Colchicine to Prevent Post-Pericardiotomy Syndrome and Atrial Fibrillation

Colchicine Versus Placebo in Post-Cardiac Surgery Patients to Prevent Post-Pericardiotomy Syndrome and Atrial Fibrillation

The study will determine the benefit of Colchicine versus placebo for cardiac surgery patients on the post-operative development of atrial fibrillation and post-pericardiotomy syndrome.

Primary Objective. Colchicine will reduce the composite endpoint of incidence of post-operative atrial fibrillation and post-pericardiotomy syndrome at 3 months following cardiac surgery.

Secondary Objectives.

1. Colchicine will reduce the incidence of constrictive physiology on echocardiography at 3 months following cardiac surgery.
2. Reduction in the burden of symptomatic and asymptomatic atrial fibrillation in the 3 months following cardiac surgery with the use of colchicine.

Study Overview

• Status: Terminated
• Conditions: Atrial Fibrillation; Post-pericardiotomy Syndrome; Constriction
• Intervention / Treatment: Drug: Placebo; Drug: Colchicine

Detailed Description

Background. Patients undergoing cardiac surgery are at risk for post-pericardiotomy syndrome and post-operative atrial fibrillation. It is unknown whether post-pericardiotomy syndrome predisposes patients to constrictive pericarditis, but cardiac surgery is currently the most common cause of constrictive pericarditis. A multicenter European study demonstrated that Colchicine is a promising treatment to help prevent the development of pericardial effusions, atrial fibrillation and post-pericardiotomy syndrome. However, Colchicine is not routinely given to patients after a cardiac surgery and the impact of Colchicine on post-operative atrial fibrillation and constrictive pericarditis have not been studied in the United States.

Methods. This is a randomized, double-blinded placebo controlled study for patients undergoing cardiac surgery to determine if Colchicine in comparison to placebo is effective in preventing the development of post-operative atrial fibrillation, post-pericardiotomy syndrome and constrictive physiology. The investigators will randomize 278 adults prior to undergoing cardiac surgery for coronary artery bypass graft (CABG) or aortic valve disease to receive either placebo or Colchicine 0.6mg bid for one month starting 48-72 hours preoperatively. The investigators will follow participants for 3 months to determine the development of a post-pericardiotomy syndrome. In addition, post-operative atrial fibrillation will be determined based on continuous telemetry from operation up to 5 days prior to hospital discharge and after discharge by using remote telemetry monitoring with BodyGuardianTM. C-reactive protein (CRP) will be obtained prior to hospital discharge and at 3 month follow-up. Echocardiography will be done initially in the post-operative course prior to hospital discharge and then again at 3 months to assess for the presence of pericardial effusion, diastolic dysfunction, left atrial enlargement and constrictive physiology. The presence of pleural effusion will be done by echocardiogram.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All consecutive adult patients (age > 40) undergoing standard (non-minimally invasive) coronary artery bypass surgery and/or aortic valve surgery will be approached for enrollment.
• All patients must be able to provide informed consent and comply with the 3 month follow-up.
• For women of reproductive capability, contraception is necessary and required.

Exclusion Criteria:

• Epidermal growth factor receptor (eGFR) < 30 mL/min/1.73 m^2, serum creatinine > 2.5 mg/dL or requiring dialysis
• Known permanent or current atrial fibrillation (history of paroxysmal atrial fibrillation allowed if in sinus rhythm at present)
• Allergy to colchicine or already treated with colchicine.
• Known blood dyscrasia (acute or chronic leukemia, pancytopenia, aplastic anemia, leukopenia)
• Known serious gastrointestinal disease
• Known severe liver disease (cirrhosis, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2x the upper limit of normal, Model End Stage Liver Disease (MELD) score > 20)
• Women of childbearing potential not using contraception.
• Patients with HIV or AIDS as the use of protease inhibitors can result in serious colchicine toxicity.
• Patients who are treated with strong CYP3A4 inhibitors (clarithromycin/erythromycin, chloramphenicol, ketoconazole/itraconazole, and nefazodone).
• There is a risk of rhabdomyolysis with the use of digoxin and colchicine, we will exclude patients who require ongoing treatment with digoxin.
• Inability or unwillingness of the individual to give written informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; A placebo pill (identical to the study drug Colchicine) will be given in a double-blinded fashion to study participants randomized to placebo.	Drug: Placebo; The placebo will match the study drug.
EXPERIMENTAL: Colchicine; Colchicine 0.6mg bid will be given to study participants randomized to the study drug arm beginning at 48-72 hours prior to the planned cardiac surgery and then continued for a total of 30 days.	Drug: Colchicine; Colchicine 0.6mg bid will be given to study participants randomized to the study drug arm beginning at 48-72 hours prior to the planned cardiac surgery and then continued for a total of 30 days.; Other Names: Colcrys

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Patients With Post Cardiac Surgery Atrial Fibrillation or Post-pericardiotomy Syndrome.	Baseline to 3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Trans-thoracic Echocardiography for Constriction	Baseline to 3 months

Other Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Serious and Non-Serious Adverse Events	Baseline - 3 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Jae Oh, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (ACTUAL): November 1, 2016
• Study Completion (ACTUAL): November 1, 2016

Study Registration Dates

• First Submitted: June 18, 2014
• First Submitted That Met QC Criteria: June 25, 2014
• First Posted (ESTIMATE): June 27, 2014

Study Record Updates

• Last Update Posted (ACTUAL): June 21, 2017
• Last Update Submitted That Met QC Criteria: May 24, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Postoperative Complications; Disease; Arrhythmias, Cardiac; Syndrome; Atrial Fibrillation; Postpericardiotomy Syndrome; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: 13-008553

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes