Evaluation of Analgesic Efficacy and Safety of Low-Dose Intrathecal Morphine Hydrochloride in Elective Caesarean Section: A Randomized, Controlled Trial

The primary objective of the MOTHER trial is to evaluate the **analgesic efficacy** and safety of low-dose (80 µg) intrathecal **morphine hydrochloride** compared to placebo, when added to standard multimodal postoperative pain management in patients undergoing elective **caesarean section**. This is clinically relevant as it aims to enhance postoperative pain control, potentially improving patient comfort and recovery outcomes while ensuring safety for both patients and neonates.

The clinical trial focuses on evaluating the **analgesic** efficacy and safety of low-dose intrathecal morphine in patients undergoing elective caesarean section. The study population comprises exclusively female participants, as the trial is specific to those scheduled for a caesarean section. Participants are required to be at least 18 years of age and must have a singleton pregnancy. The trial involves individuals who are scheduled for an elective caesarean section performed under spinal anaesthesia. All participants must provide written informed consent. The sponsor has not provided information regarding the total number of participants. The trial population is selected based on specific inclusion criteria, ensuring that only those who meet the necessary conditions are enrolled. The study does not include male subjects, and it involves a vulnerable population due to the nature of the medical condition and procedure involved. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the **analgesic efficacy** and safety of low-dose intrathecal **morphine hydrochloride** in patients undergoing elective caesarean section. This is a randomized, double-blind, controlled, multicenter trial. The trial will compare the effects of 80 µg of intrathecal morphine against a placebo, both administered alongside standard multimodal postoperative pain management. The primary endpoints include assessing the level of pain when mobilizing from a supine to a sitting position within 24 hours and evaluating maternal and neonatal safety through a composite outcome. Secondary endpoints focus on opioid consumption, morphine-associated adverse events, obstetric quality of recovery, participant satisfaction with pain treatment, and breastfeeding establishment at 30 days.

The trial is expected to commence recruitment on June 1, 2025, and conclude by December 1, 2027. Participants will be involved in the study for a maximum treatment period of one day. The inclusion criteria require participants to be at least 18 years old, have a singleton pregnancy, be scheduled for an elective caesarean section under spinal anesthesia, and provide written informed consent. There are no specified exclusion criteria. Study visits will include an initial screening visit to confirm eligibility, followed by the administration of the intervention during the caesarean section. Follow-up visits will occur within 24 hours to assess primary and secondary endpoints, with additional monitoring up to 30 days for breastfeeding outcomes.

Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with study procedures, or withdraw consent. The trial is categorized as a phase IV study, focusing on optimizing the use of an authorized investigational medicinal product. The study aims to provide valuable insights into the safety and efficacy of low-dose intrathecal morphine in managing acute postoperative pain following caesarean sections.

The clinical trial involves the administration of **Morphine Hydrochloride** as the experimental medication. Morphine Hydrochloride is provided in a **solution for injection** form, specifically designed for **intrathecal use**. The dosage administered is 80 micrograms (µg) per participant, with a maximum daily and total dose of 80 µg. The treatment period is limited to a single day. This medication is not formulated for pediatric use and is classified under the chemical origin of active substances. The primary objective of this trial is to assess the analgesic efficacy and safety of low-dose intrathecal morphine in patients undergoing elective caesarean section.

In addition to the experimental treatment, the study utilizes **Sodium Chloride 9 mg/ml** as a placebo. This solution for injection serves as a comparator to the active treatment, ensuring the study's blinded and controlled design. The sodium chloride solution is administered in a manner consistent with standard placebo protocols, although specific details regarding its route and frequency of administration are not provided. The use of sodium chloride as a placebo is integral to evaluating the true efficacy of the experimental treatment by providing a baseline for comparison.

The efficacy of the clinical trial titled "MOTHER trial: Efficacy and safety of low-dose intrathecal morphine following planned caesarean section" will be assessed using both primary and secondary endpoints. The primary endpoints include the level of pain when mobilizing from supine to sitting position within 24 hours and a binary composite outcome for maternal and neonatal safety. This composite outcome consists of participants experiencing respiratory depression, severe nausea/vomiting within 24 hours, neonatal admission within 48 hours, hospitalization of participant or neonate within 7 days after discharge, and death of either participant or neonate within 7 days.

Secondary endpoints will evaluate opioid consumption within 24 hours, **morphine**-associated adverse events such as vomiting, nausea, dizziness, pruritus, and urinary retention within 24 hours, obstetric quality of recovery score at 24 hours, participant satisfaction with postoperative pain treatment during the first 24 hours, and established breastfeeding at 30 days. These efficacy parameters will be measured and collected at specified time points, including within 24 hours and at 30 days, to ensure comprehensive assessment of the trial's objectives.