COlchicine in Cardiac Surgery (COCS)

• ClinicalTrials.gov Identifier: NCT04224545
• Recruitment Status: Recruiting
• First Posted: January 13, 2020
• Last Update Posted: May 29, 2020
• Sponsor: Bakulev Scientific Center of Cardiovascular Surgery
• Information provided by (Responsible Party): Bakulev Scientific Center of Cardiovascular Surgery

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Colchicine Adverse Reaction; Atrial Fibrillation New Onset	Drug: Colchicine; Drug: Placebo	Phase 4

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1000 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: A randomized double-blind controlled trial in two groups
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Colchicine for Prevention Atrial Fibrillation After Cardiac Surgery in the Early Postoperative Period
• Actual Study Start Date: December 23, 2019
• Estimated Primary Completion Date: November 30, 2021
• Estimated Study Completion Date: December 30, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Colchicine; Colchicine 1 mg day	Drug: Colchicine; Colchicine at a dose of 1 mg a day before surgery, 2, 3, 4, 5 days after surgery.
Placebo Comparator: Placebo; Sugar pill	Drug: Placebo; Placebo started a day before surgery, 2, 3, 4, 5 days after surgery.

Outcome Measures

Primary Outcome Measures :

1. Number of participants with postoperative atrial fibrillation. [ Time Frame: 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.

Secondary Outcome Measures :

1. Number of participants with lethal and non-lethal events. [ Time Frame: 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. ]
   The main nosocomial lethal and non-lethal events (death, stroke, myocardial infarction, heart failure).
2. Fluid in the pericardium. [ Time Frame: Diagnostics will be carried out on the 3rd and 5th day after surgery. ]
   Fluid in the pericardium evaluated by echocardiography.
3. Fluid in the pleura. [ Time Frame: Diagnostics will be carried out on the 3rd and 5th day after surgery. ]
   Fluid in the pleura evaluated by echocardiography.
4. Acute kidney damage (according to the dynamics of creatinine clearance). [ Time Frame: Diagnostics will be carried out a day before surgery and on the 3rd and 5th day after surgery. ]
   Dynamics of creatinine clearance.
5. Inflammation in blood plasma. [ Time Frame: Diagnostics will be carried out a day before surgery and on the 3rd and 5th day after surgery. ]
   Dynamics of biomarker of inflammation in blood plasma (neutrophils).
6. Liver damage [ Time Frame: Diagnostics will be carried out a day before surgery and on the 3rd and 5th day after surgery. ]
   Dynamics of biomarkers of liver damage (aspartate aminotransferase, alanine aminotransferase).

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

• 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

Contacts and Locations

Contacts

Contact: Vladimir Shvartz; +74954147894; vashvarts@bakulev.ru

Locations

Russian Federation

Bakulev National Medical Research Center for Cardiovascular Surgery; Recruiting

Moscow, Russian Federation

Contact: Vladimir Shvartz

Sponsors and Collaborators

Bakulev Scientific Center of Cardiovascular Surgery

Investigators

• Principal Investigator: Vladimir Shvartz; Bakulev National Medical Research Center for Cardiovascular Surgery

More Information

• Responsible Party: Bakulev Scientific Center of Cardiovascular Surgery
• ClinicalTrials.gov Identifier: NCT04224545
• Other Study ID Numbers: 23122019
• First Posted: January 13, 2020
• Last Update Posted: May 29, 2020
• Last Verified: May 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bakulev Scientific Center of Cardiovascular Surgery:

Colchicine; Postoperative atrial fibrillation; Anti-inflammatory; Cardiac surgery; Sympatholytic

Additional relevant MeSH terms:

Atrial Fibrillation; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Colchicine; Gout Suppressants; Antirheumatic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents