Amiodarone for Preventing Postoperative Atrial Fibrillation

Overseen By Cody Carlton, BS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Stanford University

Must not be taking: Amiodarone

Disqualifiers: Prior heart surgery, Atrial fibrillation, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Immediate post-operative period

600 Participants Needed

Trial Summary

What is the purpose of this trial?

Patients undergoing first time cardiac surgery will undergo rapid atrial pacing prior to initiation of cardiopulmonary bypass to screen for AF inducibility. Patients with inducible AF will be randomized to prophylactic amiodarone treatment versus no treatment. Patients who are not inducible to AF will be treated with standard post-operative care. Patients will be monitored post-operatively to explore the value of intraoperative inducibility of AF to predict POAF and to evaluate whether the combination of intraoperative inducibility and precision amiodarone therapy is effective at reducing the incidence of POAF

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Amiodarone Injection, Cordarone, Nexterone, Pacerone for preventing postoperative atrial fibrillation?

Research shows that using amiodarone, either orally or intravenously, can help prevent atrial fibrillation (a type of irregular heartbeat) after heart surgery, reducing complications and hospital stay length. ^{1 2 3 4 5}

Is amiodarone safe for preventing postoperative atrial fibrillation?

Amiodarone is commonly used to prevent atrial fibrillation after surgery, but it can have significant side effects outside the heart, so it is usually given to high-risk patients. Some studies suggest that applying it directly to the heart during surgery might help avoid these side effects. ^{4 6 7 8 9}

How is the drug Amiodarone Injection unique in preventing postoperative atrial fibrillation?

Amiodarone Injection is unique because it can be administered intravenously during and after surgery, which may help prevent postoperative atrial fibrillation more effectively than oral forms, and it can be applied topically to the heart to avoid systemic side effects. ^{1 2 4 6 7}

Research Team

Anson Lee, MD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for patients having their first non-emergency open-heart surgery, like bypass or valve repair, with a normal heart rhythm and no history of atrial fibrillation. It's not for those who've had previous heart surgeries using cardiopulmonary bypass, any past atrial arrhythmias lasting over 30 seconds, or prior Amiodarone use.

Inclusion Criteria

I am scheduled for my first open-heart surgery for heart issues.

Your heart is beating normally.

I have never been diagnosed with atrial fibrillation.

Exclusion Criteria

I have been treated with Amiodarone for irregular heartbeats before.

I have had heart surgery with cardiopulmonary bypass.

I have had a heart rhythm problem lasting more than 30 seconds.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Intraoperative Assessment

Rapid atrial pacing is performed to assess AF inducibility prior to cardiopulmonary bypass

1 day

During surgery

Treatment

Participants with inducible AF are randomized to receive prophylactic Amiodarone or no treatment

Immediate post-operative period

Follow-up

Participants are monitored for the incidence of post-operative atrial fibrillation and other outcomes

30 days

Regular monitoring during hospital stay and follow-up visits

Treatment Details

Interventions

• Amiodarone Injection
• Intraoperative Rapid Atrial Pacing

Trial Overview The study tests if inducing and then treating atrial fibrillation (AF) during surgery can prevent postoperative AF. Patients with inducible AF are randomly chosen to receive Amiodarone treatment or no treatment; others get standard care. The goal is to see if this method predicts and reduces post-surgery AF.

Participant Groups

Group I: Non-Inducible Atrial Fibrillation Experimental Treatment 1 Intervention

Amiodarone treatment if POAF seen on post-operative care unit

Group II: Inducible Atrial Fibrillation - Standard Care Experimental Treatment 2 Interventions

No initial Amiodarone Treatment unless POAF seen on post operative care unit.

Group III: Inducible Atrial Fibrillation Active Control 2 Interventions

Treatment with Amiodarone

Amiodarone Injection is already approved in United States, European Union for the following indications:

Approved in United States as Cordarone for:

• Life-threatening ventricular arrhythmias
• Ventricular fibrillation
• Pulseless ventricular tachycardia

Approved in European Union as Cordarone for:

• Life-threatening ventricular arrhythmias
• Ventricular fibrillation
• Pulseless ventricular tachycardia

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Findings from Research

A single-day loading dose of oral amiodarone (1200 mg) did not significantly reduce the overall incidence of postoperative atrial fibrillation in 315 patients after coronary artery bypass surgery, with similar rates in both the amiodarone and placebo groups.

However, in elderly patients (aged 60 and above), amiodarone was effective in reducing the incidence of atrial fibrillation, suggesting it may be beneficial for this specific demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-day loading dose of oral amiodarone for the prevention of new-onset atrial fibrillation after coronary artery bypass surgery. Maras, D., Bosković, SD., Popović, Z., et al.[2013]

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]

Intraoperative use of intravenous amiodarone did not significantly reduce the incidence of new onset atrial fibrillation after coronary artery bypass grafting, with rates of 24% in the high-dose group and 28% in the low-dose group compared to 34% in the placebo group.

Although amiodarone did not prevent atrial fibrillation, it was associated with a higher incidence of temporary atrial pacing due to bradycardia in the high-dose group, indicating potential safety concerns with its use in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative amiodarone as prophylaxis against atrial fibrillation after coronary operations. Dörge, H., Schoendube, FA., Schoberer, M., et al.[2019]

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]

Prophylactic amiodarone has been validated as a safe and effective treatment to prevent postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting, which is the most common heart rhythm problem after this surgery.

The study aims to assess the effectiveness of the current amiodarone treatment protocol in reducing the incidence of postoperative atrial fibrillation and to identify any perioperative risk factors that may contribute to this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of an evidence-based practice implementation: prophylactic amiodarone following coronary artery revascularization. Hoffmann, MC.[2019]

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]

In a study of 100 patients undergoing cardiac surgery, the use of an amiodarone-releasing hydrogel applied to the heart's surface significantly reduced the incidence of postoperative atrial fibrillation (POAF) from 26% in the control group to 8% in the treatment group.

The hydrogel method resulted in higher concentrations of amiodarone in the heart tissue while keeping plasma levels low, minimizing the risk of side effects, and also led to fewer instances of bradycardia compared to the control group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of biatrial epicardial application of amiodarone-releasing adhesive hydrogel to prevent postoperative atrial fibrillation. Feng, XD., Wang, XN., Yuan, XH., et al.[2022]

In a study of 393 patients undergoing coronary artery bypass grafting (CABG), ranolazine was found to significantly reduce the incidence of postoperative atrial fibrillation (AF) by 34% compared to amiodarone (17.5% vs. 26.5%).

Both ranolazine and amiodarone showed similar safety profiles, with no significant differences in adverse events, suggesting that ranolazine could be a safe and effective alternative for preventing postoperative AF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ranolazine versus amiodarone for prevention of postoperative atrial fibrillation. Burashnikov, A., Antzelevitch, C.[2021]

A meta-analysis of 18 trials involving 3408 patients found that prophylactic use of amiodarone significantly increases the risk of bradycardia and hypotension, with odds ratios of 1.70 and 1.62, respectively.

The highest risk for these adverse effects was associated with intravenous amiodarone administration, particularly when given postoperatively and at doses exceeding 1 g per day.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of amiodarone in the prevention of postoperative atrial fibrillation: a meta-analysis. Patel, AA., White, CM., Gillespie, EL., et al.[2019]

References

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

Single-day loading dose of oral amiodarone for the prevention of new-onset atrial fibrillation after coronary artery bypass surgery. [2013]

2. 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]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Intraoperative amiodarone as prophylaxis against atrial fibrillation after coronary operations. [2019]

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

Simple amiodarone protocol reduces postoperative atrial fibrillation. [2012]

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

Evaluation of an evidence-based practice implementation: prophylactic amiodarone following coronary artery revascularization. [2019]

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

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

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

Effectiveness of biatrial epicardial application of amiodarone-releasing adhesive hydrogel to prevent postoperative atrial fibrillation. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Ranolazine versus amiodarone for prevention of postoperative atrial fibrillation. [2021]

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

Safety of amiodarone in the prevention of postoperative atrial fibrillation: a meta-analysis. [2019]