Naldebain for Pain Control After Bariatric Surgery

E-DA Hospital

Status and phase: Unknown; Phase 3; Phase 2

Conditions: Bariatric Surgery; Pain, Postoperative; Obesity; Pain, Chronic; Pharmacokinetics

Treatments: Drug: Dinalbuphine sebacate; Drug: Placebo solution

Study type: Interventional

Funder types: Other

Identifiers

NCT04651361

EMRP-73109N

Details and patient eligibility

About

Laparoscopic gastric sleeve and bypass surgeries the most common bariatric procedures for weight loss and improved management of metabolic syndromes. Patients may suffer from wound pain or referred pain after laparoscopic bariatric operation. Most importantly, 11.8% of these patients complained surgical-related pain one year after operation, and 8% of them required 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 gastric sleeve or bypass surgery, and prevention of the development of CPSP after surgery. This study will also analyze the plasma levels of nalbuphine following a single intramuscular injection in obese patients.

Full 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 gastric sleeve and bypass surgeries the most common bariatric procedures for weight loss and improved management of metabolic syndromes. Patients may suffer from wound pain or referred pain after laparoscopic bariatric operation. Most importantly, 11.8% of these patients complained surgical-related pain one year after operation, and 8% of them required prolonged use of opioid to control 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. 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 bariatric surgery and its pharmacokinetic profiles in overweight patients are undetermined. 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 gastric sleeve or bypass surgery, and prevention of the development of CPSP after surgery. This study will also analyze the plasma levels of nalbuphine following a single intramuscular injection in obese patients.

Enrollment: 60 estimated patients

Sex: All

Ages: 20 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patient scheduled to receive laparoscopic gastric sleeve surgery or laparoscopic gastric bypass surgery

Exclusion criteria

• Laparotomy bariatric surgery
• 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
• Not able for verbal pain assessment or not able to participate questionnaire survey

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 2 patient groups, including a placebo group

Naldebain group

Active Comparator group

Description:

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.

Treatment:

Drug: Dinalbuphine sebacate

Placebo group

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo solution