Clinical trial NCT06118034: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Inflammatory Response
Cardiac Disease
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital of Zhejiang University
name: Jinan Central Hospital
name: The First People's Hospital of Changzhou
name: Xinhua hospital of ILi in Kazakhstan automomous district
name: First Affiliated Hospital of Harbin Medical University
name: The Affiliated Hospital of Yangzhou University
name: Shandong Provincial Hospital
name: The First People's Hospital of Huai'an
name: The First Affiliated Hospital of Shihezi University Medical College
name: Affiliated Hospital of Nantong University
First posted: 2023-11-07
Enrollment: 768
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: Inclusion criteria

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

Exclusion criteria

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

Primary outcomes:
measure: Number of Participants with POAF
timeFrame: postoperative 10 days
measure: Number of Participants with PMI
timeFrame: postoperative 10 days
measure: Number of Participants with ARDS
timeFrame: postoperative 10 days
measure: Number of Participants with PPS
timeFrame: postoperative 10 days
Secondary outcomes:
measure: Oxygenation index
timeFrame: postoperative day 1, 3, 5 and 7
measure: Inflammatory index
timeFrame: postoperative day 1, 3, 5 and 7
measure: Myocardial injury marker
timeFrame: postoperative day 1, 3, 5 and 7
measure: Acute physiology and chronic health evaluation(APACHE II) socre
timeFrame: postoperative day 1, 3, 5 and 7
measure: Murray lung injury score
timeFrame: postoperative day 1, 3, 5 and 7
measure: Liver and kidney function
timeFrame: postoperative day 1, 3, 5 and 7
measure: DVMV
timeFrame: postoperative 28 days
measure: ICU time
timeFrame: postoperative 28 days
measure: In-hospital time
timeFrame: postoperative 28 days
measure: 30-day all-cause mortality
timeFrame: postoperative 30 days
measure: 90-day all-cause mortality
timeFrame: postoperative 90 days
measure: Incidence of gastrointestinal reactions
timeFrame: postoperative 7 days
measure: Surgical data
timeFrame: Surgical day
measure: Surgical data
timeFrame: Surgical day
measure: blood transfusion
timeFrame: Surgical day
measure: Rate of exudates on chest radiograph
timeFrame: postoperative 14 days
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Dong-Jin Wang
state: Jiangsu
Study officials:
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Tuo Pan, M.D
role: STUDY_DIRECTOR
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: DongJin Wang, M.D
role: STUDY_CHAIR
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: DongJin Wang, M.D
role: PRINCIPAL_INVESTIGATOR
References: