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

Cardiac Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06118034
• Other study ID #: DJ Wang
• Status: Recruiting
• Phase: Phase 3
• Start date: January 28, 2024
• Est. completion date: December 30, 2026

Study information

• Verified date: August 2023
• Source: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Contact: Tuo Pan, MD
• Phone: +8615205160210
• Email: pan_tuo[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 768
• Est. completion date: December 30, 2026
• Est. primary completion date: August 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiac Disease
• Heart Diseases
• Inflammatory Response

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	Dong-Jin Wang	Nanjing	Jiangsu

Sponsors (8)

Lead Sponsor	Collaborator
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School	First Affiliated Hospital of Harbin Medical University, First Affiliated Hospital of Zhejiang University, Jinan Central Hospital, Renji Hospital Affiliated to The Shanghai Jiao Tong University Medical School, The First People's Hospital of Changzhou, Xinhua hospital of ILi in Kazakhstan automomous district, Yangzhou University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with POAF	POAF: Onset of new atrial fibrillation in patients within 10 days post-surgery.	postoperative 10 days
Primary	Number of Participants with PMI	PMI: Patient's high-sensitivity cardiac troponin T (hs-cTnT) exceeds 0.8 ng/L on the first day after surgery, and there is an increase of 10% or more on the second day compared to the first day postoperatively.	postoperative 10 days
Primary	Number of Participants with ARDS	ARDS: Acute Respiratory Distress Syndrome	postoperative 10 days
Primary	Number of Participants with PPS	PPS: post-pericardiotomy syndrome	postoperative 10 days
Secondary	Oxygenation index	SpO2 /FIO2	postoperative day 1, 3, 5 and 7
Secondary	Inflammatory index	WBC[×109/L], Neutrophil[NEU,%], Interleukin(IL)-1ß[pg/mL], IL-6[pg/mL], IL-8[pg/mL], TNF-a[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
Secondary	Myocardial injury marker	myoglobin[Myo, ng/ml], CK-MB[ng/ml], hs-cTnT[ng/ml]	postoperative day 1, 3, 5 and 7
Secondary	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
Secondary	Murray lung injury score	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
Secondary	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
Secondary	DVMV	Duration of mechanical ventilation	postoperative 28 days
Secondary	ICU time	Time to stay in the intensive care unit	postoperative 28 days
Secondary	In-hospital time	All time during hospitalization	postoperative 28 days
Secondary	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
Secondary	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
Secondary	Incidence of gastrointestinal reactions	Adverse reactions related to colchicine	postoperative 7 days
Secondary	Surgical data	cardiopulmonary bypass time (min)	Surgical day
Secondary	Surgical data	aortic cross-clamp time (min)	Surgical day
Secondary	blood transfusion	blood transfusion volume(ml)	Surgical day
Secondary	Rate of exudates on chest radiograph	Chest radiograph on postoperative days 1, 2, and 3, and chest CT within 14 days after surgery	postoperative 14 days