Efficacy of Clostridium Botulinum Neurotoxin Type A Injections for Postoperative Atrial Fibrillation Prevention in Cardiac Surgery Patients

The primary objective of this study is to evaluate the **efficacy** of Botulinum toxin injections into epicardial fat pads for the prevention of postoperative atrial fibrillation (AF) in patients undergoing cardiac surgery. This is clinically relevant as postoperative AF is a common complication following cardiac surgery, which can lead to increased morbidity, prolonged hospital stays, and higher healthcare costs. By potentially reducing the incidence of postoperative AF, the study aims to improve patient outcomes and optimize resource utilization in cardiac surgical care.

The clinical trial involves **adult patients** with an indication for conventional cardiac surgery, such as coronary artery bypass grafting (CABG), aortic valve repair or replacement, and ascending aorta surgery. The study population includes both male and female participants, aged between 18 and 80 years, who are in a hemodynamically stable condition and maintain sinus rhythm at the time of randomization. Participants are required to have a negative serum or urinary β-hCG test if they are women of child-bearing potential. The trial population was selected based on their ability to attend multiple consultations at the center and their affiliation with the French social security regime. The sponsor has not provided information regarding the total number of participants. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, and all participants have provided informed consent to partake in the study.

The clinical trial is designed to evaluate the efficacy of **botulinum toxin** injections into epicardial fat pads for the prevention of postoperative atrial fibrillation (AF) in patients undergoing cardiac surgery. This is a randomized, double-blind, controlled trial involving adult patients who are indicated for conventional cardiac surgery, such as coronary artery bypass grafting (CABG), aortic valve repair, or ascending aorta surgery. The trial will utilize a parallel-group design, with participants randomly assigned to receive either the active treatment, XEOMIN 200 units, or a placebo. The trial is expected to span from the estimated recruitment start date of September 30, 2019, to the estimated end date of September 30, 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, hemodynamic stability, and sinus rhythm at the time of randomization. Following successful screening, participants will be randomized and receive the assigned treatment during their cardiac surgery. The primary endpoint, the incidence of rhythm disorders of postoperative AF, will be assessed through continuous monitoring using a Holter ECG Spiderflash-t recorder for the first 21 days post-operation and daily ECG monitoring for the first 7 days. Two blinded cardiologists will independently adjudicate the primary endpoint.

Follow-up visits will be scheduled to monitor the participants' health status and collect data on any adverse events or complications. The end-of-study visit will occur at the conclusion of the 21-day monitoring period, where final assessments will be conducted. The expected length of participant involvement is approximately three weeks post-surgery. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial aims to provide robust data on the potential benefits of botulinum toxin in reducing the incidence of postoperative AF, contributing to improved patient outcomes in cardiac surgery.

The clinical trial involves the administration of **XEOMIN 200 unités**, a **poudre pour solution injectable** containing **Clostridium botulinum neurotoxin type A (150 kD), free of complexing proteins**. This experimental medication is provided in the form of a solution for injection. The active substance, also known by synonyms such as IncobotulinumtoxinA and NT 201, is classified under the ATC code M03AX01, which corresponds to **botulinum toxin**. The medication is administered via **infiltration** into epicardial fat pads around the pulmonary veins. The maximum daily dose is 200 units, with a total treatment period of one day. The product is manufactured by Merz Pharmaceuticals GmbH and is not a pediatric formulation.

The study also includes a **placebo** treatment, referred to as the Placebo of Xeomin 200 U. This non-experimental treatment serves as a comparator to the active medication. The placebo is designed to mimic the administration process of the experimental drug but does not contain any active substance. The placebo is utilized to assess the efficacy of the botulinum toxin injection in preventing postoperative atrial fibrillation in patients undergoing cardiac surgery. The administration route and frequency for the placebo are consistent with those of the experimental treatment to ensure blinding and maintain the integrity of the trial results.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the incidence of rhythm disorders, specifically postoperative **atrial fibrillation (AF)**, in patients undergoing cardiac surgery. The primary endpoint is defined as the occurrence of atrial arrhythmia lasting at least 30 seconds continuously within 21 days following cardiac surgery. This will be measured using a Holter ECG Spiderflash-t recorder during the first 21 days post-operation and through daily ECG monitoring during the first 7 days after surgery. Two blinded cardiologists will independently adjudicate the primary endpoint to ensure objective assessment.