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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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

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Postoperative Nausea and Vomiting
Placebos
Nausea
Inpatients
Antiemetics
Incidence
sultopride
Postoperative Period
General Anesthesia
Vomiting
Anesthesia
Safety
Population

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Intravenous Amisulpride for the Prevention of Postoperative Nausea and Vomiting : Two Concurrent, Randomized, Double-blind, Placebo-controlled Trials. / Gan, Tong J.; Kranke, Peter; Minkowitz, Harold S.; Bergese, Sergio D.; Motsch, Johann; Eberhart, Leopold; Leiman, David G.; Melson, Timothy I.; Chassard, Dominique; Kovac, Anthony L.; Candiotti, Keith A; Fox, Gabriel; Diemunsch, Pierre.

In: Anesthesiology, Vol. 126, No. 2, 01.02.2017, p. 268-275.

Research output: Contribution to journalArticle

Gan, TJ, Kranke, P, Minkowitz, HS, Bergese, SD, Motsch, J, Eberhart, L, Leiman, DG, Melson, TI, Chassard, D, Kovac, AL, Candiotti, KA, Fox, G & Diemunsch, P 2017, 'Intravenous Amisulpride for the Prevention of Postoperative Nausea and Vomiting: Two Concurrent, Randomized, Double-blind, Placebo-controlled Trials', Anesthesiology, vol. 126, no. 2, pp. 268-275. https://doi.org/10.1097/ALN.0000000000001458
Gan, Tong J. ; Kranke, Peter ; Minkowitz, Harold S. ; Bergese, Sergio D. ; Motsch, Johann ; Eberhart, Leopold ; Leiman, David G. ; Melson, Timothy I. ; Chassard, Dominique ; Kovac, Anthony L. ; Candiotti, Keith A ; Fox, Gabriel ; Diemunsch, Pierre. / Intravenous Amisulpride for the Prevention of Postoperative Nausea and Vomiting : Two Concurrent, Randomized, Double-blind, Placebo-controlled Trials. In: Anesthesiology. 2017 ; Vol. 126, No. 2. pp. 268-275.
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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.",
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AU - Minkowitz, Harold S.

AU - Bergese, Sergio D.

AU - Motsch, Johann

AU - Eberhart, Leopold

AU - Leiman, David G.

AU - Melson, Timothy I.

AU - Chassard, Dominique

AU - Kovac, Anthony L.

AU - Candiotti, Keith A

AU - Fox, Gabriel

AU - Diemunsch, Pierre

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