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

Trial Summary

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 data supports the effectiveness of the drug Intra-Pericardial Amiodarone for preventing postoperative atrial fibrillation?

Research suggests that amiodarone, when used as part of a prevention plan, may reduce the occurrence of atrial fibrillation (a type of irregular heartbeat) after surgery and shorten hospital stays. Intrapericardial amiodarone, specifically, is considered potentially effective in preventing this condition, although more studies are needed to confirm its benefits. ^{1 2 3 4 5}

Is intra-pericardial amiodarone safe for humans?

Amiodarone, including formulations like Nexterone, has been shown to be generally safe in humans for treating heart rhythm problems, though it can have side effects like low blood pressure. It has been used safely in patients with heart conditions like heart attacks and heart failure, but its safety specifically for intra-pericardial use is not detailed in the available studies. ^{6 7 8 9 10}

How is intrapericardial amiodarone different from other drugs for postoperative atrial fibrillation?

Intrapericardial amiodarone is unique because it is administered directly into the pericardium (the sac surrounding the heart), which may help prevent postoperative atrial fibrillation while minimizing the systemic side effects typically associated with oral or intravenous amiodarone. ^{1 2 3 5 11}

What is the purpose of this trial?

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.

Research Team

Valluvan Jeevanandam, MD

Principal Investigator

Director of Heart and Vascular Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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 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]

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 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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Simple amiodarone protocol reduces postoperative atrial fibrillation. [2012]

2. England pubmed.ncbi.nlm.nih.gov

The effect of amiodarone on cardiac rhythm after cardiopulmonary bypass in patients with atrial fibrillation. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Intrapericardial Amiodarone for the Prevention of Postoperative Atrial Fibrillation. [2016]

4. United States 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. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Perioperative intravenous amiodarone does not reduce the burden of atrial fibrillation in patients undergoing cardiac valvular surgery. [2013]

6. England pubmed.ncbi.nlm.nih.gov

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

7. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Efficacy of amiodarone versus propafenone in the prevention of rhythm disorders in patients after aortocoronary bypass surgery]. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Amiodarone: clinical trials. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Acute intraoperative effect of intravenous amiodarone on right ventricular function in patients undergoing valvular surgery. [2017]

10. United States pubmed.ncbi.nlm.nih.gov

Amiodarone and mortality among elderly patients with acute myocardial infarction with atrial fibrillation. [2013]

11. United States pubmed.ncbi.nlm.nih.gov

Topical amiodarone during cardiac surgery: Does epicardial application of amiodarone prevent postoperative atrial fibrillation? [2019]