Prevention of Postoperative Atrial Fibrillation (POAF) Using Intra-Pericardial Amiodarone

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the combination of CardiaMend, with the addition of amiodarone in the prevention of postoperative atrial fibrillation (POAF) in patients undergoing cardiac arterial bypass grafting (CABG) or valve surgery.

Detailed Description
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This study involves using CardiaMend, an FDA cleared (K210331) pericardial reconstruction matrix with the addition of amiodarone, an FDA approved antiarrhythmic drug, as a prevention of post operative atrial fibrillation. This is a single-center, prospective randomized study enrolling adult subjects undergoing isolated cardiac arterial bypass or valve surgery, via complete median sternotomy. CardiaMend will be used according to the Instructions for Use, and then patted dry to facilitate implantation. Four ampules of amiodarone (150mg/3ml; 12cc total volume) will be drawn into a syringe. 2cc will be dripped over the right atrium and a small CardiaMend patch placed to cover this area. Another 2cc will be used over the left atrium and covered with the CardiaMend. The anterior pericardial space will be closed without putting pressure on the underlying structures using the CardiaMend attached to the native pericardium utilizing running 4-0 monofilament suture. A small edge may be left open for drain placement and a small slit for the Left Internal Mammary Artery (LIMA) in case of CABG. The remaining 8 cc of amiodarone will be instilled to the closed pericardial space. Patients will have continuous electrocardiogram (EKG) until discharge. If clinically indicated, patients will receive a monitor for home monitoring per standard of care.

Official Title
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A Prospective Study Using Intra-Pericardial Amiodarone for the Prevention of Postoperative Atrial Fibrillation (POAF) in Patients Undergoing Cardiac Arterial Bypass Grafting and/or Valve Surgery

Conditions
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Atrial Fibrillation, Post-Op Complication

Intervention / Treatment
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* Combination Product: CardiaMend in Combination with Amiodarone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject aged 20-85 years old. Patients able to provide written informed consent, understand, and be willing to comply with study-related procedures. Participants who are scheduled to undergo open-chest cardiac surgery via complete median sternotomy. Includes: Coronary artery bypass graft (CABG) and/or valve repair/replacement procedures (aortic, mitral, or tricuspid) Isolated ascending aortic aneurysm replacement/repair Note: Left atrial appendage (LAA) procedures are allowed if CABG and/or valve repair or replacement is the qualifying surgical procedure, but is not a qualifying surgical procedure on its own. In sinus rhythm at the time of office visit and prior electrocardiogram (EKG) (note: continuous EKG monitoring for 48 hours is not required). Exclusion Criteria: Subject unable to give voluntary written informed consent, is unlikely to cooperate or is legally incompetent, including subjects who are institutionalized by court or official order, or in a dependency relationship with, testing center or investigator. Any condition which could interfere with the subject's ability to comply with the study. Ongoing participation in an interventional clinical study or during the preceding 30 days. Female subjects who are pregnant, breastfeeding, were pregnant within the last three months, or are planning to become pregnant during the course of the study. Active skin or deep infection at the site of implantation. History of chronic wounds or wound-healing disorders. Known connective tissue diseases (e.g. Ehlers-Danlos syndrome, Epidermolysis bullosa, Marfan syndrome, Osteogenesis imperfecta). Immune-suppressed subjects, immune-deficiency subjects (properly managed diabetes mellitus is not an exclusion criterion). Concomitant oral or IV systemic corticosteroid therapy and/or other constant anti-inflammatory therapies. Patients already receiving amiodarone as a treatment for atrial fibrillation or ventricular arrhythmias. Disease of the left pleura, previous intervention in the left pleural space, or chest deformity. Subjects with end-stage chronic-renal disease / dialysis. STS (Society of Thoracic Surgeons Score) risk score >5.5% for 30 day mortality.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: To demonstrate that there is no systemic presence of amiodarone, the first three patient will receive 600 mg amiodarone into the intact pericardial space (IPS). Amiodarone serum levels will be tested at post operative days 2 and 6. The study will only proceed if there is a serum amiodarone level less than 25% of the normal therapeutic level. This should insure lack of systemic toxicity. After the first 3 patients have demonstrated low amiodarone blood levels, a total of up to 60 patients will be enrolled in the study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CardiaMend Pericardial and Epicardial Reconstruction Matrix used in combination with amiodarone<br>Patients randomized to this study arm includes the CardiaMend which will be used according to the instructions for use. It will be patted dry to facilitate implantation. Pieces will be cut to cover the right and left atria. The remaining piece will be contoured to close the anterior pericardial space. Four ampules of amiodarone (150mg/3ml; 12cc total volume) will be drawn into a syringe. 2cc will be dripped over the right atrium and a small CardiaMend patch placed to cover this area. Another 2cc will be used over the left atrium and covered with the CardiaMend. The anterior pericardial space will be closed without putting pressure on the underlying structures using the CardiaMend attached to the native pericardium utilizing running 4-0 monofilament suture. | Combination Product: CardiaMend in Combination with Amiodarone<br>* The first three patient will receive 600 mg amiodarone into the intact pericardial space. Amiodarone serum levels will be tested at post operative days 2 and 6. The study will only proceed if there is a serum amiodarone level less than 25% of the normal therapeutic level. This should insure lack of systemic toxicity. After the first 3 patients have demonstrated low amiodarone blood levels, a total of up to 60 patients will be enrolled in the study. The CardiaMend patch will saturated per the instructions and be sutured into place. Amiodarone will be dripped directly over the heart.<br>|
| No Intervention: University of Chicago's standard of care in patients undergoing isolated CABG or valve surgery<br>The standard of care for this study at The University of Chicago is to ligate the left atrial appendage (LAA) during the proposed cardiac surgery (intra-operative) to reduce the occurrence of post operative atrial fibrillation (A-FIB) in combination with amiodarone injections (if applicable). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post Operative Atrial Fibrillation | The patients have continuous electrocardiogram (EKG) monitoring until discharge to evaluate for any evidence of atrial fibrillation or atrial flutter which lasts longer than one hour or if less than one hour, requires medical or procedural intervention. Evidence of atrial fibrillation or atrial flutter will be confirmed by 12 lead electrocardiogram by loss or changes to the P wave, as well as irregularities in the QRS wave interval, heart rhythm, or rate. If clinically indicated, patients will receive a monitor for home monitoring per standard of care. | Through discharge, an average 7 days to 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Additional Hospital Time Required Due to Atrial Fibrillation/Flutter | Burden of atrial fibrillation as defined by additional treatment regimen, additional time in intensive care unit (ICU), complications directly associated with atrial fibrillation | Through discharge, an average 7 days to 2 weeks |