trial on venous leg ulcers. Joint Scientific Meeting of ETRS, EWMA and DGfW; 2005 September 15‐16; Stuttgart, Germany. 2005:284. [Poster 180]
Jull 2008 {published data only}
    1. Jull A. Honey and venous leg ulceration: a systematic review and randomised controlled trial [PhD thesis]. Auckland, New Zealand: University of Auckland, 2007.
    1. Jull A, Walker N, Parag V, Molan P, Arroll B, Waters J, et al. Honey as adjuvant therapy for leg ulcers (HALT) trial: a randomized controlled trial. 16th Conference of the European Wound Management Association; 2006 May 18‐20; Prague, Czech Republic. 2006:Abstract 29.
    1. Jull A, Walker N, Parag V, Molan P, Rodgers A, on behalf of the Honey as Adjuvant Leg Ulcer Therapy trial collaborators. Randomized clinical trial of honey‐impregnated dressings for venous leg ulcers. British Journal of Surgery 2008;95(2):175‐82. - PubMed
    1. Jull A, Walker N, Rodgers A, Bennett D, Molan P, Arroll B, et al. Honey for leg ulcers ‐ the HALT trial. Second World Union of Wound Healing Societies Meeting; 2004 July 8‐13; Paris, France. 2004:88.
Jørgensen 2005 {published data only}
    1. Jørgensen B, Price P, Andersen KE, Gottrup F, Bech‐Thomsen N, Scanlon E, et al. The silver‐releasing foam dressing, Contreet Foam, promotes faster healing of critically colonised venous leg ulcers: a randomised, controlled trial. International Wound Journal 2005;2(1):64‐73. - PMC - PubMed
    1. Jørgensen B, Thomsen JK. Safety and efficacy of a new hydrocapillary dressing in the treatment of leg ulcers. 13th Conference of the European Wound Management Association; 2003 May 22‐24; Pisa, Italy. 2003:221.
Kalis 1993 {published data only}
    1. Kalis B. Clinical evaluation of Granuflex and dextranomer dressing in leg ulcers. Second European Conference on Advances in Wound Management; 1993 October 20‐23; Harrogate, UK. 1993:212.
Kelechi 2012 {published data only}
    1. Kelechi T, Mueller M, Hankin C, Bronstone A, Samies J, Bonham P. A randomized, investigator‐blinded, controlled pilot study to evaluate the safety and efficacy of a poly‐N‐acetyl glucosamine‐derived membrane material in patients with venous leg ulcers. Journal of Wound, Ostomy and Continence Nursing 2011;38:S91. - PubMed
    1. Kelechi TJ, Mueller M, Hankin CS, Bronstone A, Samies J, Bonham PA. A randomized, investigator‐blinded, controlled pilot study to evaluate the safety and efficacy of a poly‐N‐acetyl glucosamine‐derived membrane material in patients with venous leg ulcers. Journal of the American Academy of Dermatology 2012;66(6):e209‐15. - PubMed
Kucharzewski 2013 {published data only}
    1. Kucharzewski M, Wilemska‐Kucharzewska K, Kozka M, Splakowska M. Leg venous ulcer healing process after application of membranous dressing with silver ions. Phlebologie 2013;42(6):340‐6.
Lanzara 2008 {published data only}
    1. Lanzara S, Tacconi G, Gianesini S, Menegatti E, Federici F, Liboni A, et al. A pilot randomized trial to determine the effects of a new active dressing on wound healing of venous leg ulcers [Abstract no. 114]. EWMA Journal 2008;8(Suppl 2):76. [Abstract 114]
Leaper 1991 {published data only}
    1. Leaper DJ, Cameron S, Hewitt H, Winter A, Lucarotti ME. A community‐ and hospital‐based comparative evaluation of Comfeel ulcer dressing for chronic leg ulcers. Journal of Dermatological Treatment 1991;2(3):103‐6.
Lindsay 1986 {published data only}
    1. Lindsay G, Latta D, Lyons KG, Livingstone ED, Thomson W. A study in general practice of the efficacy of cadexomer iodine in venous leg ulcers treated on alternate days. Acta Therapeutica 1986;12:141‐7.
Luiza 2015 {published data only}
    1. Luiza Soares Rodrigues A, Guitton Renaud Baptista de Oliveira B, Omena Futuro D, Regina Secoli S. Effectiveness of papain gel in venous ulcer treatment: randomized clinical trial. Revista Latino‐Americana de Enfermagem 2015;23(3):458‐65. - PMC - PubMed
Meaume 2012 {published data only}
    1. Augustin M, Herberger K, Kroeger K, Muenter KC, Goepel L, Rychlik R. Cost‐effectiveness of treating vascular leg ulcers with UrgoStart and UrgoCell Contact. International Wound Journal 2016;13(1):82‐7. - PMC - PubMed
    1. Meaume S, Truchetet F, Cambazard F, Lok C, Debure C, Dalac S, et al. A randomized, controlled, double‐blind prospective trial with a Lipido‐Colloid Technology: Nano‐Oligo Saccharide Factor wound dressing in the local management of venous leg ulcers. Wound Repair and Regeneration 2012;20(4):500‐11. - PubMed
Meredith 1988 {published data only}
    1. Meredith K, Gray E. Dressed to heal. Jounral of District Nursing 1988;7(3):8‐10.
Michaels 2009 {published data only}
    1. Michaels JA, Campbell B, King B, Palfreyman SJ, Shackley P, Stevenson M. Randomized controlled trial and cost‐effectiveness analysis of silver‐donating antimicrobial dressings for venous leg ulcers (VULCAN trial). British Journal of Surgery 2009;96(10):1147‐56. - PubMed
    1. Michaels JA, Campbell WB, King BM, Macintyre J, Palfreyman SJ, Shackley P, et al. A prospective randomised controlled trial and economic modelling of antimicrobial silver dressings versus non‐adherent control dressings for venous leg ulcers: the VULCAN trial. Health Technology Assessment 2009;13(56):1‐114. - PubMed
Moffatt 1992a {published data only}
    1. Moffatt CJ, Franks PJ, Oldroyd MI, Greenhalgh RM. A randomized trial of an occlusive dressing to treat chronic non‐healing venous ulcers. Second European Conference on Advances in Wound Management; 1992 October 20‐23; Harrogate, UK. 1993:210‐1.
    1. Moffatt CJ, Franks PJ, Oldroyd MI, Greenhalgh RM. Randomized trial of an occlusive dressing in the treatment of chronic non‐healing leg ulcers. Phlebology 1992;7(3):105‐7.
    1. Moffatt CJ, Oldroyd MI, Dickson D. A trial of hydrocolloid dressing in the management of indolent ulceration. Journal of Wound Care 1992;1(3):20‐2. - PubMed
Moffatt 1992b {published data only}
    1. Moffatt CJ, Oldroyd MI, Franks PJ. Assessing a calcium alginate dressing for venous ulcers of the leg. Journal of Wound Care 1992;1(4):22‐4. - PubMed
Moss 1987 {published data only}
    1. Moss C, Taylor A, Shuster S. Comparative study of cadexomer iodine and dextranomer in chronic leg ulcers. Scottish Medical Journal 1984;54:25.
    1. Moss C, Taylor AE, Shuster S. Comparison of cadexomer iodine and dextranomer for chronic venous ulcers. Clinical and Experimental Dermatology 1987;12(6):413‐8. - PubMed
Nelson 2007 {published data only}
    1. Dale JJ, Ruckley CV, Harper DR, Gibson B, Nelson EA, Prescott RJ. A factorial clinical trial of drugs, dressings and bandages in the treatment of leg ulcers. Fifth European Conference on Advances in Wound Management; 1995 November 21‐24; Harrogate, UK. 1996:193‐4.
    1. Franks PJ, Bosanquet N, Brown D, Straub J, Harper DR, Ruckley CV. Perceived health in a randomised trial of single and multilayer bandaging for chronic ulceration. Phlebology 1995;95(Suppl 1):17‐9. - PubMed
    1. Franks PJ, Bosanquet N, Brown D, Straub J, Harper DR, Ruckley CV. Perceived health in a randomised trial of treatment for chronic venous ulceration. European Journal of Vascular and Endovascular Surgery 1999;17(2):155‐9. - PubMed
    1. Franks PJ, Bosanquet N, Brown D, Straub J, Harper DR, Ruckley CV. Perceived health in a randomised trial of treatment for chronic venous ulceration [personal communication]. Letter to: CV Ruckley (Lothian & Forth Valley Leg Ulcer Study) 11 June 1996.
    1. Nelson EA, Prescott RJ, Harper DR, Gibson B, Brown D, Ruckley CV. A factorial, randomized trial of pentoxifylline or placebo, four‐layer or single‐layer compression, and knitted viscose or hydrocolloid dressings for venous ulcers. Journal of Vascular Surgery 2007;45(1):134‐41. - PubMed
Norkus 2005 {published data only}
    1. Norkus A, Dargis V, Thomsen JK, Harding KG, Ivins N, Serra N, et al. Use of a hydrocapillary dressing in the management of highly exuding ulcers: a comparative study. Journal of Wound Care 2005;14(9):429‐32. - PubMed
Ohlsson 1994 {published data only}
    1. Lindholm C, Larsson K, Holmgren T, Möller M, Ohlsson P. Leg ulcer treatment in primary care ‐ comparison of gauze and DuoDERM in a prospective randomised study. Second European Conference on Advances in Wound Management; 1992 October 20‐23; Harrogate, UK. 1993:131.
    1. Ohlsson P, Larsson K, Lindholm C, Möller M. A cost‐effectiveness study of leg ulcer treatment in primary care. Comparison of saline‐gauze and hydrocolloid treatment in a prospective, randomized study. Scandinavian Journal of Primary Health Care 1994;12(4):295‐9. - PubMed
Ormiston 1985 {published data only}
    1. Ormiston MC, Seymour MT, Venn GE, Cohen RI, Fox JA. A randomised comparison of cadexomer iodine and a standard treatment in out‐patients with chronic venous ulcers. Cadexomer Iodine: a Roundtable Discussion; 1983 January 22; Munich, Germany. Berlin: Schattauer, 1983:63‐9.
    1. Ormiston MC, Seymour MT, Venn GE, Cohen RI, Fox JA. Controlled trial of Iodosorb in chronic venous ulcers. British Medical Journal 1985;291(6491):308‐10. - PMC - PubMed
Petkov 1997 {published data only}
    1. Petkov L. A comparative study of the influence of two topical wound dressings used during healing on subsequent venous ulcer recurrence. Sixth European Conference on Advances in Wound Management; 1996 October 1‐4; Amsterdam, The Netherlands. 1997:267.
Rasmussen 1991 {published data only}
    1. Rasmussen LH, Karlsmark T, Avnstorp C, Peters K, Jorgensen M, Jensen LT. Topical human growth hormone treatment of chronic leg ulcers. Phlebology 1991;6(1):23‐30.
Robson 1995 {published data only}
    1. Robson MC, Phillip LG, Cooper DM, Lyle WG, Robson LE, Odom L, et al. Safety and effect of transforming growth factor‐beta(2) for treatment of venous stasis ulcers. Wound Repair and Regeneration 1995;3(2):157‐67. - PubMed
Robson 2001 {published data only}
    1. Robson MC, Phillips TJ, Falanga V, Odenheimer DJ, Parish LC, Jensen JL, et al. Randomized trial of topically applied repifermin (recombinant human keratinocyte growth factor‐2) to accelerate wound healing in venous ulcers. Wound Repair and Regeneration 2001;9(5):347‐52. - PubMed
Robson 2004 {published data only}
    1. Brennan M, Serena TE, Hanft J, Snyder R. Patients with venous leg ulcerations have diminished quality of life: analysis of a multi‐center randomized clinical trial. Symposium on Advanced Wound Care and The Wound Healing Society; 2010 April 17‐20; Orlando, Florida. 2010:S19. [Abstract CR‐017]
    1. Robson MC, Hanfnt J, Garner W, Jenson J, Serena T, Payne WG, et al. Healing of chronic venous ulcers is not enhanced by the addition of topical repifermin (KGF‐2) to standardized care. Journal of Applied Research 2004;4(2):302‐11.
Romanelli 2015a {published data only}
    1. Romanelli M, Mulder G, Paggi B, Macchia M, Panduri S, Dini V. The use of a collagen matrix in hard‐to‐heal venous leg ulcers. Journal of Wound Care 2015;24(11):543‐4, 546. - PubMed
Romero‐Cerecero 2012 {published data only}
    1. Romero‐Cerecero O, Zamilpa‐Álvarez A, Jiménez‐Ferrer E, Tortoriello J. Exploratory study on the effectiveness of a standardized extract from Ageratina pichinchensis in patients with chronic venous leg ulcers. Planta Medica 2012;78(4):304‐10. - PubMed
Rubin 1990 {published data only}
    1. Rubin JR, Alexander J, Plecha EJ, Marman C. Unna's boot vs polyurethane foam dressings for the treatment of venous ulceration. A randomized prospective study. Archives of Surgery 1990;125(4):489‐90. - PubMed
Salim 1992 {published data only}
    1. Salim AS. Role of sulphydryl‐containing agents in the management of venous (varicose) ulceration. A new approach. Clinical and Experimental Dermatology 1992;17(6):427‐32. - PubMed
    1. Salim AS. The role of oxygen‐derived free radicals in the management of venous (varicose) ulceration: a new approach. World Journal of Surgery 1991;15(2):264‐9. - PubMed
Schulze 2001 {published data only}
    1. Schulze HJ, Lane C, Charles H, Ballard K, Hampton S, Moll I. Evaluating a superabsorbent hydropolymer dressing for exuding venous leg ulcers. Journal of Wound Care 2001;10(1):511‐8. - PubMed
Scurr 1994 {published data only}
    1. Scurr JH, Wilson L A, Coleridge‐Smith PD. A comparison of calcium alginate and hydrocolloid dressings in the management of chronic venous ulcers. Wounds 1994;6(1):1‐8.
Senet 2003 {published data only}
    1. Senet P. Clinical and biological study of platelets used as adjuvant therapy for venous ulcers. 20th World Congress of Dermatology; 2002 July 1‐5; Paris, France. 2002:IC1738.
    1. Senet P, Bon FX, Benbunan M, Bussel A, Traineau R, Calvo F, et al. Randomized trial and local biological effect of autologous platelets used as adjuvant therapy for chronic venous leg ulcers. Journal of Vascular Surgery 2003;38(6):1342‐8. - PubMed
Senet 2011 {published data only}
    1. Senet P, Vicaut E, Beneton N, Debure C, Lok C, Chosidow O. Topical treatment of hypertensive leg ulcers with platelet‐derived growth factor‐BB: a randomized controlled trial. Archives of Dermatology 2011;147(8):926‐30. - PubMed
Senet 2014 {published data only}
    1. Senet P, Bause R, Jørgensen B, Fogh K. Clinical efficacy of a silver‐releasing foam dressing in venous leg ulcer healing: a randomised controlled trial. International Wound Journal 2014;11(6):649‐55. - PMC - PubMed
    1. Senet P, Petersen B. Hard‐to‐heal venous leg ulcers: results from a double‐blind RCT of a silver foam dressing. EWMA Journal 2012;12(2):188.
Smith 1992 {published data only}
    1. Smith JM, Dore CJ, Charlett A, Lewis JD. A randomized trial of biofilm dressing for venous leg ulcers. Phlebology 1992;7(3):108‐13.
Smith 1994 {published data only}
    1. Smith BA. The dressing makes the difference. Trial of two modern dressings on venous ulcers. Professional Nurse 1994;9(5):348, 350‐2. - PubMed
    1. Smith BA. Venous ulcers ‐ a well‐healed dresser. Second European Conference on Advances in Wound Management; 1992 October 23‐23; Harrogate, UK. 1993:211.
Solovastru 2015 {published data only}
    1. Solovastru LG, Stincanu A, Ascentii A, Cappare G, Mattana P, Vata D. Randomized, controlled study of innovative spray formulation containing ozonated oil and alpha‐bisabolol in the topical treatment of chronic venous leg ulcers. Advances in Skin & Wound Care 2015;28(9):406‐9. - PubMed
Sopata 2016 {published data only}
    1. Sopata M, Kucharzewski M, Tomaszewska E. Antiseptic with modern wound dressings in the treatment of venous leg ulcers: clinical and microbiological aspects. Journal of Wound Care 2016;25(8):419‐26. - PubMed
    1. Sopata M, Tomaszewska E, Muszynski Z, Ciupinska M. Can antiseptics with modern wound dressings have beneficial effect on venous leg ulcers treatment? Clinical and microbiological aspects. 24th Annual Meeting of the Wound Healing Society; 2014 April 23‐27; Orlando (FL). 2014:A60.
Stacey 1997 {published data only}
    1. Stacey MC, Jopp McKay AG, Rashid P, Hoskin SE, Thompson PM. The influence of dressings on venous ulcer healing. First European Conference on Advances in Wound Management; 1991 September 4‐6; Cardiff, UK. 1992:145‐6.
    1. Stacey MC, Jopp‐Mckay AG, Rashid P, Hoskin SE, Thompson PJ. The influence of dressings on venous ulcer healing ‐ a randomised trial. European Journal of Vascular and Endovascular Surgery 1997;13(2):174‐9. - PubMed
Stacey 2000 {published data only}
    1. Stacey MC, Mata SD, Trengove NJ, Mather CA. Randomised double‐blind placebo controlled trial of tropical autologous platelet lysate in venous ulcer healing. European Journal of Vascular and Endovascular Surgery 2000;20(3):296‐301. - PubMed
Steele 1986 {published data only}
    1. Steele K, Irwin G, Dowds N. Cadexomer iodine in the management of venous leg ulcers in general practice. Practitioner 1986;230(1411):63‐8. - PubMed
Taddeucci 2004 {published data only}
    1. Taddeucci P, Pianigiani E, Colletta V, Torasso F, Andreassi L, Andreassi A. An evaluation of Hyalofill‐F plus compression bandaging in the treatment of chronic venous ulcers. Journal of Wound Care 2004;13(5):202‐4. - PubMed
Tarvainen 1988 {published data only}
    1. Tarvainen K. Cadexomer iodine (Iodosorb) compared with dextranomer (Debrisan) in the treatment of chronic leg ulcers. Acta Chirurgica Scandinavica. Supplementum 1988;544:57‐9. - PubMed
Thomas 1997 {published data only}
    1. Banks V, Fear M, Orpin J, Hagelstein S, Colgate G, Humphreys J, et al. A comparative open multi‐centre trial of Tielle hydropolymer dressing and Granuflex improved formulation. Fifth European Conference on Advances in Wound Management; 1995 November 21‐24; Harrogate, UK. 1996:163‐7.
    1. Thomas S, Banks V, Bale S, Fear‐Price M, Hagelstein S, Harding KG, et al. Evaluation. A comparison of two dressings in the management of chronic wounds. Journal of Wound Care 1997;6(8):383‐6. - PubMed
Tumino 2008 {published data only}
    1. Tumino G, Masuelli L, Bei R, Simonelli L, Santoro A, Francipane S. Topical treatment of chronic venous ulcers with sucralfate: a placebo controlled randomized study. International Journal of Molecular Medicine 2008;22(1):17‐23. - PubMed
Vanscheidt 2012 {published data only}
    1. Vanscheidt W, Harding K, Téot L, Siebert J. Effectiveness and tissue compatibility of a 12‐week treatment of chronic venous leg ulcers with an octenidine based antiseptic ‐ a randomized, double‐blind controlled study. International Wound Journal 2012;9(3):316‐23. - PMC - PubMed
Vin 2002 {published data only}
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    1. Vin F, Téot L, Meaume S. The healing properties of Promogran in venous leg ulcers. Journal of Wound Care 2002;11(9):335‐41. - PubMed
    1. Vin F, Téot L, Meaume S. The healing properties of Promogran in venous leg ulcers. Phlébologie 2003;56(1):77‐86. - PubMed
Zuccarelli 1992 {published data only}
    1. Zuccarelli F. A comparative study of the hydrocellular dressing Allevyn and the hydrocolloid dressing Duoderm in the local treatment of leg ulcers [Étude comparative du pansement hydrocellulaire Allevyn et du pansement hydrocolloide Duoderm dans le traitement local des ulcères de jambe]. Phlébologie 1992;45(4):529‐33. - PubMed
    1. Zuccarelli F. A study to evaluate and compare the performance of a hydrocellular dressing with a hydrocolloid dressing in the treatment of venous leg ulcers. Second European Conference on Advances in Wound Management; 1992 October 20‐23; Harrogate, UK. 1993:98.

References to studies excluded from this review

Acosta 1992 {published data only}
    1. Acosta FJ, Novoa Mogollon FJ, Cobo P, Bilbao Arechabaleta G, Alvarez Cantalapiedra I. Topical treatment of ulcers with growth hormone: comparative study with hydrocolloid occlusive dressing [Tratamiento tópico de las úlceras con hormona de crecimiento: estudio comparativo con apósito oclusivo hidrocoloide]. Actas Dermo‐Sifiliograficas 1992;83(11):603‐4.
Alvarez 2004 {published data only}
    1. Alvarez OM, Patel M, Booker J, Markowitz L. Effectiveness of a biocellulose wound dressing for the treatment of chronic venous leg ulcers: results of a single center randomized study involving 24 patients. Wounds 2004;16(7):224‐33.
Andersen 2002 {published data only}
    1. Andersen KE, Franken CP, Gad P, Larsen A, Larsen JR, Neer PA, et al. A randomized, controlled study to compare the effectiveness of two foam dressings in the management of lower leg ulcers. Ostomy/Wound Management 2002;48(8):34‐41.
Andreev 2010 {published data only}
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Andriessen 2009 {published data only}
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Asselman 1995 {published data only}
    1. Asselman AH, Veraart J, Gronenschild E, Neumann HA. Wound healing with a new growth factor formula. 5th Annual Meeting of the European Tissue Repair Society; 1995 August 30‐September 2; Padua, Italy. 1995:362.
Bale 2004 {published data only}
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Bartoletti 1997 {published data only}
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Bartoszewicz 2013 {published data only}
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Bastami 2012 {published data only}
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Beitner 1985 {published data only}
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Belcaro 2007 {published data only}
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Bianchi 2018 {published data only}
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Binic 2010 {published data only}
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Bruckner 2009 {published data only}
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Bull 1995a {published data only}
    1. Bull RH, Andersen KE, Larsen AM, Leigh IM. A comparative study on two alginate dressings: Kaltostat and Comfeel: alginate dressing for exudating venous leg ulcers. Fifth European Conference on Advances in Wound Management; 1995 November 21‐24; Harrogate, UK. 1996:273.
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Burgess 1993 {published data only}
    1. Burgess B. An investigation of hydrocolloids: a comparative prospective randomised trial of the performance of three hydrocolloid dressings. Professional Nurse 1993;8(Suppl 7):3‐6. - PubMed
    1. Burgess B, Robinson B. Comparative benefits. Nursing Times 1993;89(13):90‐2. - PubMed
Burgos 1989 {published data only}
    1. Burgos H, Herd A, Bennett JP. Placental angiogenic and growth factors in the treatment of chronic varicose ulcers: preliminary communication. Journal of the Royal Society of Medicine 1989;82(10):598‐9. - PMC - PubMed
Cabete 2004 {published data only}
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Caetano 2009 {published data only}
    1. Caetano KS, Frade MA, Minatel DG, Santana LA, Enwemeka CS. Phototherapy improves healing of chronic venous ulcers. Photomedicine and Laser Surgery 2009;27(1):111‐8. - PubMed
Callam 1987a {published data only}
    1. Callam MJ, Harper DR, Dale JJ, Ruckley CV, Prescott RJ. A controlled trial of weekly ultrasound therapy in chronic leg ulceration. Lancet 1987;2(8552):204‐6. - PubMed
Cardinal 2009a {published data only}
    1. Cardinal M, Eisenbud DE, Armstrong DG. Wound shape geometry measurements correlate to eventual wound healing. Wound Repair and Regeneration 2009;17(2):173‐8. - PubMed
Cardinal 2009b {published data only}
    1. Cardinal M, Phillips T, Eisenbud DE, Harding K, Mansbridge J, Armstrong DG. Nonlinear modeling of venous leg ulcer healing rates. BMC Dermatology 2009;9:2. - PMC - PubMed
Carville 2008 {published data only}
    1. Carville K, Kapp S, Newall N, Saflekas S, Lewin G, Gliddon T, et al. Predicting covert and overt infection in leg ulcers: a randomised controlled trial. Third Congress of the World Union of Wound Healing Societies Meeting; 2008 June 4‐8; Toronto, Canada. 2008:OR124.
Casoni 2006 {published data only}
    1. Casoni P. Laser treatment in chronic leg ulcers. Phlebolymphology 2006;14(2):113.
    1. Casoni P, Japichino G. Laser treatment in chronic nonhealing leg ulcers. UIP World Congress Chapter Meeting; 2003 August 27‐31; San Diego (CA). 2003:33.
Cervadoro 2003 {published data only}
    1. Cervadoro G, Bachini L, Andreoli S, Pedrinazzi C, Cervadoro E. Valuation of re‐epithelisation of venous leg ulcers by measurement of transcutaneous oxygen tension during systemic and topical therapy [Valutazione della riepitelizzazione di lesioni ulcero‐venose agli arti inferiori mediante rilevazione ossimetrica transcutanea in corso di terapia topica e sistemica]. Giornale Italiano di Dermatologia e Venereologia 2003;138(3):237‐42.
Chaloner 1992 {published data only}
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Chaloner 2004a {published data only}
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Charles 2002a {published data only}
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Cherry 1992 {published data only}
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Cherry 1998 {published data only}
    1. Cherry GW, Hofman D, Poore S. Tissue repair in patients with chronic venous leg ulcers treated with Prezatide copper acetate gel or standard compression therapy. Wound Repair and Regeneration 1998;6(3):A243.
Chiummariello 2009 {published data only}
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Choucair 1998 {published data only}
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Collier 1992 {published data only}
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Cordts 1992 {published data only}
    1. Cordts PR, Hanrahan LM, Rodriguez AA, Woodson J, LaMorte WW, Menzoian JO. A prospective, randomized trial of Unna's boot versus Duoderm CGF hydroactive dressing plus compression in the management of venous leg ulcers [see comments]. Journal of Vascular Surgery 1992;15(3):480‐6. - PubMed
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D'Alicandro 2003 {published data only}
    1. D'Alicandro G, Infascelli RM, Iuliano P, Silvestro M, Aprea G. Treatment of severe wounds using a multilayer dressing releasing silver crystals plus oxygen hyperbaric therapy [Abstract]. 13th Conference of the European Wound Management Association 2003 May 22‐24; Pisa, Italy. 2003:182.
Daltrey 1981 {published data only}
    1. Daltrey DC, Cunliffe WJ. A double‐blind study of the effects of benzoyl peroxide 20% and eusol and liquid paraffin on the microbial flora of leg ulcers. Acta Dermato‐Venereologica 1981;61(6):575‐7. - PubMed
Davis 1992 {published data only}
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    1. Dereure O, Mikosinki J, Zegota Z, Allaert FA. RCT to evaluate a hyaluronic acid containing gauze pad in leg ulcers of venous or mixed aetiology. Journal of Wound Care 2012;21(11):539‐42, 544, 546. - PubMed
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Dini 2013 {published data only}
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Dmochowska 1999 {published data only}
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Duhra 1992 {published data only}
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Egan 1983 {published data only}
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Eriksson 1984b {published data only}
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Eriksson 1984c {published data only}
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Eriksson 1991 {published data only}
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Falanga 1999 {published data only}
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Falanga 2000 {published data only}
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Farina 1997 {published data only}
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Fernández‐Gines 2017 {published data only}
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Galiano 2017 {published data only}
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Garkaz 2014 {published data only}
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Gibson 1995 {published data only}
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    1. Gilligan AM, Waycaster C. Cost‐effectiveness of small intestinal submucosa extracellular matrix on wound closure in patients with difficult‐to‐heal wound of mixed arterial/venous and venous etiology. ISPOR 19th Annual International Meeting; 2014 May 31‐June 4; Montreal, Canada. 2014:A272‐3.
Gravante 2013 {published data only}
    1. Gravante G, Sorge R, Giordan N, Georgescu SR, Morariu SH, Stoicescu I, et al. Multicenter clinical trial on the performance and tolerability of the Hyaluronic acid‐collagenase ointment for the treatment of chronic venous ulcers: A preliminary pilot study. European Review for Medical and Pharmacological Sciences 2013;17(20):2721‐7. - PubMed
Groenewald 1980 {published data only}
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Grotewohl 1994 {published data only}
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Handfield‐Jones 1988 {published data only}
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    1. Harding KG, Krieg T, Eming SA, Flour ML, Jawien A, Cencora A, et al. Efficacy and safety of the freeze‐dried cultured human keratinocyte lysate, LyphoDermTM 0.9%, in the treatment of hard‐to‐heal venous leg ulcers. Wound Repair and Regeneration 2005;13(2):138‐47. - PubMed
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Harvey 1985 {published data only}
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Jasiel 1997a {published data only}
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Jasiel 1997b {published data only}
    1. Jasiel E, Nowak A, Gwiezdzinksi Z, Bowszyc J, Szarmach H, Czabanowska J, et al. A randomized, controlled, parallel‐group clinical trial of a new debriding agent (Sterigel) versus paraffin gauze in the treatment of necrotic venous leg ulcers. Sixth European Conference on Advances in Wound Management; 1996 October 1‐4; Amsterdam, The Netherlands. 1997:81.
Jones 2003 {published data only}
    1. Jones V. Comparison of the new multilayer composite wound dressing Versiva with Allevyn hydrocellular for managing venous leg ulcers: results of an international multicentre randomised trial [Abstract].. 13th Conference of the European Wound Management Association; 2003 May 22‐24; Pisa, Italy. 2003:217.
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Judy 2010 {published data only}
    1. Judy D, Burton C, Johnson J, Yates S. Silver impregnated dressings: Do they help chronic venous ulcers heal?. 68th Annual Meeting of the American Academy of Dermatology; 2010 March 5‐9; Miami, FL. 2010:AB150. [Poster P3701]
Jørgensen 2006 {published data only}
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Larsen 1997 {published data only}
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Laudanska 1988 {published data only}
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Purcell 2017 {published data only}
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Romanelli 2008 {published data only}
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Romanelli 2009 {published data only}
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Serena 2011 {published data only}
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Serena 2014 {published data only}
    1. Serena TE, Carter MJ, Le LT, Sabo MJ, Dimarco DT, Lullove E, et al. A multicenter, randomized, controlled clinical trial evaluating the use of dehydrated human amnion/chorion membrane allografts and multilayer compression therapy vs. multilayer compression therapy alone in the treatment of venous leg ulcers. Wound Repair and Regeneration 2014;22(6):668‐93. - PubMed
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Siqueira 2014 {published data only}
    1. Siqueira CP, Paula Ramos S, Gobbi CA, Shigaki L, Kashimoto RK, Venancio EJ, et al. Effects of weekly LED therapy at 625 nm on the treatment of chronic lower ulcers. Lasers in Medical Science 2014;30(1):367‐73. - PubMed
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Smeets 2008 {published data only}
    1. Smeets R, Ulrich D, Unglaub F, Wöltje M, Pallua N. Effect of oxidised regenerated cellulose/collagen matrix on proteases in wound exudate of patients with chronic venous ulceration. International Wound Journal 2008;5(2):195‐203. - PMC - PubMed
Smith‐Strom 2006 {published data only}
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Soares 2009 {published data only}
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Sparholt 2002 {published data only}
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    1. Sridhar S, Nanjappa N. Microbiological and clinical response of superoxidized solution versus povidone iodine in the management of lower limb ulcers. National Journal of Physiology, Pharmacy and pharmacology 2017;7(10):1074‐80.
Sriram 2014 {published data only}
    1. Sriram S, Kavitha MM, Tamilselvam TN, Euphrasia Latha J, Rajeswari S. Role and efficacy of platelet rich plasma (PRP) in chronic non healing resistant vasculitic ulcers. Indian Journal of Rheumatology 2014;9((5 Supplement)):S1‐2.
Sriram 2015 {published data only}
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Stiller 1992 {published data only}
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Stone 2016a {published data only}
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Stone 2016b {published data only}
    1. Stone RC, Stojadinovic O, Sawaya AP, Rosa AM, Badiavas E, Blumenberg M. Treatment of chronic venous leg ulcers with a bioengineered living cell construct induces metallothioneins and MMP8 to resolve matrix fibrosis and reactivates a healthy remodeling response. Wound Repair and Regeneration. 2016; Vol. 24 (2):A25.
Taradaj 2008 {published data only}
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Vanscheidt 2007 {published data only}
    1. Vanscheidt W, Ukat A, Horak V, Brüning H, Hunyadi J, Pavlicek R, et al. Treatment of recalcitrant venous leg ulcers with autologous keratinocytes in fibrin sealant: A multinational randomized controlled clinical trial. Wound Repair and Regeneration 2007;15(3):308‐15. - PubMed
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Vitse 2017 {published data only}
    1. Vitse J, Bekara F, Byun S, Herlin C, Teot, L. A double‐blind, placebo‐controlled randomized evaluation of the effect of low‐level laser therapy on venous leg ulcers. International Journal of Lower Extremity Wounds 2017;16(1):29‐35. - PubMed
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References to studies awaiting assessment

Alvarez 2017 {published data only}
    1. Alvarez OM, Makowitz L, Patel M. Venous ulcers treated with a hyaluronic acid extracellular matrix and compression therapy: interim analysis of a randomized controlled trial. Wounds‐A Compendium of Clinical Research & Practice 2017;29(7):E51‐4. - PubMed
Belcaro 2011 {published data only}
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    1. Belcaro G, Cesarone MR, Errichi BM, Ricci A, Dugall M, Pellegrini L, et al. Venous and diabetic ulcerations: management with topical multivalent silver oxide ointment. Panminerva Medica 2010;52(2 (Suppl 1)):37‐42. - PubMed
Cavalcanti 2017 {published data only}
    1. Cavalcanti LM. Pinto FC, Oliveira GM, Lima SV, Aguiar JL, Lins EM. Efficacy of bacterial cellulose membrane for the treatment of lower limbs chronic varicose ulcers: a randomized and controlled trial. [Eficácia da membrana de celulose bacteriana no tratamento de úlceras venosas de membros inferiores: estudo randomizado e controlado]. Revista do Colegio Brasileiro de Cirurgioes 2017;44(1):72‐80. - PubMed
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    1. Colenci R, Jacinto, JS, Miot HA, Marques ME, Schmitt JV, Abbade LP. Biomembrane of hemicellulose dressing versus collagenase in the treatment of chronic venous ulcers: randomized clinical trial, open and controlled study. Wound Repair and Regeneration. Conference: 28th Annual Meeting of the Wound Healing Society, sawc‐spring/whs joint meeting.. 2016; Vol. 24 (2):A5.
Cullen 2017 {published data only}
    1. Cullen BM, Serena TE, Gibson MC, Snyder RJ, Hanft JR, Yaakov RA. Randomized controlled trial comparing collagen/oxidized regenerated cellulose/silver to standard of care in the management of venous leg ulcers. Advances in Skin & Wound Care 2017;30(10):464‐8. - PubMed
Glukhov 2017 {published data only}
    1. Glukhov AA, Aralova MV. The study of the effectiveness of the drug combination of collagen and platelet‐rich plasma for the regional treatment of venous ulcers. Research Journal of Pharmaceutical, Biological and Chemical Sciences 2017;8(2):2258‐63.
Moreno‐Eutimio 2017 {published data only}
    1. Moreno‐Eutimio MA, Moreno J, Cueto‐Garcia J. Effect of a polymer polysaccharide with zinc oxide in the reduction of the ulcer size in chronic venous ulcers. Revista Mexicana de Angiologia 2016;44(2):67‐71.
Oliveira 2017 {published data only}
    1. Oliveira MG, Abbade LP, Miot HA, Ferreira RR, Deffune E. Pilot study of homologous platelet gel in venous ulcers. Anais Brasileiros de Dermatologia 2017;92(4):499‐504. - PMC - PubMed
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    1. Polignano R, Terriaca P, Pavanelli A, Forma O, Ponti I, Sparavigna A. Evaluation of the efficacy of a cream with purified omental lipids (P.O.L.) in the management of peri‐lesional skin in chronic vascular ulcers. Journal of Plastic Dermatology 2010;6(3):235‐44.
Robinson 1988 {published data only}
    1. Robinson BJ. Randomized comparative trial of Duoderm vs Viscopaste PB7 bandage in the management of venous leg ulceration and cost to the community.. Beyond Occlusion: wound care proceedings. International Congress and Symposium Series, Royal Society of Medicine, London. (1988); Vol. 136:101‐4.
Somani 2017 {published data only}
    1. Somani A, Rai R. Comparison of efficacy of autologous platelet‐rich fibrin versus saline dressing in chronic venous leg ulcers: a randomised controlled trial. Journal of Cutaneous and Aaesthetic Surgery 2017;10(1):8‐12. - PMC - PubMed

References to ongoing studies

Jull 2018 {published data only}
    1. Jull A, Wadham A, Bullen C, Parag V, Waters J. Wool‐derived keratin dressings versus usual care dressings for treatment of slow‐healing venous leg ulceration: study protocol for a randomised controlled trial (Keratin4VLU). BMJ Open 2018;8(2):e020319.. - PMC - PubMed

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References to other published versions of this review

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