Casopitant and Ondansetron for Postoperative Nausea and Vomiting Prevention in Women at High Risk for Emesis: A Phase 3 Study | Surgery | JAMA Surgery | JAMA Network
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Original Article
February 2011February 21, 2011

Casopitant and Ondansetron for Postoperative Nausea and Vomiting Prevention in Women at High Risk for Emesis: A Phase 3 Study

Author Affiliations

Author Affiliations: Department of Surgery, St. George University Teaching Hospital, Sz[[eacute]]kesfeh[[eacute]]rv[[aacute]]r, Hungary (Dr Altorjay); Department of Anesthesia, Helen Keller Hospital, Sheffield, Alabama (Dr Melson); Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand (Dr Chinachoit); Department of Anesthesiology, Saint Peter's University Hospital, New Brunswick, New Jersey (Dr Kett); Visions Clinical Research, Boynton Beach, Florida (Dr Aqua); Oncology Medicines Development, GlaxoSmithKline plc, Collegeville, Pennsylvania (Dr Levin, Ms Blackburn, and Mr Lane); and Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, and Department of Anesthesiology and Pain Medicine, Georgetown University School of Medicine, Washington, DC (Dr Pergolizzi).

Arch Surg. 2011;146(2):201-206. 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