Effect of Oliceridine Analgesia on Postoperative Nause and Vomiting

Postoperative Nausea and Vomiting Clinical Trial

Official title:

Effect of Oliceridine Analgesia on Postoperative Nause and Vomiting in Laparoscopic Colorectal Surgery: A Randomized Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06411665
• Other study ID #: 2024-073
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: June 2024
• Est. completion date: December 2026

Study information

• Verified date: May 2024
• Source: Peking University First Hospital
• Contact: Xue Li, M.D.
• Phone: +8618810527114
• Email: 3999165[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Postoperative nausea and vomiting (PONV) is common after surgery and impede rapid recovery after surgery. Patients who undergo laparoscopic colorectal surgery are more likely to develop PONV due to the pneumoperitoneum, interruption of gastrointestinal system, delay of oral feeding, and nasogastric catheterization, as well as postoperative opioid analgesic requirement to control acute pain. Oliceridine is a novel selective μ-opioid agonist. It stimulates G protein signalling but is markedly less potent than morphine for β-arrestin recruitment; the latter contributes to opioid-related adverse events including PONV. It is postulated that G protein-biased agonists may deliver effective analgesia with fewer opioid-related adverse events. This randomized trial aimed to investigate whether oliceridine for patient-controlled analgesia can decrease the incidence of PONV in patients recovering from laparoscopic colorectal surgery.

Description:

Postoperative nausea and vomiting (PONV) is a common adverse event after surgery. A retrospective study found that PONV occurred in 14.4% of enrolled 106860 patients. The reported incidences in prospective studies varied between 25.5% to 33.3%. Certain types of laparoscopic surgery are associated with an increased risk of PONV, including bariatric surgery, gynecological surgery, and cholecystectomy. PONV can lead to dehydration and electrolyte imbalances, delay early ambulation, impede rapid recovery after surgery, decrease patients' satisfactory, and potentially prolong hospital stay and increase cost. Opioids are commonly used during the perioperative period and are associated with increased PONV. Conventional opioids such as morphine and sufentanil activate both the G protein and β-arrestin pathways; the latter approach contributes to opioid-related PONV through multiple mechanisms, such as enhanced vestibular sensitivity, direct effects on the chemoreceptor trigger zone, and delayed gastric emptying. Oliceridine is a novel selective μ-opioid agonist. It stimulates G protein signalling but is markedly less potent than morphine for β-arrestin recruitment. It is therefore postulated that G protein-biased agonists may deliver effective analgesia with fewer opioid-related PONV. Previous studies in patients with moderate-to-severe pain following orthopaedic surgery-bunionectomy or plastic surgery-abdominoplasty showed that oliceridine provided an excellent analgesic efficacy compared with morphine and placebo. The analgesic efficiency of 0.35 mg or 0.5 mg oliceridine was equal to 1 mg morphine. However, the rate of PONV was significantly lower in patients given oliceridine than in those given morphine. Patients who undergo laparoscopic colorectal surgery are more likely to develop PONV due to the pneumoperitoneum, interruption of gastrointestinal system, delay of oral feeding, and nasogastric catheterization, as well as postoperative opioid analgesia to control pain. Thus, selective μ-opioid agonist might be more suitable for postoperative analgesia for these patients. This randomized trial aimed to investigate whether oliceridine compared with morphine for postoperative analgesia can decrease the incidence of PONV in patients after laparoscopic colorectal surgery.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 250
• Est. completion date: December 2026
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Aged between 18 and 80 years;

2. Scheduled to undergo elective laparoscopic colorectal surgery;

3. Required patient-controlled intravenous analgesia.

Exclusion Criteria:

1. Pregnancy.

2. Severe heart dysfunction (New York Heart Association functional classification 4), hepatic insufficiency (Child-Pugh grade C), renal insufficiency (serum creatinine of 442 µmol/L or above, or requirement of renal replacement therapy), or Amercian Society of Anesthesiologists classification IV or above.

3. Unable to complete preoperative assessment due to severe dementia or language barrier.

4. Other conditions that are considered unsuitable for study participation.

Related Conditions & MeSH terms

• Nausea
• Postoperative Nausea and Vomiting
• Vomiting

Intervention

Drug:
• Oliceridine
Patient-controlled intravenous analgesia with oliceridine for up to 3 days after surgery.
• Morphine
Patient-controlled intravenous analgesia with morphine for up to 3 days after surgery.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Peking University First Hospital

References & Publications (19)

Beard TL, Michalsky C, Candiotti KA, Rider P, Wase L, Habib AS, Demitrack MA, Fossler MJ, Viscusi ER. Oliceridine is Associated with Reduced Risk of Vomiting and Need for Rescue Antiemetics Compared to Morphine: Exploratory Analysis from Two Phase 3 Rando — View Citation

DeWire SM, Yamashita DS, Rominger DH, Liu G, Cowan CL, Graczyk TM, Chen XT, Pitis PM, Gotchev D, Yuan C, Koblish M, Lark MW, Violin JD. A G protein-biased ligand at the mu-opioid receptor is potently analgesic with reduced gastrointestinal and respiratory — View Citation

DREAMS Trial Collaborators and West Midlands Research Collaborative. Dexamethasone versus standard treatment for postoperative nausea and vomiting in gastrointestinal surgery: randomised controlled trial (DREAMS Trial). BMJ. 2017 Apr 18;357:j1455. doi: 10 — View Citation

Gan TJ, Belani KG, Bergese S, Chung F, Diemunsch P, Habib AS, Jin Z, Kovac AL, Meyer TA, Urman RD, Apfel CC, Ayad S, Beagley L, Candiotti K, Englesakis M, Hedrick TL, Kranke P, Lee S, Lipman D, Minkowitz HS, Morton J, Philip BK. Fourth Consensus Guideline — View Citation

Gustafsson UO, Scott MJ, Hubner M, Nygren J, Demartines N, Francis N, Rockall TA, Young-Fadok TM, Hill AG, Soop M, de Boer HD, Urman RD, Chang GJ, Fichera A, Kessler H, Grass F, Whang EE, Fawcett WJ, Carli F, Lobo DN, Rollins KE, Balfour A, Baldini G, Rie — View Citation

Habib AS, Chen YT, Taguchi A, Hu XH, Gan TJ. Postoperative nausea and vomiting following inpatient surgeries in a teaching hospital: a retrospective database analysis. Curr Med Res Opin. 2006 Jun;22(6):1093-9. doi: 10.1185/030079906X104830. — View Citation

Hammer GB, Khanna AK, Michalsky C, Wase L, Demitrack MA, Little R, Fossler MJ, Ayad S. Oliceridine Exhibits Improved Tolerability Compared to Morphine at Equianalgesic Conditions: Exploratory Analysis from Two Phase 3 Randomized Placebo and Active Control — View Citation

Kim JH, Cheon BR, Kim MG, Hwang SM, Lim SY, Lee JJ, Kwon YS. Postoperative Nausea and Vomiting Prediction: Machine Learning Insights from a Comprehensive Analysis of Perioperative Data. Bioengineering (Basel). 2023 Oct 1;10(10):1152. doi: 10.3390/bioengin — View Citation

Liu Y, Xiao S, Yang H, Lv X, Hou A, Ma Y, Jiang Y, Duan C, Mi W; CAPOPS Group. Postoperative pain-related outcomes and perioperative pain management in China: a population-based study. Lancet Reg Health West Pac. 2023 Jun 10;39:100822. doi: 10.1016/j.lanw — View Citation

Markham A. Oliceridine: First Approval. Drugs. 2020 Nov;80(16):1739-1744. doi: 10.1007/s40265-020-01414-9. Erratum In: Drugs. 2020 Nov;80(17):1871. — View Citation

Matsumoto A, Satomi S, Kakuta N, Narasaki S, Toyota Y, Miyoshi H, Horikawa YT, Saeki N, Tanaka K, Tsutsumi YM. Remimazolam's Effects on Postoperative Nausea and Vomiting Are Similar to Those of Propofol after Laparoscopic Gynecological Surgery: A Randomiz — View Citation

Mauermann E, Clamer D, Ruppen W, Bandschapp O. Association between intra-operative fentanyl dosing and postoperative nausea/vomiting and pain: A prospective cohort study. Eur J Anaesthesiol. 2019 Nov;36(11):871-880. doi: 10.1097/EJA.0000000000001081. — View Citation

Myles PS, Williams DL, Hendrata M, Anderson H, Weeks AM. Patient satisfaction after anaesthesia and surgery: results of a prospective survey of 10,811 patients. Br J Anaesth. 2000 Jan;84(1):6-10. doi: 10.1093/oxfordjournals.bja.a013383. — View Citation

Singla NK, Skobieranda F, Soergel DG, Salamea M, Burt DA, Demitrack MA, Viscusi ER. APOLLO-2: A Randomized, Placebo and Active-Controlled Phase III Study Investigating Oliceridine (TRV130), a G Protein-Biased Ligand at the mu-Opioid Receptor, for Manageme — View Citation

Smith HS, Laufer A. Opioid induced nausea and vomiting. Eur J Pharmacol. 2014 Jan 5;722:67-78. doi: 10.1016/j.ejphar.2013.09.074. Epub 2013 Oct 21. — View Citation

Song Y, Zhu J, Dong Z, Wang C, Xiao J, Yang W. Incidence and risk factors of postoperative nausea and vomiting following laparoscopic sleeve gastrectomy and its relationship with Helicobacter pylori: A propensity score matching analysis. Front Endocrinol — View Citation

Suh S, Helm M, Kindel TL, Goldblatt MI, Gould JC, Higgins RM. The impact of nausea on post-operative outcomes in bariatric surgery patients. Surg Endosc. 2020 Jul;34(7):3085-3091. doi: 10.1007/s00464-019-07058-5. Epub 2019 Aug 6. — View Citation

Viscusi ER, Skobieranda F, Soergel DG, Cook E, Burt DA, Singla N. APOLLO-1: a randomized placebo and active-controlled phase III study investigating oliceridine (TRV130), a G protein-biased ligand at the micro-opioid receptor, for management of moderate-t — View Citation

Zhang R, Zhang WX, Ma XR, Feng Y. Intraoperative Sufentanil Consumption and the Risk of Postoperative Nausea and/or Vomiting: A Retrospective Observational Study. Pain Ther. 2023 Oct;12(5):1271-1281. doi: 10.1007/s40122-023-00546-6. Epub 2023 Aug 9. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Time to first ambulation after surgery.	Time to first ambulation after surgery.	Up to 5 days after surgery.
Other	Patients' satisfaction score with postoperative analgesia.	Patients' satisfaction is assessed with a visual analogue scale, a 0-100 scale where 0=very dissatisfied and 100=very satisfied.	At 72 hours after surgery.
Other	Total opioid consumption within 72 hours after surgery.	Total opioid consumption within 72 hours after surgery.	Up to 72 hours after surgery.
Other	Subjective sleep quality during the first 3 nights after surgery.	Subjective sleep quality is assessed with the numeric rating scale, an 11-point scale where 0=the best sleep and 10=the worst sleep.	Up to 72 hours after surgery.
Other	Length of hospital stay after surgery.	Length of hospital stay after surgery.	Up to 30 days after surgery.
Other	Major complications within 30 days after surgery.	Major complications are defined as new-onset medical events that are deemed harmful and required therapeutic intervention, that is grade II or higher on the Clavien-Dindo classification.	Up to 30 days after surgery.
Primary	The incidence of postoperative nause and vomiting (PONV) with 72 hours.	Defined as the development of any nausea, retching, or vomiting within 72 h after surgery.	Up to 72 hours after surgery.
Secondary	The incidence of postoperative vomiting within 72 hours.	Defined as the development of any retching or vomiting within 72 h after surgery.	Up to 72 hours after surgery
Secondary	Area under curve of nausea intensity at predefined timepoints.	Nausea intensity is assessed with the numeric rating scale, an 11-point scale where 0=no nausea and 10=the most severe nausea.	Up to 72 hours after surgery
Secondary	Area under curve of pain intensity at rest at predefined timepoints.	Pain intensity is assessed with the numeric rating scale, an 11-point scale where 0=no pain and 10=the worst pain.	Up to 72 hours after surgery
Secondary	Area under curve of pain intensity with movement at predefined timepoints	Pain intensity is assessed with the numeric rating scale, an 11-point scale where 0=no pain and 10=the worst pain.	Up to 72 hours after surgery
Secondary	Quality of recovery at 24 hours and 72 hours after surgery.	Quality of recovery (QoR) is assessed with the QOR-15 scale, a 15-item scale that provides a global measure of postoperative recovery, with a score ranging from 0 (extremely poor QoR) to 150 (excellent QoR).	Up to 72 hours after surgery
Secondary	Time to first flatus after surgery.	Time to first flatus after surgery.	Up to 5 days after surgery.