COlchicine for prevention of Vascular Inflammation in Non-CardioEmbolic stroke - a randomised clinical trial (CONVINCE). German Extension

• Applicants: Professor Dr. Karl-Heinz Jöckel; Professor Dr. Christian Weimar
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 397530000

Inflammation contributes to unstable atherosclerotic plaque, thromboembolic stroke, myocardial infarction and vascular death. In randomised trials in patients with coronary disease, colchicine (a tubulin inhibitor with pleiotropic anti-inflammatory effects) reduced recurrent vascular events. Hypothesis: Anti-inflammatory therapy with low-dose colchicine (0.5mg/day) plus usual care will reduce recurrent vascular events in patients with non-cardioembolic, ischemic stroke or TIA compared with usual care alone. Design: CONVINCE is a multi-centre, international, Prospective, Randomised Open-label, Blinded-Endpoint assessment (PROBE) controlled Phase 3 clinical trial in 3154 participants. The intervention is colchicine 0.5 mg/day and usual care versus usual care alone (antiplatelet, lipid-lowering, antihypertensive treatment, lifestyle advice). Included patients are at least 40 years old, with non-severe ischaemic stroke (modified Rankin score ≤3) or high-risk TIA (ABCD2 > 3, or positive DWI, or cranio-cervical artery stenosis) within 72 hours-28 days of randomisation, with qualifying stroke/TIA most likely caused by large artery stenosis, lacunar disease, or cryptogenic embolism. Exclusions are stroke/TIA caused by cardio-embolism or other defined cause (e.g. dissection), contra-indication to colchicine (including potential drug interactions), or incapacity for participation in a clinical trial. The anticipated median follow-up will be 36 months. The primary analysis will be by intention-to-treat. The primary outcome is time to first recurrent ischaemic stroke, myocardial infarction, cardiac arrest, or hospitalisation with unstable angina (non-fatal or fatal). Schedule: CONVINCE is currently recruiting in 14 countries (13 European and Canada). Until February 2022, 2700 participants have been randomized (342 in Germany). After planned inclusion of 524 German participants, this grant application will secure their follow-up in 25 centers in Germany. Summary: CONVINCE will provide high-quality randomised data on the efficacy and safety of anti-inflammatory therapy with colchicine for secondary prevention after stroke.

• DFG Programme: Clinical Trials