Postsurgical PainPhase 2/3NCT06344169
Dinalbuphine Ester (Naldebain) for Pain Management After Cesarean Section
A Phase 2/3 study testing Sebacoyl Dinalbuphine Ester and Morphine in people with Postsurgical Pain and Cesarean Section, run by Dalin Tzu Chi General Hospital at 1 site in Taiwan.
Trial summary
Inadequate postoperative pain management can lead to physical and psychological distress in patients as well as impact surgical wound healing and increase the risk of developing postoperative delirium and cardiopulmonary and thromboembolic events. Read more about this study
- Who is it for?
- Ages 20 years and older, women only
- Conditions the study is for
- Postsurgical Pain, Cesarean Section, Chronic Post-surgical Pain
- What is being tested?
- Sebacoyl Dinalbuphine Ester and Morphine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteTaiwan
- Study dates
- 6 May 2024to 14 Jun 2026
- Phase
- Phase 2/3
- 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 20 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- term primipara or multipara who are scheduled for elective cesarean section
Who cannot join
- Severe pregnancy-induced complication (such as preeclampsia, eclampsia, poorly control pregnancy-induced hypertension and/or diabetes)
- High risk for postpartum hemorrhage
- Contraindicated for neuraxial block
- Preterm (gestational age< 36 week) delivery
- Emergency cesarean section
- After-office hour schedule
Show all 9Show fewer
- History of substance abuse
- Known allergy to nalbuphine, benzyl benzoate or sesame oil
- Eligible parturient who are not willing to follow the assignment of treatment after randomization
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Taiwan1 site, 1 recruiting
- Recruiting
Dalin Tzu Chi Hospital
Dalin, Chai-Yi, 622
Chen-Fuh Lam, MD, PhD, 866-982922554, lamcf@mail.ncku.edu.tw
About this study
Official title: Efficacy of Parenteral Injection of an Extended Release Kappa-receptor Opioid Sebacoyl Dinalbuphine Ester for Pain Management After Cesarean Section: a Randomized, Open-label, Non-inferiority Trial
Inadequate postoperative pain management can lead to physical and psychological distress in patients as well as impact surgical wound healing and increase the risk of developing postoperative delirium and cardiopulmonary and thromboembolic events. Severe postoperative pain may also result in the development of chronic post-surgical pain (CPSP), which in turn can lead to prolonged use of opioids and increased health-care costs. A descriptive survey study in 60 postpartum women who received cesarean section suggested that the presence of postoperative pain significantly reduced the willingness of breastfeeding and infant care. The incidence of CPSP after cesarean delivery has been reported to vary from 1% to 18% up to 1 year after operation. Intrathecal morphine (ITM) injection is considered as the standard pain management strategy for post-cesarean pain. However, the overall analgesic effect of ITM is about 8-12h and it is associated with pruritus, nausea/vomiting, urinary retention, constipation, mental status change, and respiratory depression. Therefore, the development of a safe, conveniently operated, and long-lasting analgesic strategy, which serves as background pain control modality up to several days after cesarean section should provide clinically beneficial advantages in the management of acute postoperative pain and prevention of CPSP in postpartum women. Naldebain® is prodrug of nalbuphine, which was approved by the Taiwan FDA in 2017. Naldebain® is rapidly hydrolyzed by tissue of plasma esterase to release nalbuphine. The bioavailability of nalbuphine following intramuscular injection Naldebain® was 85.4%, and it took approximately 6 days for the complete release of Naldebain® into the blood circulation. Therefore, a single parenteral injection of Naldebain® could provide long lasting analgesic effect in several phase II trials. However, Naldebain® has not been tested in the pain control after cesarean section. Therefore, this PI-initiated prospective, randomized, open-label, non-inferiority trial aims to investigate the clinical efficacy of Naldebain® in management of acute postoperative pain in term parturient who receive elective cesarean section to provide analgesic effect that is not inferior to the standard ITM and prevent the development of CPSP.
Read the detailed description
Inadequate postoperative pain management can lead to physical and psychological distress in patients as well as impact surgical wound healing and increase the risk of developing postoperative delirium and cardiopulmonary and thromboembolic events. Severe postoperative pain may also result in the development of chronic post-surgical pain (CPSP), which in turn can lead to prolonged use of opioids and increased health-care costs. A descriptive survey study in 60 postpartum women who received cesarean section suggested that the presence of postoperative pain significantly reduced the willingness of breastfeeding and infant care. Furthermore, the incidence of CPSP after cesarean delivery has been reported to vary from 1% to 18% up to 1 year after operation. More specifically, an US nationwide survey reported that 79% of mothers who received cesarean section reported experiencing pain at the incision site in the first two months and 18% had persistent pain at least 6 months after operation. Placement of an epidural catheter can be used for epidural anesthesia during cesarean section and continuous epidural infusions of opioids or combined with local anesthetic after cesarean section can result in high-quality analgesia effect for postpartum and postsurgical pain. Intrathecal injection of morphine (ITM) is considered as the standard pain management strategies for post-cesarean pain in Taiwan. However, correct placement of epidural catheter for effective postoperative pain management is more technical demanding, and accidental dural puncture is associated with increased risk of postdural puncture headache. ITM is associated with severe mu-receptor agonist adverse reactions, such as pruritus, nausea/vomiting, urinary retention, constipation, mental status change, and respiratory depression. Therefore, the development of a safe, conveniently operated, and long-lasting non-mu agonism analgesic strategy, which serves as background pain control modality up to several days after cesarean section should provide clinically beneficial advantages in the management of acute postoperative pain and prevention of development of CPSP in postpartum women.
Sebacoyl dinalbuphine ester Naldebain® (SDE) is prodrug of nalbuphine, which was approved by the Taiwan FDA in 2017. SDE is rapidly hydrolyzed by tissue of plasma esterase to release nalbuphine. The bioavailability of nalbuphine following intramuscular injection SDE was 85.4% with a mean absorption time up to 145 h, and it took approximately 6 days for the complete release of SDE into the blood circulation. Therefore, a single parenteral injection of SDE could provide long lasting analgesic effect in several phase II trials. However, SDE has not been tested in the pain control after cesarean section. Therefore, this PI-initiated prospective, randomized, open-label, non-inferiority trial aims to investigate the clinical efficacy of SDE in management of acute postoperative pain in term parturient who receive elective cesarean section to provide analgesic effect that is not inferior to the standard ITM. A single intramuscular injection of SDE may also prevent the development of CPSP after cesarean delivery, as SDE can provide prolonged analgesic effect for up to 7 days.
- Being tested
- Sebacoyl Dinalbuphine Ester, Morphine
- Keywords
- kappa agonist, mu agonist, Intrathecal morphine
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sebacoyl Dinalbuphine EsterDrug
Also called Naldebain
SDE will be dissolved in benzyl benzoate and sesame oil (a total volume of 2ml) will be prepared in a 5-ml syringe 30 min before administration. Intramuscular injection into the gluteal muscles will be performed by an anesthesiologist under sonography-guidance
MorphineDrug
A single dose of morphine (0.15mg) will be administered along with bupivacaine during spinal anesthesia.
| Study group | Role | What they receive |
|---|---|---|
| ITM group | Active comparator | Participants assigned to intrathecal morphine (ITM) group will receive intrathecal injection of morphine (0.15mg) for post-cesarean section pain Receives: Drug: Morphine |
| SDE group | Experimental | Participants assigned to sebacoyl dinalbuphine ester (SDE) group will receive intramuscular injection of SDE (150mg) for post-cesarean section pain Receives: Drug: Sebacoyl Dinalbuphine Ester |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intensity of surgical pain after operation as assessed by visual analogue scale
Visual analogue scale (VAS 1-10, a continuum scale in which 0 represents "no pain" and and 10 represents "worst pain.")
Measured: 5 days after cesarean section
Rescue doses of analgesics administered after operation
Total doses of parenteral administered opioids, NSAIDs, cyclooxygenase-2 inhibitors
Measured: 5 days after cesarean section
Secondary outcomes (2)
Incidence of chronic post-surgical pain
Pain that newly develops after operation and lasts >2 months and other causes of pain are excluded
Measured: 3 months after cesarean section
Satisfaction of living after surgery as assessed by the HRQoL short-form (SF)-12
Quality of life will be assessed by the HRQoL short-form (SF) Questionnaire, which consists a physical component summary (PCS) and a mental component summary (MCS). The rating scales range from yes-no to likert scales, and the final score of PCS and MCS will be calculated by an algorithm (QualityMetric's SF-12v1®). Scores range from 0 to 100, in which lower scores mean lower health related quality of life
Measured: 3 months after cesarean section
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2024
- Study start6 May 2024
- Primary completion14 Mar 2026 (estimated)
- Study completion14 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postsurgical PainStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, open-label, non-inferiority trial
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dalin Tzu Chi General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- NING-SHENG LAI, Study chair, Buddhist Tzu Chi Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06344169
- Sponsor's protocol ID
- DTCRD112(2)-I-15
- Status last verified
- Feb 2025
- First submitted
- 27 Mar 2024
- Last updated
- 9 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Parenteral Injection of an Extended Release Kappa-receptor Opioid Sebacoyl Dinalbuphine Ester for Pain Management After Cesarean Section: a Randomized, Open-label, Non-inferiority Trial
- ClinicalTrials.gov ID
- NCT06344169
- Acronym / sponsor ID
- DTCRD112(2)-I-15
- Keywords
- kappa agonist, mu agonist, Intrathecal morphine
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Dalin Tzu Chi General HospitalUniversity, hospital or other
- Study start
- 6 May 2024 (actual)
- Primary completion
- 14 Mar 2026 (estimated)
- Study completion
- 14 Jun 2026 (estimated)
- First posted
- 3 Apr 2024 (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.
Inadequate postoperative pain management can lead to physical and psychological distress in patients as well as impact surgical wound healing and increase the risk of developing postoperative delirium and cardiopulmonary and thromboembolic events. Severe postoperative pain may also result in the development of chronic post-surgical pain (CPSP), which in turn can lead to prolonged use of opioids and increased health-care costs. A descriptive survey study in 60 postpartum women who received cesarean section suggested that the presence of postoperative pain significantly reduced the willingness of breastfeeding and infant care. The incidence of CPSP after cesarean delivery has been reported to vary from 1% to 18% up to 1 year after operation. Intrathecal morphine (ITM) injection is considered as the standard pain management strategy for post-cesarean pain. However, the overall analgesic effect of ITM is about 8-12h and it is associated with pruritus, nausea/vomiting, urinary retention, constipation, mental status change, and respiratory depression. Therefore, the development of a safe, conveniently operated, and long-lasting analgesic strategy, which serves as background pain control modality up to several days after cesarean section should provide clinically beneficial advantages in the management of acute postoperative pain and prevention of CPSP in postpartum women. Naldebain® is prodrug of nalbuphine, which was approved by the Taiwan FDA in 2017. Naldebain® is rapidly hydrolyzed by tissue of plasma esterase to release nalbuphine. The bioavailability of nalbuphine following intramuscular injection Naldebain® was 85.4%, and it took approximately 6 days for the complete release of Naldebain® into the blood circulation. Therefore, a single parenteral injection of Naldebain® could provide long lasting analgesic effect in several phase II trials. However, Naldebain® has not been tested in the pain control after cesarean section. Therefore, this PI-initiated prospective, randomized, open-label, non-inferiority trial aims to investigate the clinical efficacy of Naldebain® in management of acute postoperative pain in term parturient who receive elective cesarean section to provide analgesic effect that is not inferior to the standard ITM and prevent the development of CPSP.
Detailed description
Inadequate postoperative pain management can lead to physical and psychological distress in patients as well as impact surgical wound healing and increase the risk of developing postoperative delirium and cardiopulmonary and thromboembolic events. Severe postoperative pain may also result in the development of chronic post-surgical pain (CPSP), which in turn can lead to prolonged use of opioids and increased health-care costs. A descriptive survey study in 60 postpartum women who received cesarean section suggested that the presence of postoperative pain significantly reduced the willingness of breastfeeding and infant care. Furthermore, the incidence of CPSP after cesarean delivery has been reported to vary from 1% to 18% up to 1 year after operation. More specifically, an US nationwide survey reported that 79% of mothers who received cesarean section reported experiencing pain at the incision site in the first two months and 18% had persistent pain at least 6 months after operation. Placement of an epidural catheter can be used for epidural anesthesia during cesarean section and continuous epidural infusions of opioids or combined with local anesthetic after cesarean section can result in high-quality analgesia effect for postpartum and postsurgical pain. Intrathecal injection of morphine (ITM) is considered as the standard pain management strategies for post-cesarean pain in Taiwan. However, correct placement of epidural catheter for effective postoperative pain management is more technical demanding, and accidental dural puncture is associated with increased risk of postdural puncture headache. ITM is associated with severe mu-receptor agonist adverse reactions, such as pruritus, nausea/vomiting, urinary retention, constipation, mental status change, and respiratory depression. Therefore, the development of a safe, conveniently operated, and long-lasting non-mu agonism analgesic strategy, which serves as background pain control modality up to several days after cesarean section should provide clinically beneficial advantages in the management of acute postoperative pain and prevention of development of CPSP in postpartum women.
Sebacoyl dinalbuphine ester Naldebain® (SDE) is prodrug of nalbuphine, which was approved by the Taiwan FDA in 2017. SDE is rapidly hydrolyzed by tissue of plasma esterase to release nalbuphine. The bioavailability of nalbuphine following intramuscular injection SDE was 85.4% with a mean absorption time up to 145 h, and it took approximately 6 days for the complete release of SDE into the blood circulation. Therefore, a single parenteral injection of SDE could provide long lasting analgesic effect in several phase II trials. However, SDE has not been tested in the pain control after cesarean section. Therefore, this PI-initiated prospective, randomized, open-label, non-inferiority trial aims to investigate the clinical efficacy of SDE in management of acute postoperative pain in term parturient who receive elective cesarean section to provide analgesic effect that is not inferior to the standard ITM. A single intramuscular injection of SDE may also prevent the development of CPSP after cesarean delivery, as SDE can provide prolonged analgesic effect for up to 7 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized, open-label, non-inferiority trial
| Arm | Type | Receives |
|---|---|---|
| ITM group | Active comparator | Drug: MorphineParticipants assigned to intrathecal morphine (ITM) group will receive intrathecal injection of morphine (0.15mg) for post-cesarean section pain |
| SDE group | Experimental | Drug: Sebacoyl Dinalbuphine EsterParticipants assigned to sebacoyl dinalbuphine ester (SDE) group will receive intramuscular injection of SDE (150mg) for post-cesarean section pain |
Who may qualify
- Ages
- 20 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- term primipara or multipara who are scheduled for elective cesarean section
Key exclusion criteria (9 listed)
- Severe pregnancy-induced complication (such as preeclampsia, eclampsia, poorly control pregnancy-induced hypertension and/or diabetes)
- High risk for postpartum hemorrhage
- Contraindicated for neuraxial block
- Preterm (gestational age< 36 week) delivery
- Emergency cesarean section
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 |
|---|---|---|
| Sebacoyl Dinalbuphine EsterAlso: NaldebainSDE will be dissolved in benzyl benzoate and sesame oil (a total volume of 2ml) will be prepared in a 5-ml syringe 30 min before administration. Intramuscular injection into the gluteal muscles will be performed by an anesthesiologist under sonography-guidance | Drug | SDE group |
| MorphineA single dose of morphine (0.15mg) will be administered along with bupivacaine during spinal anesthesia. | Drug | ITM group |
Primary outcome
Intensity of surgical pain after operation as assessed by visual analogue scale
Time frame: 5 days after cesarean section
Visual analogue scale (VAS 1-10, a continuum scale in which 0 represents "no pain" and and 10 represents "worst pain.")
Rescue doses of analgesics administered after operation
Time frame: 5 days after cesarean section
Total doses of parenteral administered opioids, NSAIDs, cyclooxygenase-2 inhibitors
2 secondary outcomes
Incidence of chronic post-surgical pain
Time frame: 3 months after cesarean section
Satisfaction of living after surgery as assessed by the HRQoL short-form (SF)-12
Time frame: 3 months after cesarean section
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 9 May 2025.
- Individual participant dataSharing planned: No
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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.
NING-SHENG LAI study chair
Buddhist Tzu Chi Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Sebacoyl Dinalbuphine Ester and Morphine in people with Postsurgical Pain and Cesarean Section, run by Dalin Tzu Chi General Hospital at 1 site in Taiwan.
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 1 inclusion and 9 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 9 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Chen-Fuh Lam, MD, PhD (8865-2648000 ext. 2291, lamcf@mail.ncku.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intensity of surgical pain after operation as assessed by visual analogue scale (time frame: 5 days after cesarean section). 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 9 May 2025.