Efficacy and Safety of Intrathecal Morphine for Postoperative Pain Management Following Planned Caesarean Section (MOTHER)

Anne Juul Wikkelsø

Status and phase

Enrolling

Phase 4

Conditions

Postoperative Pain

Caesarean Section

Treatments

Drug: Intrathecal Morphine

Drug: Placebo (Sodium Chloride Injection, 0.9%)

Study type

Interventional

Funder types

Other

Identifiers

NCT06797973

2024-518678-16-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

The goal of this clinical trial is to learn if morphine added to the spinal anaesthesia can improve postoperative pain treatment for patients undergoing caesarean section, without increasing the risk of serious adverse events in mother and baby.

The main questions it aims to answer are:

Is the treatment effective in preventing postoperative pain?
Is the treatment safe for both mother and baby?

Participants will be given a normal spinal anaesthesia with addition of either morphine or sodium chloride (inactive substance). All participants will receive standard postoperative pain treatment, including morphine tablets as needed. Researchers will collect data from the electronic medical record and ask the participants to fill out questionnaires about pain levels and possible side effects.

Full description

BACKGROUND AND OBJECTIVE:

Caesarean section is surgical procedure associated with moderate to severe postoperative pain, which can negatively affect recovery, mother-child bonding and the initiation of breastfeeding. Intrathecal morphine may offer pain relief for up to 24 hours, and is widely implemented and recommended as part of multimodal postoperative pain management. Despite the widespread use, there is limited evidence for the balance between benefits and harms of low-dose intrathecal morphine in patients undergoing caesarean section.

The objective of the trial is to evaluate analgesic efficacy as well as maternal and neonatal safety associated with addition of low-dose (80 µg) intrathecal morphine versus placebo to standard multimodal postoperative pain management in patients undergoing planned caesarean section.

The trial is a superiority, investigator-initiated, pragmatic, randomised, blinded, placebo-controlled multicentre trial.

TRIAL SIZE: A total of 1,312 participants is required to show/reject a 35% relative increase in the composite co-primary safety outcome, with an estimated baseline incidence of 21% without intrathecal morphine and a power of 80%. We adjust statistically for having two primary outcomes by using an alpha of 2.5%. We reach a power of 99.9% for the co-primary outcome of pain score with an estimated mean Numeric Rating Scale (0-10) of 4.88, standard deviation of 2.0 and relevant mean difference of 1.0.

ETHICAL CONSIDERATIONS: Intrathecal morphine for caesarean delivery represents a common medical practice which is not supported by robust evidence. High-quality data on efficacy and safety of the treatment will enable clinicians to tailor postoperative pain treatment to each patient, thus improving care for future patients. Choosing low-dose morphine minimises the risk of adverse effects, and all trial participants will receive standard multimodal pain treatment. There is no evidence of any harmful neonatal effects. All trial participants will give informed consent, and the trial will adhere to the Declaration of Helsinki as well as national and international standards of good clinical practice.

PLANNED SUBSTUDIES:

Incidence of desaturation and bradypnea during the first 24 hours following surgery, assessed using continuous wireless respiratory monitoring in a subpopulation of 100 patients at 3 trial sites.
Efficacy and safety of intrathecal morphine in participant subgroups: The influence of different pre-existing factors on the primary outcomes

Enrollment

1,312 estimated patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients ≥ 18 years
Singleton pregnancy
Scheduled for planned caesarean section performed under spinal anaesthesia
Written informed consent

Exclusion criteria

Allergy to or contraindications towards trial medication
Patients planned for postoperative epidural due to expected difficult postoperative pain management
Patients planned for combined spinal-epidural as primary anaesthesia
Inability to understand and read Danish
Previous inclusion in the trial