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

Study Overview
=================
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.

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

Conditions
-----------------
Inflammatory Response, Cardiac Disease

Intervention / Treatment
-----------------
* Drug: Colchicine 0.5 MG
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 18 and 80 years, any gender; Patients undergoing elective cardiac surgery; Signed informed consent. Exclusion Criteria: Patients undergoing emergency surgery; Patients undergoing deep hypothermic circulatory arrest surgery; Predicted mortality rate exceeding 3% according to the European System for Cardiac Operative Risk Evaluation (EuroSCORE II); Patients undergoing off-pump coronary artery bypass grafting (CABG) surgery; Patients undergoing left or right ventricular outflow tract surgery; Patients undergoing complex congenital heart disease correction surgery; Patients with an expected extracorporeal circulation time exceeding 180 minutes or Anticipated aortic cross-clamp time exceeding 120 minutes; Patients with an expected postoperative extubation time exceeding 24 hours; Patients with long-term fasting or those unable to self-feed; Patients with a history of malignant tumors; Patients with unstable preoperative vital signs requiring ECMO or IABP assistance; Patients with a history of previous cardiac surgery; Patients with preoperative gastrointestinal symptoms; Patients on long-term hepatoprotective medication; Patients with impaired liver and kidney function (Child-Pugh class B or C); Estimated glomerular filtration rate <35 mL/min/1.73 m2); 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 disorders, infectious diseases, or malignant diseases; Patients who have received immunosuppressive or anti-inflammatory treatments; Patients allergic to or intolerant of colchicine; Breastfeeding or pregnant women; Other circumstances in which the investigator deems the patient unsuitable for participation in this study. Patients with a history of dialysis before surgery; Patients with a history of atrial fibrillation before surgery

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group (colchicine group)<br>The experimental group take 0.5mg of colchicine tablets orally for 3 days before surgery, and continue to take 0.5mg every other day (qod) for 10 days after tracheal extubation. | Drug: Colchicine 0.5 MG<br>* 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.<br>* Other names: Routine cardiovascular surgery and peri-operative management;|
| Placebo Comparator: Control group<br>The control group take 0.5mg of placebo tablets orally for 3 days before surgery, and continue to take 0.5mg every other day (qod) for 10 days after tracheal extubation. | Drug: Placebo<br>* 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.<br>* Other names: Routine cardiovascular surgery and peri-operative management;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of postoperative inflammatory diseases | Postoperative inflammatory diseases include: postoperative atrial fibrillation; perioperative myocardial injury; acute respiratory distress syndrome; Post-pericardial syndrome | postoperative 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxygenation index | SpO2 /FIO2 | postoperative day 1, 3, 5 and 7 | 
| Inflammatory index | WBC[×109/L], Neutrophil[NEU,%], Interleukin(IL)-1β[pg/mL], IL-6[pg/mL], IL-8[pg/mL], TNF-α[pg/mL], CRP[mg/L], PCT[ng/mL], neutrophil elastase[NE,ng/mL] and myeloperoxidase[MPO, ng/ml] | postoperative day 1, 3, 5 and 7 | 
| Myocardial injury marker | myoglobin[Myo, ng/ml], CK-MB[ng/ml], hs-cTnT[ng/ml] | postoperative day 1, 3, 5 and 7 | 
| Acute physiology and chronic health evaluation(APACHE II) socre | Interpretation of APACHE II : minimum 0 and maximum 71; increasing score is associated with an increasing risk of hospital death. acute physiology score, chronic health status score, and age adjustment score | postoperative day 1, 3, 5 and 7 | 
| Murray socre | 0 score - Indicates no lung injury; Less than 2.5 score - Indicates mild to moderate lung injury; More than 2.5 score - Indicates presence of severe ARDS. rs: respiratory rate, oxygenation, temperature, blood pressure, heart rate, and mental status | postoperative day 1, 3, 5 and 7 | 
| Liver and kidney function | ALT[U/L], AST[U/L], BUN[mmol/L], creatinine[μmol/L], eGFR[mL/min/1.73m2], total bilirubin[mg/dL] | postoperative day 1, 3, 5 and 7 | 
| DVMV | Duration of mechanical ventilation | postoperative 28 days | 
| ICU time | Time to stay in the intensive care unit | postoperative 28 days | 
| In-hospital time | All time during hospitalization | postoperative 28 days | 
| 30-day all-cause mortality | Proportion of deaths caused by various reasons within a certain period of time (30 days) compared to the total number of people in a certain group | postoperative 30 days | 
| 90-day all-cause mortality | Proportion of deaths caused by various reasons within a certain period of time (90 days) compared to the total number of people in a certain group | postoperative 90 days | 
| Incidence of gastrointestinal reactions | Adverse reactions related to colchicine | postoperative 7 days |