Rajagopalan 2003.

Methods	Study design: multi‐centre phase II double‐blind placebo‐controlled RCT Intention‐to‐treat: yes, missing data analysed via last observation carried forward procedure Country: USA
Participants	Number randomised: N = 105 (low‐dose AdVEGF121 n = 32; high‐dose AdVEGF121 n = 40; placebo n = 33) Losses to follow‐up and withdrawals: N = 18 (low dose AdVEGF121 n = 9; high‐dose AdVEGF121 n = 2; placebo n = 8) Age (mean years ± SD): low‐dose AdVEGF121 66 ± 9; high‐dose AdVEGF121 64 ± 9; placebo 68 ± 10 Gender (M): low‐dose AdVEGF121 81%; high‐dose AdVEGF121 68%; placebo 91% Inclusion criteria: male and female; 40 to 80 years of age, with PAD (resting ABI < 0.80 in affected limb) and chronic, stable, predominantly unilateral intermittent claudication ≥ 6 months on a stable medication regimen, with exercise‐associated flow limitation (> 20% fall in ABI with exercise) and unilateral exercise‐limiting claudication, with exercise duration between 1 and 10 minutes (and variability within 20%) on 2 consecutive graded Gardner‐Skinner protocols Exclusion criteria: significant contralateral lower extremity symptoms and signs
Interventions	Treatment: Low‐dose AdVEGF121 4 × 10⁹ particle units ‐ 20 1.0‐mL intramuscular injections into the index leg in a single session both anterior and posteriorly into the lower thigh or into the lower thigh and the upper calf High‐dose AdVEGF121 4 × 10¹⁰ particle units, given in the same manner as above Control: vehicle alone, given in the same manner as above
Outcomes	Follow‐up times: 12 weeks and 26 weeks Outcomes: PWT (graded Gardner‐Skinner protocol), ABPI, COT, QoL (using SF‐36 and WIQ), Safety (adverse event monitoring, physical exam, lab tests, resting ECGs, ophthalmological exams, and cancer screens)
Notes	Study period: not specified
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information provided to determine adequate random sequence generation; stratified on the basis of diabetic status
Allocation concealment (selection bias)	Unclear risk	Insufficient information provided to determine allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Described as double‐blind and used placebo but did not describe how placebo was disguised for personnel
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information provided to determine blinding of outcome assessment
Incomplete outcome data (attrition bias) All outcomes	Low risk	Utilised ITT analysis and clearly stated numbers and reasons for loss to follow‐up
Selective reporting (reporting bias)	Low risk	All outcomes from trial design paper reported
Other bias	Unclear risk	Funded by GenVec; several study authors are employees of or own stock in GenVec Sample size calculation estimated for 35 people in each treatment group to provide 80% power to detect a mean difference of 1.5 minutes in change in PWT