Naldebain for Pain Management of Laparoscopic Cholecystectomy

NCT04808544 | Completed Phase 2

• 1 other identifier: EMRP28110N
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Laparoscopic cholecystectomy is the most common surgical procedure for removal of the inflamed gall bladder or other gall bladder pathologies. There are more than 12,000 cases of cholecystectomy performed in Taiwan annually, and more than 85% of this procedure are undertook with laparoscopic techniques. Even with minimally invasive laparoscopic operation, patients may still suffer from postoperative wound pain, deep visceral or referred pain. About 80% of patients who received laparoscopic procedures complain of moderate-to-severe pain within the first day after cholecystectomy. Most importantly, up to 20% (range from 3 to 20%) of these patients complained surgical-related pain one year after operation and they require prolonged use of opioid to control chronic postoperative pain (CPSP). However, there are currently lack of clinical practice guidelines or recommendations for prevention of CPSP after laparoscopic abdominal surgery. Although regional block techniques (i.e. truncal block or intrathecal opioid) are considered as effective supplementary analgesic approaches to improve postoperative pain control, parenteral administration of analgesics remain as the mainstay for pain management of laparoscopic abdominal surgery. Naldebain® is prodrug of nalbuphine, which was approved by the Taiwan FDA in 2017. Naldebain® is an extended-release dinalbuphine sebacate, and is rapidly hydrolyzed by tissue of plasma esterase to release nalbuphine. A number of clinical studies have shown that single-dose of pre-operative intramuscular administration of Naldebain® provides significantly higher analgesic effect up to 1 week in hemorrhoidectomy and laparotomy surgery with a well-tolerated safety profile. Therefore, this PI-initiated randomized, double-blind, placebo-control trial aims to investigate the clinical efficacy of Naldebain® in management of acute postoperative pain in patients receiving laparoscopic cholecystectomy, and prevention of the development of CPSP after surgery.

Conditions

Pain, Postoperative; Pain, Chronic; Cholecystitis; Quality of Life

Keywords

Nalbupine; Dinalbuphine sebacate; Naldebain; Opioid; Laparoscopic cholecystectomy

Outcome Measures

Primary Outcomes (2)

• Acute postoperative pain

  Pain score measured by visual analogue scale (VAS 1-10, a continuum scale in which 0 represents "no pain" and and 10 represents "worst pain.")

  7 days after surgery

• Total requirement dose of rescue analgesics

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

  7 days after surgery

Secondary Outcomes (2)

• Incidence of chronic post-surgical pain

  3 months after surgery

• Quality of life after surgery

  3 months after surgery

Study Arms (2)

Placebo group

PLACEBO COMPARATOR

Patients assigned to placebo group will receive a single intramuscular injection of 2 ml solvent containing benzyl benzoate and sesame oil into the gluteus muscles under ultrasound-guidance.

Drug: Placebo solution

Naldebain group

ACTIVE COMPARATOR

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.

Drug: Dinalbuphine sebacate

Interventions

Dinalbuphine sebacate 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 group

Placebo solution DRUG

Benzyl benzoate and sesame oil served as placebo solution (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: Benzyl benzoate and sesame oil

Placebo group

Eligibility Criteria

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

You may qualify if:

• Patient scheduled to receive laparoscopic cholecystectomy

You may not qualify if:

• Emergency operation
• Open cholecystectomy
• American Society of Anesthesiologists physical status \> or =4
• Chronic opioid user
• Allergy to nalbuphine, benzyl benzoate or sesame oil
• Anticipated to receive ventilator support via an endotracheal tube after operation
• Unable for verbal pain assessment or not able to participate questionnaire survey

Sponsors & Collaborators

• E-DA Hospital: lead

Study Sites (1)

E-Da Hospital

Yanchao, Kaohsiung, 824, Taiwan

Location

MeSH Terms

Conditions

Pain, Postoperative; Chronic Pain; Cholecystitis

Interventions

sebacoyl dinalbuphine ester; benzyl benzoate; Sesame Oil

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Gallbladder Diseases; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fats, Unsaturated; Plant Oils; Oils; Plant Preparations; Biological Products; Complex Mixtures; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Naldebain (active drug in solvent containing benzyl benzoate and sesame oil) or placebo drug (solvent containing benzyl benzoate and sesame oil) will be prepared by the clinical pharmacists in an identical injection syringe within 30 min before injection. The participants, anesthesiologists, surgeons, investigators and outcomes assessors will be blinded to the treatment groups.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2021
• First Posted: March 22, 2021
• Study Start: August 30, 2021
• Primary Completion: January 21, 2022
• Study Completion: April 18, 2022
• Last Updated: April 20, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)