Evaluation of Epinephrine Efficacy in Cardiopulmonary Resuscitation for Term Neonates with Cardiorespiratory Arrest in the Delivery Room

The primary objective of this study is to estimate the success rate of **cardiopulmonary resuscitation** within 90 seconds using the umbilical vein catheterization through Wharton's jelly (VOW) procedure as the first intention in newborns experiencing circulatory arrest in the delivery room, where an adrenaline injection is indicated. This objective is clinically relevant as it aims to improve the rapidity and effectiveness of resuscitation efforts in critical neonatal situations, potentially enhancing survival outcomes.

Secondary objectives include: - Measuring the duration of the VOW procedure from cord asepsis to the start of adrenaline injection, and comparing it to the duration via KTVO if applicable. - Measuring the time from the start of the VOW procedure to achieving a heart rate greater than 100 bpm, compared to KTVO. - Measuring the time between adrenaline injection and resumption of a heart rate above 100 bpm, comparing VOW and KTVO approaches. - Measuring the frequency of VOW procedure failures. - Describing the types and causes of procedural failures necessitating alternative approaches. - Measuring immediate mortality at one hour and upon discharge or at 28 days, overall and by approach used. - Assessing tolerance and safety through adverse events within 72 hours, overall and by approach. - Studying the relationship between injection time with the VOW procedure and practitioner experience or cord condition. - Describing difficulties encountered with the VOW procedure.

The clinical trial focuses on **full-term newborns** experiencing **cardiorespiratory arrest at birth**. The study population includes both male and female newborns, specifically those born at or beyond 37 weeks of amenorrhea. Participants are selected based on the necessity for resuscitation due to circulatory arrest or deep bradycardia, with a heart rate of less than 60 beats per minute, requiring adrenaline injection in the delivery room. The trial targets a vulnerable population, as it involves newborns in critical health conditions. The sponsor has not provided the total number of participants involved in the study. Participants must be beneficiaries of a social security system or entitled to one. The selection criteria ensure that the study population is homogenous in terms of age and health status, focusing on those requiring immediate medical intervention at birth.

The clinical trial is designed to evaluate the efficacy and safety of **epinephrine** in the context of cardiopulmonary resuscitation for full-term newborns experiencing cardiorespiratory arrest at birth. This is a Phase II, low-intervention trial, conducted in a randomized, double-blind, controlled manner. The trial aims to estimate the success rate of cardiopulmonary resuscitation within 90 seconds using the VOW procedure as the first intention. The trial is expected to commence recruitment on February 1, 2025, and conclude by March 1, 2027.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as being a full-term newborn (≥ 37 weeks of Amenorrhea) and requiring resuscitation with an **adrenaline** injection. Follow-up visits will be scheduled to monitor the duration of the umbilical route placement through Wharton's jelly, the time taken to achieve a heart rate greater than 100 bpm, and the frequency and causes of VOW procedure failures. The end-of-study visit will assess the overall success of the resuscitation efforts and any adverse events within 72 hours post-injection.

The expected length of participant involvement is determined by the immediate resuscitation needs and subsequent monitoring, with the trial procedures being completed within a short timeframe post-birth. Conditions that may lead to early termination from the study include the inability to meet inclusion criteria, withdrawal of consent, or any adverse events that compromise the safety of the participant. The trial will adhere to the recommendations of the European Resuscitation Council, ensuring that the investigational medicinal product is used in accordance with its marketing authorization.

The clinical trial involves the administration of **ADRENALINE AGUETTANT 1 mg/ml**, a **solution for injection** provided in ampoule form. The active substance in this experimental medication is **epinephrine**, a chemical compound. The pharmaceutical form is a solution intended for **intravenous** administration. The dosage is calculated based on the participant's body weight, with a maximum daily dose of 0.03 mg/kg. The total dose administered over the treatment period is also capped at 0.03 mg/kg. The maximum treatment period is limited to one day. This medication is not formulated specifically for pediatric use, and it is not classified as an orphan drug. The product is manufactured by **Laboratoire Aguettant** and is authorized for use in France.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of the experimental medication, **ADRENALINE AGUETTANT 1 mg/ml**, to evaluate its efficacy in the context of the trial's objectives. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol. The trial aims to assess the success rate of cardiopulmonary resuscitation in newborns with circulatory arrest, where an adrenaline injection is indicated, using the VOW procedure as the first intention.

Efficacy in this clinical trial will be assessed primarily by estimating the success rate of cardiopulmonary resuscitation within 90 seconds using the VOW procedure as the first intention in newborns experiencing circulatory arrest in the delivery room, where an injection of **adrenaline** is indicated. This primary endpoint will provide a direct measure of the procedure's effectiveness in achieving rapid resuscitation.

Secondary endpoints will include several parameters to further evaluate the efficacy of the intervention. These include the duration of placement of the umbilical route through Wharton's jelly (VOW), measured as the delay in seconds from the start of asepsis to the start of the adrenaline injection. This will be compared to the KTVO application time, if applicable. Additionally, the delay in seconds between the start of the VOW procedure and achieving a heart rate greater than 100 bpm will be recorded, both overall and depending on the approach used. The delay between the adrenaline injection and obtaining a heart rate greater than 100 bpm will also be assessed.

Other secondary endpoints include the frequency of VOW procedure failures, described by the number of failures over the number of attempts, and the types and causes of these failures. Mortality rates at one hour and at hospital discharge (or at 28 days) will be documented, as well as adverse events occurring within 72 hours following the injection. The relationship between the success or duration of placement and factors such as the state of the cord or the practitioner's experience will be modeled using a GLM model. Additionally, difficulties encountered during the VOW procedure will be collected from healthcare professionals and described, with a Likert questionnaire used to gauge caregivers' perceptions of the procedure's complexity.