Meaume 2008.

Study characteristics
Methods	Research design: randomised, parallel‐group, prospective, open, multicentre Care setting: inpatients or outpatients, 18 centres in 3 countries (France, 15 centres; Italy, 2 centres; Switzerland, 1 centre) Country of origin: France, Italy, and Switzerland Publication source:Current Medical Research and Opinion Year of publication: 2008 Duration of follow‐up: 42 days Sources of funding: IBSA Institut Biochimique SA (Pambio‐Noranco, Switzerland) and Laboratoires Genévrier (Antibes, France) Unit of randomisation: participant Unit of analysis: participant Inclusion criteria: inpatients or outpatients of any gender, of 18 years of age or more; with life expectation longer than the duration of the study and having given their written informed consent to the participation in the study; participants should have 1 or more leg ulcers of varicose, post‐thrombotic or mixed venous‐arterial origin assessed by clinical criteria and venous Doppler examination, showing signs of post‐phlebitic, residual thrombosis or either a superficial or a profound return flow on the venous system; ulcers must have been present for more than 2 months but less than 1 year, and sized between 5 and 40 cm2 Exclusion criteria: the presence of fibrin was tolerated if corresponding to less than 50% of the lesion area, whereas the presence of necrotic tissue was reason for exclusion; serum albumin values < 25 g/L; a systolic pressure index < 0.8 (ankle pressure/humeral pressure); ulcers of non‐vascular origin or caused by a systemic disease, or patients suffering from uncontrolled diabetes; suspicion of infection (e.g. erysipelas, phlegmon); a venous thrombosis in the previous 3 months, presence of diffuse eczema around the ulcer; known hypersensitivity to 1 of the hydrocolloid dressings components; use of local treatments (e.g. topical proteolytic enzymes) other than the tested medical devices, concomitant use of drugs that can negatively influence the wound‐healing process such as systemic corticosteroids, cytostatics, and immunosuppressants; patients having participated in another trial during the 2 months preceding the inclusion in our study; pregnant or breastfeeding women; and participants not willing or not able to respect the protocol restrictions
Participants	Number of participants: 125 participants (group 1: 62 participants; group 2: 63 participants). All 125 included participants were assessed for efficacy and safety in the ITT analysis, whereas the per‐protocol analysis was performed on the 108 participants (group 1: 56 participants; group 2: 52 participants who had either achieved a complete wound healing before day 42 or completed the 42‐day treatment period without major protocol violations). Male gender: group 1: 30.15% (n = 19); group 2: 56.45% (n = 35) Age: group 1: 73 ± 1.4; group 2: 75 ± 1.4
Interventions	Details of the intervention Group 1: hydrocolloid dressing containing 0.2% of HA Group 2: hydrocolloid dressing not containing HA Dressing procedure: "at the inclusion visit (day 1), a surgical debridement of the ulcer area was performed when necessary. For this purpose, use of local anaesthetics – either in liquid or cream forms – was allowed. The lesion was then cleaned with physiological solution at each control visit, before the application of the hydrocolloid dressing. For participants having several ulcers or a bilateral ulcer, the investigator selected 1 lesion only to be treated with the tested medical devices according the above‐mentioned criteria, whereas the other ulcers were treated according to standard treatment protocols of the centres." Co‐interventions: "a suitable and individually adapted, effective elastic stocking was prescribed by the investigator and worn by all participants. A secondary bandage was used only if strictly necessary, according to the judgement of the investigator." Duration of treatment: for a maximum treatment period of 6 consecutive weeks (42 days). Once included, participants were always assessed by the same personnel in charge of the study at each control visit, after 7, 14, 28, and 42 days or until a complete wound healing was recorded.
Outcomes	Primary outcomes of the review: complete healing; adverse events Secondary outcomes: reduction of the wound area; evolution of the wound bed conditions; pain and itching were assessed by participants on a 100‐millimetre VAS
Notes	Losses to follow‐up: 22 participants dropped out before day 42: complete healing of their ulcer (group 1: n = 4; group 2: n = 4) and due to adverse events (group 1: n = 3; group 2: n = 4) or other reason (group 1: n = 4; group 2: n = 3)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Following inclusion, patients were randomly assigned to one of the two arms of treatment, both in form of a hydrocolloid dressing of 10X10 cm, according to a computer generated randomisation list"
Allocation concealment (selection bias)	Unclear risk	Quote: "Sealed envelopes containing the treatment code for each individual patient were given to the investigator at each centre. The investigator could open the envelope only after having included a patient in the study and only then know to which treatment group that patient had been allocated" Comment: authors did not specify if envelops were sequentially numbered and opaque. We could not obtain this information from authors; therefore, we judged this study as unclear for this domain.
Blinding of participants and personnel (performance bias) All outcomes	High risk	The study was open‐label.
Blinding of outcome assessment (detection bias) All outcomes	High risk	The study was open‐label.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "Twenty‐two patients stopped the treatment before day 42: 8 patients (4 in each treatment arm) for the complete healing of their ulcer, and 14 patients (7 in each experimental group) due to AEs or other reason. No statistical difference was found between the 2 groups as far as the number of patients withdrawn and the reason for withdrawal were concerned. Three patients were identified as protocol violators, all in the HC group: 1 had an ulcer area of 80 cm2 at inclusion (inclusion criterion was a maximum ulcer area of 40 cm2), and 2 other patients used non‐authorized local treatments."
Selective reporting (reporting bias)	Low risk	All proposed outcomes described in methods section are presented and properly analysed.
Other bias	Low risk	The proportion of males was higher in the control group but other participants characteristics were balanced between groups. Only 1 ulcer was assessed per volunteer. No conflict of interest was reported by authors.