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

Aliment Pharmacol Ther. 2008 Aug 1;28(3):312-25. doi: 10.1111/j.1365-2036.2008.03696.x.

Abstract

Background: Post-operative ileus (POI) affects most patients undergoing abdominal surgery.

Aim: 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.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Defecation / drug effects
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Gastrointestinal Motility / drug effects
  • Humans
  • Ileus / drug therapy*
  • Ileus / surgery
  • Male
  • Middle Aged
  • Narcotic Antagonists / therapeutic use*
  • Pain Measurement / methods
  • Piperidines / therapeutic use*
  • Postoperative Complications / drug therapy*
  • Postoperative Complications / surgery
  • Stomach Diseases / drug therapy
  • Stomach Diseases / surgery*
  • Treatment Outcome

Substances

  • Narcotic Antagonists
  • Piperidines
  • alvimopan