Treatment of ACuTe Coronary Syndromes With Low-dose colchICine

Treatment of ACuTe Coronary Syndromes With Low-dose colchICine (TACTIC): a Randomised, Double-blinded, Placebo-controlled, Multicentric Trial

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.

Study Overview

• Status: Recruiting
• Conditions: ST Elevation Myocardial Infarction; Acute Coronary Syndrome; Unstable Angina; Non ST Segment Elevation Myocardial Infarction; Colchicine
• Intervention / Treatment: Drug: Colchicine Pill; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 6574
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yujie Zhou, PhD, MD; Phone Number: 8613901330652; Email: azzyj12@163.com
• Study Contact Backup: Name: Xiaoteng Ma, MD; Phone Number: 8618810616459; Email: maxiaotengai@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100029
      • Recruiting
      • Beijing Anzhen Hospital
      • Contact: Xiaoteng Ma, MD; Phone Number: 8618810616459; Email: maxiaotengai@163.com
      • Contact: Xiaoli Liu, PhD, MD; Phone Number: 8613581633895; Email: liuxl9881@163.com
      • Principal Investigator: Xiaoli Liu, PhD, MD
      • Sub-Investigator: Xiaoteng Ma, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo group; Patients are randomized within 48 hours after diagnosis of ACS, and on the day of randomization, eligible patients undergo standard treatment plus placebo (1 tablet qd from 1st month to 12th month).	Drug: Placebo; Placebo one tablet once daily will be given on the basis of standard treatment of ACS recommended by guidelines
Experimental: Colchicine group; Patients are randomized within 48 hours after diagnosis of ACS, and on the day of randomization, eligible patients undergo standard treatment plus colchicine (0.5mg qd from 1st month to 12th month).	Drug: Colchicine Pill; Colchicine 0.5mg once daily will be given on the basis of standard treatment of ACS recommended by guidelines; Other Names: Colchicine 0.5 MG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary endpoint	Rate of 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	1 year after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Key secondary endpoint	Rate of the composite of cardiovascular death, non-fatal ischemic stroke, and non-fatal spontaneous (non-operation related) myocardial infarction	1 year after randomization
Secondary endpoint 1	Rate of all-cause death	1 year after randomization
Secondary endpoint 2	Rate of cardiovascular death	1 year after randomization
Secondary endpoint 3	Rate of non-fatal ischemic stroke	1 year after randomization
Secondary endpoint 4	Rate of non-fatal spontaneous (non-operation related) myocardial infarction	1 year after randomization
Secondary endpoint 5	Readmission rate for ACS	1 year after randomization
Secondary endpoint 6	Rate of ischaemia-driven (unplanned) revascularization	1 year after randomization
Secondary endpoint 7	Rate of type 3-5 bleeding events as defined by the BARC bleeding criteria	1 year after randomization

Collaborators and Investigators

• Sponsor: Beijing Anzhen Hospital
• Investigators: Study Chair: Yujie Zhou, PhD, MD, Beijing Anzhen Hospital; Study Director: Xiaoli Liu, PhD, MD, Beijing Anzhen Hospital; Principal Investigator: Xiaoteng Ma, MD, Beijing Anzhen Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: January 11, 2024
• First Submitted That Met QC Criteria: January 11, 2024
• First Posted (Actual): January 22, 2024

Study Record Updates

• Last Update Posted (Actual): October 30, 2024
• Last Update Submitted That Met QC Criteria: October 27, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Disease; Necrosis; Myocardial Ischemia; Ischemia; Chest Pain; Angina Pectoris; ST Elevation Myocardial Infarction; Syndrome; Myocardial Infarction; Infarction; Acute Coronary Syndrome; Angina, Unstable; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Gout Suppressants; Antirheumatic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Colchicine
• Other Study ID Numbers: TACTIC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No