ESTAbLIsh – Endovascular strategy versus Surgical strategy for the Treatment for Acute Limb Ischaemia Assessing the clinical- and cost-effectiveness of endovascular strategy compared to surgical strategy for the treatment of acute limb ischaemia.

Research Question: Does open surgical revascularisation strategy have a superior amputation-free survival rate at six months compared to endovascular revascularisation for people with acute limb ischaemia, and is it more cost-effective? Background: Acute limb ischaemia (ALI) is a common emergency where leg arteries become blocked (by thrombus), leading to potential amputation or death. 1 in 10 patients with ALI treated in the NHS dies in the hospital, and four in ten die within a year. ALI is a leading cause of amputations in the NHS. There are two emergency approaches for ALI: open surgery, involving a skin incision and artery repair, typically under general anaesthesia, and endovascular procedures, which are minimally invasive and use only local anaesthetic. It is unclear which approach better prevents amputations and deaths or which procedure provides better value for money for the NHS. Patients prefer minimally invasive treatments but are willing to consider surgery if it proves more effective for limb salvage. A survey found equipoise among clinicians about which approach is better, with both approaches being used in the NHS. This study aims to address the uncertainty around ALI treatment. The Vascular Society of Great Britain and Ireland JLA identified improving outcomes and reducing amputations as a key research priority in 2021. Aims: To conduct a randomised controlled trial comparing open surgical and endovascular strategies for amputation-free survival, re-interventions, cardiovascular events, health status, and quality of life at 6 months. Objectives: To compare open and endovascular strategies in terms of amputations, deaths, benefits, and harms. To conduct an economic evaluation of the relative cost-effectiveness of both strategies. To undertake a process evaluation. Design and Methods: A multi-centre, individual superiority randomised controlled trial with an internal pilot, process evaluation, and economic evaluation. Participants with ALI will be recruited from 30 NHS hospitals (n=470). Follow-up will occur at 6 months with assessments of amputations, deaths, quality of life (HRQoL), complications, and NHS costs. Timeline: 44 months total: Months 0-6: approvals, documentation, data management. Months 7-15: internal pilot. Months 7-30: participant recruitment. Months 13-38: trial follow-up completion. Months 38-43: data analysis. Months 42-44: reporting and dissemination. Anticipated Impact and Dissemination: Findings will be shared with the public and experts via charities (e.g., Limbless Association) and societies (e.g., Vascular Society of Great Britain and Ireland, British Society of Interventional Radiology). Patient groups will produce accessible summaries (video media, newsletters, graphics) and updates, shared via social media, a dedicated website with publication in medical journals, and presentation at conferences. The results will influence clinical guidelines (European Society of Vascular Surgery and Cardiovascular and Interventional Radiological Society of Europe) for ALI management. Patient and Public Involvement: This RCT addresses the 2021 survey involving 400 patients and NHS staff which identified key research questions on arterial problems, including preventing major amputations and improving surgery outcomes. Two patients are co-applicants, supported by an independent PPI group; PPI co-developed the effect size, follow-up and were willing to be randomised.