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

Sponsor
Population Health Research Institute (Other)
Overall Status
Recruiting
CT.gov ID
NCT04774159
Collaborator
(none)
150
1
2
27.9
5.4

Study Details

Study Description

Brief Summary

The vanguard phase of the Low dose ColchicinE in pAtients with peripheral Artery DiseasE to address residual vascular Risk (LEADER-PAD) trial will evaluate the feasibility of conducting a full randomized trial to determine if anti-inflammatory therapy with colchicine will reduce vascular events in patients with symptomatic peripheral artery disease.

Condition or Disease Intervention/Treatment Phase
  • Drug: Colchicine 0.5 MG Oral Tablet
  • Drug: Colchicine-Placebo
Phase 3

Detailed Description

The LEADER-PAD trial is a randomized, double blind, multicenter pilot trial with a 2-week active run-in period, comparing low dose colchicine 0.5 mg daily with placebo in patients with PAD to prevent vascular events (myocardial infarction, stroke, cardiovascular deaths, acute limb ischemia and vascular amputation) in patients with symptomatic peripheral artery disease. The sample size for the vanguard phase is 150 patients over 1-year accrual with a 1-year follow-up.The primary outcome is the feasibility of recruitment. If feasibility is demonstrated, patients from the vanguard phase will be rolled over into the full multicenter trial if there are no major protocol modifications.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
150 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double blind and use of similarly active and placebo tablets.
Primary Purpose:
Treatment
Official Title:
Low Dose ColchicinE in pAtients With Peripheral Artery DiseasE to Address Residual Vascular Risk: A Randomized Trial (Vanguard Phase)
Actual Study Start Date :
May 6, 2021
Anticipated Primary Completion Date :
Mar 1, 2023
Anticipated Study Completion Date :
Sep 1, 2023

Arms and Interventions

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
  • Outcome Measures

    Primary Outcome Measures

    1. Mean number of patients recruited per center per month [at least 12 months recruitment phase]

      Primary feasibility outcome for the vanguard phase is the mean number of patients recruited per center per month.

    Secondary Outcome Measures

    1. Proportion of patients undergoing successful randomization after the active run-in period [12 months]

      Secondary feasibility outcomes

    2. Rates of loss to follow-up and discontinuation rates after randomization [12 months]

      Secondary feasibility outcomes

    3. Adherence rate with colchicine at 12 months of follow-up [12 months]

      Secondary feasibility outcomes

    Other Outcome Measures

    1. Gastrointestinal toxicity that leads to treatment interruption or discontinuation, infection (e.g., pneumonia) and incident cancer [12 months]

      Safety outcomes

    2. Major Adverse cardiovascular and limb events (MACE or MALE). [12 months]

      Efficacy outcomes

    3. Vascular Quality of Life Questionnaire-6 (VascQOL-6) at baseline, 6 and 12 months. [12 months]

      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.

    4. Standard Assessment of Global Everyday Activities (SAGEA) [12 months]

      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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Patients need to meet the following criteria for inclusion:
    1. Age > 18 years

    2. History of symptomatic lower extremity PAD* with one or more high risk features:

    3. symptomatic lower extremity PAD with one of the following risk factors: [>1 vascular bed affected by atherosclerosis, presence of diabetes, history of heart failure or lower eGFR (< 60 ml/min)]

    4. or prior lower extremity revascularization

    5. or prior limb or foot amputation

    6. or Fontaine 3 or 4 symptoms/signs

    7. Written or verbal informed consent from the patient

    Note:
    • Lower extremity PAD is defined by one or more of the following:
    1. presence of intermittent claudication and one or more of ankle/arm blood pressure ratio (ABI) < 0.90 or peripheral artery stenosis >50% documented by angiography or duplex ultrasound; or

    2. a history of revascularization defined as limb bypass surgery or percutaneous transluminal angioplasty of iliac or infra-inguinal arteries or extra-anatomical limb bypass surgery; or

    3. limb or foot amputation for macrovascular arterial vascular disease

    Exclusion Criteria:
    1. Contraindication to colchicine

    2. Requirement for colchicine for another clinical indication

    3. Active diarrhoea

    4. Creatinine Clearance < 15 ml/min

    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 use of any 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Hamilton General Hospital Hamilton Ontario Canada L8L 2X2

    Sponsors and Collaborators

    • Population Health Research Institute

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Noel Chan, Principal Investigator, Population Health Research Institute
    ClinicalTrials.gov Identifier:
    NCT04774159
    Other Study ID Numbers:
    • 11344
    First Posted:
    Mar 1, 2021
    Last Update Posted:
    Sep 20, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Noel Chan, Principal Investigator, Population Health Research Institute
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Sep 20, 2021