TY - JOUR
T1 - Colchicine for prevention of vascular inflammation in Non-CardioEmbolic stroke (CONVINCE) – study protocol for a randomised controlled trial
AU - Kelly, Peter
AU - Weimar, Christian
AU - Lemmens, Robin
AU - Murphy, Sean
AU - Purroy, Francisco
AU - Arsovska, Anita
AU - Bornstein, Natan M.
AU - Czlonkowska, Anna
AU - Fischer, Urs
AU - Fonseca, Ana Catarina
AU - Forbes, John
AU - Hill, Michael D.
AU - Jatuzis, Dalius
AU - Kõrv, Janika
AU - Kruuse, Christina
AU - Mikulik, Robert
AU - J Nederkoorn, Paul
AU - O’Donnell, Martin
AU - Sandercock, Peter
AU - Tanne, David
AU - Tsivgoulis, Georgios
AU - Walsh, Cathal
AU - Williams, David
AU - Zedde, Marialuisa
AU - Price, Christopher I.
N1 - Publisher Copyright:
© European Stroke Organisation 2020.
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
KW - Ischaemic stroke
KW - colchicine
KW - inflammation
KW - randomised controlled trial
UR - http://www.scopus.com/inward/record.url?scp=85108239628&partnerID=8YFLogxK
U2 - 10.1177/2396987320972566
DO - 10.1177/2396987320972566
M3 - Article
C2 - 34414298
AN - SCOPUS:85108239628
SN - 2396-9873
VL - 6
SP - 222
EP - 228
JO - European Stroke Journal
JF - European Stroke Journal
IS - 2
ER -
