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

NCT ID: NCT06797973

Last Updated: 2025-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

1312 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-15

Study Completion Date

2027-06-30

Brief Summary

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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.

Detailed Description

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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

Conditions

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Caesarean Section Postoperative Pain

Keywords

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Caesarean section Cesarean section Cesarean delivery Caesarean delivery Postoperative pain Intrathecal morphine Spinal morphine elective caesarean

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Intrathecal morphine

Group Type EXPERIMENTAL

Intrathecal Morphine

Intervention Type 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

Group Type PLACEBO_COMPARATOR

Placebo (Sodium Chloride Injection, 0.9%)

Intervention Type 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.

Interventions

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Intrathecal Morphine

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

Intervention Type DRUG

Placebo (Sodium Chloride Injection, 0.9%)

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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Anne Juul Wikkelsø

OTHER

Sponsor Role lead

Responsible Party

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Anne Juul Wikkelsø

Associate Professor, Senior Consultant, PhD

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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Aarhus University Hospital

Aarhus, , Denmark

Site Status RECRUITING

Copenhagen University Hospital - Rigshospitalet

Copenhagen, , Denmark

Site Status NOT_YET_RECRUITING

Copenhagen University Hospital - Herlev and Gentofte, Herlev

Herlev, , Denmark

Site Status NOT_YET_RECRUITING

Copenhagen University Hospital - North Zealand, Hillerød

Hillerød, , Denmark

Site Status NOT_YET_RECRUITING

Copenhagen University Hospital - Amager and Hvidovre, Hvidovre

Hvidovre, , Denmark

Site Status RECRUITING

University Hospital of Southern Denmark - Lillebælt Hospital, Kolding

Kolding, , Denmark

Site Status RECRUITING

University Hospital of Southern Denmark - Odense University Hospital

Odense C, , Denmark

Site Status RECRUITING

Zealand University Hospital

Roskilde, , Denmark

Site Status RECRUITING

Countries

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Denmark

Central Contacts

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Anneline B Seegert, MD

Role: CONTACT

Phone: +4547326397

Email: [email protected]

Anne J Wikkelsø, MD, PhD

Role: CONTACT

Phone: +4547325046

Email: [email protected]

Facility Contacts

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Deepti Jain, MD

Role: primary

Kim Ekelund, MD, PhD

Role: primary

Kim Lindelof, MD, PhD

Role: backup

Kim Wildgaard, MD, PhD

Role: primary

Patricia Duch, MD

Role: primary

Maria E Kromann, MD, PhD

Role: primary

Helene K Nedergaard, MD, PhD

Role: primary

Mette L Andersson

Role: primary

Anne J Wikkelsø, MD, PhD

Role: primary

Other Identifiers

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2024-518678-16-00

Identifier Type: CTIS

Identifier Source: secondary_id

2024-518678-16-00

Identifier Type: -

Identifier Source: org_study_id