Low Dose ColchicinE in pAtients With Peripheral Artery DiseasE to Address Residual Vascular Risk

Phase 3

Recruiting

• Conditions: Peripheral Arterial Disease; Atherosclerosis of Extremities; Inflammation
• Interventions: Drug: Colchicine 0.5 MG Oral Tablet; Drug: Colchicine-Placebo

• Registration Number: NCT04774159
• Lead Sponsor: Population Health Research Institute

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 Timeline

• Study First Submitted: 2021-02-21
• Study First Submitted QC: 2021-02-24
• Study First Posted: 2021-03-01
• Study Start: 2021-05-06
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-14
• Last Update Posted: 2024-06-18
• Primary Completion: 2029-04
• Study Completion: 2029-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 6150

Inclusion Criteria

Not provided

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Exclusion Criteria

1. Contraindication to colchicine
2. Long term requirement for colchicine for another clinical indication
3. Active diarrhoea
4. eGFR < 30 mL/min/1.73 m2
5. Cirrhosis or severe chronic liver disease
6. Woman who is pregnant, or breast-feeding or of child-bearing potential not protected by reliable contraception or is planning conception during the study
7. Current or planned long term use of cyclosporine, verapamil, HIV protease inhibitors, azole antifungals, or macrolide antibiotics (with the exception of azithromycin)
8. Patients who are deemed unlikely to return for follow-up
9. Patients with life expectancy < 1 year

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Colchicine	Colchicine 0.5 MG Oral Tablet	Colchicine 0.5mg daily for the duration of the trial
Colchicine-Placebo	Colchicine-Placebo	Colchicine-Placebo daily

Primary Outcome Measures

Name	Time	Method
Major adverse cardiovascular and limb events (MACE or MALE)	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 Outcome Measures

Name	Time	Method
Any thrombosis or thromboembolism (arterial and venous)	3-5 years	All arterial and venous thromboembolism
Extended MALE	3-5 years	This composite outcome includes major adverse limb events (MALE) as well as revascularization for new or worsening claudication of new stenosis or occlusion detected on screening after a previous intervention
Cardiovascular death	3-5 years	Death will be classified as cardiovascular or non-cardiovascular. All deaths with a clear cardiovascular or unknown cause will be classified as cardiovascular. Only deaths due to a documented non-cardiovascular cause (e.g., cancer) will be classified as non-cardiovascular.
Myocardial infarction	3-5 years	Acute myocardial infarction (AMI) requires evidence of acute myocardial injury with clinical evidence of acute myocardial ischemia
Stroke	3-5 years	Stroke requires the presence of acute focal or global\* neurological dysfunction caused by brain or retinal vascular injury due to primary hemorrhage or infarction.
Overall mortality	3-5 years	All cause (CV and non CV) deaths
Fontaine Stage	3-5 years	This classification system grades the clinical presentation of patients to four stages of PAD
Hospitalization	3-5 years	Admission to hospital for any reason
Acute or chronic limb-threatening ischemia	3-5 years	This is defined as an episode severe limb ischemia that requires an acute vascular intervention (i.e., pharmacological reperfusion, endovascular or surgical revascularization) or a major vascular amputation (defined as at ankle or transtibial amputation or higher).
All revascularization coronary or cerebrovascular or lower limb or other peripheral revascularization)	3-5 years	Defined as coronary or cerebrovascular or lower limb or other peripheral revascularization
Total vascular amputation	3-5 years	All vascular amputations
Standard Assessment of Global Everyday Activities (SAGEA)	3-5 years	The Standard Assessment of Global Everyday Activities (SAGEA) is a 15 item tool to assess activities of daily living including higher executive function used in social situations, everyday activities and basic activities of daily living. Scores range from 0 to 24 with higher scores indicating poorer function.It is a 15 items questionnaire and the scores will range from 0, describing a very independent participant over a broad spectrum of activities, to 48 describing a very dependent participant
Vascular Quality of Life Questionnaire-6 (VascQOL-6)	3-5 years	Six item vascular quality of life instrument: The total score is achieved by summarizing the score on each question, resulting in a score between 6 and 24. Higher value indicates better health status.
EuroQol 5 Dimension 5 Level (EQ-5D-5L)	3-5 years	A survey that measures quality of life across 5 domains. Each domain is scored on a 5-level severity ranking that ranges from "no problems" to "extreme problems".

Trial Locations

Locations (4)

Hamilton General Hospital; 🇨🇦 Hamilton, Ontario, Canada

London Health Sciences Centre; 🇨🇦 London, Ontario, Canada

Corcare Cardiovascular Research Inc.; 🇨🇦 Scarborough, Ontario, Canada

Sunnybrook Research Institute; 🇨🇦 Toronto, Ontario, Canada