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

Официальное название

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

Обзор

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.

Подробное описание

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).

Вмешательства

• Препарат 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.
• Препарат Colchicine-Placebo
  Colchicine-Placebo tablet

Первичные конечные точки

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

Вторичные конечные точки (12)

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

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 19 центров

• 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
• … и ещё 11 центров

Великобритания · 15 центров

• 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
• … и ещё 7 центров

Канада · 11 центров

• 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
• … и ещё 3 центра

Бразилия · 10 центров

• 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
• … и ещё 2 центра

Швейцария · 5 центров

• 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 центра

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

Нидерланды · 4 центра

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

Австралия · 1 центр

• Sir Charles Gairdner Hospital — Perth

Бельгия · 1 центр

• Universitair Ziekenhuis Leuven — Leuven

Идентификаторы

NCT: NCT04774159 · LEADER-PAD

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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