Dinalbuphine Ester (Naldebain) for Pain Management After Cesarean Section

NCT ID: NCT06344169

Last Updated: 2025-05-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-06
• Study Completion Date: 2026-06-14

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.

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.

Conditions

Postsurgical Pain; Cesarean Section; Chronic Post-surgical Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ITM group

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

Group Type: ACTIVE_COMPARATOR

Morphine

Intervention Type: DRUG

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

SDE group

Participants assigned to sebacoyl dinalbuphine ester (SDE) group will receive intramuscular injection of SDE (150mg) for post-cesarean section pain

Group Type: EXPERIMENTAL

Sebacoyl Dinalbuphine Ester

Intervention Type: 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

Interventions

Sebacoyl Dinalbuphine Ester

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

Intervention Type: DRUG

Morphine

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

Intervention Type: DRUG

Other Intervention Names

Naldebain

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

1. Severe pregnancy-induced complication (such as preeclampsia, eclampsia, poorly control pregnancy-induced hypertension and/or diabetes)

2. High risk for postpartum hemorrhage

3. Contraindicated for neuraxial block

4. Preterm (gestational age< 36 week) delivery

5. Emergency cesarean section

6. After-office hour schedule

7. History of substance abuse

8. Known allergy to nalbuphine, benzyl benzoate or sesame oil

9. Eligible parturient who are not willing to follow the assignment of treatment after randomization

• Minimum Eligible Age: 20 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Dalin Tzu Chi General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

NING-SHENG LAI

Role: STUDY_CHAIR

Buddhist Tzu Chi Hospital

Locations

Dalin Tzu Chi Hospital

Dalin, Chai-Yi, Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Chen-Fuh Lam, MD, PhD

Role: CONTACT

lamcf@mail.ncku.edu.tw

8865-2648000 ext. 2291

Facility Contacts

Chen-Fuh Lam, MD, PhD

Role: primary

lamcf@mail.ncku.edu.tw

866-982922554

Other Identifiers

DTCRD112(2)-I-15

Identifier Type: -

Identifier Source: org_study_id