RAVE.

Methods	Study design: stated as randomised, placebo‐controlled, double‐blind, phase II trial. Randomisation 1:1:1 Recruitment: no data (USA)
Participants	People with unilateral exercise‐limiting intermittent claudication (N randomised and received treatment = 105) Age (mean): 68 years (control), 66 (low‐dose), 64 years (high‐dose) Sex (N males/females): 91%/9% (control), 81%/19% (low‐dose), 67%/33% (high‐dose) Severity: ABI (index leg): 0.6 (placebo), 0.6 (low‐dose), 0.6 (high‐dose)
Interventions	AdVEGF121 ‐ recombinant adenovirus encoding vascular endothelial growth factor 4 × 1010 particle units AdVEGF121, n = 40; MITTa: 40 participants at week 12, 38 at week 26. 4 × 109 particle units AdVEGF121, n = 32; MITTa: 31 participants at week 12, 24 at week 26. Placebo, n = 33; MITTa: 30 participants at week 12, 25 at week 26. Delivered as 20 × 1‐mL IM injections
Outcomes	Change in peak walking time to week 12 (primary), to week 26 Change in claudication onset time to week 12, to week 26 Ankle‐brachial index (ABI) at 12 weeks, at 26 weeks Quality of life measures at 12 weeks, at 26 weeks
Notes	ITT analysis: missing data analysed using the last observation carried forward procedure. Peak walking time and claudication onset time recorded as 0 after mechanical intervention (revascularisation) or inability to walk on the treadmill aModified ITT (MITT) analysis: missing data and data collected after revascularisation or treatment with cilostazol were excluded
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Procedure is not reported
Allocation concealment (selection bias)	Unclear risk	Procedure is not reported
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Blinding procedure is not explicitly reported
Blinding of outcome assessment (detection bias) Objective outcomes	Low risk	Outcome measurement is not likely to be influenced by lack of blinding
Blinding of outcome assessment (detection bias) Subjective outcomes	Unclear risk	Blinding procedure is not explicitly reported
Incomplete outcome data (attrition bias) Death	Low risk	Data for almost all participants
Incomplete outcome data (attrition bias) Limb amputation	Low risk	Data for almost all participants
Incomplete outcome data (attrition bias) Ulceration	Unclear risk	The study did not address this outcome
Incomplete outcome data (attrition bias) Rest pain	Unclear risk	The study did not address this outcome
Incomplete outcome data (attrition bias) Walking ability	Low risk	N missing data at week 12 low (< 5%), at week 26 higher (< 20%); results are not likely to be influenced.
Incomplete outcome data (attrition bias) Haemodynamic measures	Unclear risk	No data for number of participants with measurements
Incomplete outcome data (attrition bias) Adverse events /severe complications	Low risk	Data for almost all participants (no aggregate data)
Selective reporting (reporting bias)	Low risk	The study protocol is not available, but results for all relevant outcomes are provided
Other bias	Low risk	The study appears to be free of other sources of bias