NALDEBAIN for Postoperative Pain Management in Take Down of Anastomosis

Study Overview
=================
Brief Summary
-----------------
NALDEBAIN ER injection, invented by Taiwanese, launched in 2017, is a nalbuphine synthetic prodrug with oil-based solution to extend the release in human body by intramuscular injection. It was approved for the premedication use for moderate to severe pain relief, expected after surgery. There was limited experience with the combination of medication and different type of surgeries. Only the effect of operative analgesia on the hemorrhoidectomy patients have been well studied. Through reviewing the past medical cases, the pain intensity after receiving take down of anastomosis was about 4 to 7 points (moderate pain), lasing about 1 to 3 days. It was a suitable population with multi-day analgesic unmet need. At present, the standard treatment after take down of anastomosis in the CMUH was morphine as needed. This treatment might not provide for well-controlled postoperative pain management. Patients might receive more painkillers when they needed than before pain occurred. Plus, it also cost more postoperative medical care. Therefore, this study intended to compare the standard treatment and NALDEBAIN for postoperative outcomes, safety and satisfaction. The study will enroll patients scheduled to electively undergo take down of anastomosis. Eligible subjects were randomly divided into two groups, one receiving NALDEBAIN and the other receiving standard treatment. The study will evaluate pain intensity, dosage of supplement analgesics, incidence of adverse reactions, patient satisfaction, time of the first fart after surgery, and duration of postoperative hospital stay.

Detailed Description
-----------------
This is an open-labeled, randomized clinical trial. After ICFs are signed, patients' medical history will be gained for checking if they are eligible for this study or not. And then, on Day -1, eligible ones will randomly be divide into two separate group: NALDEBAIN or MORPHINE. Group NALDEBAIN will receive Nadebain by gluteus maximus injection between 12 and 24 hours prior to surgery for postoperative pain relief. Group MORPHINE will receive morphine as needed after surgery. All necessary data will be gain form EMR or patient dairies.

Official Title
-----------------
NALDEBAIN for Postoperative Pain Management in Take Down of Anastomosis

Conditions
-----------------
Postoperative Pain

Intervention / Treatment
-----------------
* Drug: Naldebain
* Drug: Morpine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and Women between 20 and 80 years of age History of laparoscopic surgery American Society of Anesthesiology Physical Class 1-3 Ability and willingness to provide informed consent Exclusion Criteria: History of hypersensitivity or allergy to opioid, NSAIDs, or Acetaminophen Chronic preoperative opioid use Severe comorbidity which is able to interfere pain assessment Ostomy surgery of intestine within the past 8 weeks Pregnant or breastfeeding

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NALDEBAIN<br>In group NALDEBAIN, subjects will receive single dose of Naldebain (150 mg/2 ml) by gluteus maximus injection between 12 and 24 hours prior to surgery. | Drug: Naldebain<br>* In Naldebain group, patients will be injected with Naldebain (150 mg/2 ml, IM injection) between 12 and 24 hours prior to surgery.<br>|
| Active Comparator: MORPHINE<br>In group MORPHINE, subjects will receive morphine as needed after surgery. | Drug: Morpine<br>* In Morphine group, patients will receive morphine as needed after surgery.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Supplemental analgesics | The consumption of total amount (mg) of supplemental analgesics administered after surgery. | From Day 0 to Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain assessment: VAS | Using visual analog scale (VAS) with grades from 0 (no pain) to 10 (worst pain) | 2 hours after surgery | 
| Pain assessment: VAS | Using visual analog scale (VAS) with grades from 0 (no pain) to 10 (worst pain) | 6 hours after surgery | 
| Pain assessment: VAS | Using visual analog scale (VAS) with grades from 0 (no pain) to 10 (worst pain) | 24 hours after surgery | 
| Pain assessment: VAS | Using visual analog scale (VAS) with grades from 0 (no pain) to 10 (worst pain), once daily | From Day 2 to Day 7 | 
| Pain assessment: area under the curve of VAS | Pain assessment (time-specific pain intensity) calculated as the area under the curve of VAS pain intensity scores through 7 days after surgery | From post-OP to Day 7 | 
| Patient satisfaction: frequency of each option | Calculating the frequency of each option: highly satisfied, satisfied, uncertain, dissatisfied and very dissatisfied | Day 7 | 
| frequency of adverse event | Recording the frequency of treatment-emergent adverse event (TEAE) | From Day-1 to Day 7 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Naldebain, long-term analgesia, take down of anastomosis