Colchicine for the Prevention of Post-Operative Atrial Fibrillation After Coronary Artery Bypass Grafting: A Single-Center, Strategy-Stratified, Randomized, Double-Blind, Placebo-Controlled Trial

This single-center, prospective, randomized, double-blind, placebo-controlled clinical trial aims to evaluate the efficacy of colchicine in preventing post-operative atrial fibrillation (POAF) following coronary artery bypass grafting (CABG) and to compare its pharmacologic and clinical effects between different surgical strategies - off-pump CABG (OPCAB) and on-pump CABG (ONCAB).

Post-operative atrial fibrillation is one of the most common arrhythmias after CABG, with an incidence of approximately 50%, and is associated with prolonged ICU and hospital stay and increased healthcare utilization. Intravenous amiodarone is commonly used for POAF treatment but may increase the risk of catheter-related infection. Colchicine, an anti-inflammatory and immunomodulatory agent, has shown potential to reduce postpericardiotomy syndrome and POAF in small-scale studies, but existing evidence remains inconsistent, and most prior trials did not distinguish between surgical strategies.

In this trial, 400 adult patients undergoing elective CABG will be enrolled and randomized in a 1:1 ratio within each stratum (OPCAB and ONCAB) to receive either colchicine or placebo. The treatment group will receive colchicine 0.5 mg orally twice daily, starting on postoperative day -3 and continuing through postoperative day 7. The placebo group will receive identically appearing tablets on the same schedule.

The primary endpoint is the incidence of new-onset atrial fibrillation within 14 days after surgery, defined as any episode lasting ≥30 seconds documented by 12-lead ECG, continuous telemetry, or Holter monitoring.

Secondary outcomes include the incidence and management of other arrhythmias (atrial flutter, supraventricular tachycardia), total dose and duration of intravenous amiodarone, ICU and total hospital length of stay, ischemic stroke or TIA, infection events (including catheter-related infection), and 30-day readmission. Safety outcomes will include gastrointestinal intolerance, hepatic enzyme elevation, creatine kinase elevation with myalgia, hematologic abnormalities, and serious adverse events (SAE).

Pharmacokinetic (PK) and pharmacodynamic (PD) analyses will measure colchicine concentrations in plasma and pericardial fluid and correlate these with inflammatory biomarkers (CRP, IL-6, TNF-α, white blood cell profile, and immune cell phenotyping by flow cytometry). This integrated approach aims to elucidate the relationship between colchicine exposure, inflammation, and POAF occurrence.

Statistical analyses will primarily follow an intention-to-treat (ITT) approach. The primary endpoint will be evaluated using a log-binomial or Poisson-robust model to estimate relative risk (RR) with 95% confidence intervals, including treatment, surgical strategy, and their interaction terms. Time-to-event outcomes will be analyzed using Cox proportional hazards or Kaplan-Meier methods, and continuous variables by linear mixed-effects models. Missing data will be handled conservatively with multiple imputation where appropriate. An independent Data and Safety Monitoring Board (DSMB) will review blinded safety data once 50% of subjects have been enrolled.

The trial is expected to clarify the pharmacokinetic and clinical effects of colchicine in different CABG surgical strategies. If colchicine is shown to effectively reduce POAF in OPCAB patients or in those achieving sufficient plasma concentrations, it may provide a simple, low-cost preventive strategy that reduces the need for intravenous amiodarone, lowers infection risk, and shortens ICU and hospital stay. The results could guide future optimization of dosing and timing strategies in ONCAB patients and improve perioperative management and resource utilization in cardiac surgery.

• Total duration of post-operative atrial fibrillation (POAF) [Срок оценки: From the day of surgery through postoperative day 14.]
• Proportion of patients requiring cardioversion for POAF [Срок оценки: From the day of surgery through postoperative day 14.]
• Total dose of intravenous amiodarone used for POAF treatment [Срок оценки: From the day of surgery through postoperative day 14.]
• Length of stay in the intensive care unit (ICU) [Срок оценки: From the date of surgery until discharge from the intensive care unit or death, whichever occurred first, assessed up to 30 days after surgery.]
• Total hospital length of stay [Срок оценки: From hospital admission until hospital discharge or death, whichever occurred first, assessed up to 60 days after surgery.]
• 30-day hospital readmission [Срок оценки: From hospital discharge until 30 days after discharge.]
• Plasma and pericardial fluid colchicine concentrations [Срок оценки: From preoperative day 1 through postoperative day 7.]