Remimazolam and Postoperative Nausea and Vomiting in High-risk Patients

NCT04861337 | Completed Phase 4 DMC

• 1 other identifier: 2020-429
• Study Type: interventional
• Target: 552
• Locations: 1 country
• Sites: 10

Brief Summary

This trial aims to explore whether the intraoperative use of remimazolam can reduce the incidence of postoperative nausea and vomiting (PONV) in high-risk patients. According to the Apfel's simplified score, patients with 3 or more of the following factors are at high risk of postoperative nausea and vomiting (PONV), i.e., women, non-smokers, history of PONV, and postoperative use of opioids.

Conditions

Postoperative Nausea and Vomiting; Benzodiazepine; High-risk Patients

Keywords

Postoperative nausea and vomiting; Benzodiazepines; High-risk patients

Outcome Measures

Primary Outcomes (1)

• Incidence of postoperative nausea and vomiting (PONV) within 24 hours following surgery

  Nausea is diagnosed when the patient has gastrointestinal symptoms but does not vomit stomach contents. The severity of nausea is assessed using a digital subjective score scale (the scale ranges from 0 to 10, where 0 points represent no nausea, and 10 points represent the most severe nausea). Vomiting is diagnosed when the patient has gastrointestinal symptoms and retching or vomits gastric contents. Retching refers to the act of vomiting, but no stomach contents are vomited out.

  Up to 24 hours after surgery

Secondary Outcomes (6)

• Incidence of PONV within 48 hours after surgery

  Up to 48 hours after surgery

• Incidence of complications within 30 days after surgery

  Up to 30 days after surgery

• Subjective sleep quality score within 3 days after surgery

  Up to 3 days after surgery

• Incidence of emergence delirium (ED)

  Up to 30 minutes after surgery or during the stay in PACU

• Incidence of delirium within 3 days after surgery

  Up to 3 days after surgery

Other Outcomes (2)

• Incidence of intraoperative awareness

  Up to 24 hours after surgery

• Incidence of dreaming during general anesthesia

  Up to 24 hours after surgery

Study Arms (2)

Remimazolam Group

EXPERIMENTAL

Remimazolam infusion is initiated after induction of general anesthesia at a rate of 0.25 mg/kg/h and stopped 15 minutes before the end of surgery.

Drug: Remimazolam

Placebo Group

PLACEBO COMPARATOR

Placebo (0.9% saline) infusion is initiated after induction of general anesthesia at the same rate as in the remimazolam group and stopped 15 minutes before the end of surgery.

Drug: Placebo

Interventions

Remimazolam DRUG

Remimazolam is infused at a rate of 0.25 mg/kg/h from end of anesthesia induction until 15 minutes before the end of surgery.

Also known as: Remimazolam group

Remimazolam Group

Placebo DRUG

Normal saline is infused at a rate same as in the remimazolam group from end of anesthesia induction until 15 minutes before the end of surgery.

Also known as: Placebo group

Placebo Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years old;
• Scheduled to undergo elective surgery under general anesthesia;
• Judged to be at high risk of postoperative nausea and vomiting. According to the Apfel's simplified score, patients with 3 or more of the following factors are at high-risk: women, non-smokers, history of PONV, postoperative use of opioids.

You may not qualify if:

• Refuse to participate;
• Previous history of schizophrenia, epilepsy, Parkinson's disease or myasthenia gravis;
• Severe liver dysfunction (Child-Pugh class C);
• Severe renal dysfunction (dialysis required);
• Patients of the American Society of Anesthesiologists (ASA) grade 4 and above;
• Emergency surgery;
• Continuously taking benzodiazepines for more than 1 week before surgery;
• Any other circumstances that are considered unsuitable for study participation by attending physicians or investigators.

Sponsors & Collaborators

• Peking University First Hospital: lead

Study Sites (10)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

Beijing Hospital of the Ministry of Health

Beijing, Beijing Municipality, China

Location

Beijing YouAn Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Location

Fuwai Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Location

Tongji Hospital, Tongji Medical College of HUST

Wuhan, Hubei, China

Location

Wuhan Puai Hospital

Wuhan, Hubei, China

Location

Suzhou Municipal Hospital

Suzhou, Jiangsu, China

Location

Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, China

Location

Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

Hangzhou, Zhejiang, China

Location

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Location

Related Publications (18)

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• Gan TJ, Diemunsch P, Habib AS, Kovac A, Kranke P, Meyer TA, Watcha M, Chung F, Angus S, Apfel CC, Bergese SD, Candiotti KA, Chan MT, Davis PJ, Hooper VD, Lagoo-Deenadayalan S, Myles P, Nezat G, Philip BK, Tramer MR; Society for Ambulatory Anesthesia. Consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg. 2014 Jan;118(1):85-113. doi: 10.1213/ANE.0000000000000002.

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• Li CJ, Wang BJ, Mu DL, Hu J, Guo C, Li XY, Ma D, Wang DX. Randomized clinical trial of intraoperative dexmedetomidine to prevent delirium in the elderly undergoing major non-cardiac surgery. Br J Surg. 2020 Jan;107(2):e123-e132. doi: 10.1002/bjs.11354.

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• Joo J, Park S, Park HJ, Shin SY. Ramosetron versus ondansetron for postoperative nausea and vomiting in strabismus surgery patients. BMC Anesthesiol. 2016 Jul 22;16(1):41. doi: 10.1186/s12871-016-0210-5.

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• Pym A, Ben-Menachem E. The effect of a multifaceted postoperative nausea and vomiting reduction strategy on prophylaxis administration amongst higher-risk adult surgical patients. Anaesth Intensive Care. 2018 Mar;46(2):185-189. doi: 10.1177/0310057X1804600207.

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• Burkhardt T, Czorlich P, Mende KC, Treitz A, Kiefmann R, Westphal M, Schmidt NO. Postoperative Nausea and Vomiting Following Craniotomy: Risk Factors and Complications in Context of Perioperative High-dose Dexamethasone Application. J Neurol Surg A Cent Eur Neurosurg. 2019 Sep;80(5):381-386. doi: 10.1055/s-0039-1685194. Epub 2019 May 10.

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• de Boer HD, Detriche O, Forget P. Opioid-related side effects: Postoperative ileus, urinary retention, nausea and vomiting, and shivering. A review of the literature. Best Pract Res Clin Anaesthesiol. 2017 Dec;31(4):499-504. doi: 10.1016/j.bpa.2017.07.002. Epub 2017 Jul 8.

  PMID: 29739538 BACKGROUND

• Horn CC, Wallisch WJ, Homanics GE, Williams JP. Pathophysiological and neurochemical mechanisms of postoperative nausea and vomiting. Eur J Pharmacol. 2014 Jan 5;722:55-66. doi: 10.1016/j.ejphar.2013.10.037. Epub 2013 Oct 26.

  PMID: 24495419 BACKGROUND

• 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.

  PMID: 32467512 BACKGROUND

• Grant MC, Kim J, Page AJ, Hobson D, Wick E, Wu CL. The Effect of Intravenous Midazolam on Postoperative Nausea and Vomiting: A Meta-Analysis. Anesth Analg. 2016 Mar;122(3):656-663. doi: 10.1213/ANE.0000000000000941.

  PMID: 26332858 BACKGROUND

• Ahn EJ, Kang H, Choi GJ, Baek CW, Jung YH, Woo YC. The Effectiveness of Midazolam for Preventing Postoperative Nausea and Vomiting: A Systematic Review and Meta-Analysis. Anesth Analg. 2016 Mar;122(3):664-676. doi: 10.1213/ANE.0000000000001062.

  PMID: 26516802 BACKGROUND

• Barends CRM, Absalom AR, Struys MMRF. Drug selection for ambulatory procedural sedation. Curr Opin Anaesthesiol. 2018 Dec;31(6):673-678. doi: 10.1097/ACO.0000000000000652.

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• Horiguchi Y, Ohta N, Yamamoto S, Koide M, Fujino Y. Midazolam suppresses the lipopolysaccharide-stimulated immune responses of human macrophages via translocator protein signaling. Int Immunopharmacol. 2019 Jan;66:373-382. doi: 10.1016/j.intimp.2018.11.050. Epub 2018 Dec 5.

  PMID: 30530051 BACKGROUND

• Wesolowski AM, Zaccagnino MP, Malapero RJ, Kaye AD, Urman RD. Remimazolam: Pharmacologic Considerations and Clinical Role in Anesthesiology. Pharmacotherapy. 2016 Sep;36(9):1021-7. doi: 10.1002/phar.1806. Epub 2016 Sep 1.

  PMID: 27496519 BACKGROUND

• Brice DD, Hetherington RR, Utting JE. A simple study of awareness and dreaming during anaesthesia. Br J Anaesth. 1970 Jun;42(6):535-42. doi: 10.1093/bja/42.6.535. No abstract available.

  PMID: 5423844 BACKGROUND

• Hines S, Steels E, Chang A, Gibbons K. Aromatherapy for treatment of postoperative nausea and vomiting. Cochrane Database Syst Rev. 2018 Mar 10;3(3):CD007598. doi: 10.1002/14651858.CD007598.pub3.

  PMID: 29523018 BACKGROUND

MeSH Terms

Conditions

Postoperative Nausea and Vomiting

Interventions

remimazolam

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nausea; Signs and Symptoms, Digestive; Signs and Symptoms; Vomiting

Study Officials

• Dong-Xin Wang, MD, PhD

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 24, 2021
• First Posted: April 27, 2021
• Study Start: May 19, 2021
• Primary Completion: December 31, 2022
• Study Completion: April 22, 2023
• Last Updated: January 3, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (10)