Colchicine in Belgium in Patients With Coronary Artery Disease
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 2,770
- 试验地点
- 19
- 主要终点
- Time from randomisation to first occurrence of a composite endpoint consisting of: all-cause death, spontaneous (non-procedural) non-fatal myocardial infarction (Type 1, 4B & C), non-fatal stroke, or coronary revascularisation.
研究概览
简要总结
The main aim of this trial is to determine whether there are fewer cardiovascular events when patients with coronary artery disease take a low dose of colchicine of 0.5 mg daily on top of optimal standard treatment after treatment with PCI, compared with placebo in combination with optimal standard treatment. More specifically, we aim to investigate the benefits of a daily low dose of colchicine in patients with coronary artery disease after treatment with PCI, to confirm that a daily low dose of colchicine helps prevent additional incidents in coronary artery disease, and to identify a subgroup of patients with CAD who are at increased risk for cardiovascular events and could benefit most from colchicine.
详细描述
This is a prospective, randomised, double-blind, multicenter, placebo-controlled phase III pragmatic superiority trial comparing colchicine 0.5 mg with placebo administered orally once-daily in up to 2770 participants with CAD treated with PCI. Participants will be randomised in a 1:1 ratio to receive either colchicine 0.5 mg or placebo as an adjunct to standard of care. The trial is event driven with trial closure being performed when the targeted number of 566 primary endpoint events has been reached.
Participants will be seen by the site staff 1 month after randomisation and thereafter every 12 months as per standard of care (SOC) and for IMP dispense and compliance, completing questionnaires and outcome event assessment until end of study. After the first month, a telephone visit will be scheduled every 6 months in between two standard of care on-site visits.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
盲法说明
Double-blind
入排标准
- 年龄范围
- 45 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥45 years.
- •Coronary artery disease treated with PCI and optimal medical therapy, with at least one additional risk factor (based on SMART):
- •Diabetes mellitus, on treatment or new diagnosis with HbA1c ≥6.5%
- •Current smoking
- •Treated hypertension or lood pressure systolic ≥ 4 mmHg or diastolic ≥ mmHg
- •Total cholesterol >240 mg/dl untreated, or treated LDL >70 mg/dl
- •HDL <40 mg/dl
- •hsCRP >2 mg/L AND chronic coronary syndrome (CCS)
- •eGFR <60 ml/min (MDRD)
- •history of vascular disease:
- •CAD (PCI prior to index, CABG, MI)
- •stroke (ischemic or hemorrhagic)
- •carotid artery revascularisation
- •PAD (revascularisation, ABI <0.85 at rest, amputation due to atherosclerotic disease)
- •AAA (repair, distal aortic anteroposterior diameter >3.0cm)
- •Able to be enrolled/randomized between 2 hour and 5 days post PCI.
- •Written informed consent.
排除标准
- •Women who are pregnant, breastfeeding, or of childbearing potential who are not using an effective method of contraception. Or women who intend to donate oocytes.
- •Men who plan to father children during the study period or who are unwilling to use effective forms of contraception. Or men who intend to donate sperm.
- •Any contraindication or known intolerance to colchicine.
- •Chronic use of -or need for- colchicine.
- •Auto-immune disease or other condition requiring current or planned chronic systemic steroids, immunosuppressant or biologic drug targeting the immune system (for example, TNF blockers, anakinra, rituximab, abatacept, tocilizumab etc.).
- •Creatinine clearance <30 mL/min/1.73 m
- •Cirrhosis Child-Pugh stadium B and C, or acute severe liver disease
- •Neuromuscular disease or non-transient CK levels > 5 x ULN (unless due to MI).
- •History of cancer or lymphoproliferative disease within the last 3 years, other than successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma, or localized cervix carcinoma in situ.
- •Current or planned use of any strong inhibitor of CYP3A4 or p-glycoprotein: macrolide antibiotics (clarithromycin, telithromycin), azole antifungal agents (ketoconazole, voriconazole, fluconazole, itraconazole), cyclosporine, HIV medication (ritonavir, lopinavir, tipranavir, atazanavir, darunavir, indinavir, saquinavir).
- •Chronic diarrhea, or inflammatory owel disease (Crohn's disease or ulcerative colitis).
- •Drug or alcohol abuse.
- •Planned cardiovascular intervention known on the day of screening.
- •Currently enrolled in another investigational trial.
- •Considered to be an unsuitable candidate by the investigator.
研究组 & 干预措施
Colchicine
Colchicine 0.5 mg oral once daily, in addition to SOC
干预措施: Colchicine 0.5 MG Oral Tablet (Drug)
Placebo
Placebo oral once daily, in addition to SOC
干预措施: Placebo (Drug)
结局指标
主要结局
Time from randomisation to first occurrence of a composite endpoint consisting of: all-cause death, spontaneous (non-procedural) non-fatal myocardial infarction (Type 1, 4B & C), non-fatal stroke, or coronary revascularisation.
时间窗: 44 months
次要结局
- Change from randomisation to year 1 and to end of study of participants reported outcomes (based on ICHOM Standard Set for CAD): Depression.(44 months)
- Time from randomisation to first occurrence of a composite of specific cardiovascular endpoints(44 months)
- Time from randomisation to first occurrence of a composite of hard endpoints consisting of: all-cause death, spontaneous (non-procedural) non-fatal myocardial infarction (Type 1, 4B & C), non-fatal stroke(44 months)
- Time from randomisation to first occurrence of breakdown components of primary endpoint and atherosclerosis-related diseases(44 months)
- Time from randomisation to occurrence of first as well as recurrent endpoints consisting of: all-cause death, spontaneous (non-procedural) non-fatal myocardial infarction (Type 1, 4B & C), non-fatal stroke, or coronary revascularisation.(44 months)
- Change from randomisation to year 1 and to end of study of participants reported outcomes (based on ICHOM Standard Set for CAD): Angina Frequency scale(44 months)
- Change from randomisation to year 1 and to end of study of participants reported outcomes (based on ICHOM Standard Set for CAD): Dyspnea(44 months)
- Change from randomisation to year 1 and to end of study of participants reported outcomes (based on ICHOM Standard Set for CAD): Health-related quality of life.(44 months)
研究者
Ian Buysschaert, MD PhD
MD, PhD, Chief investigator
AZ Sint-Jan AV