Single-dose aprepitant vs ondansetron for the prevention of postoperative nausea and vomiting: a randomized, double-blind phase III trial in patients undergoing open abdominal surgery.
BACKGROUND
The neurokinin(1) antagonist aprepitant is effective for prevention of chemotherapy-induced nausea and vomiting. We compared aprepitant with ondansetron for prevention of postoperative nausea and vomiting.


METHODS
Nine hundred and twenty-two patients receiving general anaesthesia for major abdominal surgery were assigned to receive a single preoperative dose of oral aprepitant 40 mg, oral aprepitant 125 mg, or i.v. ondansetron 4 mg in a randomized, double-blind trial. Vomiting episodes, use of rescue therapy, and nausea severity (verbal rating scale) were documented for 48 h after surgery. Primary efficacy endpoints were complete response (no vomiting and no use of rescue therapy) 0-24 h after surgery and no vomiting 0-24 h after surgery. The secondary endpoint was no vomiting 0-48 h after surgery.


RESULTS
Aprepitant at both doses was non-inferior to ondansetron for complete response 0-24 h after surgery (64% for aprepitant 40 mg, 63% for aprepitant 125 mg, and 55% for ondansetron, lower bound of 1-sided 95% CI > 0.65), superior to ondansetron for no vomiting 0-24 h after surgery (84% for aprepitant 40 mg, 86% for aprepitant 125 mg, and 71% for ondansetron; P < 0.001), and superior for no vomiting 0-48 h after surgery (82% for aprepitant, 40 mg, 85% for aprepitant, 125 mg, and 66% for ondansetron; P < 0.001). The distribution of peak nausea scores was lower in both aprepitant groups vs ondansetron (P < 0.05).


CONCLUSIONS
Aprepitant was non-inferior to ondansetron in achieving complete response for 24 h after surgery. Aprepitant was significantly more effective than ondansetron for preventing vomiting at 24 and 48 h after surgery, and in reducing nausea severity in the first 48 h after surgery. Aprepitant was generally well tolerated.
Diemunsch
P
P
Services d'Anesthesiologie-Reanimation Chirurgicale, CHU, Hôpital de Hautepierre, 1 Avenue de Moliere, Strasbourg 67000, France. pierre.diemunsch@chru-strasbourg.fr
Gan
T J
TJ
Philip
B K
BK
Girao
M J
MJ
Eberhart
L
L
Irwin
M G
MG
Pueyo
J
J
Chelly
J E
JE
Carides
A D
AD
Reiss
T
T
Evans
J K
JK
Lawson
F C
FC
D000005:Abdomen / Q000601:surgery*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000932:Antiemetics / Q000008:administration & dosage / Q000627:therapeutic use*; D000077608:Aprepitant; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000627:therapeutic use*; D017294:Ondansetron / Q000627:therapeutic use*; D020250:Postoperative Nausea and Vomiting / Q000517:prevention & control*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000932:Antiemetics; D009025:Morpholines; D000077608:Aprepitant; D017294:Ondansetron