BACKGROUND: Inflammation contributes to unstable atherosclerotic plaque and stroke. In randomised trials in patients with coronary disease, canukinumab (an interleukin-1B antagonist) and colchicine (a tubulin inhibitor with pleiotropic anti-inflammatory effects) reduced recurrent vascular events.Hypothesis: Anti-inflammatory therapy with low-dose colchicine plus usual care will reduce recurrent vascular events in patients with non-severe, non-cardioembolic stroke and TIA compared with usual care alone. DESIGN: CONVINCE is a multi-centre international (in 17 countries) 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, 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. OUTCOME: The primary outcome is time to first recurrent ischaemic stroke, myocardial infarction, cardiac arrest, or hospitalisation with unstable angina (non-fatal or fatal). SUMMARY: CONVINCE will provide high-quality randomised data on the efficacy and safety of anti-inflammatory therapy with colchicine for secondary prevention after stroke. SCHEDULE: First-patient first-visit was December 2016. Recruitment to complete in 2021, follow-up to complete in 2023.

2nd Department of Neurology Attikon Hospital National and Kapodistrian University of Athens School of Medicine Athens Greece

2nd Department of Neurology Institute of Psychiatry and Neurology Warsaw Poland

Amsterdam University Medical Centers Department of Neurology | Location AMC Amsterdam The Netherlands

Centre for Clinical Brain Sciences Edinburgh UK

Centre for Clinical Brain Sciences University of Edinburgh UK

Centre of Neurology Institute of Clinical Medicine Faculty of Medicine Vilnius University Lithuania

Department of Neurology and Neurosurgery University of Tartu Tartu Estonia

Department of Neurology University Hospital Bern Inselspital University of Bern Bern Switzerland

Health Research Board Stroke Clinical Trials Network Ireland

Herlev Gentofte Hospital and University of Copenhagen Denmark

HRB Clinical Research Facility Galway and National University of Ireland Galway Ireland

Institut für Medizinische Informatik Biometrie und Epidemiologie Universitätsklinikum Essen University Duisburg Essen Essen Germany

Institute of Neuroscience Newcastle University Newcastle UK

International Clinical Research Center and Neurology Department St Anne's University Hospital and Masaryk University Brno Czech Republic

Mater University Hospital and University College Dublin Ireland

Mathematics Applications Consortium for Science and Industry and Health Research Institute University of Limerick Ireland

Neurology Unit Stroke Unit Azienda Unità Sanitaria locale IRCCS di Reggio Emilia Italy

RCSI University of Medicine and Health Sciences and Beaumont Hospital Dublin Ireland

School of Medicine University of Limerick Limerick Ireland

Shaare Zedek Medical Center Jerusalem Israel

Stroke Centre and Clinical Trial Unit University of Bern Bern Switzerland

Stroke Unit Department of Neurology Hospitalt Universitari Arnau de Vilanova de Lleida Spain

Universitat de Lleida Biomedical Research Institute of Lleida Spain

University Clinic of Neurology Medical Faculty University Ss Cyril and Methodius Skopje North Macedonia

University Hospitals Leuven Department of Neurology Leuven Belgium

University of Calgary and Foothills Medical Centre Calgary Alberta Canada

VIB Center for Brain and Disease Research Laboratory of Neurobiology Leuven Belgium

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