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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат 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.

Первичные конечные точки

• Number of Participants with POAF [Срок оценки: postoperative 10 days]
• Number of Participants with PMI [Срок оценки: postoperative 10 days]
• Number of Participants with ARDS [Срок оценки: postoperative 10 days]
• Number of Participants with PPS [Срок оценки: postoperative 10 days]

Вторичные конечные точки (12)

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

Критерии участия

Критерии включения

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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Dong-Jin Wang — Нанкин

Публикации

• 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

Идентификаторы

NCT: NCT06118034 · 2023-LCYJ-ZD-03

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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