Exploring the Impact of Genetic Variations on The Clinical Efficacy of Nalbuphine in Postoperative Pain Management

Dr. Asma Abdus Salam

Status and phase: Not yet enrolling; Phase 3; Phase 2

Conditions: Postoperative Pain; Laparatomy; Cholecystectomy; Hernia, Abdominal; Cystectomy; Hysterectomy; Open Colorectal Surgery; Appendectomy

Treatments: Genetic: whole exome sequencing; Genetic: Next Generation Sequencing; Drug: Nalbuphine Injection

Study type: Interventional

Funder types: Other

Identifiers

NCT06996561

Nal-Gene123

Details and patient eligibility

About

The goal of this study is to identify the genes as well as their association with Nalbuphine. This will help the investigator to identify opioid vulnerability in Pakistani 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.

Full 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 this genetically distinct population. This highlights the need to investigate the genetic variability and to establish the analgesic efficacy of nalbuphine within Pakistani population. There is no molecular data from the region where the investigator belongs, 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 clinical practice, the investigator can offer more personalized, effective, and safer opioid use, addressing the challenges associated with opioid therapy in diverse patient populations.

Enrollment: 263 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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263 participants in 1 patient group

nalbuphine

Experimental group

Description:

Given as intravenously, 0.1-0.2 mg / kg at induction and intermittently

Treatment:

Drug: Nalbuphine Injection

Genetic: whole exome sequencing

Genetic: Next Generation Sequencing