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NCT04774159PHASE3Recruiting

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

Population Health Research Institute

Start Date

5/6/2021

Completion Date

12/1/2029

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).

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion criteria: 1. Age \> 18 years 2. 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 3. Written or verbal informed consent from the patient 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

Interventions

DRUG

Colchicine 0.5 MG Oral Tablet

DRUG

Colchicine-Placebo

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Conditions

Peripheral Arterial DiseaseAtherosclerosis of ExtremitiesInflammation

Locations

Yale School of Medicine

New Haven, Connecticut 06511

United States

University of Florida - Gainesville

Gainesville, Florida 32611

United States

Tampa General Hospital

Tampa, Florida 33606

United States

University of Chicago Medical Center

Chicago, Illinois 60615

United States

Henry Ford Health System

Detroit, Michigan 48202

United States

Mayo Clinic

Rochester, Minnesota 55905

United States

Rutgers University

Newark, New Jersey 07103

United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina 27599

United States

Duke Regional Hospital

Durham, North Carolina 27704

United States

Duke University Medical Center

Durham, North Carolina 27710

United States

Duke Raleigh Hospital

Raleigh, North Carolina 27609

United States

Ohio State University Wexner Medical Center

Columbus, Ohio 43210

United States

Vanderbilt University Medical Center

Nashville, Tennessee 37232

United States

Southwest Family Medicine

Dallas, Texas 75235

United States

University of Texas Southwestern Medical Center

Dallas, Texas 75390

United States

Texas Tech University Health Sciences

Lubbock, Texas 79430

United States

Sentara Norfolk General Hospital

Norfolk, Virginia 23507

United States

University of Washington Medical Center

Seattle, Washington 98195

United States

Medical College of Wisconsin

Milwaukee, Wisconsin 53226

United States

Sir Charles Gairdner Hospital

Perth, Western Australia

Australia

Universitair Ziekenhuis Leuven

Leuven,

Belgium

Clínica Procárdio

Blumenau, Santa Catarina

Brazil

Sociedade Hospitalar Angelina Caron

Campina Grande do Sul,

Brazil

Hospital Universitário (CoraCentro Pesquisa Clinica)

Canoas,

Brazil

Incore

Dois Vizinhos,

Brazil

Via Medica

Goiânia,

Brazil

Hospital Carlos Fernando Malzoni

Matão,

Brazil

Santa Casa de Misericórdia de Ponta Grossa

Ponta Grossa,

Brazil

Instituto de Cardiologia do Rio Grande do Sul

Porto Alegre,

Brazil

CPTEM - Centro de Pesquisa e Tecnologia Multidisciplinar

São Paulo,

Brazil

Hospital Alemão Oswaldo Cruz

São Paulo,

Brazil

University of Calgary, Peter Lougheed Centre Vascular Clinic

Calgary, Alberta

Canada

University of Alberta, Mazankowski Heart Institute

Edmonton, Alberta

Canada

Hamilton General Hospital

Hamilton, Ontario L8L 2X2

Canada

London Health Sciences Centre

London, Ontario

Canada

Vascular Health Bronte

Oakville, Ontario

Canada

Corcare Cardiovascular Research Inc.

Scarborough Village, Ontario

Canada

Niagara Health System

St. Catharines, Ontario

Canada

Sunnybrook Research Institute

Toronto, Ontario

Canada

Toronto General Hospital

Toronto, Ontario

Canada

CIUSSS du Nord-de-l'île-de-Montréal, Hôpital du Sacré-Cœur-de-Montréal

Montreal, Quebec

Canada

Centre intégré de santé et de services sociaux du Bas-Saint-Laurent

Rimouski, Quebec G5L 3N2

Canada

Cardiolife

Quito, Pichincha

Ecuador

Hospital de Especialidades de las Fuerzas Armadas N 1

Quito, Pichincha

Ecuador

UniCarMeDr.D

Quito, Pichincha

Ecuador

AMCOR

Quito,

Ecuador

Deventer Hospital

Deventer,

Netherlands

Slingeland Hospital

Doetinchem,

Netherlands

University Medical Center Groningen

Groningen,

Netherlands

University Medical Center Utrecht

Utrecht,

Netherlands

University Hospital Basel, Angiology

Basel,

Switzerland

Ospedale Regionale Bellinzona e Valli - Ente Ospedaliero Cantonale

Bellinzona,

Switzerland

HFR Fribourg

Fribourg,

Switzerland

Hôpitaux Universitaires de Genève

Geneva,

Switzerland

University Hospital Zurich, Clinic of Angiology

Zurich,

Switzerland

Royal Sussex County Hospital

Brighton, England

United Kingdom

Southmead Hospital

Bristol, England

United Kingdom

Kent and Canterbury Hospital

Canterbury, England

United Kingdom

Derriford Hospital

Plymouth, England

United Kingdom

Pinderfields Hospital

Wakefield, England

United Kingdom

Royal Infirmary Edinburgh

Edinburgh, Scotland

United Kingdom

Bradford Teaching Hospital

Bradford,

United Kingdom

Cambridge University Hospitals

Cambridge,

United Kingdom

Hull Royal Infirmary

Hull,

United Kingdom

The Leeds Teaching Hospital

Leeds,

United Kingdom

Glenfield Hospital

Leicester,

United Kingdom

St. George's University Hospitals

London,

United Kingdom

St. Thomas Hospital

London,

United Kingdom

Norfolk and Norwich University Hospitals

Norwich,

United Kingdom

University Hospital Southampton

Southampton,

United Kingdom