Alvimopan, a peripherally acting mu-opioid receptor antagonist, compared with placebo in postoperative ileus after major abdominal surgery: results of a randomized, double-blind, controlled study.
BACKGROUND
Alvimopan is a peripherally acting mu-opioid receptor (PAM-OR) antagonist for accelerating gastrointestinal recovery after surgery.


METHODS
Patients undergoing open laparotomy (bowel resection, n = 418; hysterectomy, n = 197) were randomized to receive alvimopan 6 or 12 mg or placebo orally > or = 2 h before surgery and then b.i.d. until hospital discharge (up to 7 days). The primary efficacy endpoint was time to gastrointestinal (GI) recovery (measured by toleration of solid food and passage of flatus/stool; GI-3). Secondary endpoints included time to GI-2 recovery (toleration of solid food and passage of stool) and hospital discharge order written (DCO).


RESULTS
Alvimopan did not significantly accelerate GI-3 compared with placebo [6 mg: hazard ratio (HR) = 1.20, p = 0.080; 12 mg: HR = 1.24, p = 0.038). However, after adjustment for significant covariates (sex/surgical duration), benefits were significant for both doses (6 mg: HR = 1.24, p = 0.037; 12 mg: HR = 1.26, p = 0.028). Alvimopan also significantly accelerated time to GI-2 (6 mg: HR = 1.37, p = 0.008; 12 mg: HR = 1.33, p = 0.018) and DCO (6 mg: HR = 1.31, p = 0.008; 12 mg: HR = 1.28, p = 0.015). Adverse events were similar between groups.


CONCLUSIONS
Alvimopan (6 or 12 mg) accelerates GI recovery and is well tolerated in patients undergoing open laparotomy.
Viscusi
E R
ER
Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107-5092, USA. eugene.viscusi@jefferson.edu
Goldstein
S
S
Witkowski
T
T
Andonakakis
A
A
Jan
R
R
Gabriel
K
K
Du
W
W
Techner
L
L
Wallin
B
B
D000005:Abdomen / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D041981:Gastrointestinal Tract / Q000503:physiopathology; D006801:Humans; D007044:Hysterectomy / Q000009:adverse effects*; D045823:Ileus / Q000188:drug therapy* / Q000209:etiology*; D007813:Laparotomy / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy / Q000503:physiopathology; D010388:Pelvis / Q000601:surgery; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*; D020127:Recovery of Function; D016019:Survival Analysis; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D010880:Piperidines; D017450:Receptors, Opioid, mu; C419502:alvimopan