Kusumanto 2006.

Methods	Study design: multi‐centre double‐blind placebo‐controlled RCT Intention‐to‐treat: not specified but all participants evaluated for all endpoints Country: The Netherlands
Participants	Number randomised: N = 54 (phVEGF165 n = 27; placebo n = 27) Losses to follow‐up and withdrawals: N = 0 Age (mean years (range)): phVEGF165 68.7 (45 to 85); control 68.4 (40 to 84) Gender (M): phVEGF165 59.2%; control 55.6% Inclusion criteria: type 1 or type 2 diabetes mellitus established according to current American Diabetes Association criteria; evidence of CLI including rest pain and/or ulcers that had not healed for a minimum of 2 weeks despite conventional therapy; compressible vessels with resting ankle systolic blood pressure < 50 mmHg or toe systolic blood pressure < 30 mmHg; unsuitable candidates for surgical or percutaneous revascularisation judged after contrast angiography by vascular surgeon and intervention radiologist Exclusion criteria: active proliferative diabetic retinopathy; history of malignancy; severe comorbidity, compromising comedications
Interventions	Treatment: phVEGF165, 2000 µg, on days 0 and 28, 4 aliquots, 500 µg each, diluted in 1.0 mL NaCl, injected intramuscularly into the thigh and calf of the most ischaemic limb; injection sites chosen arbitrarily according to available muscle mass Control: placebo, on days 0 and 28
Outcomes	Follow‐up times: days 7, 14, 35, 42, 72, and 100 Outcomes: Amputation, ABI, TBI, Skin improvements, Pain, QoL using RAND‐36 questionnaire, Safety outcomes
Notes	Study period: February 2000 to January 2004
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computerised block randomisation without stratification or matching, performed by the pharmacy of the University Medical Center Groningen
Allocation concealment (selection bias)	Unclear risk	Not specified how allocation concealment was carried out
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Reported as double‐blind; "no difference between the phVEGF165 and placebo could be seen or felt by the physician who performed the injection"
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	All participants accounted for
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Unclear risk	Supported by a grant from Fornix BioSciences