Clinical trial NCT06472908: Efficacy and Safety of Colchicine After PCI
Official title: Efficacy and Safety of Colchicine After Percutaneous Coronary Intervention
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Coronary Heart Disease
Percutaneous Coronary Intervention
Colchicine
Lead sponsor: Wuhan Union Hospital, China
Sponsor class: OTHER
First posted: 2024-06-25
Enrollment: 8862
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* (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.

Exclusion Criteria:

* (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.

Primary outcomes:
measure: Composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and ischemia-driven revascularization
timeFrame: An estimated 2-4 years period
Secondary outcomes:
measure: Composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke
timeFrame: An estimated 2-4 years period
measure: Ischemia-driven revascularization
timeFrame: An estimated 2-4 years period
measure: Nonfatal myocardial infarction
timeFrame: An estimated 2-4 years period
measure: Nonfatal stroke
timeFrame: An estimated 2-4 years period
measure: Urgent hospitalization for unstable angina
timeFrame: An estimated 2-4 years period
measure: In-stent restenosis
timeFrame: An estimated 2-4 years period
measure: Stent thrombosis
timeFrame: An estimated 2-4 years period
measure: Cardiovascular death
timeFrame: An estimated 2-4 years period
measure: All-cause mortality
timeFrame: An estimated 2-4 years period
Other outcomes:
Locations:
city: Lanzhou
country: China
facility: The Second Hospital & Clinical Medical School, Lanzhou University
state: Gansu
city: Wuhan
country: China
facility: Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Beijing
country: China
facility: Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
city: Dalian
country: China
facility: The First Affiliated Hospital of Dalian Medical University
city: Enshi
country: China
facility: The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture
city: Harbin
country: China
facility: The First Affiliated Hospital of Harbin Medical University
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
city: Huangshi
country: China
facility: Huangshi Central Hospital
city: Jinan
country: China
facility: Shandong Provincial Hospital
city: Jingzhou
country: China
facility: Jingzhou Central Hospital
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital
city: Shanghai
country: China
facility: Songjiang Hospital Affiliated with Shanghai Jiao Tong University School of Medicine
city: Shenyang
country: China
facility: The General Hospital of Northern Theater Command of the Chinese People's Liberation Army
city: Shiyan
country: China
facility: Dongfeng General Hospital, Hubei University of Medicine
city: Shiyan
country: China
facility: Shiyan Renmin Hospital
city: Shiyan
country: China
facility: Taihe hospital
city: Suizhou
country: China
facility: Suizhou Central Hospital
city: Taiyuan
country: China
facility: Shanxi Cardiovascular Disease Hospital
city: Wuhan
country: China
facility: China Resources and WISCO General Hospital
city: Wuhan
country: China
facility: Fifth Hospital in Wuhan
city: Wuhan
country: China
facility: Wuhan Asia Heart Hospital
city: Wuhan
country: China
facility: Wuhan Central Hospital
city: Wuhan
country: China
facility: Wuhan First Hospital
city: Wuhan
country: China
facility: Wuhan Fourth Hospital
city: Wuhan
country: China
facility: Wuhan Puren Hospital
city: Wuhan
country: China
facility: Wuhan Sixth Hospital, Affiliated Hospital of Jianghan University
city: Wuhan
country: China
facility: Wuhan Third Hospital
city: Wuhan
country: China
facility: Wuhan Wuchang Hospital
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
city: Xiangyang
country: China
facility: Xiangyang Central Hospital
city: Xiangyang
country: China
facility: Xiangyang First People's Hospital
city: Xianning
country: China
facility: Xianning Central Hospital
city: Yichang
country: China
facility: Yichang Central People's Hospital
city: Zhengzhou
country: China
facility: Fuwai Huazhong Cardiovascular Hospital
Study officials:
affiliation: Wuhan Union Hospital, China
name: Xiang Cheng, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.