Precision Colchicine Intervention to Suppress Atherosclerosis in TET2 Clonal Hematopoiesis

Prior treatment

• Prior coronary artery bypass grafting (CABG) before documented ACS;
• Colchicine use within 30 days prior to randomization, or planned colchicine therapy for other indications;
• Existing or planned treatment with other anti-inflammatory or immunosuppressive drugs;
• Significant radiation exposure (≥40 mSv) within the past 12 months;

Other illness

• Other clinically significant cardiovascular diseases, including moderate-to-severe valvular heart disease (moderate or severe), heart failure (NYHA class III-IV), or atrial fibrillation;
• Inflammatory bowel disease (Crohn's or ulcerative colitis) or active diarrhea;
• Symptomatic peripheral neuropathy, pre-existing progressive neuromuscular disease or creatine kinase (CK) level \> 3 times the upper limit of normal range as measured within the past 30 days and determined to be non-transient through repeat testing;
• Any contraindication, known allergy or intolerance to colchicine;
• Current or planned use of any of cyclosporine, verapamil, HIV protease inhibitors, azole antifungals, or macrolide antibiotics;
• History of malignancy (hematologic or solid-tumor);
• History of transplantation (hematopoietic stem cell or solid-organ);
• Known hypersensitivity to iodinated contrast media or uncontrolled active hyperthyroidism;

Lab values

• Abnormal liver function (ALT \>3 times the upper limit of normal range) at randomization;
• Abnormal renal function (serum creatinine \>1.5 times the upper limit of normal range or estimated eGFR \<45 mL/min/1.73 m²) at randomization;
• Hematologic abnormalities: anemia (hemoglobin \<100g/L), thrombocytopenia (platelet count \<100×109/L) or leukopenia (white blood cell \<3×109/L) at randomization;

Other

• Non-culprit coronary anatomy (e.g., marked tortuosity, bifurcation lesions, or small vessels \<1.5 mm in diameter) deemed to preclude plaque assessment by CCTA;
• Planned PCI or CABG;
• Pregnancy, breastfeeding, or women of childbearing potential who are not using an effective method of contraception;
• Current enrollment in another clinical trial;
• A predicted life expectancy \< 1 year;
• Any other circumstances in which the investigator judges that the patient is not suitable to participate in the clinical trial.

• Age 40-85 years;
• Patients with recent hospitalization for documented ACS (the index event occurring 30-90 days before randomization) and meeting all of the following:
  • During the index hospitalization, patients underwent either PCI or diagnostic coronary angiography alone,
  • At least one non-culprit coronary lesion with 30%-70% diameter stenosis by visual estimation on coronary angiography,
  • Clinically stable throughout the screening period,
  • Receiving standard of care therapy for ACS in accordance with national guidelines,
  • Peripheral blood DNA available for targeted sequencing, with results demonstrating either TET2-CHIP or no CHIP-associated variants;
• Written informed consent.