Efficacy and Safety of Colchicine After PCI

Официальное название

Efficacy and Safety of Colchicine After Percutaneous Coronary Intervention

Обзор

Colchicine (0.5 mg/day) was recommended by the U.S. Food and Drug Administration in 2023 for the anti-inflammatory treatment of coronary heart disease (CHD). However, colchicine is still not approved for CHD treatment in China. There is no large-scale clinical evidence that colchicine can be used to treat Chinese patients with CHD. Considering the low body weight of the East Asian population, it is unclear whether the recommended standard dose (0.5 mg/day) is suitable for Chinese patients. Therefore, we need to further explore the effects of different doses of colchicine on the efficacy and safety of clinical endpoints in the Chinese population with CHD. This study is a multicenter, prospective, randomized, controlled, double-blind, event-driven clinical study conducted in China. The primary objective of this study is to determine whether long-term treatment with different doses of colchicine reduces the incidence of cardiovascular events in Chinese patients undergoing PCI. The secondary objective is to determine the safety of long-term treatment with different doses of colchicine in this patient population.

Подробное описание

After informed consent, 8862 subjects who meet all inclusion will be randomly assigned to receive colchicine (0.5 mg/day), colchicine (0.375 mg/day), or placebo (1:1:1 allocation ratio), with follow-up at months (1, 6, 12, 18, 24…) after randomization, and phone assessments at months (3, 9, 15, 21…). The occurrence of any endpoints or other adverse events will be assessed every 3 months. Subjects will also receive standard medical care for antiplatelets, control of dyslipidemia, hypertension, angina and diabetes as directed by national guidelines. All suspected cardiovascular endpoints will be adjudicated by the Clinical Event Committee (CEC, consisting of three experienced members blinded as to allocation of therapy). The Data and Safety Monitoring Board (DSMB, consisting of five fully independent members) will review unblinded safety data as detailed in the DSMB charter. An interim analysis is planned after approximately 50% of primary endpoints have been positively adjudicated. The DSMB charter will pre-specify the methodology for the interim analysis and the rules for early termination of the study.

Вмешательства

• Препарат Colchicine 0.5 mg
  Colchicine 0.5 mg, one pill a day, oral intake
• Препарат Colchicine 0.375 mg
  Colchicine 0.375 mg, one pill a day, oral intake
• Препарат Placebo
  Placebo, one pill a day, oral intake

Первичные конечные точки

• Composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and ischemia-driven revascularization [Срок оценки: An estimated 2-4 years period]

Вторичные конечные точки (9)

• Composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke [Срок оценки: An estimated 2-4 years period]
• Ischemia-driven revascularization [Срок оценки: An estimated 2-4 years period]
• Nonfatal myocardial infarction [Срок оценки: An estimated 2-4 years period]
• Nonfatal stroke [Срок оценки: An estimated 2-4 years period]
• Urgent hospitalization for unstable angina [Срок оценки: An estimated 2-4 years period]
• In-stent restenosis [Срок оценки: An estimated 2-4 years period]
• Stent thrombosis [Срок оценки: An estimated 2-4 years period]
• Cardiovascular death [Срок оценки: An estimated 2-4 years period]
• All-cause mortality [Срок оценки: An estimated 2-4 years period]

Критерии участия

Критерии включения

• (1) Capable and willing to provide informed consent;
• (2) Age ≥18 and ≤80 years old, regardless of sex;
• (3) Hospitalized patients with CHD requiring PCI;
• (4) Completion of all planned PCI during hospitalization;
• (5) Standardized treatment of coronary artery disease according to national guidelines.

Критерии исключения

• (1) Known allergy to colchicine;
• (2) Colchicine taken within 10 days prior to randomization group;
• (3) Patients currently in cardiogenic shock or hemodynamically unstable;
• (4) Patients with known inflammatory bowel disease or chronic diarrhea;
• (5) Abnormal liver function (ALT> 3 times the upper limit of normal);
• (6) Abnormal renal function (eGFR<30mL/min/1.73m2);
• (7) Active malignant tumors reported in past medical history;
• (8) Existing or planned treatment with other anti-inflammatory or immunosuppressive drugs;
• (9) Pregnant women, lactating women or women of childbearing age who did not use effective contraceptives;
• (10) Any other circumstances in which the investigator judges that the patient is not suitable to participate in the clinical trial.

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

Китай · 36 центров

• The Second Hospital & Clinical Medical School, Lanzhou University — Lanzhou
• Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of S — Ухань
• Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sc — Пекин
• The Second Affiliated Hospital of Chongqing Medical University — Чунцин
• The First Affiliated Hospital of Dalian Medical University — Dalian
• The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture — Enshi
• The First Affiliated Hospital of Harbin Medical University — Харбин
• The First Affiliated Hospital of Anhui Medical University — Хэфэй
• … и ещё 28 центров

Публикации

• Lawler PR, Bhatt DL, Godoy LC, Luscher TF, Bonow RO, Verma S, Ridker PM. Targeting cardiovascular inflammation: next steps in clinical translation. Eur Heart J. 2021 Jan 1;42(1):113-131. doi: 10.1093/eurheartj/ehaa099. PMID 32176778
• Nelson K, Fuster V, Ridker PM. Low-Dose Colchicine for Secondary Prevention of Coronary Artery Disease: JACC Review Topic of the Week. J Am Coll Cardiol. 2023 Aug 15;82(7):648-660. doi: 10.1016/j.jacc.2023.05.055. PMID 37558377
• Fiolet ATL, Opstal TSJ, Mosterd A, Eikelboom JW, Jolly SS, Keech AC, Kelly P, Tong DC, Layland J, Nidorf SM, Thompson PL, Budgeon C, Tijssen JGP, Cornel JH. Efficacy and safety of low-dose colchicine in patients with coronary disease: a systematic review and meta-analysis of randomized trials. Eur Heart J. 2021 Jul 21;42(28):2765-2775. doi: 10.1093/eurheartj/ehab115. PMID 33769515

Идентификаторы

NCT: NCT06472908 · COLPCI

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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