The Efficacy and Safety of NALDEBAIN for the Treatment of Post-Laparotomy Surgery

Study Overview
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Brief Summary
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The primary objective of this study is to determine the safety and efficacy of single doses of intramuscular NALDEBAIN on patients scheduled to undergo elective laparotomy. This will be performed by administering NALDEBAIN pre-operatively to subjects scheduled to undergo elective laparotomy, and assessing the safety and efficacy of the drug compared to PCA with fentanyl. The study will demonstrate whether single use of NALDEBAIN is noninferior to PCA with fentanyl or not.

Detailed Description
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Screening (Days -30 to -1) (All Study Subjects) The nature of the study, as well as the potential risks and benefits associated with study participation, will be fully explained to all potential subjects. The following will then be obtained: Informed consent. Demographic information, including sex, age, BMI and type of surgery. Vital signs, including temperature, respiratory rate, blood pressure and heart rate. Medical history, including medication use and history of allergy. Physical examination. Laboratory testing, including hematological and biochemical tests, and urinalysis. ECG and X-ray. Study Day -1 (All Eligible Subjects) Eligible subjects will be required to check into the clinical site before surgery (Day -1). The following procedures will be performed upon check-in: Review inclusion/exclusion criteria Randomization Review of concomitant medications Review of adverse events Additional laboratory tests will be requested as needed deciding by the investigator. All eligible subjects will hospitalize and be randomized into one of two treatment groups: Group 1 - Intramuscular NALDEBAIN. Group 2 - Intravenous PCA with fentanyl. Group 1 will receive single dose of NALDEBAIN (150 mg Nalbuphine Sebacate) intramuscularly 24±12 hours before surgery. Group 2 will receive intravenous patient-controlled analgesia with fentanyl through 48 hours after surgery. Pain assessment: group 1 and 2 will rate their pain intensity using a VAS pain scale prior dosing or at Day -1 respectively. Brief Pain Inventory (BPI) will be evaluated at Day -1. Vital signs will be checked prior to dosing and once daily before Day 6. Group 1 received NALDEBAIN will evaluate injection site within 1 hour prior to dosing. Study Day 0-5 All subjects will be given general anesthesia prior to their scheduled surgical procedure. If patients need additional medication for treatment of pain, Ketorolac and Morphine could be used as supplemental analgesics when they needed. After surgery, the following evaluations will be performed: Pain assessment: All subjects will rate their average pain intensity using a VAS pain scale. The assessment will perform before the first use of PCA or supplemental analgesics and at 4±1, 24±2, 32±3, 48±4 hours and once daily on Days 3 to Day 5 after the surgery. Brief Pain Inventory (BPI) will be evaluated at Day 2. Vital signs (temperature, respiratory rate, blood pressure and heart rate) will be checked once daily before Day 6. In Group 1 (NALDEBAIN group), the injection site will be evaluated once daily before final visit. Review of concomitant medication and adverse event record. In Group 2 (PCA group), the amount of fentanyl used will be recorded on Days 0 through 2. Study Day 6 Evaluate the following items at Day 6. Pain assessment: Subjects will rate their pain intensity in the patient diary. Brief Pain Inventory (BPI) will be evaluated. Vital signs (temperature, respiratory rate, blood pressure and heart rate) will be checked. Injection site evaluation. Review of the adverse event record. Review of concomitant medication. Final Visit (Day of Discharge, Day 6 30) Vital signs (temperature, respiratory rate, blood pressure and heart rate) will be checked Injection site evaluation Laboratory tests, including hematological and biochemical tests, and urinalysis. Patient satisfaction: At the final visit, each subject was asked the following question: How satisfied were you with your postsurgical analgesia? Subjects were asked to classify themselves as either highly satisfied, satisfied, uncertain, dissatisfied, or very dissatisfied. Physical examination. Review of the adverse event record. Review of concomitant medication.

Official Title
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A Randomized Controlled Trial to Compare the Efficacy and Safety of NALDEBAIN With Intravenous Patient-Controlled Analgesia With Fentanyl for the Treatment of Post-Laparotomy Surgery

Conditions
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Pain, Postoperative

Intervention / Treatment
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* Drug: Nalbuphine Sebacate
* Drug: Fentanyl Citrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female who is among 20 to 80 years of age at screening. Scheduled to electively undergo open-laparotomy. American Society of Anesthesiology Physical Class 1-3. Ability and willingness to provide informed consent Exclusion Criteria: Body mass index less than 18 kg/m2 or greater than 30 kg/m2. History of previous open-laparotomy. Surgery with major complication, or need blood transfusion. History of hypersensitivity or adverse reaction to local anesthetics, opioid, or any ingredient of the medications administered in this study. Severe comorbidity. Chronic preoperative opioid consumption. Pregnant or breastfeeding. Inability to use the PCA device.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nalbuphine Sebacate<br>receive single dose of NALDEBAIN (150 mg Nalbuphine Sebacate, 75 mg/ml, 2 ml/vial) intramuscularly 24±12 hours before surgery. | Drug: Nalbuphine Sebacate<br>* intramuscular single dose of NALDEBAIN 24±12 hours before surgery.<br>* Other names: NALDEBAIN;|
| Active Comparator: Fentanyl Citrate<br>receive intravenous patient-controlled analgesia with fentanyl through 48 hours after surgery. | Drug: Fentanyl Citrate<br>* Intravenous patient-controlled analgesia with fentanyl through 48 hours after surgery.<br>* Other names: PCA with fentanyl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pain assessment (post-OP 48 hours) | Pain assessment (time-specific pain intensity) calculated as the area under the curve of VAS pain intensity scores through 48 hours after surgery. | During post-OP 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| supplemental analgesics | The consumption of total amount (mg) of supplemental analgesics administered after surgery. | From post-OP to Day 6 | 
| Pain assessment (post-OP to Day 6) | Pain assessment calculated as the area under the curve of VAS pain intensity scores through end of surgery to Day 6 | From post-OP to Day 6 | 
| Brief Pain Inventory | Pain intensity and interference of Brief Pain Inventory (BPI) | pre-OP Day -1, post-OP Day 2 and Day 6 | 
| Patient satisfaction | Patient satisfaction on a 5-point rating. | On discharge Day, between post-OP Day 7 and Day 14 | 
| Length of postoperative hospital stay | Length of postoperative hospital stay. | From post-OP to Discharge Day, about 1 to 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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post-laparotomy wound pain, NALDEBAIN (150 mg Nalbuphine Sebacate), PCA (patient-control-ed alagesia)