Deev 2015.

Methods	Study design: multi‐centre phase IIb/III open‐label RCT Intention‐to‐treat: not specified; for PWD, n = 5 in treatment group and n = 1 in control group had amputation before enrolment and therefore could not perform treadmill test; reported "analyzed population in the study included 94 patients: 70‐in the test group and 24‐in the control group" Country: Russia
Participants	Number randomised: N = 100 (pCMV‐vegf165 n = 75; control n = 25) Losses to follow‐up and withdrawals: not specified Age (mean years ± SD): pCMV‐vegf165 67.8 ± 9.0; control 70.9 ± 7.8 Gender (M): pCMV‐vegf165 80%; control 80% Inclusion criteria: inclusion decision made by a team of vascular surgeons and radiologists based on angiographic and echographic findings, history of the disease, previous procedures, and concomitant pathology; age > 40 years; history of stable claudication for at least 3 months; stage II to III chronic ischaemia according to Fontaine classification; absence of haemodynamically significant (> 70%) stenosis of the aortoiliofemoral arterial segment or (if present) a patent proximal bypass graft if revascularisation surgery was performed no earlier than 3 months before inclusion in the study; satisfactory patency of the deep femoral artery in the presence of haemodynamically significant femoropopliteal arterial lesions; presence of haemodynamically significant stenosis (stenosis > 70% and/or occlusion); diffuse lesions of the anterior and/or posterior tibial arteries; voluntary informed consent signed Exclusion criteria: CLI of non‐atherosclerotic genesis (autoimmune disorders, Buerger's disease, congenital abnormalities, vascular injuries, etc.); stage IV chronic ischaemia according to Fontaine classification; severe concomitant pathology with life expectancy < 1 year; infectious disease; history of cancer or suspected malignancy; decompensated diabetes mellitus
Interventions	Treatment: pCMV‐vegf165 (Neovasculgen) ‐ intramuscular injection of 1.2 mg of pCMV‐vegf165, administered at 4 to 5 injection sites in the lower and middle thirds of the posterior part of the calf; a second 1.2‐mg injection administered 14 days after first treatment, in conjunction with standard treatment Control: standard treatment only
Outcomes	Follow‐up times: 6 months, 1 and 2 years Outcomes: PWD, ABI, Blood flow velocity; Additionally QoL (SF‐36) at 6 months only; Safety (adverse events, blood and urine lab tests, chest X‐rays, and abdominal echography)
Notes	Study period: protocol approved April 2010 NCT03068585
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; randomised to 2 groups at a ratio of 3:1
Allocation concealment (selection bias)	Unclear risk	Insufficient information provided to determine allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	High risk	Blinding not undertaken and not feasible due to the nature of treatment and control
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	Unclear risk	Losses and withdrawals not reported
Selective reporting (reporting bias)	Unclear risk	ClinicalTrials.gov protocol states researchers will evaluate transcutaneous oximetry, but this is not reported in the results
Other bias	Unclear risk	With 3:1 randomisation, there were only 25 participants in the control group, which limited the subgroup analysis; as stated in the report, no participants in the control group had stage IIa disease Sample size calculation estimated 28 participants in each group to detect a 0.75 standardised difference (80% power) Several study authors are employees of the OJSC Human Stem Cell Institute, which funded the study