Colchicine to Prevent Post-Pericardiotomy Syndrome and Atrial Fibrillation

• Sponsor: Mayo Clinic (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02177266
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arms: 2
• Duration (Months): 18.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation; Post-pericardiotomy Syndrome; Constriction	Drug: Colchicine; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Colchicine Versus Placebo in Post-Cardiac Surgery Patients to Prevent Post-Pericardiotomy Syndrome and Atrial Fibrillation
• Study Start Date: May 1, 2015
• Actual Primary Completion Date: Nov 1, 2016
• Actual Study Completion Date: Nov 1, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Post Cardiac Surgery Atrial Fibrillation or Post-pericardiotomy Syndrome. [Baseline to 3 months]

Secondary Outcome Measures

1. Trans-thoracic Echocardiography for Constriction [Baseline to 3 months]

Other Outcome Measures

1. Number of Participants With Serious and Non-Serious Adverse Events [Baseline - 3 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic

Investigators

• Principal Investigator: Jae Oh, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jae K. Oh, M.D., Professor of Medicine, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT02177266
• Other Study ID Numbers: 13-008553
• First Posted: Jun 27, 2014
• Last Update Posted: Jun 21, 2017
• Last Verified: May 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Additional relevant MeSH terms: Atrial Fibrillation; Postpericardiotomy Syndrome; Syndrome; Colchicine

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled at Mayo Clinic in Rochester, Minnesota.

Arm/Group Title	Placebo	Colchicine
Arm/Group Description	A placebo pill (identical to the study drug Colchicine) will be given in a double-blinded fashion to study participants randomized to placebo.	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.
Period Title: Overall Study
STARTED	1	1
COMPLETED	0	0
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Placebo	Colchicine	Total
Arm/Group Description	A placebo pill (identical to the study drug Colchicine) will be given in a double-blinded fashion to study participants randomized to placebo.	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.	Total of all reporting groups
Overall Participants	1	1	2
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	1 100%	1 100%	2 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	1 100%	1 100%	2 100%
Region of Enrollment (participants) [Number]
United States	1 100%	1 100%	2 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The data were not analyzed because the 2 subjects enrolled withdrew before completing the study; the study was terminated early due to the difficulty in enrolling subjects.

Arm/Group Title	Placebo	Colchicine
Arm/Group Description	A placebo pill (identical to the study drug Colchicine) will be given in a double-blinded fashion to study participants randomized to placebo.	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.
Measure Participants	0	0

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The data were not analyzed because the 2 subjects enrolled withdrew before completing the study; the study was terminated early due to the difficulty in enrolling subjects.

Arm/Group Title	Placebo	Colchicine
Arm/Group Description	A placebo pill (identical to the study drug Colchicine) will be given in a double-blinded fashion to study participants randomized to placebo.	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.
Measure Participants	0	0

3. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

The data were not analyzed because the 2 subjects enrolled withdrew before completing the study; the study was terminated early due to the difficulty in enrolling subjects.

Arm/Group Title	Placebo	Colchicine
Arm/Group Description	A placebo pill (identical to the study drug Colchicine) will be given in a double-blinded fashion to study participants randomized to placebo.	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.
Measure Participants	0	0

Adverse Events

Time Frame	3 months
Arm/Group Title	Placebo		Colchicine
Arm/Group Description	A placebo pill (identical to the study drug Colchicine) will be given in a double-blinded fashion to study participants randomized to placebo.		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.
All Cause Mortality
	Placebo		Colchicine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Serious Adverse Events
	Placebo		Colchicine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Colchicine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		1/1 (100%)
Gastrointestinal disorders
Nausea and dry heaves	0/1 (0%)	0	1/1 (100%)	1
Skin and subcutaneous tissue disorders
Skin breakdown	0/1 (0%)	0	1/1 (100%)	1

Limitations/Caveats

The data were not analyzed because the 2 subjects enrolled withdrew before completing the study; the study was terminated early due to the difficulty in enrolling subjects.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.