Comparison of Spinal Anesthesia with Bupivacaine Hydrochloride and Sedation with Midazolam for External Cephalic Version Success in Breech Presentation

The primary objective of this study is to demonstrate that **spinal anaesthesia** results in a higher success rate compared to simple sedation for programmed external cephalic version (VME). This procedure aims to convert a podalic or transverse fetal presentation into a cephalic presentation, which is clinically significant as it can reduce the need for cesarean sections and associated complications.

Secondary objectives include evaluating:

• The occurrence of events secondary to the procedure, such as cesarean section for permanent bradycardia, retroplacental hematoma, and rupture of the amniotic membranes.
• The pain experienced by the patient, assessed subjectively using the visual analogue scale (VAS), an internationally validated tool.
• The final route of delivery, whether natural or via cesarean section.
• The presentation at delivery, whether cephalic or podalic.

The clinical trial involves a study population consisting exclusively of **female** participants aged 18 years and older. The participants are required to present with a dystocic fetus, either podalic or transverse, at 36 weeks' gestation. The trial does not include any vulnerable populations. Participants must be covered by a social insurance system and have provided signed informed consent. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on specific inclusion criteria, ensuring that all participants meet the necessary health and demographic requirements. No specific lifestyle considerations such as diet or physical activity are mentioned as part of the selection criteria.

The clinical trial is designed to evaluate the impact of **analgesia** on the success of external version procedures, comparing spinal anesthesia with sedation. This is a prospective, controlled, randomized study. The trial aims to demonstrate that spinal anesthesia results in a higher success rate than sedation for transforming a podalic or transverse fetal presentation into a cephalic presentation. The trial is expected to conclude by November 30, 2024, with recruitment having started on May 31, 2016.

Participants will be randomly assigned to receive either spinal anesthesia or sedation. The trial will employ a double-blind methodology to ensure unbiased results. The primary endpoint is the successful external version maneuver, resulting in a fetus in cephalic presentation. Secondary endpoints include the occurrence of events related to the procedure, such as caesarean section for permanent bradycardia, retroplacental hematoma, rupture of membranes, and events related to the anesthetic, including hypotension, bradycardia, desaturation, nausea/vomiting, and the number of punctures required.

The study will involve several visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥ 18 years), gestational age (36 weeks), and informed consent. Follow-up visits will monitor the procedure's success and any adverse events. The end-of-study visit will assess the final route of delivery and presentation at delivery. Participant involvement is expected to last for the duration of the procedure and follow-up period, with early termination possible in cases of significant adverse events or withdrawal of consent.

The trial will utilize **midazolam** and **bupivacaine hydrochloride, anhydrous** as the active substances, administered as solutions for injection. The maximum treatment period for each participant is one day, with specific dosing regimens for each substance. The trial is conducted under the authorization of relevant regulatory bodies, ensuring compliance with ethical and safety standards.

The clinical trial involves the administration of **Midazolam**, a **solution for injection or infusion**. The pharmaceutical form is a solution with a concentration of 1 mg/ml. The active substance, midazolam, is of chemical origin and is provided by Accord Healthcare Limited. The administration route is via injection or infusion, with a maximum daily dose of 0.10 mg/kg. The treatment period is limited to one day. Midazolam is utilized in the context of anaesthesia, and its role in the trial is as a test medication. Participant compliance with the dosing schedule will be monitored to ensure adherence to the protocol.

In addition to the experimental treatment, the trial includes the use of **Bupivacaine Hydrochloride, Anhydrous**, marketed as BUPIVACAINE VIATRIS 20 mg/4 ml. This is a solution for injection specifically designed for intrathecal administration. The active substance is also of chemical origin, provided by Viatris Sante. The maximum daily dose is 10 mg, with the treatment period similarly restricted to one day. Bupivacaine serves as a comparator treatment in the study, and its administration is part of the anaesthesia protocol. Compliance with the administration schedule will be closely monitored to ensure the integrity of the trial results.

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the successful external cephalic version (ECV), defined as the transformation of a fetus from a podalic or transverse presentation to a cephalic presentation upon completion of the procedure. This will be the main measure of efficacy to determine the success rate of spinal anesthesia compared to sedation.

Secondary endpoints will include the occurrence of events related to the procedure, such as caesarean section due to permanent bradycardia, retroplacental hematoma, and rupture of membranes. Additionally, events related to the anesthetic, including hypotension, bradycardia, desaturation, nausea/vomiting, and the number of punctures exceeding 11, will be monitored. Patient-reported outcomes will also be considered, with pain levels assessed using the Visual Analog Scale (VAS). The final route of delivery and the presentation at delivery will be documented as part of the secondary efficacy measures.