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

NCT06063538 | Recruiting Early Phase 1 FDA Drug FDA Device

• 1 other identifier: IRB23-0847
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Atrial Fibrillation; Post-Op Complication

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Additional Hospital Time Required Due to Atrial Fibrillation/Flutter

  Through discharge, an average 7 days to 2 weeks

Study Arms (2)

CardiaMend Pericardial and Epicardial Reconstruction Matrix used in combination with amiodarone

EXPERIMENTAL

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

University of Chicago's standard of care in patients undergoing isolated CABG or valve surgery

NO INTERVENTION

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).

Interventions

CardiaMend in Combination with Amiodarone COMBINATION_PRODUCT

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.

CardiaMend Pericardial and Epicardial Reconstruction Matrix used in combination with amiodarone

Eligibility Criteria

• Age: 20 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• University of Chicago: lead
• Helios Cardio Inc.: collaborator

Study Sites (1)

The University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Related Publications (14)

• 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.

  PMID: 26833498 BACKGROUND

• 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.

  PMID: 18191470 BACKGROUND

• 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.

  PMID: 25129609 BACKGROUND

• 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.

  PMID: 26806512 BACKGROUND

• de Lima Conceicao MR, Teixeira-Fonseca JL, Marques LP, Souza DS, da Silva Alcantara F, Orts DJB, Roman-Campos D. Extracellular acidification reveals the antiarrhythmic properties of amiodarone related to late sodium current-induced atrial arrhythmia. Pharmacol Rep. 2024 Jun;76(3):585-599. doi: 10.1007/s43440-024-00597-2. Epub 2024 Apr 15.

  PMID: 38619735 BACKGROUND

• Egan S, Collins-Smyth C, Chitnis S, Head J, Chiu A, Bhatti G, McLean SR. Prevention of postoperative atrial fibrillation in cardiac surgery: a quality improvement project. Can J Anaesth. 2023 Dec;70(12):1880-1891. doi: 10.1007/s12630-023-02619-8. Epub 2023 Nov 2.

  PMID: 37919634 BACKGROUND

• Piccini JP, Ahlsson A, Dorian P, Gillinov AM, Kowey PR, Mack MJ, Milano CA, Noiseux N, Perrault LP, Ryan W, Steinberg JS, Voisine P, Waldron NH, Gleason KJ, Titanji W, Leaback RD, O'Sullivan A, Ferguson WG, Benussi S; NOVA-AF Investigators. Efficacy and Safety of Botulinum Toxin Type A for the Prevention of Postoperative Atrial Fibrillation. JACC Clin Electrophysiol. 2024 May;10(5):930-940. doi: 10.1016/j.jacep.2024.01.020. Epub 2024 Apr 24.

  PMID: 38661602 BACKGROUND

• 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.

  PMID: 18294562 RESULT

• 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.

  PMID: 29161419 RESULT

• 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.

  PMID: 30876459 RESULT

• 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.

  PMID: 25043862 RESULT

• 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.

  PMID: 8856462 RESULT

• 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.

  PMID: 10395122 RESULT

• 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.

  PMID: 24364084 RESULT

MeSH Terms

Conditions

Atrial Fibrillation; Postoperative Complications

Interventions

Amiodarone

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Valluvan Jeevanandam, MD

  Director of Heart and Vascular Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Valluvan Jeevanandam, MD

CONTACT

773-702-2500; jeevan@bsd.uchicago.edu

Leila Yazdanbakhsh, MSCI

CONTACT

773-834-5087; leila.yazdanbakhsh@bsd.uchicago.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 21, 2023
• First Posted: October 2, 2023
• Study Start: February 15, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: March 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)