Evaluation of Prophylactic Amiodarone Hydrochloride in Critically Ill Patients Post Out-of-Hospital Cardiac Arrest with Initial Shockable Rhythm

The primary objective of this study is to determine if the **prophylactic administration** of amiodarone for 72 hours in critically ill patients admitted after an out-of-hospital cardiac arrest (OHCA) with an initial shockable rhythm, and with a confirmed or presumed cardiac cause, reduces the incidence of a composite endpoint. This endpoint includes 30-day all-cause mortality and/or severe in-hospital ventricular arrhythmia recurrence, such as ventricular fibrillation and/or ventricular tachycardia requiring intervention, including re-arrest. This is clinically relevant as it addresses the potential to improve survival rates and reduce severe cardiac events in a high-risk patient population.

Secondary objectives include the comparative evaluation of the prophylactic administration of amiodarone on outcomes related to cardiac events. This aims to further understand the broader impact of amiodarone on cardiac health in the specified patient group.

The clinical trial focuses on patients who have experienced an **out-of-hospital cardiac arrest** with an initial shockable rhythm. The study population includes both male and female participants aged 18 years and older, who are admitted to an intensive care unit. Participants are selected based on specific criteria, including a presumed cardiac or unknown cause of arrest and a delay of less than 6 hours between return of spontaneous circulation (ROSC) and screening for randomization. The trial involves a vulnerable population, as it includes critically ill patients. The sponsor has not provided information regarding the total number of participants. Participants must be affiliated with or benefit from social insurance, and informed consent is required from the patient, a surrogate, or through deferred consent. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **amiodarone hydrochloride** in critically ill patients who have experienced an out-of-hospital cardiac arrest with an initial shockable rhythm. This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know who is receiving the treatment or placebo, thus minimizing bias. The trial is expected to commence recruitment on October 1, 2024, and is estimated to conclude by January 1, 2027. The primary objective is to assess whether the prophylactic administration of amiodarone for 72 hours reduces the incidence of a composite endpoint of 30-day all-cause mortality and severe in-hospital ventricular arrhythmia recurrence.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years), admission to an intensive care unit, and a delay of less than six hours between return of spontaneous circulation and screening for randomization. Informed consent is required from the patient or a surrogate. Follow-up visits will be conducted to monitor the participants' health status and any occurrence of ventricular arrhythmias. The end-of-study visit will occur at hospital discharge or 30 days post-inclusion, whichever is sooner, to evaluate the primary endpoint.

The expected length of participant involvement is up to 30 days, depending on the duration of hospital stay. Conditions that may lead to early termination from the study include withdrawal of consent, occurrence of adverse events that contraindicate continued participation, or any other medical reasons deemed necessary by the investigator. The trial is classified as a low-intervention study, as the investigational medicinal product is used according to its marketing authorization. The study will adhere to rigorous ethical standards and regulatory requirements to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **amiodarone hydrochloride** as the experimental medication. The product used is CORDARONE 150 mg/3 ml, a **solution for injection** provided in ampoules. This pharmaceutical form is specifically designed for intravenous administration, either as a bolus injection or via IV infusion. The maximum daily dose of amiodarone hydrochloride is 900 mg, with a total maximum dose of 2700 mg over the treatment period. The treatment is administered over a maximum period of 3 days. The active substance, amiodarone hydrochloride, is of chemical origin and is classified under the ATC code C01BD01, indicating its use as an antiarrhythmic agent.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of the experimental medication, CORDARONE, to evaluate its efficacy in reducing the incidence of a composite endpoint of 30-day all-cause mortality and/or severe in-hospital ventricular arrhythmia recurrence in critically ill patients admitted after an out-of-hospital cardiac arrest with a shockable rhythm. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the treatment protocol.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is a composite of 30-day all-cause mortality and the occurrence of severe in-hospital ventricular arrhythmia. This arrhythmia is defined by the presence of **ventricular fibrillation** and/or **ventricular tachycardia** requiring intervention, occurring between inclusion and hospital discharge, or within 30 days, whichever is sooner. The trial aims to determine if the prophylactic administration of amiodarone for 72 hours in critically ill patients admitted after an out-of-hospital cardiac arrest with shockable rhythm decreases the incidence of this composite endpoint. The efficacy parameters will be collected and analyzed from the time of inclusion up to 30 days post-inclusion or until hospital discharge. The trial is designed to provide a comparative analysis of the outcomes in patients receiving amiodarone versus those who do not, with the primary focus on reducing mortality and severe arrhythmia recurrence.