Colchicine to Prevent Post-Pericardiotomy Syndrome and Atrial Fibrillation

Atrial Fibrillation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02177266
• Other study ID #: 13-008553
• Status: Not yet recruiting
• Phase: Phase 3
• First received: June 18, 2014
• Last updated: June 25, 2014
• Start date: June 2014

Study information

• Verified date: June 2014
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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 (Imazio et al, Circulation 2011;124:2290-5). 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 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 242
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria The study population will consist participants enrolled at the Mayo Clinic, Rochester Minnesota.

• 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

All candidates meeting any of the exclusion criteria at baseline will be excluded from study participation:

• eGFR < 30 mL/min/1.73 m2, 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, AST/ALT > 2x the upper limit of normal, 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/erythyromycin, 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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrial Fibrillation
• Constriction
• Constriction, Pathologic
• Post-pericardiotomy Syndrome
• Postpericardiotomy Syndrome
• Syndrome

Intervention

Drug:
• Colchicine

• Placebo

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants with Serious and Non-Serious Adverse Events		Baseline - 3 months	Yes
Primary	Number of patients with post cardiac surgery atrial fibrillation or post-pericardiotomy syndrome.		Baseline to 3 months	No
Secondary	Trans-thoracic echocardiography for constriction		Baseline to 3 months	No