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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation; Post-Op Complication
• Intervention / Treatment: Combination product: CardiaMend in Combination with Amiodarone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 63
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Kayla Moore, BS; Phone Number: 773-702-8228; Email: kaymoore@bsd.uchicago.edu
• Study Contact Backup: Name: Valluvan Jeevanandam, MD; Phone Number: 773-702-2500; Email: jeevan@bsd.uchicago.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • The University of Chicago
      • Contact: Aaron Manewith; Phone Number: 773-702-2500; Email: amanewith@bsd.uchicago.edu
      • Contact: Arijus Kavaliauskas; Phone Number: 773-702-2500; Email: arijus.kavaliauskas@bsd.uchicago.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CardiaMend Pericardial and Epicardial Reconstruction Matrix used in combination with amiodarone; 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; 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.
No Intervention: University of Chicago's standard of care in patients undergoing isolated CABG or valve surgery; 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?

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

Collaborators and Investigators

• Sponsor: University of Chicago
• Collaborators: Helios Cardio Inc
• Investigators: Principal Investigator: Valluvan Jeevanandam, MD, Director of Heart and Vascular Center

Publications and helpful links

General Publications

• Rego A, Cheung PC, Harris WJ, Brady KM, Newman J, Still R. Pericardial closure with extracellular matrix scaffold following cardiac surgery associated with a reduction of postoperative complications and 30-day hospital readmissions. J Cardiothorac Surg. 2019 Mar 15;14(1):61. doi: 10.1186/s13019-019-0871-5.
• Echahidi N, Pibarot P, O'Hara G, Mathieu P. Mechanisms, prevention, and treatment of atrial fibrillation after cardiac surgery. J Am Coll Cardiol. 2008 Feb 26;51(8):793-801. doi: 10.1016/j.jacc.2007.10.043.
• Lowres N, Mulcahy G, Jin K, Gallagher R, Neubeck L, Freedman B. Incidence of postoperative atrial fibrillation recurrence in patients discharged in sinus rhythm after cardiac surgery: a systematic review and meta-analysis. Interact Cardiovasc Thorac Surg. 2018 Mar 1;26(3):504-511. doi: 10.1093/icvts/ivx348.
• Frendl G, Sodickson AC, Chung MK, Waldo AL, Gersh BJ, Tisdale JE, Calkins H, Aranki S, Kaneko T, Cassivi S, Smith SC Jr, Darbar D, Wee JO, Waddell TK, Amar D, Adler D; American Association for Thoracic Surgery. 2014 AATS guidelines for the prevention and management of perioperative atrial fibrillation and flutter for thoracic surgical procedures. J Thorac Cardiovasc Surg. 2014 Sep;148(3):e153-93. doi: 10.1016/j.jtcvs.2014.06.036. Epub 2014 Jun 30. No abstract available.
• Habbab LM, Chu FV. Intrapericardial Amiodarone for the Prevention of Postoperative Atrial Fibrillation. J Card Surg. 2016 Apr;31(4):253-8. doi: 10.1111/jocs.12700. Epub 2016 Feb 2.
• Camm AJ. Safety considerations in the pharmacological management of atrial fibrillation. Int J Cardiol. 2008 Jul 21;127(3):299-306. doi: 10.1016/j.ijcard.2007.11.006. Epub 2008 Jan 8.
• Beau J, Kulik A. Topical amiodarone to prevent postoperative atrial fibrillation: Need for further study. J Thorac Cardiovasc Surg. 2016 Feb;151(2):600. doi: 10.1016/j.jtcvs.2015.10.007. No abstract available.
• Feng XD, Wang XN, Yuan XH, Wang W. Effectiveness of biatrial epicardial application of amiodarone-releasing adhesive hydrogel to prevent postoperative atrial fibrillation. J Thorac Cardiovasc Surg. 2014 Sep;148(3):939-43. doi: 10.1016/j.jtcvs.2014.05.049. Epub 2014 May 22.
• Ayers GM, Rho TH, Ben-David J, Besch HR Jr, Zipes DP. Amiodarone instilled into the canine pericardial sac migrates transmurally to produce electrophysiologic effects and suppress atrial fibrillation. J Cardiovasc Electrophysiol. 1996 Aug;7(8):713-21. doi: 10.1111/j.1540-8167.1996.tb00579.x.
• Darsinos JT, Karli JN, Samouilidou EC, Krumbholz B, Pistevos AC, Levis GM. Distribution of amiodarone in heart tissues following intrapericardial administration. Int J Clin Pharmacol Ther. 1999 Jun;37(6):301-6.
• Marcano J, Campos K, Rodriguez V, Handy K, Brewer MA, Cohn WE. Intrapericardial delivery of amiodarone rapidly achieves therapeutic levels in the atrium. Heart Surg Forum. 2013 Oct;16(5):E279-86. doi: 10.1532/hsf98.2013188.

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2024
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: September 21, 2023
• First Submitted That Met QC Criteria: September 28, 2023
• First Posted (Actual): October 2, 2023

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Postoperative Complications; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Enzyme Inhibitors; Membrane Transport Modulators; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Sodium Channel Blockers; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Potassium Channel Blockers; Amiodarone
• Other Study ID Numbers: IRB23-0847

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Helios Cardio Inc., who will be the study collaborator will have access to only de-identified form of the data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes