CONVINCE - (COlchicine for PreventioN of Vascular Inflammation in Non- CardioEmbolic Stroke) - a Randomised Clinical Trial of Low-dose Colchicine for Secondary Prevention After Stroke
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 3,154
- 试验地点
- 144
- 主要终点
- on-fatal Major Cardiac event
研究概览
简要总结
This study evaluates the use of Colchicine in adults over 40 years of age who have suffered an ischaemic stroke or transient ischaemic attack NOT caused by cardiac embolism or other defined causes. Patients will be randomised to 0.5 mg/day of Colchicine plus usual care, or to usual care alone.
To investigate the efficacy of low dose colchicine (0.5mg/day) plus usual care (defined as antiplatelet, lipid-lowering, antihypertensive treatment, and appropriate lifestyle advice) compared with usual care alone to prevent non-fatal recurrent ischaemic stroke, myocardial infarction, cardiac arrest, hospitalization for unstable angina and vascular death after ischaemic stroke or transient ischaemic attack (TIA) not caused by cardiac embolism or other defined causes unrelated to atherosclerosis
详细描述
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, noncardioembolic 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 prespecified subgroups, and impact on direct health care costs, adjusted for quality-adjusted life years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent consistent with ICH-GCP guidelines and local laws signed prior to all trial-related procedures.
- •Age 40 years or greater
- •ischaemic stroke without major disability (modified Rankin score 3 or less)
- •or high-risk TIA
- •Qualifying stroke/TIA probably caused by large artery stenosis, small artery occlusion (lacunar stroke), or cryptogenic embolism, with cardiac embolism or other defined stroke mechanism deemed unlikely in the opinion of the treating physician.
- •GFRgreater than or equal to 50 ml/min.
- •In the opinion of the treating physician, patient is medically-stable, capable of participating in a randomised trial, and willing to attend follow-up.
排除标准
- •Cardio-embolic stroke/TIA, probably caused by identified atrial fibrillation (permanent or paroxysmal), in the opinion of the treating physician.
- •Cardio-embolic stroke/TIA probably caused by other identified cardiac source (intra-cardiac thrombus, endocarditis, metallic heart valve, low ejection fraction <30%), in the opinion of the treating physician.
- •Stroke/TIA caused by dissection, endocarditis, paradoxical embolism, drug use, venous thrombosis, within 48 hours aftercarotid or cardiac surgery, hypercoagulability states, migraine, or inherited cerebrovascular disorders (eg. Fabry's disease, CADASIL), in the opinion of the treating physician.
- •History of myopathy or myalgias with raised creatine kinase (CK) on statin therapy.
- •Blood dyscrasia defined as anaemia (haemoglobin <10g/dL), thrombocytopenia (platelet count <150 x109/L) or leucopenia (white cell count <4 x109/L) at randomisation.
- •Impaired hepatic function (transaminases greater than twice upper limit of normal) at randomisation.
- •Concurrent treatment with moderate or strong CYP3A4 inhibitors (clarithromycin, erythromycin, telithromycin, other macrolide antibiotics, ketoconazole, itraconazole, voriconazole, ritonavir, atazanavir, indinavir, other HIV protease inhibitors, verapamil, diltiazem, quinidine, digoxin, disulfiram) or P-gp inhibitors (cyclosporine) at randomisation.
- •Symptomatic peripheral neuropathy and pre-existing progressive neuromuscular disease
- •Inflammatory bowel disease (Crohn's or ulcerative colitis) or chronic diarrhoea.
- •Dementia, sufficient to impair independence in basic activities of daily living.
- •Active malignancy, known hepatitis B or C, or HIV infection prior to qualifying stroke/TIA.
- •Impaired swallow preventing oral administration of study medication.
- •History of poor medication compliance.
- •Unlikely to comply with study procedures and follow-up visits due to severe or fatal comorbid illness or other factor (eg. inability to travel for follow up visits), in opinion of randomising physician.
- •Pregnancy, breast-feeding, or pre-menopausal women
- •Patient concurrently participating in another clinical trial with an investigational drug or device, or use of investigational drug within 30 days or 5 half-lives before the Screening visit (whichever is longer)
- •Known allergy or sensitivity to colchicine.
研究组 & 干预措施
Colchicine treatment
Colchicine 0.5mg/day plus usual care for 60 months
干预措施: Colchicine (Drug)
结局指标
主要结局
on-fatal Major Cardiac event
时间窗: any time within 60 months
Non-fatal hospitalization for unstable angina, myocardial infarction, cardiac arrest
Recurrence of non-fatal ischemic stroke
时间窗: any time within 60 month
Any recurrence of non-fatal ischemic stroke
Vascular death
时间窗: 60 months
Fatal ischemic stroke, myocardial infarction, cardiac arrest
次要结局
未报告次要终点