Grossman 2007.

Methods	Study design: multi‐centre phase II double‐blind placebo‐controlled trial Intention‐to‐treat: not specified Country: USA
Participants	Number randomised: N = 105 (VLTS‐589 n = 52; control n = 53) Losses to follow‐up and withdrawals: N = 7 withdrew (VLTS‐589 n = 4; control n = 3); reasons: death n = 3, withdrawal of consent n = 1, loss to follow‐up n = 2, pre‐existing condition n = 1 Age (mean years ± SD): 67.7 ± 8.95 (VLTS‐589 67.3 ± 8.16; control 68.1 ± 9.73) Gender (M): 84.8% (VLTS‐589 88.5%; control 81.1%) Inclusion criteria: between the ages of 40 and 81; significant bilateral infrainguinal PAD as assessed by duplex ultrasound, magnetic resonance angiography, computed tomography angiography, or cineangiography within 6 months before screening; stable exercise limiting IC of the lower extremities of > 2 months' duration with a diagnosis of PAD confirmed with ABI ≤ 0.80 in both lower extremities or TBI < 0.70 Exclusion criteria: significant in‐flow disease defined as > 50% stenosis in the distal aorta, common iliac, external iliac, or common femoral arteries; CLI, change in claudication symptoms within 2 months; terminated the treadmill for reasons other than claudication; lower extremity percutaneous intervention within 2 months; lower limb surgical revascularisation within 6 months before study entry or participation in a structured exercise treatment protocol within 30 days of the study; unstable angina; recent MI; recent coronary artery bypass grafting or coronary percutaneous intervention; stroke; congestive heart failure or deep venous thrombosis; history of malignant neoplasm within the past 5 years or presence of proliferative retinopathy; women of reproductive potential required to have a negative pregnancy test at the time of study drug administration
Interventions	Treatment: 42 mg VLTS‐589 (Del‐1) ‐ an investigational, non‐viral, plasmid‐based therapeutic comprising a plasmid (pDL1680) expression system formulated with poloxamer 188 ‐ delivered via 21 percutaneous intramuscular injections of 2 mL each Control: placebo, poloxamer 188 alone, delivered in the same manner as treatment
Outcomes	Follow‐up times: 30, 90, and 180 days Outcomes: PWT (Gardner exercise treadmill test protocol), ABI, COT, QoL (WIQ and SF‐36 v2)
Notes	Study period: June 2003 to June 2005 ‐ estimated dates NCT00068133
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information provided to determine random sequence generation
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 saline 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	Seven dropouts clearly described and similar between groups
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Unclear risk	Sponsored by Valentis, Inc.