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

Inflammation Clinical Trial

— LEADER-PAD  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04774159
• Other study ID #: LEADER-PAD
• Status: Recruiting
• Phase: Phase 3
• Start date: May 6, 2021
• Est. completion date: April 2029

Study information

• Verified date: June 2024
• Source: Population Health Research Institute
• Contact: Noel C Chan, MD
• Phone: 905-521-2100
• Email: Noel.Chan[@]TAARI.CA
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6150
• Est. completion date: April 2029
• Est. primary completion date: April 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis
• Atherosclerosis of Extremities
• Inflammation
• Peripheral Arterial Disease
• Peripheral Vascular Diseases

Intervention

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.
• Colchicine-Placebo
Colchicine-Placebo tablet

Locations

Country	Name	City	State
Canada	Hamilton General Hospital	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Corcare Cardiovascular Research Inc.	Scarborough	Ontario
Canada	Sunnybrook Research Institute	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Population Health Research Institute

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Occurrence of gastrointestinal toxicity (such as diarrhoea, nausea or vomiting) that results in study drug discontinuation	Safety outcome	3-5 years
Other	Muscle pain (myalgia or myositis), that results in study drug discontinuation	Safety outcome	3-5 years
Other	Infection (e.g., pneumonia) leading to hospitalization	Safety outcome	3-5 years
Other	New diagnosis of cancer	Safety outcome	3-5 years
Other	Renal insufficiency (defined as the need for dialysis or kidney transplant)	Other outcomes of interest	3-5 years
Other	Neuropathy leading to study drug discontinuation	Other outcomes of interest	3-5 years
Other	Neutropenia leading to study drug discontinuation	Other outcomes of interest	3-5 years
Other	Bleeding	Other outcomes of interest	3-5 years
Primary	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	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
Secondary	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
Secondary	Myocardial infarction	Acute myocardial infarction (AMI) requires evidence of acute myocardial injury with clinical evidence of acute myocardial ischemia	3-5 years
Secondary	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
Secondary	Hospitalization	Admission to hospital for any reason	3-5 years
Secondary	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
Secondary	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
Secondary	Total vascular amputation	All vascular amputations	3-5 years
Secondary	Overall mortality	All cause (CV and non CV) deaths	3-5 years
Secondary	Any thrombosis or thromboembolism (arterial and venous)	All arterial and venous thromboembolism	3-5 years
Secondary	Fontaine Stage	This classification system grades the clinical presentation of patients to four stages of PAD	3-5 years
Secondary	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
Secondary	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
Secondary	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