Naldebain for Pain Management of Laparoscopic Cholecystectomy

NCT ID: NCT04808544

Last Updated: 2022-04-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-30
• Study Completion Date: 2022-04-18

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.

Detailed Description

Clinical studies indicate that more than 80% of patients suffer from surgical-related pain in the first few days after major laparotomy or laparoscopic abdominal surgery and about 10% of these patients may develop chronic postoperative pain (CPSP), which can last up to several years after surgery. One of the major risk factors for developing CPSP is inadequate management of the acute postoperative pain. 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 the minimally invasive laparoscopic operation, patients may still suffer from acute postoperative surgical-related 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 CPSP. The proposed mechanisms of CPSP after laparoscopic cholecystectomy include somatic component (incisional wound pain), visceral component (deep abdominal pain) and referred pain component (shoulder pain). Several important clinical observational studies suggested that inadequate management of surgical-related pain within one week after cholecystectomy is one of the major risk factors for developing CPSP. In addition to pain-related complications, CPSP may also impair patient's quality of life after surgery. 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. Nalbuphine is a semi-synthetic opioid that acts as a mixed kappa opioid agonist and mu opioid antagonist, but its clinical applications in relieving acute postoperative pain is limited by the relatively short duration of action of 3-6h. 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. Naldebain® has not been tested in laparoscopic surgery. 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo group

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.

Group Type: PLACEBO_COMPARATOR

Placebo solution

Intervention Type: 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.

Naldebain group

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.

Group Type: ACTIVE_COMPARATOR

Dinalbuphine sebacate

Intervention Type: 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.

Interventions

Dinalbuphine sebacate

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.

Intervention Type: DRUG

Placebo solution

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.

Intervention Type: DRUG

Other Intervention Names

Naldebain ER®; Sebacoyl Dinalbuphine Ester Injection; Benzyl benzoate and sesame oil

Eligibility Criteria

Inclusion Criteria

• Patient scheduled to receive laparoscopic cholecystectomy

Exclusion Criteria

• 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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

E-DA Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

E-Da Hospital

Yanchao, Kaohsiung, Taiwan

Countries

Taiwan

Other Identifiers

EMRP28110N

Identifier Type: -

Identifier Source: org_study_id