Intravenous Amisulpride for the Prevention of Postoperative Nausea and Vomiting: Two Concurrent, Randomized, Double-blind, Placebo-controlled Trials

Tong J. Gan, Peter Kranke, Harold S. Minkowitz, Sergio D. Bergese, Johann Motsch, Leopold Eberhart, David G. Leiman, Timothy I. Melson, Dominique Chassard, Anthony L. Kovac, Keith A Candiotti, Gabriel Fox, Pierre Diemunsch

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17 Scopus citations

Abstract

Background: Two essentially identical, randomized, double-blind, placebo-controlled, parallel-group phase III studies evaluated the efficacy of intravenous amisulpride, a dopamine D2/D3 antagonist, in the prevention of postoperative nausea and vomiting in adult surgical patients. Methods: Adult inpatients undergoing elective surgery during general anesthesia and having at least two of the four Apfel risk factors for postoperative nausea and vomiting were enrolled at 9 U.S. and 10 European sites. A single 5-mg dose of amisulpride or matching placebo was given at induction of anesthesia. The primary endpoint was complete response, defined as no vomiting/retching and no use of antiemetic rescue medication in the 24-h postoperative period. Nausea incidence was a secondary endpoint. Results: Across the two studies, 689 patients were randomized and dosed with study medication, of whom 626 were evaluable per protocol. In the U.S. study, 46.9% (95% CI, 39.0 to 54.9) of patients achieved complete response in the amisulpride group compared to 33.8% (95% CI, 26.2 to 42.0) in the placebo group (P = 0.026). In the European study, complete response rates were 57.4% (95% CI, 49.2 to 65.3) for amisulpride and 46.6% (95% CI, 38.8 to 54.6) for placebo (P = 0.070). Nausea occurred less often in patients who received amisulpride than those who received placebo. There was no clinically significant difference in the safety profile of amisulpride and placebo; in particular, there were no differences in terms of QT prolongation, extrapyramidal side effects, or sedation. Conclusions: One of the two trials demonstrated superiority, while pooling both in a post hoc change to the plan of analysis supported the hypothesis that amisulpride was safe and superior to placebo in reducing the incidence of postoperative nausea and vomiting in a population of adult inpatients at moderate to high risk of postoperative nausea and vomiting.

Original languageEnglish (US)
Pages (from-to)268-275
Number of pages8
JournalAnesthesiology
Volume126
Issue number2
DOIs
StatePublished - Feb 1 2017

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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    Gan, T. J., Kranke, P., Minkowitz, H. S., Bergese, S. D., Motsch, J., Eberhart, L., Leiman, D. G., Melson, T. I., Chassard, D., Kovac, A. L., Candiotti, K. A., Fox, G., & Diemunsch, P. (2017). Intravenous Amisulpride for the Prevention of Postoperative Nausea and Vomiting: Two Concurrent, Randomized, Double-blind, Placebo-controlled Trials. Anesthesiology, 126(2), 268-275. https://doi.org/10.1097/ALN.0000000000001458