A randomised controlled trial assessing the clinical and cost-effectiveness of Endovascular vs. Open revascularisation in severe oCClusive aorto-iliac disease. The EVOCC trial.

Research question Is the clinical and cost-effectiveness of open surgery for severe aorto-iliac occlusive disease superior to endovascular treatment? Background Peripheral Arterial Disease (PAD) affects 20% of those over 55. Patients with PAD can develop rest pain or necrosis, called Chronic Limb Threatening Ischaemia (CLTI), which is life-threatening if untreated. Patients with CLTI and aorto-iliac disease need revascularisation either with open surgery or keyhole techniques i.e. endovascular treatment. Open surgery is associated with a 3% early mortality. Endovascular treatment is less invasive but costly and 43% of patients need re-intervention within 3 years. No trial has compared these techniques, identified as a research priority by the James Lind Alliance (JLA). Aims & objectives Main aim: Identify whether the clinical and cost-effectiveness of open surgery for severe occlusive aorto-iliac disease is superior to endovascular treatment. Objectives: Identify whether open surgery is superior regarding amputation-free survival and cost-effectiveness, including quality of life (QoL), over a minimum 2 years (median 3 years). Methods Multicentre randomised controlled trial with an internal pilot. Population: Adult patients with CLTI having revascularisation for severe occlusive aorto-iliac disease in 30 NHS hospital networks nationally. Patients will have been deemed suitable for either treatment by a multi-disciplinary team meeting. Intervention: Endovascular treatment. Comparator: Open surgery. We will compare any type of endovascular treatment to open surgery with or without inflow/outflow treatment. Local clinicians will decide treatment configuration (pragmatic trial). Medical care and risk-factor control will follow NHS and National Institute for Health and Care (NICE) guidance. Primary outcome: Death and/or major lower limb amputation (time to first event). Secondary outcomes: Mortality, cardiovascular events, re-admissions, re-interventions, renal function, quality-of-life, healthcare costs. Patients will undergo assessments at baseline, discharge, 30-days, 6, 12 months, then annually. We will link to national datasets to record 5 year deaths/amputations. Sample size & analysis: Calculations are based on our published meta-analysis, cohort study, and event rates in a Hospital Episodes Statistics (HES) analysis. 596 patients will provide 90% (a=0.05) to detect an increase in restricted mean survival time of 3 months for death and/or amputation, corresponding to a hazard ratio of 0.66 or absolute risk reduction of 13.3% (50% vs 63.3%) at 3 years. With 5% loss to follow-up, the final sample size is 628. Patients will be minimised for age, sex, diabetes, chronic kidney disease, site, unilateral vs. bilateral disease, and tissue loss. Primary analysis will be by intention-to-treat. A full economic evaluation will be performed. Timelines 6 months for approvals & 3 months to open pilot sites Internal pilot: 6 months, 10 sites Main recruitment: 24 months, 30 sites. Follow-up: minimum 2 years, median 3 Analysis/dissemination: 6 months Impact & dissemination This will be the first trial in this context, ending uncertainty, saving lives/legs, improving QoL, and reducing costs. Our patient partners will prepare lay updates 3-monthly. We will disseminate updates to societies across disciplines and patient groups. Besides conferences/journals, we will hold an annual PPI/stakeholder event and report directly to NICE.