Inflammation is a key pathophysiological contributor to unstable atherosclerotic plaque and thrombo-embolic events, stroke, myocardial infarction, and vascular death. Internationally, clinical trials are targeting atherosclerotic inflammation in patients with coronary disease using methotrexate, colchicine, and canukinumab.
Aims:The primary aim is to compare low-dose colchicine (0.5mg/day) plus usual care, to usual care alone, to prevent non-fatal recurrent ischaemic stroke and coronary events and vascular death after non-severe, non-cardioembolic TIA/stroke. Secondary objectives will investigate safety of low-dose colchicine, and efficacy for each component of the primary outcome, fatal and non-fatal events, disabling and non-disabling stroke, effect modification by pre-specified subgroups, and impact on direct health care costs, adjusted for quality-adjusted life years.
Methods: CONVINCE is a Prospective, Randomised Open-label, Blinded Endpoint assessment (PROBE) controlled Phase 3 clinical trial. Intervention is colchicine 0.5mg/day, and usual care is defined as antiplatelet, lipid-lowering, antihypertensive treatment, and appropriate lifestyle advice.
Main inclusion criteria are:1.Written informed consent2.Age 40 years or greater3.Non-severe ischaemic stroke (modified Rankin score 3 or less) or high-risk TIA (ABCD2 3 with motor/speech symptoms, positive DWI or cranio-cervical artery stenosis) of onset within 72 hours-28 days of randomization, with exclusion of primary intracranial haemorrhage by CT/MRI4.Qualifying stroke/TIA probably caused by large artery stenosis, lacunar disease, or cryptogenic embolism5.GFR 50 ml/min.
Patients with stroke/TIA caused by cardio-embolism or other defined cause (eg. dissection), contra-indication to colchicine treatment, or incapacity for participation in a clinical trial will be excluded.
The anticipated median duration of follow up will be 36 months. The Primary efficacy analysis will be by intention to treat, comparing time to the composite primary outcome event in colchicine-treated and usual-care groups via a log-rank test. Pre-specified secondary analyses will be performed.
CONVINCE is funded for recruitment in Ireland, UK, Spain, Greece, and Norway, but currently relies on achieving approximately 60% recruitment in the UK, supported by the UK Clinical Research Network infrastructure. This application is to expand the trial into Northern Europe (Belgium, Netherlands, Estonia, Lithuania, Germany), to broaden the recruitment base, reducing the dependence on UK recruitment to 30-40% at most.
