Comparative Study of Early Ablation Versus Amiodarone, Bisoprolol, and Sotalol in Preventing Atrial Fibrillation Recurrence in Hypertrophic Cardiomyopathy Patients

The primary objective of this study is to evaluate the efficacy of three different strategies in preventing the recurrence of **atrial fibrillation (AF)** in patients diagnosed with **hypertrophic cardiomyopathy (HCM)**. The study will compare two pharmacotherapy-based strategies, utilizing either amiodarone or beta-blockers/sotalol, against an invasive method of early ablation. This is clinically relevant as AF significantly impacts the prognosis of patients with HCM, increasing the risk of systemic embolism, heart failure progression, sudden cardiac death, and all-cause mortality. The study aims to determine the most effective approach to maintain sinus rhythm and improve patient outcomes in this population.

The clinical trial involves a total of **725 participants** diagnosed with **hypertrophic cardiomyopathy (HCM)**, a genetically determined heart disease. The study population includes both male and female subjects, aged 18 years and older, who are not considered part of a vulnerable population. Participants were selected based on their diagnosis of HCM as defined by the European Society of Cardiology, and all have provided informed consent to participate. The trial aims to observe these individuals, with a subset of 300 participants who have documented episodes of atrial fibrillation (AF) lasting more than 30 seconds, proceeding to a randomized therapeutic intervention phase. The sponsor has not provided specific information regarding the general health status, lifestyle considerations, or additional selection criteria for the trial population.

The clinical trial is designed to evaluate the efficacy of three strategies in preventing the recurrence of **atrial fibrillation** (AF) in patients diagnosed with **hypertrophic cardiomyopathy** (HCM). This study is a randomized, controlled, and double-blind trial, involving a total of 725 patients in the observation phase, with 300 patients progressing to the randomized therapeutic intervention phase. The trial will compare two pharmacotherapy strategies using **amiodarone** or beta-blockers such as **bisoprolol fumarate**, **metoprolol tartrate**, and **sotalol hydrochloride**, against an invasive method of early ablation. The trial is expected to commence on January 1, 2024, and conclude by March 31, 2029, with a maximum treatment period of 36 months for each participant.

Participants will undergo a series of study visits, beginning with an inclusion visit to confirm eligibility based on criteria such as a diagnosis of HCM, age of 18 years or older, and signed informed consent. Follow-up visits will be scheduled to monitor the primary endpoints, which include death, stroke, transient ischemic attack (TIA), or any extra-scheduled medical intervention. Secondary endpoints will assess the AF load, occurrence of silent AF, ventricular arrhythmias, new ischemic changes in CNS MRI, and quality of life changes. The end-of-study visit will evaluate the overall outcomes and any adverse events experienced by the participants.

The expected length of participant involvement is up to 36 months, with conditions for early termination including significant adverse events or withdrawal of consent. The trial aims to provide robust data on the effectiveness of early ablation compared to pharmacotherapy in managing AF in HCM patients, addressing a significant gap in current treatment guidelines. The study will adhere to ethical standards and regulatory requirements, ensuring the safety and well-being of all participants throughout the trial duration.

The clinical trial involves the administration of several **experimental medications** and comparator treatments to evaluate their efficacy in preventing the recurrence of atrial fibrillation in patients with hypertrophic cardiomyopathy. The experimental medications include **amiodarone hydrochloride**, **bisoprolol fumarate**, **metoprolol tartrate**, and **sotalol hydrochloride**. Each medication is administered orally in tablet form, with specific dosages and treatment periods.

**Amiodarone hydrochloride** is provided in two formulations: Cordarone 200 mg tablets and Opacorden 200 mg film-coated tablets. The maximum daily dose for amiodarone hydrochloride is 600 mg, with a total maximum dose of 800 mg. The treatment period extends up to 36 months. This medication is used as a comparator in the study.

**Bisoprolol fumarate** is available in three dosages: Bisocard 2.5 mg, 5 mg, and 10 mg film-coated tablets. The maximum daily and total dose for bisoprolol fumarate is 10 mg, with a treatment period of up to 36 months. Bisoprolol fumarate serves as a comparator in the trial.

**Metoprolol tartrate** is administered as Betaloc ZOK 100 mg and 50 mg prolonged-release tablets. The maximum daily and total dose for metoprolol tartrate is 150 mg, with a treatment period of up to 36 months. This medication is used as a comparator in the study.

**Sotalol hydrochloride** is provided in two formulations: SotaHEXAL 80 mg and 160 mg tablets. The maximum daily and total dose for sotalol hydrochloride is 160 mg, with a treatment period of up to 36 months. Sotalol hydrochloride is used as a comparator in the trial.

All medications are administered orally, and participant compliance is monitored throughout the study. The trial aims to compare the effectiveness of these pharmacotherapy strategies against invasive methods of early ablation in preventing atrial fibrillation recurrence. The study includes a population of 725 patients diagnosed with hypertrophic cardiomyopathy, with 300 patients experiencing documented atrial fibrillation episodes being included in the randomized therapeutic intervention phase.

The efficacy of the clinical trial will be assessed through a combination of primary and secondary endpoints. The primary endpoints include the occurrence of death, stroke, transient ischemic attack (TIA), or any extra-scheduled medical intervention such as hospitalization, emergency room visits, or medical consultations. These endpoints are critical in evaluating the overall effectiveness of the treatment strategies in preventing severe outcomes in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF).

Secondary endpoints will provide additional insights into the efficacy of the interventions. These include the measurement of **atrial fibrillation** load exceeding 12 hours during any observation day, the mean fibrillation load throughout the follow-up period, and the occurrence of silent AF within the HCM patient population. Other secondary endpoints involve the occurrence of ventricular arrhythmias, including non-sustained ventricular tachycardia, and the detection of new ischemic changes in CNS MRI. The correlation of these MRI changes with AF burden will also be analyzed. Furthermore, changes in quality of life will be assessed using the SF-36 questionnaire, comparing scores before and one year after randomization.

The trial will involve 725 patients diagnosed with HCM, with 300 patients experiencing documented AF episodes longer than 30 seconds being included in the randomized therapeutic intervention phase. The study aims to compare three strategies, including two pharmacotherapy-based approaches and one involving early ablation, to determine the most effective method for preventing AF recurrence in this patient population.