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临床试验/NCT04224545
NCT04224545已完成4 期

Colchicine for Prevention Atrial Fibrillation After Cardiac Surgery in the Early Postoperative Period

Bakulev Scientific Center of Cardiovascular Surgery2 个研究点 分布在 1 个国家目标入组 267 人开始时间: 2019年12月23日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
4 期
状态
已完成
发起方
入组人数
267
试验地点
2
主要终点
Number of participants with postoperative atrial fibrillation.

研究概览

简要总结

Postoperative atrial fibrillation (POAF) is a major complication of cardiac surgery, which could lead to high morbidity and mortality, increase duration of hospital stay and increase the cost of treatment. Colchicine possesses both anti-inflammatory and sympatholytic properties, so it has been studied to prevent POAF. The ACC/AHA guidelines for colchicine contain a class IIB recommendation, but the ESC guidelines do not recommend this drug. More researches are needed to focus on reducing of side effects by optimizing the colchicine regimen to reduce the incidence of gastrointestinal side effects. It is believed that further research is needed to investigate the efficacy and safety of colchicine in these conditions.

This research is aimed to study the effectiveness of short-term administration of the drug.

详细描述

Postoperative atrial fibrillation (POAF) is a major complication of cardiac surgery, which could lead to high morbidity and mortality, increase duration of hospital stay and increase the cost of treatment. Postoperative AF is considered as a multifactorial phenomenon. Its pathogenesis is characterized by inflammation, oxidative stress and autonomic dysfunction. Several predisposing factors lead to the development of POAF, including pre -, intra-and postoperative factors. The main of them are age, previous history of major cardiovascular risk factors and ischemic reperfusion injury during surgery. Treatment of POAF involves drugs to control the frequency of rhythm in hemodynamically stable patients and other treatment regimens usually used for the treatment of AF. Intraoperative administration of beta-blockers and some antiarrhythmic drugs is recommended by international clinical guidelines. In addition, previous treatment consisting of the use of colchicine, magnesium sulfate, statins and antioxidants have reduced the incidence of postoperative AF. However, the results of large-scale randomized trials have observed the development of undesirable adverse reactions.

Despite these recommendations, the question of the correct regimen for prevention of POAF remains controversial. Colchicine possesses both anti-inflammatory and sympatholytic properties, so it has been studied to prevent POAF. The ACC/AHA guidelines for colchicine contain a class IIB recommendation, but the ESC guidelines do not recommend this drug.

Two studies sequentially COPPS-1 and COPPS-2 evaluated the effect of colchicine on the incidence of POAF after open heart surgery (COPPS-1) and the development of postcardiotomy syndrome (COPPS-2). In COPPS-1, patients (n=336) were treated with colchicine from the third day after surgery for a month and showed a significant decrease of POAF after heart surgery over the entire follow-up period. 360 patients were evaluated in the COPPS-2 study. The incidence of POAF between the colchicine and placebo groups was comparable, although colchicine significantly reduced postpericardiotomy syndrome. The main limitation of the COPSS-2 study was the high rate of cessation of intervention (20% of participants), which had a significant impact on the outcome of the trial.

Based on the latest meta-analysis of the colchicine effect on POAF after heart surgery, it was found that it still reduces POAF compared with control (HR = 0.69, 95% IM 0.57-0.84, p = 0.0002) and the duration of hospital stay was reduced by 1.2 days (95% IM -1.89 to -0.44, p = 0.002); however, the frequency of adverse gastrointestinal events increased significantly (HR = 2.52, 95% IM 1.62-3.93, p < 0.0001). Despite the high level of side effects, a significant reduction of POAF outweighs the balance in the favor of its use. However, more researches are needed to focus on reducing of side effects by optimizing the colchicine regimen to reduce the incidence of gastrointestinal side effects. It is believed that further research is needed to investigate the efficacy and safety of colchicine in these conditions.

This research is aimed to study the effectiveness of short-term administration of the drug.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Treatment
盲法
Triple (Participant, Care Provider, Investigator)

入排标准

年龄范围
40 Years 至 80 Years(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • Adult patients awaiting elective cardiac surgery (CABG and/or AVR (aortic valve replacement), who are willing and able to give informed consent for participation in the study and who are in sinus rhythm and not taking any antiarrhythmic medication, except beta-adrenergic blocking agents, at the time before surgery.

排除标准

  • History of persistent or long-term atrial fibrillation/atrial flutter
  • Congenital heart disease, except the bicuspid AV
  • Frequent VE/SVE, AV block 2-3 degrees
  • Use of corticosteroids during the last month
  • Taking any antiarrhythmic drugs, except beta-blockers, within the last 1 month
  • Prior "open" heart surgery
  • Moderate to severe renal failure (creatinine clearance < 50 ml / min)
  • History of obstructive hepato-biliary disease or other serious hepatic disease
  • Significant mitral valve disease (moderate or severe mitral regurgitation-eg. > grade II and/or mitral stenosis & mitral annular calcification).
  • Patient participation in another clinical trial

研究组 & 干预措施

Colchicine

Experimental

Colchicine 1 mg day (COLCHICINA LIRCA ® ACARPIA Farmaceutici S.r.l.)

干预措施: Colchicine Pill (Drug)

Placebo

Placebo Comparator

Sugar pill

干预措施: Placebo (Drug)

结局指标

主要结局

Number of participants with postoperative atrial fibrillation.

时间窗: Monitoring is carried out immediately after surgery and will be continued until the end of the 7th postoperative day.

POAF detected on continuous ECG monitoring.

次要结局

  • Number of participants with lethal and non-lethal events.(Participants will be followed for the duration of the postoperative period up to the day of initial discharge from the hospital, an expected average of 7 days.)
  • Fluid in the pericardium.(Diagnostics will be carried out on the 3rd and 5th day after surgery.)
  • Acute kidney damage (according to the dynamics of creatinine clearance).(Diagnostics will be carried out a day before surgery and on the 3rd and 5th day after surgery.)
  • Fluid in the pleura.(Diagnostics will be carried out on the 3rd and 5th day after surgery.)
  • Inflammation in blood plasma.(Diagnostics will be carried out a day before surgery and on the 3rd and 5th day after surgery.)
  • Liver damage(Diagnostics will be carried out a day before surgery and on the 3rd and 5th day after surgery.)

研究者

发起方
Bakulev Scientific Center of Cardiovascular Surgery
申办方类型
Other Gov
责任方
Sponsor

研究点 (2)

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