Colchicine for prevention of vascular inflammation in Non-CardioEmbolic stroke (CONVINCE) - study protocol for a randomised controlled trial.
Ischaemic stroke
colchicine
inflammation
randomised controlled trial
Journal
European stroke journal
ISSN: 2396-9881
Titre abrégé: Eur Stroke J
Pays: England
ID NLM: 101688446
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
received:
04
08
2020
accepted:
11
10
2020
entrez:
20
8
2021
pubmed:
21
8
2021
medline:
21
8
2021
Statut:
ppublish
Résumé
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. 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. The primary outcome is time to first recurrent ischaemic stroke, myocardial infarction, cardiac arrest, or hospitalisation with unstable angina (non-fatal or fatal). CONVINCE will provide high-quality randomised data on the efficacy and safety of anti-inflammatory therapy with colchicine for secondary prevention after stroke. First-patient first-visit was December 2016. Recruitment to complete in 2021, follow-up to complete in 2023.
Sections du résumé
BACKGROUND
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
METHODS
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
RESULTS
The primary outcome is time to first recurrent ischaemic stroke, myocardial infarction, cardiac arrest, or hospitalisation with unstable angina (non-fatal or fatal).
SUMMARY
CONCLUSIONS
CONVINCE will provide high-quality randomised data on the efficacy and safety of anti-inflammatory therapy with colchicine for secondary prevention after stroke.
SCHEDULE
UNASSIGNED
First-patient first-visit was December 2016. Recruitment to complete in 2021, follow-up to complete in 2023.
Identifiants
pubmed: 34414298
doi: 10.1177/2396987320972566
pii: 10.1177_2396987320972566
pmc: PMC8370082
doi:
Types de publication
Journal Article
Langues
eng
Pagination
222-228Informations de copyright
© European Stroke Organisation 2020.
Déclaration de conflit d'intérêts
Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: All authors have collaborated on successful funding applications from HRB Ireland for CONVINCE. RL has received a grant from FWO Belgium and CW from DFG Germany for CONVINCE (non-overlapping awards). PK has received funding from the Irish Heart Foundation which supports CONVINCE.
Références
Neurology. 2004 Feb 24;62(4):569-73
pubmed: 14981172
Stroke. 2019 Jul;50(7):1766-1773
pubmed: 31167623
N Engl J Med. 2019 Dec 26;381(26):2497-2505
pubmed: 31733140
Stroke. 2009 Apr;40(4):1405-9
pubmed: 19228842
Stroke. 2019 Dec;50(12):3393-3399
pubmed: 31637970
Circulation. 2012 Oct 16;126(16):2020-35
pubmed: 22923432
Cochrane Database Syst Rev. 2016 Jan 27;(1):CD011047
pubmed: 26816301
Lancet Neurol. 2014 Apr;13(4):429-38
pubmed: 24646875
N Engl J Med. 2014 Jun 26;370(26):2478-86
pubmed: 24963567
N Engl J Med. 2017 May 4;376(18):1713-1722
pubmed: 28304224
Nature. 2011 May 19;473(7347):317-25
pubmed: 21593864
Ann Neurol. 2010 Jul;68(1):9-17
pubmed: 20582954
J Am Coll Cardiol. 2013 Jan 29;61(4):404-410
pubmed: 23265346
J Neurol Neurosurg Psychiatry. 2018 Feb;89(2):211-218
pubmed: 28935831
Stroke. 2016 Mar;47(3):659-67
pubmed: 26888535
Am J Ther. 2015 Sep-Oct;22(5):e151-7
pubmed: 24100258
Lancet. 2018 Jan 27;391(10118):319-328
pubmed: 29146124
Eur J Neurol. 2020 Jun;27(6):1035-1038
pubmed: 32134555
Lancet Neurol. 2015 Sep;14(9):903-913
pubmed: 26227434
Eur Heart J. 2018 Oct 7;39(38):3499-3507
pubmed: 30165610
Stroke. 2010 Aug;41(8):1579-86
pubmed: 20595675
Cochrane Database Syst Rev. 2020 May 11;5:CD012825
pubmed: 32392374
N Engl J Med. 2017 Sep 21;377(12):1119-1131
pubmed: 28845751
Eur J Intern Med. 2010 Dec;21(6):503-8
pubmed: 21111934
N Engl J Med. 2014 Jun 26;370(26):2467-77
pubmed: 24963566
Lancet Neurol. 2019 May;18(5):439-458
pubmed: 30871944
Circulation. 2019 Jan 8;139(2):256-268
pubmed: 30586705
J Am Heart Assoc. 2018 Jan 18;7(2):
pubmed: 29348322
N Engl J Med. 2018 Jun 07;378(23):2191-2201
pubmed: 29766772
Circ Genom Precis Med. 2020 Jun;13(3):e002872
pubmed: 32397738