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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether amiodarone, a medication, can prevent atrial fibrillation (AF) that sometimes occurs after heart surgery. Researchers aim to determine if patients who experience induced AF during surgery benefit from amiodarone compared to those who do not receive the medication. The trial focuses on individuals undergoing their first open-heart surgery, such as valve repair or coronary artery bypass, who have never had AF before. Participants will either receive amiodarone or not, based on whether their heart shows signs of AF during surgery. The goal is to assess if this treatment reduces the chance of developing AF post-surgery. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective amiodarone can benefit more patients.

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 is the safety track record for Amiodarone Injection and Intraoperative Rapid Atrial Pacing?

Research has shown that amiodarone, a medication used to manage heart rhythm problems, can safely and effectively prevent irregular heartbeats after surgery. In several studies, patients taking amiodarone experienced fewer episodes of these irregular heartbeats. However, some studies found that amiodarone might increase the risk of side effects such as a slower heart rate and low blood pressure. While these side effects are important to consider, overall, the studies indicate that amiodarone can help manage heart rhythm issues after surgery. Always discuss potential risks and benefits with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about amiodarone injections for preventing postoperative atrial fibrillation (POAF) because they offer a proactive approach to managing this condition. Unlike standard treatments that are typically initiated after POAF has already developed, amiodarone injections can be used as a preventive measure. This treatment stands out for its ability to stabilize heart rhythms before the complication even arises, potentially reducing the need for additional interventions and improving patient recovery times. By intervening earlier, amiodarone might help minimize the stress and complications associated with POAF, promising a smoother post-surgery experience for patients.

What evidence suggests that amiodarone might be an effective treatment for preventing postoperative atrial fibrillation?

Research has shown that amiodarone can lower the risk of irregular heartbeats, known as atrial fibrillation, after heart surgery. One study found that the number of patients experiencing this condition dropped from 29.5% to 16.1% with amiodarone treatment. This indicates that treating about 7 patients with amiodarone can prevent one case of atrial fibrillation. Another study reported a 10.7% decrease in these irregular heartbeats after surgery with amiodarone use. In this trial, some participants will receive amiodarone treatment if postoperative atrial fibrillation (POAF) occurs, while others will receive standard care without initial amiodarone unless POAF is observed. Overall, evidence suggests that amiodarone is both safe and effective in reducing these irregular heartbeats after surgery. ^{2 3 5 6 7}

Who Is on the Research Team?

Anson Lee, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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]

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]

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]

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]

Citations

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

Postoperative atrial fibrillation (POAF) after cardiac surgery The amiodarone group had a significantly lower rate of POAF [16.1% vs. 29.5%, hazard ratio (HR) 0.52 (0.34–0.69), P<0.005, NNT =7]. Hillis et al. found no ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0147956325000597

Amiodarone Prophylaxis against postoperative atrial ... Low-dose amiodarone reduced postoperative atrial fibrillation by 10.7 % in OPCAB patients. •. A 1 2 % decrease in AF treatment at discharge was observed with ...

3. ahajournals.org ahajournals.org/doi/10.1161/JAHA.118.009892

Use and Outcomes Associated With Perioperative ... Our analyses suggest that perioperative amiodarone was both safe and effective at reducing the occurrence of postoperative atrial arrhythmias, ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23627761/

Timing and route of amiodarone for prevention ... Results: Twenty-three studies (total N = 3,950) were included. Both regimens of amiodarone improved risk of POAF; oral-only risk ratio (RR) was 0.59 (95% ...

5. oaepublish.com oaepublish.com/articles/2574-1209.2021.115

Amiodarone and postoperative atrial fibrillation In patients in the amiodarone group who maintained sinus rhythm postoperatively, 74% had an effective amiodarone level. By contrast, in the ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/16638947/

Safety of amiodarone in the prevention of postoperative ... Conclusion: Meta-analysis showed amiodarone to be associated with an increased risk of developing bradycardia and hypotension when used for the prophylaxis of ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11067272/

The efficacy and safety of intraoperative intravenous ... The current study suggests that intraoperative administration of intravenous amiodarone may be safe and effective in preventing POAF in patients undergoing on- ...