Evaluation of Spironolactone for Sinus Rhythm Maintenance in Hypertensive Atrial Fibrillation Patients with Preserved Left Ventricular Ejection Fraction

The primary objective of this study is to determine whether the administration of **spironolactone** (initially 25 mg per day, titrated to a maximum of 50 mg per day) in addition to standard therapy results in a reduction in the recurrence of documented atrial fibrillation (AF) episodes, whether symptomatic or not, within 12 months from randomization. This is specifically evaluated in hypertensive patients with preserved left ventricular ejection fraction (LVEF). The clinical relevance of this objective lies in its potential to improve the management of AF in this patient population, potentially reducing the frequency of AF episodes and associated complications.

Secondary objectives include: - Evaluating symptomatic documented AF occurring within 12 months from randomization. - Assessing the time to recurrence of the first documented AF episode, symptomatic or not, within 12 months. - Measuring the cumulative AF burden within 12 months. - Monitoring major cardiovascular events and all-cause mortality, including stroke, myocardial infarction, and heart failure, within 12 months. - Determining the rate of cerebral/systemic thrombo-embolic and bleeding events. - Analyzing the mean ventricular rate at the recurrence of AF. - Observing blood pressure reduction and control. - Evaluating safety parameters, particularly blood pressure, serum potassium levels, and renal function, within 12 months.

The clinical trial involves a study population comprising both **male and female** participants aged 18 years and older. The trial focuses on individuals diagnosed with **atrial fibrillation** and preserved left ventricular ejection fraction, specifically targeting hypertensive patients. Participants are required to have experienced at least one episode of paroxysmal or non-long-standing persistent atrial fibrillation within the preceding 12 months and must be in sinus rhythm at the time of enrollment. The trial does not include a vulnerable population. Participants are expected to be recipients of the social security regime, possess a smartphone, and be French-speaking. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations include the current use of anti-hypertensive drugs for more than 12 months. The trial population was selected based on specific criteria, including the ability to comply with scheduled visits and the provision of signed consent. The sponsor has not disclosed the total number of participants involved in the study.

The clinical trial is designed to evaluate the efficacy of **spironolactone** in maintaining sinus rhythm in hypertensive patients with atrial fibrillation and preserved left ventricular ejection fraction. This study is a **Prospective Randomized Open Blinded End-point** (PROBE) multicenter trial. Participants will be randomly assigned to receive either spironolactone, starting at 25 mg per day and titrated to a maximum of 50 mg per day, or standard therapy alone. The trial will span a period of 12 months, with the primary objective being the reduction in the recurrence of documented atrial fibrillation episodes.

The trial will commence with an inclusion visit, where participants will undergo screening to ensure they meet the eligibility criteria, which include being 18 years or older, having hypertension, and having experienced at least one episode of atrial fibrillation in the past 12 months. Women of childbearing age will undergo a highly sensitive pregnancy test, and all participants must provide informed consent. Follow-up visits will occur at 1, 6, and 12 months to monitor the recurrence of atrial fibrillation, assess blood pressure, and evaluate safety endpoints such as changes in serum potassium and kidney function. The end-of-study visit will conclude the trial, summarizing the outcomes and any adverse events.

Participants are expected to be involved in the study for the entire 12-month duration unless conditions arise that necessitate early termination, such as significant adverse reactions or withdrawal of consent. The primary endpoint is the first documented recurrence of atrial fibrillation, defined as an episode lasting at least 30 seconds, documented on a 12-lead ECG or a wearable optical photoplethysmography device. Secondary endpoints include the recurrence of symptomatic episodes, the delay of recurrence, cumulative atrial fibrillation burden, and the occurrence of major cardiovascular events. The trial aims to provide comprehensive data on the efficacy and safety of spironolactone in this patient population.

The clinical trial involves the administration of **SPIRONOLACTONE PFIZER 25 mg**, a **tablet** formulation containing **micronised spironolactone** as the active substance. This medication is produced by Pfizer Holding France and is identified by the marketing authorization number 34009 396 279 7 7. The **oral** route is utilized for administration. The initial dosage is set at 25 mg per day, with the potential to titrate up to a maximum of 50 mg per day, depending on the patient's response and tolerance. The treatment duration is capped at 12 months. The primary objective is to assess the efficacy of spironolactone in reducing the recurrence of atrial fibrillation episodes in hypertensive patients with preserved left ventricular ejection fraction.

In addition to the experimental treatment, participants will continue to receive standard-of-care therapy as part of the study protocol. This standard therapy serves as a comparator to evaluate the added benefit of spironolactone. The study design is a Prospective Randomized Open Blinded End-point (PROBE) multicenter study, ensuring rigorous assessment of outcomes. Compliance with the dosing regimen will be monitored throughout the trial to ensure adherence and accurate evaluation of the treatment's efficacy.

Efficacy in the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the first documented recurrence of **atrial fibrillation (AF)** occurring from randomization and within 12 months. This is defined as an episode lasting at least 30 seconds, documented on a 12-lead ECG or a wearable optical photoplethysmography (PPG) device, specifically the ScanWatch 42mm® by Withings. Secondary endpoints include the recurrence of symptomatic documented AF episodes within the same timeframe, the delay in days of the first documented AF episode during follow-up, and the cumulative AF burden, which is the percentage of time in irregular rhythm as recorded by the PPG device. Additional secondary endpoints encompass a composite of major cardiovascular events and death, occurrence of cerebral/systemic thrombo-embolic and bleeding events, mean ventricular rate at AF recurrence, and blood pressure-lowering efficacy evaluated through office blood pressure measurements at 1, 6, and 12 months. Safety endpoints will also be monitored, including the occurrence of low blood pressure, changes in serum potassium, and acute kidney injury from randomization and within 12 months.