Colchicine to Prevent Post-Pericardiotomy Syndrome and Atrial Fibrillation

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.

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.