Effect of Colchicine on Perioperative Anti-inflammatory Organ Injury in Cardiac Surgery

Official title

Effect of Colchicine on Perioperative Anti-inflammatory Organ Injury in Cardiac Surgery : a Multi-center, Randomized, Controlled, Double-blind Clinical Trial

Overview

All patients will be completed collection of demographic data, clinical data, and be observed for inflammatory organ damage, oxygenation index or SpO2/ FIO2, WBC, NEU, interleukin-1β, interleukin-6, interleukin-8 (IL-1β/6/8), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), procalcitonin (PCT), myoglobin (Myo), creatine kinase-MB (CK-MB), high-sensitivity cardiac troponin T (hs-cTnT), neutrophil elastase (NE), myeloperoxidase (MPO), APACHE II score, alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin, Murray lung injury score, serum creatinine, eGFR, mechanical ventilation time, ICU length of stay, drug-related gastrointestinal reactions, and 30-day and 90-day all-cause mortality, among other indicators.

Detailed description

This study is a multicenter, randomized, controlled, double-blind, placebo- controlled clinical trial. A total of 768 patients who met the inclusion and exclusion criteria and were scheduled for cardiac surgery under cardiopulmonary bypass were enrolled. After signing informed consent, patients were randomly divided into the experimental group and the control group. Patients in the experimental group took 0.5mg of colchicine tablets orally for 3 days before surgery and continued to take 0.5mg daily for 10 days after tracheal extubation. Patients in the control group received an equivalent amount of starch placebo tablets, administered at the same times and in the same doses as the experimental group, during the colchicine/placebo treatment period, without affecting the patients' standard treatment protocols.

All patients will be completed collection of demographic data, clinical data, and be observed for inflammatory organ damage, oxygenation index or SpO2/ FIO2, WBC, NEU, interleukin-1β, interleukin-6, interleukin-8 (IL-1β/6/8), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), procalcitonin (PCT), myoglobin (Myo), creatine kinase-MB (CK-MB), high-sensitivity cardiac troponin T (hs-cTnT), neutrophil elastase (NE), myeloperoxidase (MPO), APACHE II score, alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin, Murray lung injury score, serum creatinine, eGFR, mechanical ventilation time, ICU length of stay, drug-related gastrointestinal reactions, and 30-day and 90-day all-cause mortality, among other indicators. The study aims to investigate the impact of colchicine on the levels of inflammatory factors and prognosis in patients undergoing cardiac vascular surgery and to observe the potential organ damage to the heart, lungs, liver, kidneys, and the occurrence of adverse events such as leukopenia and thrombocytopenia. This is done to assess the safety of colchicine use in cardiac surgery patients.

Interventions

• Drug Colchicine 0.5 MG
  Take 0.5mg of colchicine tablets orally for 3 days before surgery, and continued to take 0.5mg every other day (qod) for 10 days after tracheal extubation.
• Drug Placebo
  Take 0.5mg of starch tablets orally for 3 days before surgery, and continued to take 0.5mg every other day (qod) for 10 days after tracheal extubation.

Primary outcome measures

• Number of Participants with POAF [Time frame: postoperative 10 days]
• Number of Participants with PMI [Time frame: postoperative 10 days]
• Number of Participants with ARDS [Time frame: postoperative 10 days]
• Number of Participants with PPS [Time frame: postoperative 10 days]

Secondary outcome measures (12)

• Oxygenation index [Time frame: postoperative day 1, 3, 5 and 7]
• Inflammatory index [Time frame: postoperative day 1, 3, 5 and 7]
• Myocardial injury marker [Time frame: postoperative day 1, 3, 5 and 7]
• Acute physiology and chronic health evaluation(APACHE II) socre [Time frame: postoperative day 1, 3, 5 and 7]
• Murray lung injury score [Time frame: postoperative day 1, 3, 5 and 7]
• Liver and kidney function [Time frame: postoperative day 1, 3, 5 and 7]
• DVMV [Time frame: postoperative 28 days]
• ICU time [Time frame: postoperative 28 days]
• In-hospital time [Time frame: postoperative 28 days]
• 30-day all-cause mortality [Time frame: postoperative 30 days]
• 90-day all-cause mortality [Time frame: postoperative 90 days]
• Incidence of gastrointestinal reactions [Time frame: postoperative 7 days]

Eligibility criteria

Inclusion criteria

• Aged between 50 and 80 years, male or female;
• Patients undergoing elective cardiac surgery;
• Have signed the informed consent form (ICF).

Exclusion criteria

• Patients undergoing emergency surgery;
• Patients undergoing deep hypothermic circulatory arrest surgery;
• Preoperative predicted mortality >3% according to European System for Cardiac Operative Risk Evaluation II (EuroSCORE II);
• Patients undergoing off-pump coronary artery bypass grafting (off-pump CABG) surgery;
• Patients undergoing left or right ventricular outflow tract obstruction surgery;
• Patients undergoing complex corrective surgery for congenital heart disease;
• Patients with an expected CPB exceeding 180 minutes or an anticipated aortic cross-clamp time exceeding 120 minutes;
• Patients expected to have a postoperative endotracheal tube removal time exceeding 24 hours;
• Patients with prolonged fasting or inability to self-feed;
• A history of malignant tumor;
• Patients with unstable preoperative vital signs requiring intra-aortic balloon pump (IABP), extracorporeal membrane oxygenation (ECMO)assistance, or endotracheal tube-assisted ventilation;
• A history of cardiac surgery;
• Patients with preoperative gastrointestinal symptoms, such as nausea, vomiting and diarrhea;
• Patients with a history of dialysis before surgery;
• Patients with a history of atrial fibrillation before surgery;
• Patients on long-term hepatorenal protective medications;
• Patients with hepatic and renal insufficiency (Child-Pugh class B or C, estimated glomerular filtration rate <35 mL/min/1.73 m2);
• Patients with abnormal baseline inflammatory markers \[interleukin-6 (IL6) >10 pg/mL, procalcitonin (PCT) >0.5 ng/mL, C reactive protein (CRP) >10 mg/L\];
• Patients diagnosed with infectious diseases, inflammatory immune diseases, or tumor;
• Patients who have received immunosuppressive or anti-inflammatory treatment;
• Patients allergic or intolerant to colchicine;
• Breastfeeding or pregnant women;
• Other situations deemed inappropriate for participation in the study by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Dong-Jin Wang — Nanjing

Publications

• Li X, Luo Y, Cai X, Lv Z, Kong Y, Guo Q, Zhu J, Pan T, Wang D. Anti-inflammatory effect of colchicine on organ damage during the perioperative period of cardiac surgery: a study protocol for a multicentre, randomised, double-blind, placebo-controlled clinical trial. BMJ Open. 2024 Sep 12;14(9):e084368. doi: 10.1136/bmjopen-2024-084368. PMID 39266309

Identifiers

NCT: NCT06118034 · 2023-LCYJ-ZD-03

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗