Low Dose ColchicinE in pAtients With Peripheral Artery DiseasE to Address Residual Vascular Risk (LEADER-PAD)

Low Dose ColchicinE in pAtients With Peripheral Artery DiseasE to Address Residual Vascular Risk: A Randomized Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Inflammation; Peripheral Arterial Disease; Atherosclerosis of Extremities
• Intervention / Treatment: Drug: Colchicine 0.5 MG Oral Tablet; Drug: Colchicine-Placebo

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 Type: Interventional
• Enrollment (Estimated): 6150
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Noel C Chan, MD; Phone Number: 40727 905-521-2100; Email: Noel.Chan@TAARI.CA
• Study Contact Backup: Name: Jessica Tyrwhitt; Email: leaderpad@phri.ca

Study Locations

• Australia
  • Western Australia
    • Perth, Western Australia, Australia
      • Recruiting
      • Sir Charles Gairdner Hospital
      • Contact: Louise Ferguson
      • Principal Investigator: Shirley Jansen, MBChB
• Belgium
  • Leuven, Belgium
    • Recruiting
    • Universitair Ziekenhuis Leuven
    • Principal Investigator: Thomas Vanassche, MD
    • Contact: Kristine Vanheule
• Brazil
  • Campina Grande do Sul, Brazil
    • Recruiting
    • Sociedade Hospitalar Angelina Caron
    • Principal Investigator: Dalton Precoma, MD
    • Contact: Eliane Sehnem
  • Canoas, Brazil
    • Recruiting
    • Hospital Universitário (CoraCentro Pesquisa Clinica)
    • Contact: Andressa Baumbach
    • Principal Investigator: Euler Manenti, MD
  • Dois Vizinhos, Brazil
    • Recruiting
    • Incore
    • Contact: Bruna Dotto
    • Principal Investigator: Leonardo Precoma, MD
  • Goiânia, Brazil
    • Recruiting
    • Via Medica
    • Contact: Lohana Queiroz
    • Principal Investigator: Weimar Souza, MD
  • Matão, Brazil
    • Recruiting
    • Hospital Carlos Fernando Malzoni
    • Principal Investigator: Cesar Minelli, MD
    • Contact: Lucileni Borin
  • Ponta Grossa, Brazil
    • Recruiting
    • Santa Casa de Misericórdia de Ponta Grossa
    • Contact: Milena Goulart
    • Principal Investigator: Mario Costa, MD
  • Porto Alegre, Brazil
    • Recruiting
    • Instituto de Cardiologia do Rio Grande do Sul
    • Contact: Bruna Machado
    • Principal Investigator: Oscar Dutra, MD
  • São Paulo, Brazil
    • Recruiting
    • Hospital Alemao Oswaldo Cruz
    • Principal Investigator: Kenji Nishinari, MD
    • Contact: Nathalia Lys Trindade Santos
  • São Paulo, Brazil
    • Recruiting
    • CPTEM - Centro de Pesquisa e Tecnologia Multidisciplinar
    • Principal Investigator: Fabio Rossi, MD
    • Contact: Valeria Almeida
  • Santa Catarina
    • Blumenau, Santa Catarina, Brazil
      • Recruiting
      • Clínica Procárdio
      • Contact: Elizabeth Zimmermann
      • Principal Investigator: Sergio Zimmermann, MD
• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Recruiting
      • University of Calgary, Peter Lougheed Centre Vascular Clinic
      • Contact: Emi Sanders
      • Principal Investigator: Caleb Zavitz, MD
    • Edmonton, Alberta, Canada
      • Recruiting
      • University of Alberta, Mazankowski Heart Institute
      • Principal Investigator: Robert Welsh, MD
      • Contact: Suzanne Welsh
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Recruiting
      • Hamilton General Hospital
      • Principal Investigator: Noel Chan, MD
      • Contact: Michelle Zondag; Phone Number: 40430 905-527-4322
    • London, Ontario, Canada
      • Recruiting
      • London Health Sciences Centre
      • Principal Investigator: Adam Power, MD
      • Contact: Teresa Novick
    • Oakville, Ontario, Canada
      • Recruiting
      • Vascular Health Bronte
      • Contact: Christina Machon
      • Principal Investigator: Beverley Chan, MD
    • Scarborough Village, Ontario, Canada
      • Recruiting
      • Corcare Cardiovascular Research Inc.
      • Contact: Bev Bozek
      • Principal Investigator: Alan Joseph Ricci, MD
    • St. Catharines, Ontario, Canada
      • Recruiting
      • Niagara Health System
      • Principal Investigator: Blair Leonard, MD
      • Contact: Kelsey Charlebois
    • Toronto, Ontario, Canada
      • Recruiting
      • Sunnybrook Research Institute
      • Contact: Leslie Summers deLuca
      • Principal Investigator: Ahmed Kayssi, MD
    • Toronto, Ontario, Canada
      • Recruiting
      • Toronto General Hospital
      • Contact: Naomi Eisenberg
      • Principal Investigator: Graham Roche-Nagle, MD
  • Quebec
    • Montreal, Quebec, Canada
      • Recruiting
      • CIUSSS du Nord-de-l'île-de-Montréal, Hôpital du Sacré-Cœur-de-Montréal
      • Contact: Guylaine Marcotte
      • Principal Investigator: William Fortin, MD
    • Rimouski, Quebec, Canada, G5L 3N2
      • Recruiting
      • Centre Intégré de Santé et de Services Sociaux du Bas-Saint-Laurent
      • Contact: Isabelle Gagnon
      • Principal Investigator: François Caron, MD
• Ecuador
  • Quito, Ecuador
    • Recruiting
    • AMCOR
    • Contact: Ivan Zuleta
    • Principal Investigator: Ivan Zuleta, MD
  • Pichincha
    • Quito, Pichincha, Ecuador
      • Recruiting
      • Cardiolife
      • Contact: Mayra Sanchez Velez
      • Principal Investigator: Mayra Sanchez Velez, MD
    • Quito, Pichincha, Ecuador
      • Recruiting
      • Hospital de Especialidades de las Fuerzas Armadas N 1
      • Contact: Jose Patricio Lopez Villalba
      • Principal Investigator: Jose Patricio Lopez Villalba, MD
    • Quito, Pichincha, Ecuador
      • Recruiting
      • UniCarMeDr.D
      • Contact: Yan Carlos Duarte Vera
      • Principal Investigator: Yan Carlos Duarte Vera, MD
• Netherlands
  • Deventer, Netherlands
    • Recruiting
    • Deventer Hospital
    • Contact: R.B.M. van Tongeren
    • Principal Investigator: Bob van Tongeren, MD
  • Doetinchem, Netherlands
    • Recruiting
    • Slingeland Hospital
    • Contact: D.M. Scharn
    • Principal Investigator: Dirk Scharn, MD
  • Groningen, Netherlands
    • Recruiting
    • University Medical Center Groningen
    • Contact: B.R. Saleem
    • Principal Investigator: Ben Saleem, MD
  • Utrecht, Netherlands
    • Recruiting
    • University Medical Center Utrecht
    • Contact: Martin Teraa
    • Principal Investigator: Martin Teraa, MD
• Switzerland
  • Basel, Switzerland
    • Recruiting
    • University Hospital Basel, Angiology
    • Principal Investigator: Daniel Staub, MD
    • Contact: Ines Meurer
  • Bellinzona, Switzerland
    • Recruiting
    • Ospedale Regionale Bellinzona e Valli - Ente Ospedaliero Cantonale
    • Contact: Rosario del Giorno
    • Principal Investigator: Rosario del Giorno, MD
  • Fribourg, Switzerland
    • Recruiting
    • HFR Fribourg
    • Contact: Sandrine Foucras
    • Principal Investigator: Rolf Engelberger, MD
  • Geneva, Switzerland
    • Recruiting
    • Hôpitaux Universitaires de Genève
    • Contact: Nadège Koffi
    • Principal Investigator: Marc Righini, MD
  • Zurich, Switzerland
    • Recruiting
    • University Hospital Zurich, Clinic of Angiology
    • Contact: Rebecca Spescha
    • Contact: Eliane Probst
    • Principal Investigator: Stefano Barco, MD
• United Kingdom
  • Bradford, United Kingdom
    • Recruiting
    • Bradford Teaching Hospital
    • Contact: Kevin Mercer
    • Principal Investigator: Kevin Mercer, MD
  • Cambridge, United Kingdom
    • Recruiting
    • Cambridge University Hospitals
    • Contact: Mohammed Chowdhury
    • Principal Investigator: Mohammed Chowdhury, MBChB
  • Hull, United Kingdom
    • Recruiting
    • Hull Royal Infirmary
    • Contact: Ian Chetter
    • Principal Investigator: Ian Chetter, MD
  • Leeds, United Kingdom
    • Recruiting
    • The Leeds Teaching Hospital
    • Contact: Marc Bailey
    • Principal Investigator: Marc Bailey, MD
  • Leicester, United Kingdom
    • Recruiting
    • Glenfield Hospital
    • Contact: Badri Vijaynagar
    • Principal Investigator: Badri Vijaynagar, MD
  • London, United Kingdom
    • Recruiting
    • St. Thomas Hospital
    • Contact: Bijan Modarai
    • Principal Investigator: Bijan Modarai, MBBS
  • London, United Kingdom
    • Recruiting
    • St. George's University Hospitals
    • Contact: Paul Moxey
    • Principal Investigator: Paul Moxey, MD
  • Norwich, United Kingdom
    • Recruiting
    • Norfolk and Norwich University Hospitals
    • Contact: Phil Stather
    • Principal Investigator: Phil Stather, MD
  • Southampton, United Kingdom
    • Recruiting
    • University Hospital Southampton
    • Contact: Benjamin Patterson
    • Principal Investigator: Benjamin Patterson, MBBS
  • England
    • Brighton, England, United Kingdom
      • Recruiting
      • Royal Sussex County Hospital
      • Contact: Abigail Whyte
      • Principal Investigator: Mohamed Elahwal, MD
    • Bristol, England, United Kingdom
      • Recruiting
      • Southmead Hospital
      • Contact: Seeve Suppiah
      • Principal Investigator: Robert Hinchliffe, MD
    • Canterbury, England, United Kingdom
      • Recruiting
      • Kent and Canterbury Hospital
      • Contact: Vivian Edobhiye
      • Principal Investigator: Sandeep Bahia, MD
    • Plymouth, England, United Kingdom
      • Recruiting
      • Derriford Hospital
      • Contact: Lisa Shainberg
      • Principal Investigator: Devender Mittapalli, MD
    • Wakefield, England, United Kingdom
      • Recruiting
      • Pinderfields Hospital
      • Contact: Martin Sylvester
      • Principal Investigator: Patrick Coughlin, MD
  • Scotland
    • Edinburgh, Scotland, United Kingdom
      • Recruiting
      • Royal Infirmary Edinburgh
      • Contact: Rachael Forsythe
      • Principal Investigator: Rachael Forsythe, MD
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Recruiting
      • Yale School of Medicine
      • Principal Investigator: Carlos Mena-Hurtado, MD
      • Contact: Carlos Mena-Hurtado
  • Florida
    • Gainesville, Florida, United States, 32611
      • Recruiting
      • University of Florida - Gainesville
      • Principal Investigator: Samir Shah, MD
      • Contact: Samir Shah
    • Tampa, Florida, United States, 33606
      • Recruiting
      • Tampa General Hospital
      • Contact: Sashi Inkollu
      • Principal Investigator: Sashi Inkollu, MD
  • Illinois
    • Chicago, Illinois, United States, 60615
      • Recruiting
      • University of Chicago Medical Center
      • Principal Investigator: Trissa Babrowski, MD
      • Contact: Trissa Babrowski
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Health System
      • Contact: Tamer Boules
      • Principal Investigator: Tamer Boules, MD
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Contact: Stanislav Henkin
      • Principal Investigator: Stanislav Henkin, MD
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Recruiting
      • Rutgers University
      • Contact: Karim Salem
      • Principal Investigator: Karim Salem, MD
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • University of North Carolina at Chapel Hill
      • Principal Investigator: Katharine McGinigle, MD
      • Contact: Katharine McGinigle
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Principal Investigator: Jennifer Rymer, MD
      • Contact: Jennifer Rymer
    • Durham, North Carolina, United States, 27704
      • Recruiting
      • Duke Regional Hospital
      • Principal Investigator: Jennifer Rymer, MD
      • Contact: Jennifer Rymer
    • Raleigh, North Carolina, United States, 27609
      • Recruiting
      • Duke Raleigh Hospital
      • Principal Investigator: Jennifer Rymer, MD
      • Contact: Jennifer Rymer
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University Wexner Medical Center
      • Principal Investigator: Jake Hemingway, MD
      • Contact: Jake Hemingway
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
      • Contact: Aaron Aday
      • Principal Investigator: Aaron Aday, MD
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern Medical Center
      • Contact: Josh Beckman
      • Principal Investigator: Josh Beckman, MD
    • Dallas, Texas, United States, 75235
      • Recruiting
      • Southwest Family Medicine
      • Principal Investigator: Chrisette Dharma, MD
      • Contact: Chrisette Dharma
    • Lubbock, Texas, United States, 79430
      • Recruiting
      • Texas Tech University Health Sciences
      • Contact: Debarata Mukherjee
      • Principal Investigator: Debarata Mukherjee, MD
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Recruiting
      • Sentara Norfolk General Hospital
      • Principal Investigator: David Dexter, MD
      • Contact: David Dexter
  • Washington
    • Seattle, Washington, United States, 98195
      • Recruiting
      • University of Washington Medical Center
      • Principal Investigator: Jake Hemingway, MD
      • Contact: Jake Hemingway
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin
      • Contact: Mitchell Dyer
      • Principal Investigator: Mitchell Dyer, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Colchicine; Colchicine 0.5mg daily for the duration of the trial	Drug: Colchicine 0.5 MG Oral Tablet; Colchicine 0.5 mg tablet daily Active drug and placebo are of the same appearance and are indistinguishable. All investigators, study personnel and patients will be blinded to drug treatment assignment. Trial treatment supplies must be stored in a secure, limited-access location under the storage conditions specified on the IP supply label.; Other Names: Colchicine
Placebo Comparator: Colchicine-Placebo; Colchicine-Placebo daily	Drug: Colchicine-Placebo; Colchicine-Placebo tablet; Other Names: Colchicine-Placebo tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiovascular and limb events (MACE or MALE)	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)	3-5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extended MALE	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	3-5 years
Cardiovascular death	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.	3-5 years
Myocardial infarction	Acute myocardial infarction (AMI) requires evidence of acute myocardial injury with clinical evidence of acute myocardial ischemia	3-5 years
Stroke	Stroke requires the presence of acute focal or global* neurological dysfunction caused by brain or retinal vascular injury due to primary hemorrhage or infarction.	3-5 years
Hospitalization	Admission to hospital for any reason	3-5 years
Acute or chronic limb-threatening ischemia	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).	3-5 years
Total vascular amputation	All vascular amputations	3-5 years
Overall mortality	All cause (CV and non CV) deaths	3-5 years
Any thrombosis or thromboembolism (arterial and venous)	All arterial and venous thromboembolism	3-5 years
Fontaine Stage	This classification system grades the clinical presentation of patients to four stages of PAD	3-5 years
Standard Assessment of Global Everyday Activities (SAGEA)	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	3-5 years
Vascular Quality of Life Questionnaire-6 (VascQOL-6)	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.	3-5 years
EuroQol 5 Dimension 5 Level (EQ-5D-5L)	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".	3-5 years
All revascularization (coronary or cerebrovascular or lower limb or other peripheral revascularization)	Defined as coronary or cerebrovascular or lower limb or other peripheral revascularization	3-5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of gastrointestinal toxicity (such as diarrhoea, nausea or vomiting) that results in study drug discontinuation	Safety outcome	3-5 years
Muscle pain (myalgia or myositis), that results in study drug discontinuation	Safety outcome	3-5 years
Infection (e.g., pneumonia) leading to hospitalization	Safety outcome	3-5 years
New diagnosis of cancer	Safety outcome	3-5 years
Renal insufficiency (defined as the need for dialysis or kidney transplant)	Other outcomes of interest	3-5 years
Neuropathy leading to study drug discontinuation	Other outcomes of interest	3-5 years
Neutropenia leading to study drug discontinuation	Other outcomes of interest	3-5 years
Bleeding	Other outcomes of interest	3-5 years

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Investigators: Principal Investigator: Noel C Chan, MD, Population Health Research Institute, Hamilton, Ontario, Canada

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2021
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: February 21, 2021
• First Submitted That Met QC Criteria: February 24, 2021
• First Posted (Actual): March 1, 2021

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Stroke; Mortality; Myocardial Infarction; Cardiovascular death; Acute limb ischemia
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infarction; Necrosis; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Myocardial Ischemia; Ischemia; Pathological Conditions, Signs and Symptoms; Stroke; Inflammation; Peripheral Arterial Disease; Myocardial Infarction; Heterocyclic Compounds; Pharmaceutical Preparations; Dosage Forms; Alkaloids; Colchicine; Tablets
• Other Study ID Numbers: LEADER-PAD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No