Lipsky 2012a.

Methods	RCT (2:1 randomisation ratio) Setting: Diabetic foot clinics (mainly inpatients) (from study author) Country: USA and UK Duration of follow‐up: Outcome assessment planned for 2 weeks after cessation of treatment for a total study duration of 42 days Duration of treatment: At least 7 days and for a maximum of 28 days Funding source: For‐profit; "This study was funded in whole by Innocoll Technologies Ltd." Unit of analysis: Participant
Participants	56 participants Inclusion criteria: Diabetic patients aged 18 to 80 years with a single, moderately infected lower extremity ulcer. Exclusion criteria: Patients who had received any antimicrobial therapy in the preceding 2 weeks; those with ischaemia of the lower limb; and, at institutional review board request, patients with a glycated haemoglobin level of ≥ 10.0%. Ulcer characteristics at baseline (size of ulcer, number of ulcers, duration of ulceration where reported): Not reported Infection status at baseline: Infected ulcers
Interventions	Group 1: (n = 38) Systemic antibiotic therapy alone (a daily oral or intravenous dose of 750 mg of levofloxacin or alternative antimicrobial therapy, as determined by susceptibility testing). Group 2: (n = 18) Daily topical application of the gentamicin‐collagen sponge combined with systemic antibiotic therapy (a daily oral or intravenous dose of 750 mg of levofloxacin or alternative antimicrobial therapy, as determined by susceptibility testing). Additional comments: Participants in both arms also received standard diabetic wound management, including sharp surgical debridement at each visit where appropriate, pressure off‐loading as applicable, and daily dressing changes using a non‐adherent, moisture‐permeable gauze dressing followed by a second saline‐moistened gauze dressing.
Outcomes	Primary review outcomes: Resolution of infection Secondary review outcomes: Adverse events
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Comment: No information presented.
Allocation concealment (selection bias)	Low risk	Quote: "patients were randomised in a 2:1 ratio to the treatment or control group using a interactive voice response system" Comment: Confirmed centralised randomisation
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "open‐label" Comment: The authors chose not to administer placebo collagen sponges to participants in the control group due to the concern that a placebo sponge could potentially harbour bacteria and bias the results in favour of the active treatment. Consequently, to reduce the complexity of this pilot study, they chose an open‐label design.
Blinding of outcome assessment (detection bias) Wound healing	Unclear risk	Not relevant
Blinding of outcome assessment (detection bias) Infection/resolution of infection	Low risk	Quote: "assessors were also blinded to treatment" (from study author)
Blinding of outcome assessment (detection bias) Secondary outcomes	Low risk	Quote: "assessors were also blinded to treatment" (from study author)
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote "of the 56 randomised subjects, 20 (12 in group 1 and 8 in group 2) were deemed ineligible; three more subjects in the study group discontinued (1 because of adverse events, 1 because of protocol non‐compliance and 1 lost to follow up)." "we defined a modified ITT population to use of efficacy analyses to include only the 36 eligible patients" Comment: 41% of participants were not included in analysis.
Selective reporting (reporting bias)	Low risk	Comment: All outcomes reported as outlined in methods. Protocol not obtained.
Other bias	Low risk	Comment: None noted.