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

• Published in: British journal of anaesthesia : BJA Vol. 99; no. 2; pp. 202 - 211
• Main Authors: Diemunsch, P., Gan, T.J., Philip, B.K., Girao, M.J., Eberhart, L., Irwin, M.G., Pueyo, J., Chelly, J.E., Carides, A.D., Reiss, T., Evans, J.K., Lawson, F.C.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-08-2007; Oxford University Press; Oxford Publishing Limited (England)
• Subjects: Abdomen - surgery; Adolescent; Adult; Aged; Aged, 80 and over; Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; antagonism; Antiemetics - administration & dosage; Antiemetics - therapeutic use; aprepitant; Biological and medical sciences; clinical trials; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Medical sciences; Middle Aged; Morpholines - administration & dosage; Morpholines - therapeutic use; ondansetron; Ondansetron - therapeutic use; PONV; Postoperative Nausea and Vomiting - prevention & control; serotonin (5-hydroxy-tryptamine); serotonin (5-hydroxy-tryptamine), antagonism; Severity of Illness Index; Treatment Outcome; aprepitant; PONV; clinical trials; serotonin (5-hydroxy-tryptamine), antagonism; ondansetron; Aprepitant; Phase III trial; Human; Postoperative; NK1 Tachykinin receptor; Tryptamine; Serotonin; antagonism; Serotonin antagonist; Single dose; Nausea; Prevention; aprepitant; clinical trials; PONV; ondansetron; serotonin (5-hydroxy-tryptamine); Vomiting; 5-HT3 Serotonine receptor; Surgery; Neurotransmitter; Digestive diseases; Anesthesia; Antiemetic; Ondansetron
• ISSN: 0007-0912; 1471-6771
• DOI: 10.1093/bja/aem133

The neurokinin1 antagonist aprepitant is effective for prevention of chemotherapy-induced nausea and vomiting. We compared aprepitant with ondansetron for prevention of postoperative nausea and vomiting.
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.
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).
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.