Phase III trial of alvimopan, a novel, peripherally acting, mu opioid antagonist, for postoperative ileus after major abdominal surgery.
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.
Delaney
Conor P
CP
Department of Colorectal Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Weese
James L
JL
Hyman
Neil H
NH
Bauer
Joel
J
Techner
Lee
L
Gabriel
Kathie
K
Du
Wei
W
Schmidt
William K
WK
Wallin
Bruce A
BA
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
D010880:Piperidines; D017450:Receptors, Opioid, mu; C419502:alvimopan