Clinical trial NCT06996561: Exploring the Impact of Genetic Variations on The Clinical Efficacy of Nalbuphine in Postoperative Pain Management
Official title: Exploring the Impact of Genetic Variations on The Clinical Efficacy of Nalbuphine in Postoperative Pain Management
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Cholecystectomy
Hernia, Abdominal
Appendectomy
Open Colorectal Surgery
Laparatomy
Postoperative Pain
Hysterectomy
Cystectomy
Keywords: genetic variation, nalbuphine, opioids, polymorphism
Lead sponsor: Ziauddin University
Sponsor class: OTHER
First posted: 2025-05-30
Enrollment: 263
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The goal of this study is to identify the genes as well as their association with Nalbuphine. This will help us identify opioid vulnerability in our population in the postoperative patients and will contribute to overcoming the opioid crisis, resulting in better and safer outcomes.

Research question is:

Is there any association between the underlying genetic variations and the analgesic efficacy of Nalbuphine in postoperative patients? The Research Objectives are

1. To identify the underlying genes in postoperative patients having pain.
2. To find an association between identified genes and nalbuphine clinical efficacy.

Procedure: After the written informed consent adult men and women will be enrolled in the study. On the day of surgery in the preoperative area, a 5 ml blood sample will be drawn before surgery and will be sent to laboratory for analysis. After routine hemodynamic monitoring in the operative room, general anesthesia will be given including nalbuphine. Standard routine anesthesia monitoring will be done and maintained while monitoring heart rate, ECG, NIBP oxygen saturation, ETCO2 and temperature. Incremental analgesia will be provided whenever needed. After extubation and shifting to recovery room the 2nd sample of blood will be taken and will be sent for analysis. Pain score, nausea vomiting, sedation, requirement of analgesia will be assessed till 24 hours postoperatively.

Detailed description: The available data suggests that nalbuphine, tramadol, and morphine exhibit comparable efficacy in treating moderate to severe postoperative pain. However, significant individual variations exist in the analgesic response, which can be attributed to genetic differences. These are the variations that are influenced by a combination of demographic, clinical, and environmental factors with a significant contribution from genetic factors that regulate receptor function and signal transduction. Due to the limited availability of morphine, nalbuphine is an extensively used alternative for managing intraoperative and postoperative pain in many LMICs, particularly in Pakistan. While nalbuphine is clinically effective, there is a gap in understanding the molecular factors that contribute to its efficacy in our genetically distinct population. This highlights the need to investigate the genetic variability within our population and to establish the analgesic efficacy of nalbuphine within Pakistani population. There is no molecular data from our region, which highlights the importance of genetic testing to tailor opioid therapy to individual needs, optimizing pain management while minimizing risks such as overdose or inadequate pain relief. By implementing genetics into our clinical practice, we can offer more personalized, effective, and safer opioid use, addressing the challenges associated with opioid therapy in diverse patient populations.

Eligibility criteria: Inclusion Criteria:

1. All adult men or women
2. Age 18 to 70 years
3. ASA criteria 1,2 and 3
4. Abdomino-pelvic surgeries (open hernia repair, appendicectomy, open cholecystectomy, laparotomy, hysterectomy, cystectomy) lasting 2-4 hours

Exclusion Criteria:

1. Surgical procedure duration lasting more than 4 hours
2. Patients taking anti fungal fluconazole, anticoagulant (Warfarin or Clopidogrel) SNRI (Amitryptalline), Rifampicin or Buprenorphine,
3. History of hypersensitivity or allergy to opioids,
4. Pregnant or breastfeeding mothers,
5. History of narcotic dependency, addiction, and withdrawal
6. Patients experiencing any adverse side effects or complications during surgical procedure requiring intensive care admission
7. Refusing to participate in the study
8. Surgical procedures utilizing other modes of intraoperative analgesia e.g epidural analgesia or nerve blocks

Primary outcomes:
measure: pain score
timeFrame: 24 hours postoperatively
Secondary outcomes:
measure: sedation score
timeFrame: 24 hours
measure: nausea vomiting score
timeFrame: 24 hours postoperatively
measure: rescue analgesia
timeFrame: 24 hours postoperatively
Other outcomes:
Locations:
city: Karachi
country: Pakistan
facility: Ziauddin University
state: Sindh
Study officials:
affiliation: Ziauddin University
name: Talat Mirza, FCPS PhD
role: STUDY_DIRECTOR
References:
citation: Agarwal D, Udoji MA, Trescot A. Genetic Testing for Opioid Pain Management: A Primer. Pain Ther. 2017 Jun;6(1):93-105. doi: 10.1007/s40122-017-0069-2. Epub 2017 Apr 13.