Evaluation of Flecainide for Reducing Atrial Arrhythmia Risk Post-Patent Foramen Ovale Closure in Patients

The primary objective of this study is to evaluate the efficacy of **flecainide** in preventing the occurrence of **atrial arrhythmia** (AA) during the first three months following **patent foramen ovale** (PFO) closure. This is clinically relevant as atrial arrhythmias can lead to significant morbidity and impact the success of PFO closure procedures.

Secondary objectives include assessing whether a six-month treatment regimen with flecainide is more effective than a three-month regimen in preventing AA occurrence after PFO closure. This comparison aims to determine the optimal duration of flecainide therapy to minimize the risk of arrhythmias post-procedure.

The clinical trial involves participants diagnosed with **Patent Foramen Ovale** (PFO) closure and atrial arrhythmia or tachycardia. The study population includes both male and female subjects aged 18 years and older. Participants are generally in good health, as they are candidates for a PFO closure procedure, which is confirmed by a multidisciplinary team. The trial does not include a vulnerable population. Participants must be affiliated with Social Security and have provided signed written consent. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified. Key inclusion criteria include successful PFO closure without major complications, and the trial is focused on assessing the efficiency of flecainide in preventing atrial arrhythmia within three months post-procedure.

The clinical trial is designed to evaluate the efficacy of **flecainide** in preventing atrial arrhythmia (AA) following patent foramen ovale (PFO) closure. This is a Phase III, randomized, double-blind, controlled study. The trial will span approximately four years, with an estimated recruitment start date of March 23, 2022, and an estimated end date of September 23, 2026. Participants will be randomly assigned to receive either flecainide or a placebo, administered orally in the form of prolonged-release capsules. The maximum daily dose of flecainide is 150 mg, with a total treatment period of up to six months.

Study visits are structured to ensure comprehensive monitoring and data collection. The inclusion visit, or screening, will confirm eligibility based on criteria such as age (≥18 years), successful PFO closure, and consent. Follow-up visits will occur at regular intervals to assess the primary endpoint, which is the percentage of patients experiencing at least one episode of symptomatic or asymptomatic AA lasting 30 seconds or more, as recorded by an insertable cardiac monitor (ICM) during the first three months post-PFO closure. Secondary endpoints include the evaluation of AA episodes over a longer period, the occurrence of symptomatic palpitations, stroke, transient ischemic attacks, and any cardiovascular-related consultations or hospitalizations.

The expected length of participant involvement is up to six months, with regular monitoring extending beyond this period to capture long-term outcomes. Conditions that may lead to early termination from the study include the occurrence of major complications during PFO closure or adverse reactions to flecainide. The trial aims to provide robust data on the safety and efficacy of flecainide in reducing the risk of atrial arrhythmias following PFO closure, contributing valuable insights into the management of this condition.

The clinical trial involves the administration of **Flecainide**, an experimental medication, to evaluate its efficacy in preventing atrial arrhythmia following patent foramen ovale closure. **Flecainide** is provided in the form of a **prolonged-release capsule, hard**, and is administered orally. The active substance, **flecainide**, is of chemical origin. The maximum daily dose is 150 mg, with a total maximum dose of 27.45 g over the course of the study. The treatment period is limited to a maximum of 6 months. Participants are required to adhere to the dosing schedule as prescribed, and compliance will be monitored throughout the trial.

In addition to the experimental treatment, the study may include non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments, as deemed necessary by the study protocol. These treatments will be administered according to standard medical guidelines and will serve as a control to evaluate the efficacy of **Flecainide**. The administration of these non-experimental treatments will be carefully documented, and participant compliance will be monitored to ensure the integrity of the trial results.

Efficacy in this clinical trial will be assessed by evaluating the occurrence of **atrial arrhythmia (AA)** episodes in patients following patent foramen ovale (PFO) closure. The primary endpoint is the percentage of patients experiencing at least one episode of symptomatic or asymptomatic AA lasting 30 seconds or more, as recorded by long-term monitoring with an insertable cardiac monitor (ICM) during the first three months post-PFO closure. This definition of AA includes episodes of atrial fibrillation, atrial flutter, or atrial tachycardia, in accordance with the 2012 consensus statement from the Heart Rhythm Society.

Secondary endpoints include the percentage of patients with AA episodes lasting 30 seconds or more during the 3-6 month period post-PFO closure, and episodes lasting 6 minutes or more during the first three months. Additional secondary measures include the AA burden and its evolution over time, the percentage of patients with symptomatic palpitations, stroke or transient ischemic attack (TIA), non-scheduled cardiovascular consultations or hospitalizations, and all-cause mortality during the 3 and 6 months after PFO closure. The rate of flecainide-related adverse events will also be monitored. Efficacy assessments will be conducted using data collected from the ICM device, which provides continuous monitoring throughout the study period.