title: Casopitant and ondansetron for postoperative nausea and vomiting prevention in women at high risk for emesis: a phase 3 study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Forty-three centers in 11 countries.
  
  
  METHODS
  We studied 484 women at high risk for developing PONV scheduled to undergo operations associated with high emetogenic risk.
  
  
  METHODS
  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.
  
  
  METHODS
  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 clinicaltrials.gov Identifier: NCT00326248.
authors.affiliation: Department of Surgery, St. George University Teaching Hospital, Székesfehérvár, Hungary.
authors.forename: Aron
authors.initials: A
authors.lastname: Altorjay
authors.forename: Timothy
authors.initials: T
authors.lastname: Melson
authors.forename: Thitima
authors.initials: T
authors.lastname: Chinachoit
authors.forename: Attila
authors.initials: A
authors.lastname: Kett
authors.forename: Keith
authors.initials: K
authors.lastname: Aqua
authors.forename: Jeremey
authors.initials: J
authors.lastname: Levin
authors.forename: Linda M
authors.initials: LM
authors.lastname: Blackburn
authors.forename: Steve
authors.initials: S
authors.lastname: Lane
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Pergolizzi
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000932:Antiemetics / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007275:Injections, Intravenous; D008875:Middle Aged; D064729:Neurokinin-1 Receptor Antagonists; D017294:Ondansetron / Q000008:administration & dosage / Q000627:therapeutic use*; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D010880:Piperidines / Q000008:administration & dosage / Q000627:therapeutic use*; D011182:Postoperative Care; D020250:Postoperative Nausea and Vomiting / Q000453:epidemiology / Q000517:prevention & control*; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D055815:Young Adult; D014508:Urea
chemical_list: D000932:Antiemetics; D064729:Neurokinin-1 Receptor Antagonists; D017294:Ondansetron; D010879:Piperazines; D010880:Piperidines; C531951:casopitant; D014508:Urea