Amiodarone for Post-Operative Atrial Fibrillation

(START-POAF Trial)

Overseen By Ingrid Copland

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Population Health Research Institute

Must be taking: Amiodarone

Must not be taking: Class I, Class III

Disqualifiers: Preoperative AF, Heart transplant, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

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

Compensation: Varies

Number of Visits: 30

Duration: 4 weeks

400 Participants Needed

Trial Summary

What is the purpose of this trial?

The START-POAF pilot study is a prospective, open-label two-arm, randomized controlled trial with blinded assessment of outcomes (PROBE). This pilot study will assess Atrial Fibrillation (AF) recurrence and burden in patients with new-onset AF following cardiac surgery.

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 use certain heart rhythm drugs other than the study drug. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Amiodarone Hydrochloride for preventing post-operative atrial fibrillation?

Research shows that using amiodarone can help reduce the occurrence of atrial fibrillation (a type of irregular heartbeat) after heart surgery, which can also shorten the length of hospital stays. ^{1 2 3 4 5}

Is amiodarone safe for humans?

Amiodarone is generally safe for humans, but it can have side effects like low blood pressure. A newer version called Nexterone may have fewer of these side effects. ^{3 6 7 8 9}

How is the drug Amiodarone unique for treating post-operative atrial fibrillation?

Amiodarone is unique because it is one of the most effective drugs for preventing and treating post-operative atrial fibrillation, and it can be administered in various ways, such as intravenously or through a hydrogel applied directly to the heart. However, due to its potential side effects, it is typically reserved for high-risk patients. ^{1 3 4 10 11}

Research Team

William McIntyre, MD

Principal Investigator

Population Health Research Institute

Eligibility Criteria

This trial is for adults over 18 who've had cardiac surgery within the last two weeks and experienced new-onset AF or flutter. They should be ready to leave the hospital within two days of joining, and must not have started long-term anti-arrhythmic drugs.

Inclusion Criteria

I have had a new episode of atrial fibrillation or flutter, confirmed by an ECG.

I had heart surgery, such as bypass or valve surgery, within the last 14 days.

I am expected to receive a specific heart medication after surgery.

Exclusion Criteria

I have a history of atrial fibrillation.

I plan to use a specific heart rhythm medication not part of the study.

I have had heart surgery, including a transplant, ventricular assist device, or AF ablation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive amiodarone treatment with two different durations: in-hospital load only or in-hospital load plus 4 weeks after loading dose

4 weeks

In-hospital visits for loading dose, followed by monitoring

Monitoring

Participants are monitored using a continuous ECG monitor for atrial fibrillation recurrence and burden

4 weeks

Continuous monitoring with ECG

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments at 30 and 90 days

90 days

Follow-up visits at 30 and 90 days

Treatment Details

Interventions

• Amiodarone Hydrochloride

Trial Overview The START-POAF pilot study is testing if Amiodarone Hydrochloride (200 MG) can reduce Atrial Fibrillation recurrence after heart surgery. It's a randomized trial where outcomes are assessed without knowing which treatment was given.

Participant Groups

Group I: Amiodarone maintenance therapy Active Control 1 Intervention

Amiodarone 200 mg daily for four weeks

Group II: No Amiodarone maintenance therapy Active Control 1 Intervention

No ongoing Amiodarone maintenance therapy for four weeks

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

Approved in United States as Cordarone for:

• Ventricular arrhythmias
• Atrial fibrillation

Approved in European Union as Cordarone for:

• Ventricular tachycardia
• Ventricular fibrillation
• Atrial fibrillation

Approved in Canada as Pacerone for:

• Ventricular arrhythmias
• Atrial fibrillation

Who Is Running the Clinical Trial?

Population Health Research Institute

Lead Sponsor

Trials

165

Recruited

717,000+

Findings from Research

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 involving 204 cardiac surgery patients, a predictive model for atrial fibrillation (AF) was developed, which was then applied to a second group of 231 patients to identify those at high risk for AF after surgery.

Prophylactic treatment with amiodarone significantly reduced the incidence of AF in high-risk patients, with rates dropping from 34.4% to 11% in men and from 50.9% to 9.3% in women, demonstrating its efficacy as a preventive measure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective prophylaxis of atrial fibrillation with amiodarone after cardiac surgery. Carrió, ML., Fortià, C., Javierre, C., et al.[2013]

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]

Post-operative atrial fibrillation is common after cardiac surgery and leads to longer ICU and hospital stays, increasing healthcare costs.

Meta-analysis of over seventy trials indicates that interventions like beta-blockers, sotalol, amiodarone, and bi-atrial overdrive pacing are effective in preventing post-operative atrial fibrillation, with amiodarone and bi-atrial pacing potentially reducing hospital stay duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atrial fibrillation after cardiac surgery: update on the evidence on the available prophylactic interventions. Crystal, E., Healey, J., Connolly, SJ.[2019]

In a study of 1,196 patients undergoing cardiac surgery, postoperative oral amiodarone significantly reduced the incidence of new-onset atrial fibrillation (AF) from 31% in the control group to 25% in the amiodarone group.

Amiodarone treatment was also associated with a shorter hospital stay, indicating it not only helps prevent AF but may also improve overall recovery times after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of atrial fibrillation after cardiac surgery: the significance of postoperative oral amiodarone. Stamou, SC., Hill, PC., Sample, GA., 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]

Amiodarone has shown effectiveness in maintaining normal sinus rhythm in patients with atrial fibrillation (AF), particularly in cases where traditional treatments are ineffective, based on data from 8 nonrandomized and 2 randomized trials.

While amiodarone's efficacy is comparable or superior to traditional Class IA agents, it carries a risk of significant noncardiovascular side effects, necessitating careful individual assessment of benefits and risks before use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amiodarone for the maintenance of sinus rhythm in patients with atrial fibrillation. Howard, PA.[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 120 patients undergoing coronary artery surgery, prophylactic amiodarone significantly reduced the need for treatment of arrhythmias, with 10% of patients in the amiodarone group requiring treatment compared to 23% in the placebo group (p = 0.05).

While amiodarone effectively decreased the incidence of ventricular tachycardia or fibrillation (15% vs. 33% in placebo, p = 0.02), it also caused bradycardia in a higher percentage of patients (78% vs. 48%, p < 0.005), which may limit its routine use as a preventive treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amiodarone prophylaxis for tachycardias after coronary artery surgery: a randomised, double blind, placebo controlled trial. Butler, J., Harriss, DR., Sinclair, M., et al.[2019]

In a study of 273 postoperative patients, the incidence of phlebitis in those receiving intravenous amiodarone was found to be 13.9%, indicating a notable risk even when following current dosing guidelines.

The risk of developing phlebitis was significantly increased, with a 19-fold greater odds ratio compared to baseline risk, suggesting that even within recommended dosing limits, peripheral infusion of amiodarone poses a considerable complication risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The incidence of phlebitis with intravenous amiodarone at guideline dose recommendations. Slim, AM., Roth, JE., Duffy, B., et al.[2017]

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]

References

1. 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]

2. Italy pubmed.ncbi.nlm.nih.gov

Selective prophylaxis of atrial fibrillation with amiodarone after cardiac surgery. [2013]

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

Simple amiodarone protocol reduces postoperative atrial fibrillation. [2012]

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

Atrial fibrillation after cardiac surgery: update on the evidence on the available prophylactic interventions. [2019]

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

Prevention of atrial fibrillation after cardiac surgery: the significance of postoperative oral amiodarone. [2019]

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

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

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

Amiodarone for the maintenance of sinus rhythm in patients with atrial fibrillation. [2017]

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

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

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

Amiodarone prophylaxis for tachycardias after coronary artery surgery: a randomised, double blind, placebo controlled trial. [2019]

10. England pubmed.ncbi.nlm.nih.gov

The incidence of phlebitis with intravenous amiodarone at guideline dose recommendations. [2017]

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

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