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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Low Dose ColchicinE in pAtients With Peripheral Artery DiseasE to Address Residual Vascular Risk: A Randomized Trial (Vanguard Phase)

Conditions
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Peripheral Arterial Disease, Atherosclerosis of Extremities, Inflammation

Intervention / Treatment
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* Drug: Colchicine 0.5 MG Oral Tablet
* Drug: Colchicine-Placebo


Participation Criteria
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Eligibility Criteria
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Patients need to meet the following criteria for inclusion: Age > 18 years History of symptomatic lower extremity PAD* with one or more high risk features: 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)] or prior lower extremity revascularization or prior limb or foot amputation or Fontaine 3 or 4 symptoms/signs Written or verbal informed consent from the patient Note: * Lower extremity PAD is defined by one or more of the following: 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 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 limb or foot amputation for macrovascular arterial vascular disease Exclusion Criteria: Contraindication to colchicine Requirement for colchicine for another clinical indication Active diarrhoea Creatinine Clearance < 15 ml/min 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 use of any 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Colchicine<br>Colchicine 0.5mg daily for the duration of the trial | Drug: Colchicine 0.5 MG Oral Tablet<br>* 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.<br>* Other names: Colchicine;|
| Placebo Comparator: Colchicine-Placebo<br>Colchicine-Placebo daily | Drug: Colchicine-Placebo<br>* Colchicine-Placebo tablet<br>* Other names: Colchicine-Placebo tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean number of patients recruited per center per month | Primary feasibility outcome for the vanguard phase is the mean number of patients recruited per center per month. | at least 12 months recruitment phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients undergoing successful randomization after the active run-in period | Secondary feasibility outcomes | 12 months | 
| Rates of loss to follow-up and discontinuation rates after randomization | Secondary feasibility outcomes | 12 months | 
| Adherence rate with colchicine at 12 months of follow-up | Secondary feasibility outcomes | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute limb ischemia, Myocardial Infarction, Stroke, Cardiovascular death, Mortality