Ouriel 1998a.

Methods	Study design: randomised controlled trial Intention‐to‐treat analysis: yes Countries: USA and Northern Europe (113 centres)
Participants	Number randomised: total N = 548 (thrombolysis n = 272; surgery n = 272) Exclusions post randomisation: 4 Losses to follow‐up: thrombolysis 17; surgery 16 Gender M/F: thrombolysis 192/90; surgery 170/102 Mean age ± SD, years: thrombolysis 64.9 ± 0.78; surgery 64.5 ± 0.78 Inclusion criteria: 14 days or less of reversible limb‐threatening ischaemia, over 17 years of age, non‐pregnant, suitable for either open surgical treatment or thrombolysis Exclusion criteria: pregnancy, women of child‐bearing age for whom pregnancy was a possibility
Interventions	Thrombolysis with urokinase: 4000 IU/min for 2 hours, then 2000 IU/min for a maximum duration of 48 hours' therapy Surgery, including angioplasty and primary amputation
Outcomes	Follow‐up at 6 and 12 months Amputation‐free survival at 6 and 12 months, survival free of open surgical procedures at 6 months (lysis group), ABI, degree of clot lysis, rates of adverse effects of treatment, including haemorrhagic complications
Notes	Supported by a grant from Abbott
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Study utilised a centralised randomisation centre, which was contacted at the time of patient consent via telephone. Participants were stratified by whether occlusion involved native artery or bypass graft
Allocation concealment (selection bias)	Low risk	Study utilised a centralised randomisation centre, which was contacted at the time of patient consent via telephone
Blinding of participants and personnel (performance bias) All outcomes	High risk	Steps taken to blind participants to treatment were not described. Owing to the nature of the treatment, it would be very difficult to blind participants or personnel to treatment
Blinding of outcome assessment (detection bias) All outcomes	High risk	Steps taken to blind personnel to treatment were not described
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants were reported on, and intention‐to‐treat analysis was specified
Selective reporting (reporting bias)	Unclear risk	Survival free of open surgery at 6 months in the urokinase treatment group was identified as an outcome in the methods but was not included in the results. All other outcomes were reported on
Other bias	Unclear risk	Differences at baseline between treatment groups: larger numbers of men, patients with hepatic or renal insufficiency, and patients with rest pain at presentation in the thrombolysis group