Colchicine for prevention of vascular inflammation in Non-CardioEmbolic stroke (CONVINCE) – study protocol for a randomised controlled trial

Peter Kelly*, Christian Weimar, Robin Lemmens, Sean Murphy, Francisco Purroy, Anita Arsovska, Natan M. Bornstein, Anna Czlonkowska, Urs Fischer, Ana Catarina Fonseca, John Forbes, Michael D. Hill, Dalius Jatuzis, Janika Kõrv, Christina Kruuse, Robert Mikulik, Paul J Nederkoorn, Martin O’Donnell, Peter Sandercock, David TanneGeorgios Tsivgoulis, Cathal Walsh, David Williams, Marialuisa Zedde, Christopher I. Price

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)222-228
Number of pages7
JournalEuropean Stroke Journal
Volume6
Issue number2
DOIs
StatePublished - Jun 2021
Externally publishedYes

Funding

FundersFunder number
Health Research BoardDIFA-2018–006
Health Research Board
Irish Heart Foundation
Deutsche Forschungsgemeinschaft661984, WE 2858/5 -1
Deutsche Forschungsgemeinschaft
Fonds Wetenschappelijk OnderzoekT001719N
Fonds Wetenschappelijk Onderzoek

    Keywords

    • Ischaemic stroke
    • colchicine
    • inflammation
    • randomised controlled trial

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