Oral Amiodarone for Atrial Fibrillation

(AAA Trial)

Overseen By Rasha Hamzeh, RN

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Calgary

Must be taking: Anticoagulants

Must not be taking: Class III anti-arrhythmics

Disqualifiers: Hypothyroid, Recent myocardial infarction, Severe heart failure, others

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

Compensation: Varies

Number of Visits: 2

Duration: 48 hours

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a high dose of amiodarone, taken as a single pill, is safe and effective for treating sudden atrial fibrillation (a condition where the heart beats irregularly and often too fast) in both hospital and outpatient settings. Participants will receive either amiodarone or a placebo (a pill with no active drug) to compare results after 48 hours. Ideal candidates for this trial have experienced sudden atrial fibrillation for less than 14 days and have a history of symptoms like heart palpitations or shortness of breath. As a Phase 4 trial, this study involves an FDA-approved treatment, aiming to understand its benefits for more patients.

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 have taken more than 10 g of amiodarone in the past 6 months or other similar heart medications in the past 3 months.

What is the safety track record for Amiodarone Hydrochloride?

Research has shown that amiodarone is generally safe for treating heart rhythm problems. The FDA has already approved it for serious heart issues like irregular heartbeats. Studies have found that amiodarone can help restore a normal heartbeat. Some people have experienced side effects while using amiodarone, but most are not severe enough to warrant discontinuation. The most common side effects include dizziness, nausea, and fatigue. This trial uses a high dose of amiodarone, so careful monitoring is important to ensure it is well-tolerated. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for atrial fibrillation, which often include beta-blockers or calcium channel blockers, oral Amiodarone is unique because it directly alters the electrical activity of the heart. Most treatments work by slowing heart rate or reducing blood pressure, but Amiodarone targets the heart's rhythm more precisely, making it potentially more effective for those who don't respond well to other medications. Researchers are excited about Amiodarone because it has the potential to maintain normal heart rhythm with fewer side effects related to blood pressure and heart rate changes.

What is the effectiveness track record for amiodarone in treating atrial fibrillation?

In this trial, participants will receive either oral Amiodarone or a placebo. Research has shown that Amiodarone effectively treats atrial fibrillation, a condition where the heart beats irregularly. Studies indicate that Amiodarone helped maintain a normal heart rhythm in up to 84% of patients after one year. One study found that Amiodarone stopped atrial fibrillation in 88% of patients with sudden, short-term episodes. Additionally, Amiodarone has proven more effective than some other treatments, like quinidine, for this condition. Overall, these findings suggest that Amiodarone can be a strong option for managing atrial fibrillation. ^{2 6 7 8 9}

Who Is on the Research Team?

Satish R Raj, MD MSCI

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

This trial is for adults with recent atrial fibrillation or flutter, confirmed by ECG, who have symptoms and are on blood thinners like warfarin or direct oral anticoagulants. It's not for those who've had a lot of amiodarone recently, bad reactions to cardioversion, severe heart issues, very low thyroid without treatment, serious kidney/liver disease, certain heart rhythm problems without a pacemaker, extremely low blood pressure or pregnant/breastfeeding women.

Inclusion Criteria

I am on blood thinners with specific monitoring levels.

I have experienced symptoms related to an irregular heartbeat.

I have had atrial fibrillation or flutter for less than 14 days, confirmed by a heart monitor.

Exclusion Criteria

I have severe heart failure or have been hospitalized for sudden lung swelling.

I have not taken more than 10g of amiodarone or any Class III anti-arrhythmic drugs recently.

I have an underactive thyroid and am not taking medication for it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single oral dose of 2000 mg amiodarone or placebo, followed by cardiac monitoring for 48 hours

48 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse event monitoring and ECG confirmation of heart rhythm

1 week

1 follow-up call

What Are the Treatments Tested in This Trial?

Interventions

• Amiodarone Hydrochloride
• Placebo

Trial Overview The study tests if a high dose (2000mg) of Amiodarone given orally can safely and effectively treat acute atrial fibrillation in both hospital and outpatient settings compared to a placebo. Participants will be randomly assigned to receive either the drug or placebo and followed up after 48 hours.

How Is the Trial Designed?

Group I: Oral Amiodarone Experimental Treatment 1 Intervention

Amiodarone hydrochloride 2000 mg

Group II: Placebo Placebo Group 1 Intervention

Oral placebo

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?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Published Research Related to This Trial

Oral dronedarone significantly reduces the risk of hospitalization due to cardiovascular events or death compared to placebo, based on data from the ATHENA study involving patients treated for 12-30 months.

While dronedarone is generally well tolerated, it does have some side effects like diarrhea and nausea, but serious cardiac-related adverse events are rare, occurring in less than 1% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dronedarone. Hoy, SM., Keam, SJ.[2021]

Dronedarone, a potentially less toxic alternative to amiodarone, showed similar effects on action potential duration and effective refractory period in isolated rabbit atrial muscle after four weeks of treatment, indicating its potential efficacy against atrial arrhythmias.

Both dronedarone and amiodarone caused a decrease in action potential duration and effective refractory period during acute superfusion, suggesting that their immediate effects on heart muscle are comparable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic and acute effects of dronedarone on the action potential of rabbit atrial muscle preparations: comparison with amiodarone. Sun, W., Sarma, JS., Singh, BN.[2019]

Dronedarone and vernakalant have shown promising efficacy and safety in treating atrial fibrillation, with vernakalant demonstrating superior effectiveness compared to traditional drugs like amiodarone and flecainide.

New potential antiarrhythmic drugs, including ranolazine and colchicine, are emerging, and ongoing research into selective ionic channel inhibitors and anti-inflammatory compounds may enhance long-term treatment outcomes for atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging pharmacotherapies for the treatment of atrial fibrillation. Capucci, A., Cipolletta, L., Guerra, F., et al.[2018]

In a study of 53 patients with chronic atrial fibrillation, oral amiodarone significantly reduced heart rates during exercise and daily activities compared to placebo, indicating its efficacy for rate control.

Amiodarone, when used alongside digoxin, is a viable alternative for heart rate management in patients with atrial fibrillation, especially when traditional treatments like calcium channel blockers or beta-blockers are not suitable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral amiodarone in controlling heart rate in patients with persistent atrial fibrillation who have undergone digitalisation. Kochiadakis, GE., Kanoupakis, EM., Igoumenidis, NE., et al.[2018]

Both oral and intravenous Amiodarone are highly effective in converting recent-onset atrial fibrillation to sinus rhythm, with conversion rates of 85.45% and 82.30% respectively, based on a study of 223 patients.

Intravenous Amiodarone acts more quickly, achieving cardioversion in an average of 12 hours compared to 20 hours for the oral form, but the oral form maintains stable blood pressure, while intravenous administration can lead to significant drops in blood pressure and complications like superficial phlebitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous and oral administration of amiodarone for the treatment of recent onset atrial fibrillation after digoxin administration. Xanthos, T., Bassiakou, E., Vlachos, IS., et al.[2013]

Amiodarone is an investigational drug in the U.S. that has been widely used globally for treating cardiac arrhythmias, indicating its established role in managing heart rhythm disorders.

The article provides a review of the clinical pharmacology of amiodarone, highlighting its potential effectiveness as an antiarrhythmic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical use and pharmacology of amiodarone. Heger, JJ., Prystowsky, EN., Miles, WM., 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]

Dronedarone significantly prolongs the time to the first recurrence of atrial fibrillation compared to placebo, with median times of 96 days versus 41 days in the European trial, and 158 days versus 59 days in the non-European trial.

Dronedarone also reduces the ventricular rate during arrhythmia recurrences without significantly increasing the risk of serious side effects like pulmonary toxicity or thyroid and liver dysfunction, making it a safer alternative to amiodarone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. Singh, BN., Connolly, SJ., Crijns, HJ., et al.[2023]

In a study of 160 patients with recent atrial fibrillation, oral doses of flecainide, amiodarone, and propafenone were all significantly more effective than placebo in converting patients to sinus rhythm within 24 hours, with conversion rates of 87.5%, 85%, and 85% respectively compared to only 17.5% for placebo.

Flecainide and propafenone showed quicker conversion rates within 3 hours (57.5% and 45% respectively), while amiodarone was more effective between 6 and 24 hours, indicating that different antiarrhythmic drugs may have varying onset times for effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological conversion of recent atrial fibrillation: a randomized, placebo-controlled study of three antiarrhythmic drugs. Balla, I., Petrela, E., Kondili, A.[2013]

Amiodarone is effective in achieving sinus rhythm in patients with persistent atrial fibrillation, showing a significant improvement compared to placebo or rate control drugs (21.3 vs 9.2 per 100 patient-years).

The use of amiodarone does not increase long-term mortality risk, but it is associated with a higher rate of treatment discontinuation due to adverse effects (10.7 vs 1.9 per 100 patient-years).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefits and risks of long-term amiodarone therapy for persistent atrial fibrillation: a meta-analysis. Doyle, JF., Ho, KM.[2023]

Amiodarone, a medication used for heart rhythm disorders, carries significant risks that necessitate careful patient monitoring and supervision during treatment.

The Medicines and Healthcare products Regulatory Agency emphasizes the importance of awareness regarding these risks to ensure patient safety while using amiodarone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety update: monitoring patients taking amiodarone. [2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25181386/

Efficacy of amiodarone in patients with atrial fibrillation with ... In amiodarone-treated patients (N = 1,107), freedom from recurrent atrial fibrillation was 84% and 45% at 1 and 5 years, respectively, with no differences ...

2. ahajournals.org ahajournals.org/doi/10.1161/01.cir.100.19.2025

Evidence-Based Analysis of Amiodarone Efficacy and Safety The primary prevention trials have shown quite clearly that amiodarone reduced arrhythmic death, but the beneficial effect on all-cause mortality is too small ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0914508711001171

Role of oral amiodarone in patients with atrial fibrillation ... Tallying the results for patients who had never received cardioversion, amiodarone suppressed AF in 14/16 of the paroxysmal AF patients (88%), and caused ...

4. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/215367

Effectiveness of Amiodarone for Conversion of Atrial ... The relative risk (RR) for achieving sinus rhythm was 4.33 (95% confidence interval [CI], 2.76-6.77) for trials with mean AF duration of greater than 48 hours ...

5. academic.oup.com academic.oup.com/europace/article/8/4/302/2398734

Design and rationale of a randomized study to compare ... Amiodarone has been shown to be the most effective AAD in several randomized trials, with evidence suggesting superiority of amiodarone over quinidine, 5 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2664595/

Benefits and Risks of Long-term Amiodarone Therapy for ... With the limited data available, long-term amiodarone therapy appears to be safe and effective for persistent AF. However, this strategy was associated with a ...

7. innovationsincrm.com innovationsincrm.com/cardiac-rhythm-management/articles-2020/april/1581-low-dose-amiodarone-is-safe

Low-dose Amiodarone Is Safe: A Systematic Review and ... Very-low-dose amiodarone displays a low incidence of significant side effects requiring medication discontinuation.

8. mayoclinic.org mayoclinic.org/drugs-supplements/amiodarone-oral-route/description/drg-20061854

Amiodarone (oral route) - Side effects & dosage Amiodarone is used to treat life-threatening heart rhythm problems called ventricular arrhythmias. This medicine is used in patients who have already been ...

9. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK482154/

Amiodarone - StatPearls - NCBI Bookshelf - NIH Amiodarone is approved by the U.S. Food and Drug Administration (FDA) specifically for the treatment of life-threatening ventricular arrhythmias ...