• Aron Altorjay, Timothy Melson, Thitima Chinachoit, Attila Kett, Keith Aqua, Jeremey Levin, Linda M Blackburn, Steve Lane, and Joseph V Pergolizzi.
• Department of Surgery, St. George University Teaching Hospital, Székesfehérvár, Hungary.
• Arch Surg. 2011 Feb 1;146(2):201-6.

HypothesisPostoperative 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.DesignA 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.SettingForty-three centers in 11 countries.PatientsWe studied 484 women at high risk for developing PONV scheduled to undergo operations associated with high emetogenic risk.InterventionsThe 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 MeasuresThe 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.ResultsBetween 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.ConclusionsThe 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 clinicaltrials.gov Identifier: NCT00326248.

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