Intra-Pericardial Amiodarone for Postoperative Atrial Fibrillation

Overseen By Leila Yazdanbakhsh, MSCI

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Chicago

Must be taking: CardiaMend, Amiodarone

Must not be taking: Corticosteroids, Anti-inflammatories

Disqualifiers: Pregnancy, Connective tissue diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Surgery duration

63 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a combination of CardiaMend and intra-pericardial amiodarone (an antiarrhythmic drug) can prevent atrial fibrillation (irregular heartbeat) after heart surgery. The focus is on patients undergoing coronary artery bypass grafting (CABG) or valve surgery. Participants are divided into two groups: one receiving standard care and the other receiving the experimental CardiaMend and amiodarone treatment. Individuals scheduled for open-chest heart surgery and in normal heart rhythm before surgery may be suitable for this trial. As an Early Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants a chance to contribute to groundbreaking medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are already taking amiodarone or certain anti-inflammatory therapies.

What prior data suggests that this combination of CardiaMend and intra-pericardial amiodarone is safe?

Research shows that using intra-pericardial amiodarone during heart surgery can help prevent irregular heartbeats after the operation, known as postoperative atrial fibrillation (POAF). This treatment carries a low risk of causing side effects outside the heart. Previous studies found that amiodarone effectively stops POAF and is usually well-tolerated. Some individuals might experience low blood pressure or heart issues, but these are less common. Overall, the treatment appears safe for patients undergoing heart surgery. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using intra-pericardial amiodarone for postoperative atrial fibrillation because it offers a targeted delivery method. Unlike standard treatments that involve systemic administration, this approach places the medication directly within the pericardial space, potentially enhancing its effectiveness while minimizing side effects. Additionally, when combined with the CardiaMend matrix, it allows precise coverage of the atria, which may improve outcomes by stabilizing the heart tissue more effectively than conventional methods. This combination is designed to reduce the incidence of atrial fibrillation following heart surgery, offering a promising new strategy for patient care.

What evidence suggests that this trial's treatments could be effective for preventing postoperative atrial fibrillation?

Research has shown that amiodarone ranks among the best drugs for preventing irregular heartbeats after heart surgery, known as postoperative atrial fibrillation (POAF). In this trial, one arm uses CardiaMend combined with intra-pericardial amiodarone, applying amiodarone directly to the heart during surgery. Studies have found that this method can prevent POAF, reducing the risk of complications without causing significant side effects elsewhere in the body. Meanwhile, the standard care arm involves ligating the left atrial appendage during surgery, which may also include amiodarone injections if applicable. These findings suggest that using amiodarone in this manner could effectively prevent heartbeat problems after surgery. ^{1 3 5 6 7}

Who Is on the Research Team?

Valluvan Jeevanandam, MD

Principal Investigator

Director of Heart and Vascular Center

Are You a Good Fit for This Trial?

This trial is for adults aged 20-85 undergoing open-chest heart surgery, such as bypass or valve repair, who can consent and follow study procedures. Excluded are those with certain conditions that affect compliance, ongoing clinical study participation, pregnancy/breastfeeding recently or during the study, infections at implant sites, connective tissue diseases, immune deficiencies (except well-managed diabetes), high surgical risk scores (>5.5%), chronic wounds or on amiodarone already.

Inclusion Criteria

I am scheduled for open-chest heart surgery, including procedures like bypass or valve repair.

I am between 20 and 85 years old.

Your heart is beating regularly when you visit the doctor and during your previous electrocardiogram (EKG) test.

Exclusion Criteria

I am currently taking amiodarone for heart rhythm problems.

I am not pregnant, breastfeeding, have been pregnant in the last 3 months, nor plan to become pregnant during the study.

I have an infection where my implant will be placed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

CardiaMend and amiodarone are used during cardiac surgery to prevent postoperative atrial fibrillation

Surgery duration

1 visit (in-person, surgery)

Monitoring

Continuous electrocardiogram (EKG) monitoring until discharge to evaluate for atrial fibrillation

7 days to 2 weeks

Continuous monitoring (in-hospital)

Follow-up

Participants are monitored for safety and effectiveness after discharge, including home monitoring if clinically indicated

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Intra-Pericardial Amiodarone

Trial Overview The trial tests a combination of CardiaMend with Amiodarone to prevent postoperative atrial fibrillation in patients after cardiac surgery like artery bypass grafting or valve surgery. It aims to see if this combo is more effective than current methods used.

How Is the Trial Designed?

Group I: CardiaMend Pericardial and Epicardial Reconstruction Matrix used in combination with amiodarone Experimental Treatment 1 Intervention

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.

Group II: University of Chicago's standard of care in patients undergoing isolated CABG or valve surgery Active Control 1 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).

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Helios Cardio Inc

Collaborator

Trials

2

Recruited

90+

Helios Cardio Inc.

Industry Sponsor

Trials

3

Recruited

170+

Published Research Related to This Trial

In a study of 120 patients undergoing cardiac valvular surgery, intravenous amiodarone did not effectively reduce the incidence of postoperative atrial fibrillation, with rates of 59.3% in the amiodarone group compared to 40.0% in the placebo group.

Four preoperative factors were identified as increasing the risk of developing postoperative atrial fibrillation: older age, recent myocardial infarction, preoperative angina, and the use of calcium channel blockers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative intravenous amiodarone does not reduce the burden of atrial fibrillation in patients undergoing cardiac valvular surgery. Beaulieu, Y., Denault, AY., Couture, P., et al.[2013]

Intravenous amiodarone significantly reduced the incidence of atrial fibrillation after open heart surgery, with 35% of patients on amiodarone experiencing it compared to 47% on placebo (p = 0.01).

While amiodarone was effective in preventing atrial fibrillation, it did not significantly decrease the length of hospital stay, which was 7.6 days for the amiodarone group compared to 8.2 days for the placebo group (p = 0.34).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous amiodarone for the prevention of atrial fibrillation after open heart surgery: the Amiodarone Reduction in Coronary Heart (ARCH) trial. Guarnieri, T., Nolan, S., Gottlieb, SO., et al.[2019]

Amiodarone is considered the most effective drug for preventing postoperative atrial fibrillation (POAF), but it is typically used as a second-line treatment due to its potential systemic side effects.

The review focuses on the effectiveness of administering amiodarone directly into the pericardial space (intrapericardial administration) as a promising method to prevent POAF, which could change practices in cardiac surgery if future studies confirm its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrapericardial Amiodarone for the Prevention of Postoperative Atrial Fibrillation. Habbab, LM., Chu, FV.[2016]

Amiodarone is effective in reducing arrhythmic events in patients with post-myocardial infarction and congestive heart failure, but it does not significantly lower overall mortality rates, as shown in trials like EMIAT and CAMIAT.

In high-risk patients, such as those with a history of sustained ventricular tachycardia, implantable cardioverter-defibrillators (ICDs) are more effective than amiodarone in improving overall survival, indicating that while amiodarone is safe, ICDs should be prioritized for frontline therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amiodarone: clinical trials. Naccarelli, GV., Wolbrette, DL., Patel, HM., et al.[2022]

In a study of 100 patients undergoing aortocoronary bypass surgery, propafenone was found to be significantly more effective than amiodarone in preventing atrial fibrillation, with only 10% of patients experiencing AF compared to 26% in the amiodarone group (p = 0.047).

Propafenone also led to a quicker recovery of sinus rhythm, averaging 4602 minutes compared to 760 minutes for amiodarone, indicating its superior pharmacodynamic properties in this context (p = 0.049).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of amiodarone versus propafenone in the prevention of rhythm disorders in patients after aortocoronary bypass surgery]. Eremenko, AA., Galanikhina, EA., Ziuliaeva, TP., et al.[2013]

In a study of 200 cardiac surgery patients, the use of topical amiodarone applied to the heart did not significantly reduce the incidence of new-onset atrial fibrillation (AF) compared to a control group without amiodarone.

The results showed similar rates of postoperative AF across all groups, suggesting that topical amiodarone may not be effective in preventing AF after cardiac surgery, particularly in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical amiodarone during cardiac surgery: Does epicardial application of amiodarone prevent postoperative atrial fibrillation? Greenstein, D., Beau, J., Gottlieb, G., et al.[2019]

Nexterone®, a new formulation of intravenous amiodarone, has been shown to be effective in managing life-threatening ventricular arrhythmias without causing hypotension, a common side effect of traditional amiodarone.

While intravenous amiodarone is effective for treating arrhythmias, studies indicate that it does not improve survival rates after cardiac events, highlighting the need for further research into antiarrhythmic drugs that can enhance patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amiodarone (Nexterone) injection for the treatment and prophylaxis of frequently recurring ventricular fibrillation. Marinelli, A., Capucci, A.[2013]

In a study of 17,597 elderly patients hospitalized for acute myocardial infarction complicated by atrial fibrillation, amiodarone was not associated with increased short-term (30-day) or long-term (1-year) mortality after adjusting for other factors.

While patients prescribed amiodarone had a higher 1-year mortality rate compared to those not on the medication (35.6% vs 31.6%), the difference was not statistically significant when controlling for other variables, suggesting that amiodarone may be safe for this patient group, but further randomized trials are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amiodarone and mortality among elderly patients with acute myocardial infarction with atrial fibrillation. Kilborn, MJ., Rathore, SS., Gersh, BJ., et al.[2013]

In a study of 120 patients undergoing mitral valve replacement surgery, the use of amiodarone during cardiopulmonary bypass significantly improved cardiac recovery, as indicated by a higher heart auto re-beat ratio and a higher rate of patients maintaining sinus rhythm.

Patients treated with amiodarone required less dopamine for heart support post-surgery, suggesting it may enhance cardiac function after surgery, although it was associated with a lower need for temporary pacemakers compared to the control group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of amiodarone on cardiac rhythm after cardiopulmonary bypass in patients with atrial fibrillation. Jie, S., Yu, C., Xiaohu, L., et al.[2022]

Incorporating amiodarone into a postoperative atrial fibrillation prevention protocol led to a significant 45% reduction in the incidence of postoperative AF among 1,068 cardiac surgical patients, demonstrating its efficacy in this setting.

Patients receiving amiodarone also experienced a trend towards shorter hospital stays when AF occurred, with an average length of stay of 9.4 days compared to 13.1 days in those not receiving amiodarone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simple amiodarone protocol reduces postoperative atrial fibrillation. Allen, KB., Heimansohn, DA., Robison, RJ., et al.[2012]

In a randomized controlled trial involving elective cardiac surgical patients, intravenous amiodarone administration led to significant increases in pulmonary artery pressure and central venous pressure, indicating its acute hemodynamic effects.

Despite these changes, amiodarone demonstrated minimal negative impact on right ventricular systolic function, suggesting it alters diastolic properties without severely compromising heart function during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute intraoperative effect of intravenous amiodarone on right ventricular function in patients undergoing valvular surgery. Denault, AY., Beaulieu, Y., Couture, P., et al.[2017]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26833498/

Intrapericardial Amiodarone for the Prevention of ... Despite probably being the most effective prophylactic drug for postoperative atrial fibrillation (POAF), amiodarone is reserved as a second-line agent ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10944787/

Postoperative atrial fibrillation (POAF) after cardiac surgery Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery and is associated with early and late morbidity and mortality.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666602225001247

Impact of postoperative atrial fibrillation (POAF) on ... Atrial fibrillation occurring in the postoperative period is treated medically with amiodarone infusion, 56.5 (23.6), 5 (20.8), 10. Benedetto2020, Post hoc ...

4. ovid.com ovid.com/journals/jcsur/fulltext/10.1111/jocs.12700~intrapericardial-amiodarone-for-the-prevention-of

Intrapericardial Amiodarone for the Prevention of... These results demonstrate that amiodarone-releasing hydrogel could be applied during cardiac surgery to prevent POAF at minimal risk for extracardiac adverse ...

5. researchgate.net researchgate.net/publication/292949398_Intrapericardial_Amiodarone_for_the_Prevention_of_Postoperative_Atrial_Fibrillation

Intrapericardial Amiodarone for the Prevention of ... Herein, we review the available experimental and clinical trials examining the effectiveness of intrapericardial (IPC) amiodarone administration in preventing ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1538783622042532

Postoperative atrial fibrillation in non‐cardiac and ... All these effects on the cardiopulmonary hemodynamics can lead to hypotension, heart failure, and myocardial infarction. Accordingly, AF after surgery has been ...

7. cardiothoracicsurgery.biomedcentral.com cardiothoracicsurgery.biomedcentral.com/articles/10.1186/s13019-024-02732-9

a systemic review and PRISMA-compliant meta-analysis The current study suggests that intraoperative administration of intravenous amiodarone may be safe and effective in preventing POAF in patients undergoing on- ...