Clinical trial NCT04774159: Low Dose ColchicinE in pAtients With Peripheral Artery DiseasE to Address Residual Vascular Risk
Official title: Low Dose ColchicinE in pAtients With Peripheral Artery DiseasE to Address Residual Vascular Risk: A Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Peripheral Arterial Disease
Atherosclerosis of Extremities
Inflammation
Keywords: Acute limb ischemia
Myocardial Infarction
Stroke
Cardiovascular death
Mortality
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
First posted: 2021-03-01
Enrollment: 6150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Major adverse cardiovascular and limb events (MACE or MALE)
timeFrame: 3-5 years
Secondary outcomes:
measure: Extended MALE
timeFrame: 3-5 years
measure: Cardiovascular death
timeFrame: 3-5 years
measure: Myocardial infarction
timeFrame: 3-5 years
measure: Stroke
timeFrame: 3-5 years
measure: Hospitalization
timeFrame: 3-5 years
measure: Acute or chronic limb-threatening ischemia
timeFrame: 3-5 years
measure: All revascularization coronary or cerebrovascular or lower limb or other peripheral revascularization)
timeFrame: 3-5 years
measure: Total vascular amputation
timeFrame: 3-5 years
measure: Overall mortality
timeFrame: 3-5 years
measure: Any thrombosis or thromboembolism (arterial and venous)
timeFrame: 3-5 years
measure: Fontaine Stage
timeFrame: 3-5 years
measure: Standard Assessment of Global Everyday Activities (SAGEA)
timeFrame: 3-5 years
measure: Vascular Quality of Life Questionnaire-6 (VascQOL-6)
timeFrame: 3-5 years
measure: EuroQol 5 Dimension 5 Level (EQ-5D-5L)
timeFrame: 3-5 years
Other outcomes:
measure: Occurrence of gastrointestinal toxicity (such as diarrhoea, nausea or vomiting) that results in study drug discontinuation
timeFrame: 3-5 years
measure: Muscle pain (myalgia or myositis), that results in study drug discontinuation
timeFrame: 3-5 years
measure: Infection (e.g., pneumonia) leading to hospitalization
timeFrame: 3-5 years
measure: New diagnosis of cancer
timeFrame: 3-5 years
measure: Renal insufficiency (defined as the need for dialysis or kidney transplant)
timeFrame: 3-5 years
measure: Neuropathy leading to study drug discontinuation
timeFrame: 3-5 years
measure: Neutropenia leading to study drug discontinuation
timeFrame: 3-5 years
measure: Bleeding
timeFrame: 3-5 years
Locations:
city: Calgary
country: Canada
facility: University of Calgary, Peter Lougheed Centre Vascular Clinic
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta, Mazankowski Heart Institute
state: Alberta
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Oakville
country: Canada
facility: Vascular Health Bronte
state: Ontario
city: Scarborough
country: Canada
facility: Corcare Cardiovascular Research Inc.
state: Ontario
city: St. Catharines
country: Canada
facility: Niagara Health System
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Research Institute
state: Ontario
city: Montréal
country: Canada
facility: CIUSSS du Nord-de-l'île-de-Montréal, Hôpital du Sacré-Cœur-de-Montréal
state: Quebec
city: Rimouski
country: Canada
facility: Centre intégré de santé et de services sociaux du Bas-Saint-Laurent
state: Quebec
city: Basel
country: Switzerland
facility: University Hospital Basel, Angiology
city: Fribourg
country: Switzerland
facility: HFR Fribourg
city: Genève
country: Switzerland
facility: Hôpitaux Universitaires de Genève
city: Zurich
country: Switzerland
facility: University Hospital Zurich, Clinic of Angiology
Study officials:
affiliation: Population Health Research Institute, Hamilton, Ontario, Canada
name: Noel C Chan, MD
role: PRINCIPAL_INVESTIGATOR
References: