Low Dose ColchicinE in pAtients With Peripheral Artery DiseasE to Address Residual Vascular Risk: A Randomized Trial
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Enrollment
- 6,150
- Locations
- 70
- Primary Endpoint
- Major adverse cardiovascular and limb events (MACE or MALE)
Study Overview
Brief Summary
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.
Detailed Description
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Double blind and use of similarly active and placebo tablets.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Colchicine
Colchicine 0.5mg daily for the duration of the trial
Intervention: Colchicine 0.5 MG Oral Tablet (Drug)
Colchicine-Placebo
Colchicine-Placebo daily
Intervention: Colchicine-Placebo (Drug)
Outcomes
Primary Outcomes
Major adverse cardiovascular and limb events (MACE or MALE)
Time Frame: 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)
Secondary Outcomes
- Any thrombosis or thromboembolism (arterial and venous)(3-5 years)
- Extended MALE(3-5 years)
- Cardiovascular death(3-5 years)
- Myocardial infarction(3-5 years)
- Overall mortality(3-5 years)
- Stroke(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)
Investigators
Noel Chan
Principal Investigator
Population Health Research Institute