Vein bypass first vs. best endovascular treatment first revascularisation strategy for chronic limb-threatening ischaemia due to infra-popliteal disease: the BASIL-2 RCT.

Background: Chronic limb-threatening ischaemia with ischaemic pain and/or tissue loss. Objective: To examine the clinical and cost-effectiveness of a vein bypass-first compared to a best endovascular treatment-first revascularisation strategy in preventing major amputation or death. Design: Superiority, open, pragmatic, multicentre, phase III randomised trial. Setting: Thirty-nine vascular surgery units in the United Kingdom, and one each in Sweden and Denmark. Participants: Patients with chronic limb-threatening ischaemia due to atherosclerotic peripheral arterial disease who required an infra-popliteal revascularisation, with or without an additional more proximal infra-inguinal revascularisation procedure, to restore limb perfusion. Interventions: A vein bypass-first or a best endovascular treatment-first infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation strategy. Main outcome measures: The primary outcome was amputation-free survival. Secondary outcomes included overall survival, major amputation, further revascularisation interventions, major adverse limb event, health-related quality of life and serious adverse events. Methods: Participants were randomised to a vein bypass-first or a best endovascular treatment-first revascularisation strategy. The original sample size of 600 participants (247 events) was based on a hazard ratio of 0.66 with amputation-free survival rates of 0.72, 0.62, 0.53, 0.47 and 0.35 in years 1-5 in the best endovascular treatment-first group with 90% power and alpha at Results: Between 22 July 2014 and 30 November 2020, 345 participants were randomised, 172 to vein bypass-first and 173 to best endovascular treatment-first. Non-amputation-free survival occurred in 108 (63%) of 172 patients in the vein bypass-first group and 92 (53%) of 173 patients in the best endovascular treatment-first group [adjusted hazard ratio 1.35 (95% confidence interval 1.02 to 1.80); Limitations: Recruiting patients to the Bypass versus Angioplasty in Severe Ischaemia of the Leg Trial-2 trial was difficult and the target number of events was not achieved. Conclusions: A best endovascular treatment-first revascularisation strategy was associated with better amputation-free survival, which was largely driven by fewer deaths. Overall, the economic evaluation results suggest that best endovascular treatment-first dominates vein bypass-first in the cost-effectiveness analysis and cost-utility analysis as it was less costly and more effective than a vein bypass-first strategy. Future work: The Bypass versus Angioplasty in Severe Ischaemia of the Leg Trial-2 investigators have a data sharing agreement with the BEst Surgical Therapy in patients with Chronic Limb threatening Ischaemia investigators. One output of this collaboration will be an individual patient data meta-analysis. Study registration: Current Controlled Trials ISRCTN27728689. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/35/45) and is published in full in