Effect of Oliceridine Analgesia on Postoperative Nause and Vomiting

NCT ID: NCT06411665

Last Updated: 2024-10-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

252 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-07-02

Study Completion Date

2026-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Postoperative Nausea and Vomiting

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

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Oliceridine group

Patient-controlled analgesia pump is provided immediately after surgery. The pump is established with oliceridine 15 mg, diluted with normal saline to 100 ml, and programmed to deliver 2-ml boluses with a 10-min lockout interval and a background infusion rate at 1 ml/h. The pump will be used during the first 3 days after surgery.

Group Type EXPERIMENTAL

Oliceridine

Intervention Type DRUG

Patient-controlled intravenous analgesia with oliceridine for up to 3 days after surgery.

Morphine group

Patient-controlled analgesia pump is provided immediately after surgery. The pump is established with morphine 50 mg, diluted with normal saline to 100 ml, and programmed to deliver 2-ml boluses with a 10-min lockout interval and a background infusion rate at 1 ml/h. The pump will be used during the first 3 days after surgery.

Group Type ACTIVE_COMPARATOR

Morphine

Intervention Type DRUG

Patient-controlled intravenous analgesia with morphine for up to 3 days after surgery.

Interventions

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Oliceridine

Patient-controlled intravenous analgesia with oliceridine for up to 3 days after surgery.

Intervention Type DRUG

Morphine

Patient-controlled intravenous analgesia with morphine for up to 3 days after surgery.

Intervention Type DRUG

Other Intervention Names

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Oliceridine for injection Morphine for injection

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Peking University First Hospital

OTHER

Sponsor Role lead

Responsible Party

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Dong-Xin Wang

Chairman of Department of Anesthesiology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Dong-Xin Wang, PHD

Role: STUDY_DIRECTOR

Peking University First Hospital

Locations

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Dong-Xin Wang

Beijing, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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Xue Li, M.D.

Role: CONTACT

+8618810527114

Dong-Xin Wang, M.D.

Role: CONTACT

+86 010-83572784

Facility Contacts

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Xue Li

Role: primary

+8618810527114

References

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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/bioengineering10101152.

Reference Type RESULT
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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: 10.1136/bmj.j1455.

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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 (Lausanne). 2023 Feb 22;14:1102017. doi: 10.3389/fendo.2023.1102017. eCollection 2023.

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Reference Type RESULT
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Reference Type RESULT
PMID: 16846542 (View on PubMed)

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 Guidelines for the Management of Postoperative Nausea and Vomiting. Anesth Analg. 2020 Aug;131(2):411-448. doi: 10.1213/ANE.0000000000004833.

Reference Type RESULT
PMID: 32467512 (View on PubMed)

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.

Reference Type RESULT
PMID: 31567573 (View on PubMed)

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.

Reference Type RESULT
PMID: 37556070 (View on PubMed)

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Reference Type RESULT
PMID: 24157979 (View on PubMed)

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 dysfunction compared with morphine. J Pharmacol Exp Ther. 2013 Mar;344(3):708-17. doi: 10.1124/jpet.112.201616. Epub 2013 Jan 8.

Reference Type RESULT
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Reference Type RESULT
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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 Management of Moderate to Severe Acute Pain Following Abdominoplasty. Pain Pract. 2019 Sep;19(7):715-731. doi: 10.1111/papr.12801. Epub 2019 Jun 24.

Reference Type RESULT
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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-to-severe acute pain following bunionectomy. J Pain Res. 2019 Mar 11;12:927-943. doi: 10.2147/JPR.S171013. eCollection 2019.

Reference Type RESULT
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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 Controlled Trials. Pain Ther. 2021 Dec;10(2):1343-1353. doi: 10.1007/s40122-021-00299-0. Epub 2021 Aug 5.

Reference Type RESULT
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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 Randomized Placebo and Active Controlled Trials. Pain Ther. 2021 Jun;10(1):401-413. doi: 10.1007/s40122-020-00216-x. Epub 2020 Nov 18.

Reference Type RESULT
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Reference Type RESULT
PMID: 37927993 (View on PubMed)

Other Identifiers

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2024-073

Identifier Type: -

Identifier Source: org_study_id

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