Naldebain for Control of Post-Cesarean Section Pain

NCT05187520 | Unknown Phase 2

• 1 other identifier: EMRP05111N
• 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. Patient-controlled epidural analgesia (PCEA) is considered as the standard pain management strategy for post-cesarean pain. 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. It also increases risk of other complications, including urinary retention, systemic toxicity of local anesthetics and formation of epidural hematoma. 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 PCEA and prevent the development of CPSP.

Conditions

Post Operative Pain, Acute; Post Operative Pain, Chronic; Cesarean Section

Keywords

Epidural analgesia; Multimodal analgesia; Opioid use; Epidural analgesia complications; Quality of life

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 operation

• Rescue doses of analgesics administered after operation

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

  5 days after operation

Secondary Outcomes (2)

• Incidence of chronic post-surgical pain

  3 months after operation

• Satisfaction of living after surgery as assessed by the HRQoL SF-12

  3 months after operation

Study Arms (2)

Patient-controlled epidural analgesia (PCEA)

ACTIVE COMPARATOR

Patients assigned to PCEA group will receive epidural analgesia as the standard postoperative pain control strategy. After completion of cesarean section, a PCEA device will be connected to the epidural catheter to deliver mixture of local anesthetic (0.8 mg/ml) and fentanyl (2 mcg/ml) with preset continuous dose of 3-5 ml/h and a bolus dose of 3-4 ml.

Device: Patient-controlled epidural analgesia (PCEA)

Naldebain®

EXPERIMENTAL

Patients assigned to Naldebain® group will receive a single intramuscular injection of dinalbuphine sebacate (150 mg in 2 ml solvent containing benzyl benzoate and sesame oil) into the gluteus muscles under ultrasound-guidance after completion of cesarean section.

Drug: Naldebain®

Interventions

Patient-controlled epidural analgesia (PCEA) DEVICE

Epidural analgesia is a technique of neuraxial block by placement of a 20G polyether epidural catheter into the epidural lumen and fixed at the desired depth, and analgesic effect is usually achieved by administration of mixture of local anesthetics and opioids using a programmed pump.

Patient-controlled epidural analgesia (PCEA)

Naldebain® DRUG

Naldebain 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 ER®, Sebacoyl Dinalbuphine Ester Injection

Naldebain®

Eligibility Criteria

• Age: 20 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Term primipara or multipara

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
• Contraindications 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
• Not willing to follow the assignment of treatment after randomization

Sponsors & Collaborators

• E-DA Hospital: lead

Study Sites (1)

E-Da Hospital

Yanchao, Kaohsiung, 824, Taiwan

Location

MeSH Terms

Conditions

Pain, Postoperative

Interventions

sebacoyl dinalbuphine ester

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Chen-Fuh Lam, MD, PhD

CONTACT

+8867-6150011; 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: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor and Superintendent

Study Record Dates

• First Submitted: December 24, 2021
• First Posted: January 11, 2022
• Study Start: September 1, 2022
• Primary Completion: June 30, 2023
• Study Completion: October 1, 2023
• Last Updated: April 8, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)