Low Dose ColchicinE in pAtients With Peripheral Artery DiseasE to Address Residual Vascular Risk: A Randomized Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 6,150
- 试验地点
- 70
- 主要终点
- Major adverse cardiovascular and limb events (MACE or MALE)
研究概览
简要总结
The Low dose ColchicinE in pAtients with peripheral Artery DiseasE to address residual vascular Risk (LEADER-PAD) trial will evaluate if anti-inflammatory therapy with colchicine will reduce vascular events in patients with symptomatic peripheral artery disease.
详细描述
The LEADER-PAD trial is a randomized, double blind, multicenter trial with an active run-in period, comparing low dose colchicine 0.5 mg daily with placebo in patients with symptomatic peripheral artery disease (PAD) to prevent vascular events (myocardial infarction, stroke, cardiovascular deaths, acute limb ischemia and vascular amputation). The sample size for the trial is 6,150 participants. The primary outcome for the trial is major adverse cardiovascular and limb events (MACE and MALE). This composite outcome consists of cardiovascular death, myocardial infarction, stroke and severe limb ischemia that requires a vascular intervention (i.e., pharmacological reperfusion, endovascular or surgical revascularization) or a major vascular amputation (defined as ankle/transtibial amputation or higher).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double blind and use of similarly active and placebo tablets.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 years
- •Symptomatic atherosclerotic LE PAD fulfilling at least one of the following:
- •a. Intermittent claudication with ankle/arm blood pressure ratio* (ABI ≤ 0.90) or artery stenosis ≥ 50% plus one of i. >1 vascular bed affected by atherosclerosis ii. Diabetes iii. Heart failure iv. Chronic kidney disease (eGFR < 60 mL/min/1.73 m2)
- •b. Rest pain (mostly in foot) OR necrosis of limb OR gangrene of limb (corresponding to either Fontaine stages 3 or 4 OR Rutherford Classification categories 4 to 6). All must have an ankle/arm blood pressure ratio* (ABI ≤ 0.90) OR artery stenosis ≥ 50%.
- •* In cases of incompressible ankle arteries, the presence of toe pressure ≤ 60 mm Hg or toe-brachial index ≤ 0.70 is acceptable
- •c. Revascularization defined as limb bypass surgery or endovascular revascularization procedures (irrespective of the specific device used), including percutaneous transluminal angioplasty/stent of iliac or infra-inguinal arteries or extra-anatomical bypass surgery
- •d. Leg or foot amputation for arterial vascular indications
- •Written or verbal informed consent from the patient
排除标准
- •Contraindication to colchicine
- •Long term requirement for colchicine for another clinical indication
- •Active diarrhoea
- •eGFR < 30 mL/min/1.73 m2
- •Cirrhosis or severe chronic liver disease
- •Woman who is pregnant, or breast-feeding or of child-bearing potential not protected by reliable contraception or is planning conception during the study
- •Current or planned long term use of cyclosporine, verapamil, HIV protease inhibitors, azole antifungals, or macrolide antibiotics (with the exception of azithromycin)
- •Patients who are deemed unlikely to return for follow-up
- •Patients with life expectancy < 1 year
研究组 & 干预措施
Colchicine-Placebo
Colchicine-Placebo daily
干预措施: Colchicine-Placebo (Drug)
Colchicine
Colchicine 0.5mg daily for the duration of the trial
干预措施: Colchicine 0.5 MG Oral Tablet (Drug)
结局指标
主要结局
Major adverse cardiovascular and limb events (MACE or MALE)
时间窗: 3-5 years
This composite outcome consists of cardiovascular deaths, myocardial infarction, stroke, and severe limb ischemia that requires a vascular intervention (i.e., pharmacological reperfusion, endovascular or surgical revascularization) or a major vascular amputation (defined as ankle/transtibial amputation or higher)
次要结局
- Extended MALE(3-5 years)
- Any thrombosis or thromboembolism (arterial and venous)(3-5 years)
- Cardiovascular death(3-5 years)
- Myocardial infarction(3-5 years)
- Stroke(3-5 years)
- Overall mortality(3-5 years)
- Fontaine Stage(3-5 years)
- Hospitalization(3-5 years)
- Acute or chronic limb-threatening ischemia(3-5 years)
- Total vascular amputation(3-5 years)
- Standard Assessment of Global Everyday Activities (SAGEA)(3-5 years)
- Vascular Quality of Life Questionnaire-6 (VascQOL-6)(3-5 years)
- EuroQol 5 Dimension 5 Level (EQ-5D-5L)(3-5 years)
- All revascularization (coronary or cerebrovascular or lower limb or other peripheral revascularization)(3-5 years)
研究者
Noel Chan
Principal Investigator
Population Health Research Institute