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

Overview

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).

Interventions

• 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.
• Drug Colchicine-Placebo
  Colchicine-Placebo tablet

Primary outcome measures

• Major adverse cardiovascular and limb events (MACE or MALE) [Time frame: 3-5 years]

Secondary outcome measures (12)

• Extended MALE [Time frame: 3-5 years]
• Cardiovascular death [Time frame: 3-5 years]
• Myocardial infarction [Time frame: 3-5 years]
• Stroke [Time frame: 3-5 years]
• Hospitalization [Time frame: 3-5 years]
• Acute or chronic limb-threatening ischemia [Time frame: 3-5 years]
• All revascularization (coronary or cerebrovascular or lower limb or other peripheral revascularization) [Time frame: 3-5 years]
• Total vascular amputation [Time frame: 3-5 years]
• Overall mortality [Time frame: 3-5 years]
• Any thrombosis or thromboembolism (arterial and venous) [Time frame: 3-5 years]
• Fontaine Stage [Time frame: 3-5 years]
• Standard Assessment of Global Everyday Activities (SAGEA) [Time frame: 3-5 years]

Eligibility criteria

Inclusion criteria

• Age > 18 years
• 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

• Written or verbal informed consent from the patient

Exclusion criteria

• Contraindication to colchicine
• Long term requirement for colchicine for another clinical indication
• Active diarrhoea
• eGFR < 30 mL/min/1.73 m2
• 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 long term use 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
• Patients with life expectancy < 1 year

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 19 centers

• Yale School of Medicine — New Haven
• University of Florida - Gainesville — Gainesville
• Tampa General Hospital — Tampa
• University of Chicago Medical Center — Chicago
• Henry Ford Health System — Detroit
• Mayo Clinic — Rochester
• Rutgers University — Newark
• University of North Carolina at Chapel Hill — Chapel Hill
• … and 11 more centers

United Kingdom · 15 centers

• Royal Sussex County Hospital — Brighton
• Southmead Hospital — Bristol
• Kent and Canterbury Hospital — Canterbury
• Derriford Hospital — Plymouth
• Pinderfields Hospital — Wakefield
• Royal Infirmary Edinburgh — Edinburgh
• Bradford Teaching Hospital — Bradford
• Cambridge University Hospitals — Cambridge
• … and 7 more centers

Canada · 11 centers

• University of Calgary, Peter Lougheed Centre Vascular Clinic — Calgary
• University of Alberta, Mazankowski Heart Institute — Edmonton
• Hamilton General Hospital — Hamilton
• London Health Sciences Centre — London
• Vascular Health Bronte — Oakville
• Corcare Cardiovascular Research Inc. — Scarborough Village
• Niagara Health System — St. Catharines
• Sunnybrook Research Institute — Toronto
• … and 3 more centers

Brazil · 10 centers

• Clínica Procárdio — Blumenau
• Sociedade Hospitalar Angelina Caron — Campina Grande do Sul
• Hospital Universitário (CoraCentro Pesquisa Clinica) — Canoas
• Incore — Dois Vizinhos
• Via Medica — Goiânia
• Hospital Carlos Fernando Malzoni — Matão
• Santa Casa de Misericórdia de Ponta Grossa — Ponta Grossa
• Instituto de Cardiologia do Rio Grande do Sul — Porto Alegre
• … and 2 more centers

Switzerland · 5 centers

• University Hospital Basel, Angiology — Basel
• Ospedale Regionale Bellinzona e Valli - Ente Ospedaliero Cantonale — Bellinzona
• HFR Fribourg — Fribourg
• Hôpitaux Universitaires de Genève — Geneva
• University Hospital Zurich, Clinic of Angiology — Zurich

Ecuador · 4 centers

• Cardiolife — Quito
• Hospital de Especialidades de las Fuerzas Armadas N 1 — Quito
• UniCarMeDr.D — Quito
• AMCOR — Quito

Netherlands · 4 centers

• Deventer Hospital — Deventer
• Slingeland Hospital — Doetinchem
• University Medical Center Groningen — Groningen
• University Medical Center Utrecht — Utrecht

Australia · 1 center

• Sir Charles Gairdner Hospital — Perth

Belgium · 1 center

• Universitair Ziekenhuis Leuven — Leuven

Identifiers

NCT: NCT04774159 · LEADER-PAD

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗