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 study is evaluating whether a common genetic risk factor may predict how well a certain class of drugs will work for individuals with atrial fibrillation.

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 safety data exists for antiarrhythmic drugs like Flecainide and Sotalol used in atrial fibrillation?

Flecainide is generally safe for people with atrial fibrillation who do not have structural heart disease, but it can cause dizziness and blurred vision. Sotalol requires careful monitoring due to potential heart rhythm issues, such as QTc interval prolongation and torsades de pointes (a type of dangerous heart rhythm). ^{1 2 3 4 5}

How do the drugs Flecainide and Sotalol differ from other treatments for atrial fibrillation?

Flecainide and Sotalol are unique in treating atrial fibrillation because they work by different mechanisms: Flecainide increases the threshold for fibrillation, making it harder for the heart to enter an irregular rhythm, while Sotalol prolongs the heart's electrical activity to maintain a normal rhythm. Sotalol is often used in patients with structural heart disease due to its lower risk of causing additional heart rhythm problems compared to some other drugs. ^{1 6 7 8 9}

What data supports the effectiveness of the drugs Flecainide, Tambocor, Sotalol, Betapace, and Sorine for treating atrial fibrillation?

Research shows that Flecainide and Sotalol are effective in maintaining normal heart rhythm in patients with atrial fibrillation, especially when there is no significant heart disease. Sotalol, in particular, is noted for its ability to prolong the heart's electrical activity, which helps prevent irregular heartbeats. ^{1 6 7 8 10}

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

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]

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]

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]

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]

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]

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 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]

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]

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]

Citations

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

Antiarrhythmic agents for atrial fibrillation: focus on prolonging atrial repolarization. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of recent onset atrial fibrillation with intravenous sotalol and/or flecainide. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

[Therapy of atrial fibrillation with class III anti-arrhythmia agents]. [2013]

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

Outpatient Initiation of Sotalol in Patients with Atrial Fibrillation: Utility of Cardiac Implantable Electronic Devices for Therapy Monitoring. [2021]

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

New antiarrhythmic agents for atrial fibrillation and atrial flutter: United States drug market response as an indicator of acceptance. [2019]

6. United States 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. [2023]

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

Safety of flecainide. [2021]

8. England 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. [2017]

9. Italy pubmed.ncbi.nlm.nih.gov

[A comparison between flecainide and sotalol in the prevention of recurrences of paroxysmal atrial fibrillation]. [2013]

10. Germany 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. [2013]