Skip to main content
OpenTrials
Recruiting

NCT Number: NCT06797973

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

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Caesarean Section Neurologic Manifestations Pain Pain, Postoperative Pathologic Processes Pathological Conditions, Signs and Symptoms Postoperative Complications Postoperative Pain Signs and Symptoms

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 4

Primary location

Aarhus University Hospital, Aarhus, Denmark

Loading trial locations.

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Intrathecal morphine

Drug

80 μg preservative-free morphine (0.2 ml) added to a single-shot spinal anaesthesia consisting of 11.5 mg hyperbaric bupivacaine and 10 μg fentanyl

Placebo (Sodium Chloride Injection, 0.9%)

Drug

0.2 ml of isotonic sodium chloride added to a single-shot spinal anaesthesia consisting of 11.5 mg hyperbaric bupivacaine and 10 μg fentanyl.

Primary outcomes

  1. Level of pain when mobilising from supine to sitting position within 24 hours

    Time frame: 6, 12, 18 and 24 hours following spinal anaesthesia

    Longitudinal measurements of NRS (0-10) at 6, 12, 18 and 24 hours with most focus on the 24-hour pain level

  2. Maternal and neonatal serious adverse events

    Time frame: Within 7 days from discharge

    Binary composite outcome:

    • Death of either participant or neonate within 7 days
    • Participants with clinically significant respiratory depression within 24 hours, defined as respiratory depression documented in the electronic medical record, e.g. need for airway management or pharmacological intervention (subjective assessment by treating clinician, validated by 2 investigators)
    • Neonates needing admission to neonatal intensive care unit within 48 hours
    • Hospitalisation of either participant or neonate within 7 days after discharge
    • Participants with severe vomiting or nausea within 24 hours, defined as ≥5 points on the 'Simplified postoperative nausea and vomiting impact scale'63 at any time point (6, 12, 18 and 24 hours)

Secondary outcomes

  1. Opioid consumption within 24 hours

    Time frame: Within 24 hours following spinal anaesthesia

    Mg oral morphine equivalents

  2. Morphine associated adverse effects within 24 hours

    Time frame: Within 24 hours following spinal anaesthesia

    Binary composite outcome: participants experiencing either:

    • Vomiting (patient reported, yes/no)
    • Nausea
    • Dizziness
    • Pruritus Nausea, dizziness, and pruritus is assessed as "none", "little", "moderate", or "severe" with patients reporting "moderate" or "severe" categorised as having a positive outcome
    • Urinary retention, defined as need for re-catheterisation within 24 hours

  3. Obstetric quality of recovery score at 24 hours

    Time frame: Within 24 hours following spinal anaesthesia

    Obs-QoR-10 (0-100)

  4. Participants satisfaction with postoperative pain-treatment during the first 24 hours

    Time frame: Within 24 hours following spinal anaesthesia

    NRS 0-10

  5. Established breastfeeding at 30 days

    Time frame: 30 days from surgery

    Proportion of neonates being exclusively breastfed at 30 days

Other outcomes

  1. Serious adverse events, pain at 24 hours and opioid consumption, compared using Win Ratio

    Time frame: Within 7 days from discharge

    A composite outcome analysed using Win Ratio, consisting of

    • Maternal and neonatal serious adverse events (as defined in the primary outcome)
    • Level of pain when mobilising from supine to sitting position at 24 hours (NRS 0-10)
    • Opioid consumption within 24 hours (mg oral morphine equivalents)

  2. Overall severity of pruritus within 24 hours

    Time frame: Within 24 hours following spinal anaesthesia

    NRS 0-10

  3. Pharmacological treatment for opioid-related adverse effects within 24 hours

    Time frame: Within 24 hours following spinal anaesthesia

    Dexametasone, dosage (mg) 5-HT3 receptor antagonists, type, dosage (mg) Dopamine receptor antagonists, type, dosage (mg) Droperidol, dosage (mg) Antihistamines, type, dosage (mg) Pethidine, dosage (mg) Naloxone, dosage (mg) Clonidine, dosage (mg)

  4. Ability to mobilise independently

    Time frame: 6, 12, 18 and 24 hours following spinal anaesthesia

    Proportion of participants able to mobilise independently at 6, 12, 18 and 24 hours

  5. Level of pain at rest within 48 hours

    Time frame: 6, 12, 18, 24 and 48 hours following spinal anaesthesia

    Longitudinal measurements of NRS (0-10) at 6, 12, 18, 24 and 48 hours

  6. Opioid consumption within 48 hours

    Time frame: Within 48 hours following spinal anaesthesia

    Mg oral morphine equivalents

  7. "Rescue" supplemental pain treatment with truncal nerve block or epidural within 24 hours

    Time frame: Within 24 hours following spinal anaesthesia

    Binary composite outcome: participants receiving either an unplanned postoperative truncal nerve block or epidural analgesia within 24 hours

  8. Level of pain when mobilising from supine to sitting position at 48 hours

    Time frame: Within 48 hours following spinal anaesthesia

    NRS 0-10

  9. Total consumption of non-opioid analgesic medication (paracetamol, NSAIDs) within 24 hours and 48 hours

    Time frame: Within 24 and 48 hours following spinal anaesthesia

    Paracetamol, dosage (mg) NSAIDs, type, dosage (mg)

  10. Intraoperative nausea, vomiting and pruritus

    Time frame: During surgery

    Binary composite outcome: participants experiencing either

    • Intraoperative nausea
    • Intraoperative vomiting
    • Intraoperative pruritus Nausea and pruritus are assessed as "none", "little", "moderate", or "severe" with patients reporting "moderate" or "severe" categorised as having a positive outcome. Vomiting is assessed as yes/no.

    Intraoperative is defined as from administration of spinal anaesthesia until the patient is leaving the operating room

  11. Overall severity of pain within 24 hours (ObsQoR-10)

    Time frame: Within 24 hours following spinal anaesthesia

    NRS 0-10

  12. Overall severity of nausea/vomiting within 24 hours (ObsQoR-10)

    Time frame: Within 24 hours following spinal anaesthesia

    NRS 0-10

  13. Overall severity of dizziness within 24 hours (ObsQoR-10)

    Time frame: Within 24 hours following spinal anaesthesia

    NRS 0-10

  14. Overall severity of shivering within 24 hours (ObsQoR-10)

    Time frame: Within 24 hours following spinal anaesthesia

    NRS 0-10

  15. Overall feeling of being comfortable within 24 hours (ObsQoR-10)

    Time frame: Within 24 hours following spinal anaesthesia

    NRS 0-10

  16. Overall ability to mobilise independently within 24 hours (ObsQoR-10)

    Time frame: Within 24 hours following spinal anaesthesia

    NRS 0-10

  17. Overall ability to independently hold infant within 24 hours (ObsQoR-10)

    Time frame: Within 24 hours following spinal anaesthesia

    NRS 0-10

  18. Overall ability to nurse/feed infant independently within 24 hours (ObsQoR-10)

    Time frame: Within 24 hours following spinal anaesthesia

    NRS 0-10

  19. Overall ability to handle personal hygiene within 24 hours (ObsQoR-10)

    Time frame: Within 24 hours following spinal anaesthesia

    NRS 0-10

  20. Overall feeling of being in control within 24 hours (ObsQoR-10)

    Time frame: Within 24 hours following spinal anaesthesia

    NRS 0-10

  21. Length of hospital stay

    Time frame: Within 7 days from discharge

    Total length of primary hospital stay (hours)

  22. Readmission or unplanned hospital re-attendance within 7 days

    Time frame: Within 7 days following surgery

    Binary composite outcome: participants needing either:

    • Hospital readmission within 7 days
    • Re-attendance (unplanned hospital out-patient consultation) within 7 days

  23. Failed or insufficient spinal anaesthesia

    Time frame: Within 24 hours following spinal anaesthesia

    Binary composite outcome: participants needing either:

    • Conversion to general anaesthesia
    • Repeated neuraxial procedure
    • Supplemental intraoperative pain treatment

  24. Hospital-free days within 7 days

    Time frame: Within 7 days following surgery

    Number of days out of hospital for both participant and neonate within 7 days

  25. Ogilvie's syndrome/ileus within 7 days

    Time frame: Within 7 days following surgery

    Proportion of participants with Ogilvie's syndrome/ileus that requires surgery or treatment with neostigmine within 7 days

  26. Apgar score at 5 minutes following birth

    Time frame: 5 minutes following birth

    0-10

  27. Apgar score <7 at 5 minutes following birth

    Time frame: 5 minutes following birth

    Proportion of neonates with Apgar score <7 at 5 minutes following birth

  28. Neonatal need for respiratory support within 48 hours

    Time frame: Within 48 hours following birth

    Proportion of neonates needing respiratory support within 48 hours, defined as either:

    • Continuous positive airway pressure treatment
    • Positive pressure ventilation
    • HNF (high nasal flow)
    • Intubation
    • Oxygen therapy

  29. Neonatal sedation resulting in failed breast-/bottle feeding within 48 hours

    Time frame: 24 and 48 hours following birth

    Proportion of neonates not being breastfed or bottle fed due to neonatal sedation, corresponding to L=0 (too sleepy or reluctant, no sustained latch or suck achieved) on the LATCH scoring system

  30. Neonatal hospitalisation within 24 hours after discharge

    Time frame: 24 hours after discharge

    Proportion of neonates hospitalised within 24 hours after discharge of participant

Study contacts

Contact information is provided by the study sponsor or research team.

Anne J Wikkelsø, MD, PhD

CONTACT

[email protected]

+4547325046

Anneline B Seegert, MD

CONTACT

[email protected]

+4547326397

Sponsors and collaborators

Lead sponsor

Anne Juul Wikkelsø

Other

Registry information

Official study title

MOTHER Trial: Efficacy and Safety of Low-dose Intrathecal Morphine Following Planned Caesarean Section - a Randomised, Blinded, Clinical, Controlled, Multicentre Trial.

Acronym: MOTHER

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Jan 29, 2025
Registry last updated
Dec 19, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.