Casopitant and ondansetron for postoperative nausea and vomiting prevention in women at high risk for emesis: a phase 3 study

Arch Surg. 2011 Feb;146(2):201-6. doi: 10.1001/archsurg.2010.327.


Hypothesis: Postoperative nausea and vomiting (PONV) are associated with a variety of complications. Neurokinin subtype 1 receptor antagonists have antiemetic activity in the postoperative setting, and the neurokinin subtype 1 receptor antagonist casopitant mesylate (GW679769) was well tolerated and effective at reducing the incidence of PONV in phase 1 and phase 2 trials.

Design: A multicenter, randomized, double-blind, parallel-group, phase 3 analysis was designed to evaluate the safety and efficacy of casopitant in combination with a single intravenous dose of the serotonin subtype 3 receptor antagonist ondansetron hydrochloride for the prevention of PONV in the perioperative setting.

Setting: Forty-three centers in 11 countries.

Patients: We studied 484 women at high risk for developing PONV scheduled to undergo operations associated with high emetogenic risk.

Interventions: The women were randomized to receive a single dose of intravenous ondansetron, 4 mg, or oral casopitant, 50 mg, in combination with intravenous ondansetron, 4 mg.

Main outcome measures: The primary end point was the proportion of patients who achieved a complete response, defined as no vomiting, retching, or rescue therapy. Patients received a balanced anesthetic regimen.

Results: Between March 20 and August 31, 2006, 484 patients were enrolled in the study. Patients in the casopitant plus ondansetron group had a 68.7% rate of complete response during the first 24 hours after surgery compared with 58.7% in the ondansetron-only group (P = .03). The difference between groups in complete response from 24 to 48 hours (63.4% with ondansetron only vs 70.0% with ondansetron plus casopitant) was not significant. No vomiting for 0 to 24 hours was observed in 89.7% of the casopitant plus ondansetron group compared with 74.9% of the ondansetron-only group (P < .001). Oral casopitant administered in combination with ondansetron was well tolerated.

Conclusions: The results of this pivotal phase 3 study demonstrate that the combination of casopitant and ondansetron was superior to ondansetron only in patients at high risk for PONV. Trial Registration Identifier: NCT00326248.

Publication types

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

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antiemetics / administration & dosage
  • Antiemetics / therapeutic use*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Injections, Intravenous
  • Middle Aged
  • Neurokinin-1 Receptor Antagonists
  • Ondansetron / administration & dosage
  • Ondansetron / therapeutic use*
  • Piperazines / administration & dosage
  • Piperazines / therapeutic use*
  • Piperidines / administration & dosage
  • Piperidines / therapeutic use*
  • Postoperative Care
  • Postoperative Nausea and Vomiting / epidemiology
  • Postoperative Nausea and Vomiting / prevention & control*
  • Retrospective Studies
  • Risk Factors
  • Treatment Outcome
  • United States / epidemiology
  • Young Adult


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

Associated data