Oliceridine-Enhanced Analgesia and Recovery: A G-Protein Biased μ-Opioid Study

Enhanced Postoperative Analgesia and Accelerated Recovery With Oliceridine: A Study on G-Protein Biased μ-Opioid Agonist

Identifying the lowest effective opioid dose that achieves rapid pain relief while minimizing side effects is a principal objective in postoperative multimodal analgesia strategies. This study aims to determine the optimal analgesic regimen and dosage by assessing the clinical efficacy of oliceridine for postoperative pain management. It also evaluates oliceridine's contribution to accelerated postoperative recovery, examining aspects such as postoperative pulmonary complications, gastrointestinal function, nausea and vomiting, cognitive function, and emotional distress. Furthermore, the study integrates microbiomics and metabolomics to investigate the underlying molecular mechanisms by which oliceridine promotes rapid postoperative recovery. This research will broaden the clinical data and potential applications of oliceridine, addressing gaps in the field and enhancing practical knowledge. Moreover, this is the first time a clinical study combining multiple omics approaches will provide a comprehensive theoretical foundation for its clinical benefits.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Analgesia
• Intervention / Treatment: Drug: Oliceridine fumarate low dose; Drug: Oliceridine fumarate moderate dose; Drug: Oliceridine fumarate high dose; Drug: morphine

Detailed Description

This study selects 80 elective patients slated for upper abdominal laparoscopic surgery under general anesthesia, classified as ASA I-II. These patients are randomly allocated into four groups: Oliceridine low dose (OⅠ), medium dose (OⅡ), and high dose (OⅢ), and a Morphine (M) group. The postoperative analgesic protocol includes a universal loading dose of 1.5 mg for all groups. Depending on the group, the PCA doses are set at 0.1 mg, 0.35 mg, or 0.5 mg, with a lockout interval of 6 minutes. After the initial dose, patients may receive an additional 0.75 mg per hour as needed, with a daily ceiling of 27 mg for Oliceridine. In the Morphine group, the loading dose is 4 mg with a PCA dose of 1 mg and similar lockout, allowing 2 mg per hour post-loading, capped at 60 mg daily. Outcomes to monitor include systolic and diastolic blood pressures, heart rate, oxygen saturation, and respiratory rate at 6, 24, and 48 hours postoperatively; pain levels using the NRS scale; nausea and vomiting via the VAS score; and pulmonary complications evaluated by EPCO standards at specified intervals. Gastrointestinal function is assessed using the I-FEED score, and mental health through the HADS scale preoperatively and 48 hours post-surgery. Cognitive function is evaluated using the MMSE scale preoperatively and 72 hours postoperatively. Patient fecal samples are collected pre- and 48 hours post-surgery for microbial and metabolomic analyses to identify potential molecular benefits of Oliceridine, informed by its G-protein biased pharmacology. The study also uses statistical methods to compare microbiological outcomes and correlate these with clinical presentations.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hui Xu; Phone Number: +8613971001596; Email: huixu@tjh.tjmu.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Tongji Hospital
      • Contact: Hui Xu; Phone Number: +8613971001596; Email: huixu@tjh.tjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ASA grades 1-2
2. Age > 18 years and < 70 years
3. Laparoscopic upper abdominal surgery under general anesthesia is planned, and the operation time is not more than 4 hours
4. Voluntarily receive postoperative controlled intravenous analgesia
5. Subjects understand and can cooperate with this study
6. Subjects can provide and sign written informed consent prior to conducting investigation-related screening procedures

Exclusion Criteria:

1. BMI>30 kg/m2 or < 19 kg/m2
2. Patients with preoperative use of opioids, acute and chronic pain or hyperalgesia
3. Patients with coronary atherosclerotic heart disease, significant ischemic heart disease, severe angina, heart failure, valvular disease or other heart disease
4. More severe hepatic and renal insufficiency
5. A history of mental illness or alcoholism
6. A history of alcohol or drug abuse
7. Combined with cranial pressure, intraocular pressure or glaucoma
8. Poorly controlled or untreated hypertension before surgery
9. Preeclampsia or eclampsia
10. Untreated and undertreated hyperthyroidism
11. Combined with autoimmune disease
12. Unable to use the numerical rating scale
13. History of chronic cough
14. Surgery is expected to take more than 4 hours Patients enrolled in other clinical trials within 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oliceridine fumarate low dose group; The first loading dose of oliceridine fumarate was 1.5 mg in all patients after operation. The PCA dose of the patients was 0.1 mg, and the locking interval was 6 min. A supplemental dose of 0.75 mg is allowed once per hour as needed after 1 h of the load dose; The maximum cumulative daily dose is 27mg. The duration of PCA analgesia was 48 hours.	Drug: Oliceridine fumarate low dose; The first loading dose of oliceridine fumarate was 1.5 mg in all patients after operation. The PCA dose of the patients was 0.1 mg, and the locking interval was 6 min. A supplemental dose of 0.75 mg is allowed once per hour as needed after 1 h of the load dose
Experimental: Oliceridine fumarate medium dose group; The first loading dose of oliceridine fumarate was 1.5 mg in all patients after operation. The PCA dose of the patients was 0.35mg, and the locking interval was 6 min. A supplemental dose of 0.75 mg is allowed once per hour as needed after 1 h of the load dose; The maximum cumulative daily dose is 27mg. The duration of PCA analgesia was 48 hours.	Drug: Oliceridine fumarate moderate dose; The first loading dose of oliceridine fumarate was 1.5 mg in all patients after operation. The PCA dose of the patients was 0.35 mg, and the locking interval was 6 min. A supplemental dose of 0.75 mg is allowed once per hour as needed after 1 h of the load dose
Experimental: Oliceridine fumarate high dose group; The first loading dose of oliceridine fumarate was 1.5 mg in all patients after operation. The PCA dose of the patients was 0.5 mg, and the locking interval was 6 min. A supplemental dose of 0.75 mg is allowed once per hour as needed after 1 h of the load dose; The maximum cumulative daily dose is 27mg. The duration of PCA analgesia was 48 hours.	Drug: Oliceridine fumarate high dose; The first loading dose of oliceridine fumarate was 1.5 mg in all patients after operation. The PCA dose of the patients was 0.5 mg, and the locking interval was 6 min. A supplemental dose of 0.75 mg is allowed once per hour as needed after 1 h of the load dose
Experimental: Morphine group; The first loading dose of morphine was 4 mg in all patients after operation. The PCA dose of the patients was 1 mg, and the locking interval was 6 min. A supplemental dose of 2 mg is allowed once per hour as needed after 1 h of the load dose; The maximum cumulative daily dose is 60 mg. The duration of PCA analgesia was 48 hours.	Drug: morphine; The first loading dose of morphine was 4 mg in all patients after operation. The PCA dose of the patients was 1 mg, and the locking interval was 6 min. A supplemental dose of 2 mg is allowed once per hour as needed after 1 h of the load dose; The maximum cumulative daily dose is 60 mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
postoperative pain score	The NRS Numerical Pain Evaluation Scale assessed postoperative pain status: no pain (0), mild pain (1-3), moderate pain (4-6), and severe pain (7-10).	6 hour, 24hour, and 48 hour after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative cognitive function	(mini-mental state examination, MMSE) scale score，The maximum score is 30 points. The classification of dementia is related to the level of education, so if the elderly are illiterate and less than 17 points, primary school and less than 20 points, secondary school and above less than 24 points, then dementia.	Before surgery, 3 days after surgery
Flora abundance	Feces were collected from patients before surgery and 48 hours after surgery (stored at negative 80 degrees), and the fecal intestinal flora abundance of patients in each group was determined by 16S rRNA omics	One day before surgery and 48 hours after surgery
Postoperative nausea and vomiting	With a 10cm ruler as the scale, 0 at one end indicates no nausea and vomiting, and 10 at the other end indicates the most severe nausea and vomiting that is unbearable. 1 to 4 is mild, 5 to 6 is moderate, 7 to 10 is severe	6 hour, 24 hour, and 48 hour after surgery
Postoperative pulmonary complications	european perioperative clinical outcome (EPCO)	24 hour,72 hour after surgery

Collaborators and Investigators

• Sponsor: Tongji Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: May 7, 2024
• First Submitted That Met QC Criteria: May 7, 2024
• First Posted (Actual): May 10, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 2, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Perceptual Disorders; Agnosia; Physiological Effects of Drugs; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: S058

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No