Dereure 2012b.

Study characteristics
Methods	Research design: RCT, prospective, multicentre, comparative, parallel‐group, randomised, controlled, blind‐observer, non‐inferiority clinical trial Care setting: 20 centres, selected by the study sponsor, 4 centres in France and 16 in Poland Country of origin: France and Poland Publication source:Journal of Wound Care Year of publication: 2012 Duration of follow‐up: 56 days, or until complete healing Sources of funding: Laboratoires Genévrier Unit of randomisation: participant Unit of analysis: participant Inclusion criteria: surface of the selected target ulcer 5 to 40 cm2, with no necrotic tissue; wound consistent with the use of an appropriate compression device; documented past history of deep venous thrombosis of the lower limbs and/or clinical evidence of post‐thrombotic syndrome with chronic oedema and lipodermatosclerosis and/or available data of an arterial‐venous Doppler examination performed within the previous 6 months and showing post‐phlebitic sequels (residual thrombosis), and/or a superficial or profound reflux on the venous system; ABPI ≥ 0.8; daily use of compression devices for ambulatory patients; no local use of HA within the previous 3 months; albuminaemia ≥ 25 g/L; participants covered by a health insurance system; women of childbearing age had to use a reliable contraceptive method for at least 1 year Exclusion criteria: participants with an ulcer of non‐vascular origin, or due to a general cause; diabetic patients; with significant arterial insufficiency (ABPI < 0.8); with a clinical suspicion of local and/or general infection; with hepatic or renal failure, with a recent history of venous thrombosis (less than 3 months); pregnant or breastfeeding woman, or woman planning to be pregnant; with known allergies to local anaesthetics or to investigational treatments components, or under treatment delaying the healing process; participants who had participated in a clinical investigation within the 2 months preceding the inclusion visit
Participants	Number of participants: 170 participants were included in the ITT population (n = 2 in France and n = 168 in Poland; group 1: 85 participants; group 2: 85 participants). 143 participants constituted the per‐protocol population (group 1: 72 participants; group 2: 71 participants). Female gender: group 1: 61% (n = 44); group 2: 59% (n = 42) Age: group 1: 64.2 ± 14.4 (n = 72); group 2: 68.5 ± 13.1
Interventions	Details of intervention Group 1: 0.05% HA‐impregnated cotton gauze pad (ialuset gauze pad; Laboratoires Genévrier) Group 2: HC dressing (DuoDERM E; Convatec) Dressing procedure: the ulcer was cleaned with physiological serum, and the assigned dressing was then applied by a nurse or by the investigator. The gauze pad (group 1) was applied to the wound every day, covered with sterile gauze. The HC dressing (group 2) was directly applied to the wound every 2 to 3 days. Co‐interventions: both treatments were then covered by an adapted and efficient compression bandage, prescribed by investigators according to the standard care recommended by French Health Authorities (HAS) on June 2006 (grade 2; 3); low‐elasticity bandages with short stretch (< 20%), elastic bandages with long stretch (> 20%), multilayered bandages and compression stockings. Wound excision procedures were authorised if necessary. Systemic antibiotics could be used in the event of clinically relevant infection. Systemic analgesics were authorised, provided they were interrupted at least 10 hours before each visit. Duration of treatment: 56 days, or until complete healing
Outcomes	Primary outcomes of the review: percentage of participants with completely healed ulcer; adverse events Secondary outcomes: reduction of at least 40% of the initial wound surface after 56 days of treatment; percentage wound size reduction; pain (only at baseline)
Notes	Losses to follow‐up: 27 participants (15%) did not complete the study (group 1: n = 13; group 2: n = 14) primarily due to ulcer healing (n = 12, 46%). 7 participants (27%) dropped out due to treatment‐related adverse event.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The randomisation list was prepared using a validated SAS software (Institute Inc.) by an independent provider appointed for this study (Axonal). Randomisation was stratified by centre"
Allocation concealment (selection bias)	Unclear risk	The method of allocation was described, however there was no mention of allocation concealment.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Not possible due to different appearances of treatments.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Two independent readers, blind to treatment allocation, measured the wound size based on the drawings on sterile tracing papers, in a centralised fashion and using planimetrics system. The percentage reduction of the wound area between day 0 and day 14, day 28 and day 56, was calculated"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "A total of 170 patients were included (n=2 in France and n=168 in Poland) ...". "Overall, 26 patients (15%) did not complete the study (n=13 for HA, n=13 for HC dressing) primarily due to ulcer healing (n=12; 46%). Seven patients (27%) dropped out for treatment related AE" Comments: participants withdrawal were justified and balanced between groups.
Selective reporting (reporting bias)	Low risk	Outcomes in methods section were described in results section.
Other bias	Unclear risk	Groups were balanced at baseline and only one ulcer was selected in volunteers with multiple ulcers, however, only 2 volunteers were included from 4 eligible centres in France and authors did not provide reason for this imbalance. The study was sponsored by Laboratories Genévrier and authors received honoraria for their contributions to the study.