Oral Amiodarone for Atrial Fibrillation

(AAA Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Satish R Raj, MD MSCI

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

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

Trial Summary

What is the purpose of this trial?

The investigators will seek to determine the safety and efficacy of high-dose amiodarone (2000mg), given as a single uniform oral dose, for the treatment of acute atrial fibrillation in both a hospital inpatient and ambulatory outpatient setting. The investigators will conduct a placebo-controlled randomized trial, with outcome ascertainment at 48h.

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 data supports the effectiveness of the drug Amiodarone for treating atrial fibrillation?

Research shows that oral amiodarone is effective in controlling heart rate in patients with persistent atrial fibrillation, and it is also effective in converting recent atrial fibrillation to normal rhythm. Additionally, long-term use of amiodarone has been found to be safe and effective in maintaining sinus rhythm in patients with persistent atrial fibrillation.

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Is oral amiodarone generally safe for humans?

Amiodarone, used for heart rhythm problems, can have serious side effects, including low blood pressure and other toxic effects. It's important for patients to be monitored closely by healthcare providers while taking it.

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How does the drug amiodarone differ from other treatments for atrial fibrillation?

Amiodarone is unique because it can be taken orally and is effective for controlling heart rate in patients with persistent atrial fibrillation, especially after digitalisation (a process to stabilize heart rhythm). Unlike some other treatments, it is a potent antiarrhythmic drug that can be used both for rate control during exercise and daily activities.

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Eligibility Criteria

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.

Trial Timeline

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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Calgary Calgary, Canada

Who Is Running the Clinical Trial?

University of Calgary Lead Sponsor

References

1. Netherlands 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. [2018] Oral amiodarone has been suggested by some authors for rate control in patients with persistent atrial fibrillation. In this study we evaluated the efficacy and safety of oral amiodarone versus placebo for rate control during exercise and daily activities in patients with chronic atrial fibrillation who had undergone digitalisation.

2. Turkey pubmed.ncbi.nlm.nih.gov

Pharmacological conversion of recent atrial fibrillation: a randomized, placebo-controlled study of three antiarrhythmic drugs. [2013] In this study, we randomly compared single oral doses of flecainide, amiodarone and propafenone versus placebo for the conversion of recent atrial fibrillation (AF) (within 48 hours).

3. England pubmed.ncbi.nlm.nih.gov

Benefits and risks of long-term amiodarone therapy for persistent atrial fibrillation: a meta-analysis. [2023] To assess whether amiodarone, as part of a strategy to achieve sinus rhythm, is safe and effective compared with a placebo or rate control drug in patients with persistent atrial fibrillation (AF) of more than 30 days' duration.

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

Chronic and acute effects of dronedarone on the action potential of rabbit atrial muscle preparations: comparison with amiodarone. [2019] Dronedarone, a noniodinated derivative of amiodarone, is under evaluation as a potentially less toxic anti-arrhythmic alternative to amiodarone. The acute and chronic electrophysiologic effects of dronedarone and amiodarone were compared in isolated rabbit atrial muscle by microelectrode techniques. Four-week PO treatment with dronedarone or amiodarone increased action potential duration (APD90) (58 +/- 4 ms control versus 69 +/- 2 ms dronedarone, p

5. Netherlands pubmed.ncbi.nlm.nih.gov

Intravenous and oral administration of amiodarone for the treatment of recent onset atrial fibrillation after digoxin administration. [2013] Atrial fibrillation (AF) remains a significant contributor to cardiovascular morbidity. Amiodarone is a potent antiarrhythmic drug. The safety and efficacy of oral versus intravenous (i.v.) Amiodarone in the treatment of AF of recent onset (duration

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

Amiodarone (Nexterone) injection for the treatment and prophylaxis of frequently recurring ventricular fibrillation. [2013] Intravenous (IV) amiodarone is the most used and effective drug to manage life-threatening ventricular arrhythmias. However, its administration is associated with important adverse effects, the most frequent of which is hypotension. Nexterone® is a novel IV amiodarone formulation, proved to be devoid of hypotensive effects in clinical studies and may represent an improved and safer instrument in this setting.

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

Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. [2023] Amiodarone is effective in maintaining sinus rhythm in atrial fibrillation but is associated with potentially serious toxic effects. Dronedarone is a new antiarrhythmic agent pharmacologically related to amiodarone but developed to reduce the risk of side effects.

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

Safety update: monitoring patients taking amiodarone. [2022] Overview of: Medicines and Healthcare products Regulatory Agency. Amiodarone (Cordarone X): reminder of risks of treatment and need for patient monitoring and supervision. Drug Safety Update 2022;15:5-7.

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

Clinical use and pharmacology of amiodarone. [2019] Amiodarone, an investigational drug in the United States, has had considerable use in this country and worldwide in the treatment of cardiac arrhythmias. This article reviews the clinical pharmacology of this potentially useful antiarrhythmic agent.

10. New Zealand pubmed.ncbi.nlm.nih.gov

Dronedarone. [2021] Oral dronedarone is a non-iodinated benzofurane derivative structurally related to amiodarone. Although it is considered a class III antiarrhythmic agent like amiodarone, it demonstrates multi-class electrophysiological activity. Data from the ATHENA study demonstrated that patients receiving oral dronedarone 400 mg twice daily for 12-30 months had a significantly lower risk of experiencing first hospitalization due to a cardiovascular event or death from any cause than those receiving placebo. Dronedarone exhibited rate- and rhythm-controlling properties in patients with atrial fibrilation (AF) or atrial flutter, significantly reducing the risk of a first recurrence of AF versus placebo following 12 months' therapy in the ADONIS and EURIDIS studies. In the ERATO study, dronedarone was also significantly more effective than placebo in terms of ventricular rate control. Furthermore, the beneficial effects of oral dronedarone on ventricular rate control were maintained during exercise and sustained with continued therapy. Oral dronedarone was generally well tolerated in the treatment of adult patients with AF and/or atrial flutter in clinical studies. The incidence of diarrhoea, nausea, bradycardia, rash and QT-interval prolongation was significantly higher with oral dronedarone than placebo in the large ATHENA study; however, serious cardiac-related adverse events were observed in

11. England pubmed.ncbi.nlm.nih.gov

Emerging pharmacotherapies for the treatment of atrial fibrillation. [2018] The main aim of current research on the field of atrial fibrillation (AF) treatment is to find new antiarrhythmic drugs with less side effects. Areas covered: Dronedarone and vernakalant showed promising result in term of efficacy and safety in selected patients. Ranolazine and colchicine are obtaining a role as a potential antiarrhythmic drug. Ivabradine is used in experimental studies for the rate control of AF. Moreover, new compounds (vanoxerine, moxonidine, budiodarone) are still under investigation. Monoclonal antibodies or selective antagonist of potassium channel are under investigation for long term maintenance of sinus rhythm. Clinical evidence and new pharmacological investigation on new drugs will be accurately reviewed in this article. Expert opinion: Dronedarone use is not recommended in patients with symptomatic heart failure (HF), NYHA class III-IV, depressed ventricular function and permanent AF, especially in patients assuming a concomitant therapy with digoxin. Vernakalant had superior efficacy than amiodarone, flecainide and propafenone in single studies and similar efficacy to direct current cardioversion. Several of the developing drugs examined in this paper show an interesting potential, in particular the research on selective ionic channel inhibition and on compounds which reduce the inflammation state, especially after ablation or surgery.