Efficacy of Intravenous Flecainide Acetate with Oral Ranolazine vs. Intravenous Flecainide Acetate in Cardioversion of Recent-Onset Atrial Fibrillation

The primary objective of this study is to evaluate the **effectiveness** of combined antiarrhythmic therapy using intravenous (IV) **flecainide** and oral (PO) **ranolazine** compared to IV flecainide monotherapy in restoring sinus rhythm in patients with recent onset atrial fibrillation (AF) of less than 48 hours duration. This is clinically relevant as achieving timely cardioversion in AF can prevent complications such as stroke and improve patient outcomes by restoring normal heart rhythm.

The clinical trial focuses on the **restoration of sinus rhythm** in patients with recent onset atrial fibrillation (AF). The study population includes both male and female participants aged 18 years and older, with no specific mention of vulnerable populations being included. Participants are required to have electrocardiographically confirmed AF with a self-reported onset of arrhythmia within 48 hours prior to the initiation of pharmacological cardioversion. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet, physical activity, or habits. The trial population was selected based on the principal inclusion criteria, which emphasize the age and recent onset of AF. The study does not specify any additional health status requirements or exclusion criteria beyond those mentioned.

The clinical trial is designed to evaluate the effectiveness of combined antiarrhythmic therapy using **intravenous flecainide** and oral **ranolazine** compared to intravenous flecainide monotherapy in restoring sinus rhythm in patients with recent onset atrial fibrillation (AF). This study is a randomized, prospective, multicenter, open-label trial. The trial is expected to run from January 31, 2022, to June 30, 2025, with the primary objective of determining the percentage of patients who achieve sinus rhythm within three hours of treatment initiation. Secondary endpoints include the time interval to sinus rhythm restoration and the percentage of patients achieving sinus rhythm within six hours.

Participants will be involved in the study for a maximum treatment period of one day. The study will commence with an inclusion visit, where eligibility will be confirmed based on criteria such as age (≥18 years) and electrocardiographically confirmed recent onset AF (within 48 hours). Following the inclusion visit, participants will receive either the combination therapy or monotherapy as per randomization. Follow-up visits will be conducted to monitor the restoration of sinus rhythm and assess any adverse events. The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected and any remaining health concerns are addressed.

Participants may be withdrawn from the study if they experience significant adverse effects, fail to comply with the study protocol, or if the investigator deems it necessary for their safety. The trial's design ensures that the data collected will provide robust evidence on the comparative effectiveness of the treatment regimens, contributing valuable insights into the management of recent onset AF.

The clinical trial involves the administration of **Ranolazine**, an experimental medication, in the form of a **prolonged-release tablet**. The active substance, ranolazine, is of chemical origin. The maximum daily dose is 1500 mg, administered orally. The treatment period is limited to one day. Ranolazine is used in combination with another medication to evaluate its effectiveness in restoring sinus rhythm in patients with recent onset atrial fibrillation.

**Flecainide Acetate** is utilized as a comparator treatment in this study. It is provided as a **solution for injection/infusion** and is administered intravenously. The maximum daily dose is 2 mg/kg, with a treatment period of one day. Flecainide acetate is also of chemical origin and is used to assess its efficacy as a monotherapy in the cardioversion of recent onset atrial fibrillation.

In addition to the experimental and comparator treatments, a **B-Blocker** may be administered as a non-experimental treatment. The study aims to compare the effectiveness of the combined antiarrhythmic therapy of intravenous flecainide and oral ranolazine versus intravenous flecainide alone. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure accurate assessment of the treatment outcomes.

Efficacy in this clinical trial will be assessed by evaluating the restoration of sinus rhythm in patients with recent onset atrial fibrillation (AF) within specified timeframes. The primary endpoint is the percentage of patients with recent onset AF who achieve sinus rhythm within 3 hours of starting treatment with intravenous (IV) **flecainide** and oral (PO) **ranolazine** compared to IV flecainide monotherapy. Secondary endpoints include the time interval from the initiation of treatment to the restoration of sinus rhythm and the percentage of patients achieving sinus rhythm within 6 hours of treatment initiation.

The efficacy parameters will be measured and collected at specific timepoints, namely within 3 and 6 hours of treatment initiation. The analysis will focus on comparing the effectiveness of the combined antiarrhythmic therapy versus monotherapy in achieving the desired clinical outcome. The study is designed as a randomized, prospective, multicentre, open-label trial, ensuring a robust assessment of the treatment efficacy in the target patient population.