title: Intravenous Amisulpride for the Prevention of Postoperative Nausea and Vomiting: Two Concurrent, Randomized, Double-blind, Placebo-controlled Trials.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: 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.).
authors.forename: Tong J
authors.initials: TJ
authors.lastname: Gan
authors.forename: Peter
authors.initials: P
authors.lastname: Kranke
authors.forename: Harold S
authors.initials: HS
authors.lastname: Minkowitz
authors.forename: Sergio D
authors.initials: SD
authors.lastname: Bergese
authors.forename: Johann
authors.initials: J
authors.lastname: Motsch
authors.forename: Leopold
authors.initials: L
authors.lastname: Eberhart
authors.forename: David G
authors.initials: DG
authors.lastname: Leiman
authors.forename: Timothy I
authors.initials: TI
authors.lastname: Melson
authors.forename: Dominique
authors.initials: D
authors.lastname: Chassard
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Kovac
authors.forename: Keith A
authors.initials: KA
authors.lastname: Candiotti
authors.forename: Gabriel
authors.initials: G
authors.lastname: Fox
authors.forename: Pierre
authors.initials: P
authors.lastname: Diemunsch
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077582:Amisulpride; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D020250:Postoperative Nausea and Vomiting / Q000517:prevention & control*; D013469:Sulpiride / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018492:Dopamine Antagonists; D013469:Sulpiride; D000077582:Amisulpride