Caesarean SectionPhase 4MOTHERNCT06797973
Efficacy and Safety of Intrathecal Morphine for Postoperative Pain Management Following Planned Caesarean Section
A Phase 4 study testing Intrathecal Morphine in people with Caesarean Section and Postoperative Pain, run by Anne Juul Wikkelsø at 9 sites in Denmark.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Caesarean Section, Postoperative Pain
- What is being tested?
- Intrathecal Morphine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,312 participants
- Where
- 9 sitesDenmark
- Study dates
- 15 Jul 2025to 30 Jun 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients ≥ 18 years
- Singleton pregnancy
- Scheduled for planned caesarean section performed under spinal anaesthesia
- Written informed consent
Who cannot join
- 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
Trial locations and contacts
9 sites in 1 country. Contact the study team or a site near you to ask about taking part.
9 sites in 1 country
Denmark9 sites, 9 recruiting
- Recruiting
Aarhus University Hospital
Aarhus, 8200
Deepti Jain, MD, +4530911052, deepjain@rm.dk
- Recruiting
Copenhagen University Hospital - Rigshospitalet
Copenhagen, 2100
Kim Ekelund, MD, PhD, +4535450563, kim.ekelund@regionh.dk
Kim Lindelof, MD, PhD, kim.lindelof@regionh.dk
- Recruiting
Copenhagen University Hospital - Herlev and Gentofte, Herlev
Herlev, 2730
Kim Wildgaard, MD, PhD, +4538682170, Kim.Wildgaard@regionh.dk
- Recruiting
Copenhagen University Hospital - North Zealand, Hillerød
Hillerød, 3400
Patricia Duch, MD, +4548292504, patricia.duch@regionh.dk
- Recruiting
Regional Hospital Horsens
Horsens, 8700
Ulrick Skipper Espelund, Associate Professor, PhD, +4561671090, ulrick.espelund@rm.dk
- Recruiting
Copenhagen University Hospital - Amager and Hvidovre, Hvidovre
Hvidovre, 2650
Maria E Kromann, MD, PhD, +4538620694, Maria.Egede.Kromann@regionh.dk
- Recruiting
University Hospital of Southern Denmark - Lillebælt Hospital, Kolding
Kolding, 6000
Helene K Nedergaard, MD, PhD, +4553272244, helene.korvenius.nedergaard@rsyd.dk
- Recruiting
University Hospital of Southern Denmark - Odense University Hospital
Odense C, 5000
Mette L Andersson, +4565414937, mf_andersson@me.com
- Recruiting
Zealand University Hospital
Roskilde, 4000
Anne J Wikkelsø, MD, PhD, +4547325046, awik@regionsjaelland.dk
About this study
Official title: MOTHER Trial: Efficacy and Safety of Low-dose Intrathecal Morphine Following Planned Caesarean Section - a Randomised, Blinded, Clinical, Controlled, Multicentre Trial.
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:
Read more
- 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.
Read the detailed 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
- Conditions
- Caesarean Section, Postoperative Pain
- Being tested
- Intrathecal Morphine, Placebo (Sodium Chloride Injection, 0.9%)
- Keywords
- Caesarean section, Cesarean section, Cesarean delivery, Caesarean delivery, Postoperative pain, Intrathecal morphine, Spinal morphine, elective caesarean
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intrathecal MorphineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Intrathecal morphine | Experimental | Not described Receives: Drug: Intrathecal Morphine |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo (Sodium Chloride Injection, 0.9%) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Level of pain when mobilising from supine to sitting position within 24 hours
Longitudinal measurements of NRS (0-10) at 6, 12, 18 and 24 hours with most focus on the 24-hour pain level
Measured: 6, 12, 18 and 24 hours following spinal anaesthesia
Maternal and neonatal serious adverse events
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)
Measured: Within 7 days from discharge
Secondary outcomes (5)
Opioid consumption within 24 hours
Mg oral morphine equivalents
Measured: Within 24 hours following spinal anaesthesia
Morphine associated adverse effects within 24 hours
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
Measured: Within 24 hours following spinal anaesthesia
Obstetric quality of recovery score at 24 hours
Obs-QoR-10 (0-100)
Measured: Within 24 hours following spinal anaesthesia
Participants satisfaction with postoperative pain-treatment during the first 24 hours
NRS 0-10
Measured: Within 24 hours following spinal anaesthesia
Established breastfeeding at 30 days
Proportion of neonates being exclusively breastfed at 30 days
Measured: 30 days from surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2025
- Study start15 Jul 2025
- Primary completion31 May 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Caesarean SectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,312 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Anne Juul Wikkelsø
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Anne Juul Wikkelsø, Zealand University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06797973
- Sponsor's protocol ID
- 2024-518678-16-00
- Other IDs
- 2024-518678-16-00
- Acronym
- MOTHER
- Status last verified
- Sep 2026
- First submitted
- 17 Jan 2025
- Last updated
- 11 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data supporting the findings of this study are available from the corresponding author in accordance with Danish law and upon reasonable request.
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MOTHER Trial: Efficacy and Safety of Low-dose Intrathecal Morphine Following Planned Caesarean Section - a Randomised, Blinded, Clinical, Controlled, Multicentre Trial.
- ClinicalTrials.gov ID
- NCT06797973
- Acronym / sponsor ID
- MOTHER / 2024-518678-16-00
- Conditions
- Caesarean Section, Postoperative Pain
- Keywords
- Caesarean section, Cesarean section, Cesarean delivery, Caesarean delivery, Postoperative pain, Intrathecal morphine, Spinal morphine, elective caesarean
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,312 participants (estimated)
- Lead sponsor
- Anne Juul WikkelsøUniversity, hospital or other
- Study start
- 15 Jul 2025 (actual)
- Primary completion
- 31 May 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 29 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intrathecal morphine | Experimental | Drug: Intrathecal Morphine |
| Placebo | Placebo comparator | Drug: Placebo (Sodium Chloride Injection, 0.9%) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients ≥ 18 years
- Singleton pregnancy
- Scheduled for planned caesarean section performed under spinal anaesthesia
- Written informed consent
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intrathecal Morphine80 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 | Drug | Intrathecal morphine |
| 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. | Drug | Placebo |
Primary outcome
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
Maternal and neonatal serious adverse events
Time frame: Within 7 days from discharge
Binary composite outcome: 1. Death of either participant or neonate within 7 days 2. 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) 3. Neonates needing admission to neonatal intensive care unit within 48 hours 4. Hospitalisation of either participant or neonate within 7 days after discharge 5. 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)
5 secondary outcomes
Opioid consumption within 24 hours
Time frame: Within 24 hours following spinal anaesthesia
Morphine associated adverse effects within 24 hours
Time frame: Within 24 hours following spinal anaesthesia
Obstetric quality of recovery score at 24 hours
Time frame: Within 24 hours following spinal anaesthesia
Participants satisfaction with postoperative pain-treatment during the first 24 hours
Time frame: Within 24 hours following spinal anaesthesia
Established breastfeeding at 30 days
Time frame: 30 days from surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2026.
- Individual participant dataSharing planned: Yes. Data supporting the findings of this study are available from the corresponding author in accordance with Danish law and upon reasonable request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Intrathecal Morphine in people with Caesarean Section and Postoperative Pain, run by Anne Juul Wikkelsø at 9 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anneline B Seegert, MD (+4547326397, ansee@regionsjaelland.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Level of pain when mobilising from supine to sitting position within 24 hours (time frame: 6, 12, 18 and 24 hours following spinal anaesthesia). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2026.