Tong J Gan1, 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. 1. From the Department of Anesthesiology, Stony Brook University Medical Center, Stony Brook, New York (T.J.G.); Department of Anaesthesia and Critical Care, University Hospitals of Würzburg, Würzburg, Germany (P.K.); Department of Anesthesiology, Memorial Hermann Memorial City Hospital, Houston, Texas (H.S.M.); Department of Anesthesiology, Wexner Medical Center at The Ohio State University, Columbus, Ohio (S.D.B.); Department of Anesthesiology, Universitätsklinikum Heidelberg, Heidelberg, Germany (J.M.); Department of Anaesthesiology and Intensive Care, Philipps University Marburg, Marburg, Germany (L.E.); Department of Anesthesiology, Christus St John Hospital, Nassau Bay, Texas (D.G.L.); Department of Anesthesiology, Helen Keller Hospital, Sheffield, Alabama (T.I.M.); Service d'Anesthésie, Hôpital Mère Enfant, Bron, France (D.C.); Department of Anesthesiology, University of Kansas Medical Center, Kansas City, Kansas (A.L.K.); Department of Anesthesiology, Pain Management and Perioperative Medicine, University of Miami, Miller School of Medicine, Miami, Florida (K.A.C.); Clinical Development Department, Acacia Pharma Ltd, Cambridge, United Kingdom (G.F.); and Department of Anesthesiology and Intensive Care, University Hospital of Hautepierre, Strasbourg, France (P.D.).
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.
RCT Entities:
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.
Authors: Stephanie Weibel; Gerta Rücker; Leopold Hj Eberhart; Nathan L Pace; Hannah M Hartl; Olivia L Jordan; Debora Mayer; Manuel Riemer; Maximilian S Schaefer; Diana Raj; Insa Backhaus; Antonia Helf; Tobias Schlesinger; Peter Kienbaum; Peter Kranke Journal: Cochrane Database Syst Rev Date: 2020-10-19