Clinical trial: alvimopan for the management of post-operative ileus after abdominal surgery: results of an international randomized, double-blind, multicentre, placebo-controlled clinical study.
BACKGROUND
Post-operative ileus (POI) affects most patients undergoing abdominal surgery.


OBJECTIVE
To evaluate the effect of alvimopan, a peripherally acting mu-opioid receptor antagonist, on POI by negating the impact of opioids on gastrointestinal (GI) motility without affecting analgesia in patients outside North America.


METHODS
Adult subjects undergoing open abdominal surgery (n = 911) randomly received oral alvimopan 6 or 12 mg, or placebo, 2 h before, and twice daily following surgery. Opioids were administered as intravenous patient-controlled analgesia (PCA) or bolus injection. Time to recovery of GI function was assessed principally using composite endpoints in subjects undergoing bowel resection (n = 738).


RESULTS
A nonsignificant reduction in mean time to tolerate solid food and either first flatus or bowel movement (primary endpoint) was observed for both alvimopan 6 and 12 mg; 8.5 h (95% CI: 0.9, 16.0) and 4.8 h (95% CI: -3.2, 12.8), respectively. However, an exploratory post hoc analysis showed that alvimopan was more effective in the PCA (n = 317) group than in the non-PCA (n = 318) group. Alvimopan was well tolerated and did not reverse analgesia.


CONCLUSIONS
Although the significant clinical effect of alvimopan on reducing POI observed in previous trials was not reproduced, this trial suggests potential benefit in bowel resection patients who received PCA.
Büchler
M W
MW
Department of Surgery, University of Heidelberg, Heidelberg, Germany. markus.buechler@med.uni-heidelberg.de
Seiler
C M
CM
Monson
J R T
JR
Flamant
Y
Y
Thompson-Fawcett
M W
MW
Byrne
M M
MM
Mortensen
E R
ER
Altman
J F B
JF
Williamson
R
R
D000368:Aged; D003672:Defecation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D006801:Humans; D045823:Ileus / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D010147:Pain Measurement / Q000379:methods; D010880:Piperidines / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000188:drug therapy* / Q000601:surgery; D013272:Stomach Diseases / Q000188:drug therapy / Q000601:surgery*; D016896:Treatment Outcome
D009292:Narcotic Antagonists; D010880:Piperidines; C419502:alvimopan