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
Author(s): Singla NK, Singla SK, Chung F, Kutsogiannis DJ, Blackburn L, Lane SR, Levin J,
Johnson B, Pergolizzi JV Jr.
Affiliation(s): Lotus Clinical Research Inc, Huntington Hospital, Pasadena, California 91105,
Publication date & source: 2010, Anesthesiology. , 113(1):74-82
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
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.