Antiarrhythmic Drugs for Atrial Fibrillation

Recruiting at 3 trial locations

Overseen By Dawood Darbar, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Illinois at Chicago

Must not be taking: Amiodarone

Disqualifiers: Permanent AF, Cardiac surgery, 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

Compensation: Varies

Number of Visits: 1

Duration: 12 months

162 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two antiarrhythmic drugs, Flecainide (Tambocor) and Sotalol (Betapace or Sorine), to evaluate their effectiveness in treating atrial fibrillation (AF), a condition characterized by an irregular heartbeat. Researchers aim to determine if a specific gene influences the efficacy of these drugs. They seek participants who frequently experience symptomatic AF episodes, with noticeable symptoms occurring at least twice a month. Participants must be eligible to take both drugs and have an ECG showing AF. As a Phase 4 trial, the treatment has already received FDA approval and demonstrated effectiveness, and this research aims to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the study involves testing specific antiarrhythmic drugs, you might need to adjust your current medications. It's best to discuss this with the study team.

What is the safety track record for these treatments?

Research shows that both flecainide and sotalol are generally safe options for treating atrial fibrillation (AF).

Studies indicate that flecainide is safe when used as recommended. It does not increase the risk of death and effectively treats AF. In patients with stable heart disease, flecainide is considered safe. However, some evidence suggests a higher risk of heart rhythm-related death in certain cases, so monitoring is important.

Sotalol is also generally safe for AF patients. Research has found that patients starting sotalol do not have a higher risk of death compared to other treatments. However, there is a risk of side effects, so careful monitoring is necessary.

Both drugs require careful use and monitoring, but research supports their safety when guidelines are followed. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using flecainide and sotalol for atrial fibrillation because these drugs offer distinct benefits over traditional treatments like beta-blockers and anticoagulants. Flecainide is unique because it works by blocking specific sodium channels in the heart, helping to stabilize the heartbeat more effectively. Sotalol, on the other hand, combines beta-blocking properties with potassium channel blocking, potentially offering a dual-action approach to managing irregular heart rhythms. This new combination approach could provide more comprehensive control of atrial fibrillation symptoms, giving patients a better quality of life.

What evidence suggests that this trial's treatments could be effective for atrial fibrillation?

This trial will compare the effectiveness of flecainide and sotalol in treating atrial fibrillation (AF). Research has shown that flecainide can benefit people with AF, with one study reporting that 168 out of 376 patients returned to a normal heart rhythm within six hours of taking it. Patients also tolerate it well, experiencing good results over a year. Sotalol is another option in this trial for treating AF. Although studies have compared it to other drugs like dronedarone and amiodarone, they find no major difference in effectiveness. Still, it remains a popular choice for managing AF symptoms. Both medications offer different ways to help people with AF manage their condition. ^{2 3 5 6 7}

Are You a Good Fit for This Trial?

This study is for adults over 18 with frequent, symptomatic atrial fibrillation who are of African, European, or Hispanic descent. Participants must be able to consent and eligible for both Flecainide and Sotalol medications. Exclusions include severe kidney or heart dysfunction, pregnant or nursing women, those with a family member in the study, recent surgery patients, individuals with certain medical conditions or contraindications to the drugs being tested.

Inclusion Criteria

I have had two or more episodes of AFib each month.

I can take both Flecainide and Sotalol medications.

Your recent heart test shows atrial fibrillation.

Exclusion Criteria

My atrial fibrillation is caused by a treatable condition like hyperthyroidism.

I have tried two or more antiarrhythmic drugs for atrial fibrillation.

I have been diagnosed with permanent atrial fibrillation or isolated atrial flutter.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants are randomized to receive either flecainide or sotalol for 6 months, followed by a crossover to the alternate drug for another 6 months.

12 months

Monthly visits (in-person) for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment using the Medtronic Reveal LINQ ICM system.

12 months

Continuous monitoring with ICM, periodic in-person visits

Open-label extension (optional)

Participants may opt to continue monitoring with the ICM device after the study concludes.

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Flecainide
• Sotalol

Trial Overview The trial tests two antiarrhythmic drugs (Flecainide and Sotalol) on patients with atrial fibrillation to see how genetic factors affect drug response. It's a cross-over study where participants will switch between medications so researchers can compare effects directly within the same individual.

How Is the Trial Designed?

Group I: sotalol 1st Experimental Treatment 2 Interventions

sotalol x 6 months, then crossover to flecainide x 6 months

Group II: flecainide 1st Experimental Treatment 2 Interventions

flecainide x 6 months, then crossover to sotalol x 6 months

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

Approved in United States as Tambocor for:

• Paroxysmal atrial fibrillation/flutter
• Life-threatening ventricular arrhythmias

Approved in European Union as Tambocor for:

• Symptomatic paroxysmal atrial fibrillation
• Symptomatic paroxysmal supraventricular tachycardia

Approved in Canada as Tambocor for:

• Paroxysmal atrial fibrillation/flutter
• Life-threatening ventricular arrhythmias

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

Medtronic

Industry Sponsor

Trials

627

Recruited

767,000+

Geoff Martha

Medtronic

Chief Executive Officer since 2020

Finance degree from Penn State University

Dr. Richard Kuntz

Medtronic

Chief Medical Officer since 2023

MD, MSc

Published Research Related to This Trial

In a study of 4,987 patients treated with d,l-sotalol for atrial fibrillation, there was a significantly lower all-cause mortality rate compared to 27,078 patients treated with cardioselective beta-blockers, suggesting that d,l-sotalol may be a safer option for rhythm control.

The study found no significant difference in the incidence of serious ventricular arrhythmias or cardiac arrest between the two treatment groups, indicating that d,l-sotalol does not increase the risk of these serious outcomes when used with proper patient selection and follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mortality and ventricular arrhythmias in patients on d,l-sotalol for rhythm control of atrial fibrillation: A nationwide cohort study. Lenhoff, H., Järnbert-Petersson, H., Darpo, B., et al.[2023]

Flecainide is an effective antiarrhythmic medication for patients with atrial fibrillation (AF) who do not have structural heart disease, and it is recommended for various uses including cardioversion and maintenance of sinus rhythm.

While flecainide has a good safety profile with low incidence of adverse effects, careful patient selection and monitoring are essential, especially in those with renal dysfunction or potential drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of flecainide. Tamargo, J., Capucci, A., Mabo, P.[2021]

In a study of 66 patients with paroxysmal atrial fibrillation, flecainide (F) and sotalol (S) were found to be effective in preventing recurrences, with 70% of patients on flecainide and 60% on sotalol remaining arrhythmia-free after 12 months.

Both medications significantly reduced the risk of atrial fibrillation recurrences compared to placebo, with flecainide showing an 85% reduction and sotalol a 76% reduction, while side effects were common but not clinically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A comparison between flecainide and sotalol in the prevention of recurrences of paroxysmal atrial fibrillation]. Carunchio, A., Fera, MS., Mazza, A., et al.[2013]

In a study of 92 patients with recent onset atrial fibrillation, intravenous sotalol effectively restored sinus rhythm in 54% of patients, demonstrating its efficacy as a first-line treatment.

If sotalol was unsuccessful, the addition of intravenous flecainide led to a successful conversion to sinus rhythm in 84% of those patients, indicating that a combination approach can be highly effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of recent onset atrial fibrillation with intravenous sotalol and/or flecainide. Peters, FP., Braat, SH., Heymeriks, J., et al.[2019]

Dofetilide and Betapace AF (sotalol) were rarely prescribed in the U.S. during the two years following their introduction, indicating poor acceptance among physicians despite their safety guidelines.

The limited use of these drugs may be attributed to the strict risk-management programs for dofetilide and the availability of generic sotalol, leading to a preference for other antiarrhythmic medications without such restrictions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New antiarrhythmic agents for atrial fibrillation and atrial flutter: United States drug market response as an indicator of acceptance. LaPointe, NM., Pamer, CA., Kramer, JM.[2019]

Flecainide significantly increased the thresholds for both atrial and ventricular fibrillation, demonstrating its effectiveness as an antiarrhythmic agent in a study using intracavitary stimulation methods.

The drug was able to dose-dependently reduce or completely abolish '2nd Phase' ventricular arrhythmias, indicating its potential as a treatment for both atrial and ventricular reentrant arrhythmias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of flecainide on atrial and ventricular stimulation thresholds to repetitive extrasystoles and fibrillation and on "2nd Phase" ventricular arrhythmias in dogs. Heuer, H., Gülker, H., Thale, J., et al.[2013]

Outpatient initiation of sotalol for treating atrial fibrillation (AF) in patients with cardiac implantable electronic devices (CIEDs) is both effective and safe, with 73% of patients maintaining sinus rhythm over an average follow-up of 23 months.

No significant adverse effects related to QTc prolongation or torsades de pointes were observed, indicating that remote monitoring with CIEDs allows for safe management of sotalol therapy outside of a hospital setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outpatient Initiation of Sotalol in Patients with Atrial Fibrillation: Utility of Cardiac Implantable Electronic Devices for Therapy Monitoring. Mascarenhas, DAN., Mudumbi, PC., Kantharia, BK.[2021]

In a study of 173 patients with recent atrial fibrillation (AF), the combination of flecainide and metoprolol significantly reduced AF recurrences over one year compared to flecainide alone, especially in patients with persistent AF (71.1% vs. 43.6%).

Patients receiving the combination therapy also reported a significant improvement in quality of life compared to those on flecainide only, indicating better tolerability and compliance with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flecainide-metoprolol combination reduces atrial fibrillation clinical recurrences and improves tolerability at 1-year follow-up in persistent symptomatic atrial fibrillation. Capucci, A., Piangerelli, L., Ricciotti, J., et al.[2017]

Restoring and maintaining normal sinus rhythm in patients with atrial fibrillation (AF) can alleviate symptoms and potentially reduce the risk of serious complications, such as blood clots.

Antiarrhythmic agents like amiodarone and sotalol are effective in maintaining sinus rhythm, especially in patients with structural heart disease, and they have a lower risk of causing harmful arrhythmias when used correctly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiarrhythmic agents for atrial fibrillation: focus on prolonging atrial repolarization. Singh, BN., Mody, FV., Lopez, B., et al.[2019]

Class I antiarrhythmic agents like quinidine and flecainide, while effective for atrial fibrillation, have been associated with increased mortality and proarrhythmic effects, raising concerns about their safety in certain patients.

Sotalol, a class III antiarrhythmic drug, is increasingly used for treating atrial fibrillation due to its ability to prolong action potentials and refractory periods, with effective oral doses ranging from 80 to 320 mg every 12 hours, and it has shown promising results in clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapy of atrial fibrillation with class III anti-arrhythmia agents]. Follath, F., Candinas, R., Frielingsdorf, J.[2013]

Citations

1. ecrjournal.com ecrjournal.com/articles/atrial-fibrillation-and-flecainide-safety-effectiveness-and-quality-life-outcomes?language_content_entity=en

Atrial Fibrillation and Flecainide - Safety, Effectiveness and ... In this study, cardioversion of AF was successful in 168 of the 376 patients within six hours. Flecainide was the most effective drug, with a primary response ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4325304/

Flecainide: Current status and perspectives in arrhythmia ... Flecainide has proven its efficacy in the cardioversion of atrial fibrillation in sinus rhythm in both human and animal trials causing a shortening of the APD ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7343357/

Flecainide is well-tolerated and effective in patient with ... Flecainide is well-tolerated and effective in patient with atrial fibrillation at 12 months: a retrospective study - PMC.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0002870321002118

Long-term outcomes in patients treated with flecainide for ... This study found that flecainide therapy among AF patients with stable CAD had a decreased risk of death, HF hospitalization, proarrhythmia (VT), and a ...

5. jacc.org jacc.org/doi/10.1016/j.jacep.2024.02.021

Orally Inhaled Flecainide for Conversion of Atrial ... - JACC The primary efficacy outcome was the rate of conversion of AF to SR within a 90-minute observation period following completion of inhalation. AF ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34537183/

Long-term outcomes in patients treated with flecainide for ... Flecainide in select patients with stable CAD for AF has a favorable safety profile compared to class-3 AADs. These data suggest the need for prospective ...

7. jacc.org jacc.org/doi/10.1016/j.jacep.2022.12.021

The Feasibility and Safety of Flecainide Use Among ... Additionally, Burnham et al, reported favorable long-term outcomes with flecainide therapy for atrial fibrillation among patients without heart ...