Phase II study to evaluate the safety and efficacy of the oral neurokinin-1 receptor antagonist casopitant (GW679769) administered with ondansetron for the prevention of postoperative and postdischarge nausea and vomiting in high-risk patients

Anesthesiology. 2010 Jul;113(1):74-82. doi: 10.1097/ALN.0b013e3181d7b13a.

Abstract

Background: In recent years, there has been an increased interest in using a multimodal approach with combined agents to treat postoperative nausea and vomiting. This study evaluated whether the addition of an oral dose of the neurokinin-1 receptor antagonist casopitant improved the antiemetic efficacy of an intravenous dose of ondansetron hydrochloride.

Methods: The authors enrolled 702 premenopausal or perimenopausal, nonsmoking, female patients aged 18-55 yr with a history of postoperative nausea and vomiting and/or motion sickness undergoing a laparoscopic or laparotomic gynecologic surgical procedure or laparoscopic cholecystectomy with general anesthesia. Subjects were randomized to one of five treatment arms: standard ondansetron 4 mg with casopitant at 0, 50, 100, or 150 mg, or 0 mg ondansetron with casopitant at 150 mg (the latter arm was considered an exploratory study group and was included in the safety analysis but not in the efficacy analysis).

Results: A significantly greater proportion of patients in all of the active casopitant plus ondansetron groups achieved a complete response (i.e., no vomiting, retching, rescue medication, or premature withdrawal) during the first 24 h postoperatively versus those in the ondansetron-alone group (59-62% vs. 40%, respectively; P = 0.0006). All active doses seemed to be well tolerated; headache, dizziness, and constipation were the most frequently reported adverse events.

Conclusions: Compared with ondansetron alone, the casopitant and ondansetron combination results in superior emesis prevention during the first 24 h postoperatively in female patients with known risk factors for postoperative nausea and vomiting.

Trial registration: ClinicalTrials.gov NCT00108095.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Anesthesia, General / methods
  • Antiemetics / administration & dosage*
  • Antiemetics / adverse effects
  • Cholecystectomy, Laparoscopic
  • Constipation / chemically induced
  • Dizziness / chemically induced
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Gynecologic Surgical Procedures
  • Headache / chemically induced
  • Humans
  • Middle Aged
  • Neurokinin-1 Receptor Antagonists*
  • Ondansetron / administration & dosage*
  • Piperazines / administration & dosage*
  • Piperazines / adverse effects
  • Piperidines / administration & dosage*
  • Piperidines / adverse effects
  • Postoperative Nausea and Vomiting / prevention & control*
  • Risk Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Antiemetics
  • Neurokinin-1 Receptor Antagonists
  • Piperazines
  • Piperidines
  • casopitant
  • Ondansetron

Associated data

  • ClinicalTrials.gov/NCT00108095