Clinical trial NCT06215989: Treatment of ACuTe Coronary Syndromes With Low-dose colchICine
Official title: Treatment of ACuTe Coronary Syndromes With Low-dose colchICine (TACTIC): a Randomised, Double-blinded, Placebo-controlled, Multicentric Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Acute Coronary Syndrome
Unstable Angina
ST Elevation Myocardial Infarction
Non ST Segment Elevation Myocardial Infarction
Colchicine
Lead sponsor: Beijing Anzhen Hospital
Sponsor class: OTHER
First posted: 2024-01-22
Enrollment: 6574
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is designed to evaluate whether low-dose colchicine, in addition to standard treatment recommended by guidelines, further reduces the risk of major adverse cardiovascular events in patients with acute coronary syndromes (ACS) through a prospective, randomized, double-blind, placebo-controlled clinical trial.

Detailed description: Background: Colchicine is a cheap and potent oral anti-inflammatory drug that can exert its anti-inflammatory effect on the pathogenesis of ACS. The 2023 updated guidelines for the management of chronic stable coronary artery disease (SCAD) by the American Heart Association (AHA)/American College of Cardiology (ACC) have identified colchicine as the drug of choice for secondary preventive treatment in patients with SCAD to reduce the risk of recurrence of adverse cardiovascular events. Despite the current optimal medical therapies, some ACS patients still suffer recurrent adverse cardiovascular events and mortality. Existing clinical studies have not fully clarified whether early use of colchicine to reduce inflammatory responses is associated with greater clinical benefit after ACS. The effect of colchicine on cardiovascular outcomes in the ACS patients needs further elucidation.

Methods: Patients aged 18 years and older with a definite diagnosis of ACS are randomly assigned to two groups in a 1:1 ratio after signing the informed consent form. Colchicine group: standard treatment + colchicine (0.5mg qd) from 1st month to 12th month after randomization. Placebo group: standard treatment + placebo (1 tablet qd) from 1st month to 12th month after randomization. The primary endpoint is the composite of cardiovascular death, non-fatal ischemic stroke, non-fatal spontaneous (non-operation related) myocardial infarction, readmission for ACS, and ischaemia driven (unplanned) revascularization at 1 year after randomization.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years;
* Definite diagnosis of ACS;
* Ability and willingness to provide written informed consent

Exclusion Criteria:

* Type 2 myocardial infarction (Patients with symptoms or signs of myocardial ischemia and evidence of increased oxygen demand or decreased supply \[for example, tachyarrhythmia, hypotension, or anaemia\] secondary to an alternative pathology and myocardial necrosis are defined as suffering type 2 myocardial infarction. The classification of type 2 myocardial infarction also includes patients with coronary vasospasm, embolism or spontaneous dissection without evidence of atherothrombosis related to coronary artery disease);
* Valvular heart disease that is considered likely to require surgical intervention;
* History of non-skin cancer in the past 3 years;
* Inflammatory bowel disease or chronic diarrhea;
* History of gastric ulcer or previous gastric bleeding;
* Neuromuscular diseases or non-transient (At least 2 laboratory tests) creatine kinase levels greater than 3 times the upper limit of the normal range (except those associated with myocardial infarction);
* Clinically significant non-transient (At least 2 laboratory tests) blood abnormalities(Hemoglobin \<100g/L or hematocrit \< 30% or \> 52% or white blood cell count \< 3×109/L or platelet count \< 100×109/L);
* Estimated glomerular filtration rate (eGFR)\<30mL/min/1.73m2 (based on CKD-EPI formula);
* Serum alanine aminotransferase and/or aspartate aminotransferase levels greater than 2 times the upper limit of the normal range accompanied by serum total bilirubin levels greater than 2 times the upper limit of the normal range or severe liver disease with coagulation disorders(INR\>1.5)(except for elevated glutamic oxalacetic transaminase associated with myocardial infarction);
* Decline in cognitive function due to inability to perform basic activities of daily living independently;
* Drug or alcohol abuse;
* Other immunosuppressive therapies already in existence or planned;
* Other causes require long-term colchicine treatment;
* History of clear or suspected colchicine allergy;
* Strong CYP3A4 or P-glycoprotein inhibitors (such as cyclosporine, antiretrovirals, antifungals, erythromycin and clarithromycin) have been used and no other alternative drugs can be used.

Primary outcomes:
measure: Primary endpoint
timeFrame: 1 year after randomization
Secondary outcomes:
measure: Key secondary endpoint
timeFrame: 1 year after randomization
measure: Secondary endpoint 1
timeFrame: 1 year after randomization
measure: Secondary endpoint 2
timeFrame: 1 year after randomization
measure: Secondary endpoint 3
timeFrame: 1 year after randomization
measure: Secondary endpoint 4
timeFrame: 1 year after randomization
measure: Secondary endpoint 5
timeFrame: 1 year after randomization
measure: Secondary endpoint 6
timeFrame: 1 year after randomization
measure: Secondary endpoint 7
timeFrame: 1 year after randomization
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Anzhen Hospital
state: Beijing
Study officials:
affiliation: Beijing Anzhen Hospital
name: Yujie Zhou, PhD, MD
role: STUDY_CHAIR
affiliation: Beijing Anzhen Hospital
name: Xiaoli Liu, PhD, MD
role: STUDY_DIRECTOR
affiliation: Beijing Anzhen Hospital
name: Xiaoteng Ma, MD
role: PRINCIPAL_INVESTIGATOR
References: