Dinalbuphine Ester (Naldebain) for Pain Management After Cesarean Section

NCT06344169 | Recruiting Phase 2 DMC

• 1 other identifier: DTCRD112(2)-I-15
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Postsurgical Pain; Cesarean Section; Chronic Post-surgical Pain

Keywords

kappa agonist; mu agonist; Intrathecal morphine

Outcome Measures

Primary Outcomes (2)

• 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.")

  5 days after cesarean section

• Rescue doses of analgesics administered after operation

  Total doses of parenteral administered opioids, NSAIDs, cyclooxygenase-2 inhibitors

  5 days after cesarean section

Secondary Outcomes (2)

• Incidence of chronic post-surgical pain

  3 months after cesarean section

• Satisfaction of living after surgery as assessed by the HRQoL short-form (SF)-12

  3 months after cesarean section

Study Arms (2)

ITM group

ACTIVE COMPARATOR

Participants assigned to intrathecal morphine (ITM) group will receive intrathecal injection of morphine (0.15mg) for post-cesarean section pain

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

Drug: Sebacoyl Dinalbuphine Ester

Interventions

Sebacoyl Dinalbuphine Ester DRUG

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

Also known as: Naldebain

SDE group

Morphine DRUG

A single dose of morphine (0.15mg) will be administered along with bupivacaine during spinal anesthesia.

ITM group

Eligibility Criteria

• Age: 20 Years+
• Gender Eligibility Details: Female puerpera
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• term primipara or multipara who are scheduled for elective cesarean section

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Dalin Tzu Chi General Hospital: lead

Study Sites (1)

Dalin Tzu Chi Hospital

Dalin, Chai-Yi, 622, Taiwan

RECRUITING

MeSH Terms

Conditions

Pain, Postoperative

Interventions

sebacoyl dinalbuphine ester; Morphine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• NING-SHENG LAI

  Buddhist Tzu Chi Hospital

  STUDY CHAIR

Central Study Contacts

Chen-Fuh Lam, MD, PhD

CONTACT

8865-2648000; lamcf@mail.ncku.edu.tw

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, open-label, non-inferiority trial

Study Record Dates

• First Submitted: March 27, 2024
• First Posted: April 3, 2024
• Study Start: May 6, 2024
• Primary Completion: March 14, 2026
• Study Completion (Estimated): June 14, 2026
• Last Updated: May 9, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)