title: Phase III trial of alvimopan, a novel, peripherally acting, mu opioid antagonist, for postoperative ileus after major abdominal surgery.
abstract: OBJECTIVE
  Postoperative ileus presents significant clinical challenges that potentially prolong hospital stay, contribute to readmission, and increase morbidity. There is no approved treatment for postoperative ileus. Alvimopan is a novel, peripherally acting, mu opioid receptor antagonist currently in development for the management of postoperative ileus.
  
  
  METHODS
  Patients undergoing partial colectomy or simple or radical hysterectomy were randomized to receive alvimopan 6 mg (n = 152), alvimopan 12 mg (n = 146), or placebo (n = 153) orally 2 hours before surgery and twice daily thereafter until discharge or for up to seven days. The primary efficacy end point, time to return of gastrointestinal function, was a composite measure of passage of flatus or stool and tolerating solid food. Secondary end points included time to the hospital discharge order written. Adverse events were monitored throughout the study.
  
  
  RESULTS
  Mean time to gastrointestinal recovery was significantly reduced in patients treated with alvimopan 6 mg vs. placebo (hazard ratio = 1.45; P = 0.003), with a smaller reduction seen with alvimopan 12 mg (hazard ratio = 1.28; P = 0.059). Mean time to the hospital discharge order written was significantly accelerated in patients treated with alvimopan 6 mg (hazard ratio = 1.50; P < 0.001). The most common treatment-emergent adverse events across all treatment groups were nausea, vomiting, and hypotension; the incidence of nausea and vomiting was reduced by 53 percent in the alvimopan 12-mg group.
  
  
  CONCLUSIONS
  In patients undergoing major abdominal surgery, alvimopan accelerated gastrointestinal recovery and time to the hospital discharge order written compared with placebo and was well tolerated.
authors.affiliation: Department of Colorectal Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
authors.forename: Conor P
authors.initials: CP
authors.lastname: Delaney
authors.forename: James L
authors.initials: JL
authors.lastname: Weese
authors.forename: Neil H
authors.initials: NH
authors.lastname: Hyman
authors.forename: Joel
authors.initials: J
authors.lastname: Bauer
authors.forename: Lee
authors.initials: L
authors.lastname: Techner
authors.forename: Kathie
authors.initials: K
authors.lastname: Gabriel
authors.forename: Wei
authors.initials: W
authors.lastname: Du
authors.forename: William K
authors.initials: WK
authors.lastname: Schmidt
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Wallin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003082:Colectomy / Q000009:adverse effects*; D004311:Double-Blind Method; D004435:Eating / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D005769:Gastrointestinal Motility / Q000502:physiology; D006801:Humans; D007044:Hysterectomy / Q000009:adverse effects*; D045823:Ileus / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*; D020127:Recovery of Function / Q000502:physiology; D014481:United States
chemical_list: D010880:Piperidines; D017450:Receptors, Opioid, mu; C419502:alvimopan