Alvimopan, a novel, peripherally acting mu opioid antagonist: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial of major abdominal surgery and postoperative ileus.

Abstract

OBJECTIVE:

To demonstrate that alvimopan (6 or 12 mg) accelerates recovery of gastrointestinal (GI) function in patients undergoing laparotomy for bowel resection or radical hysterectomy.

SUMMARY BACKGROUND DATA:

Postoperative ileus (POI) following laparotomy may increase morbidity and extend hospitalization. Opioids can contribute to the duration of POI. Alvimopan is a novel opioid receptor antagonist in development for the management of POI.

METHODS:

A total of 510 patients scheduled for bowel resection or radical hysterectomy were randomized (1:1:1) to receive alvimopan 6 mg, alvimopan 12 mg, or placebo orally > or =2 hours before surgery, then twice a day (b.i.d.) until hospital discharge or for up to 7 days. The primary efficacy end point was a composite of time to recovery of upper and lower GI function. An associated secondary end point was time to hospital discharge order written.

RESULTS:

The modified intent-to-treat population included 469 patients (451 bowel resection and 18 radical hysterectomy patients). Time to recovery of GI function was accelerated for the alvimopan 6 mg (hazard ratio [HR] = 1.28; P < 0.05) and 12 mg (HR = 1.54; P < 0.001) groups with a mean difference of 15 and 22 hours, respectively, compared with placebo. The time to hospital discharge order written was also accelerated in the alvimopan 12 mg group (HR = 1.42; P = 0.003) with a mean difference of 20 hours compared with placebo. The incidence of adverse events was similar among treatment groups.

CONCLUSIONS:

Alvimopan accelerated GI recovery and time to hospital discharge order written compared with placebo in patients undergoing laparotomy and was well tolerated.

• Authors: Bruce G Wolff, Fabrizio Michelassi, Todd M Gerkin, Lee Techner, Kathie Gabriel, Wei Du, Bruce A Wallin, Alvimopan Postoperative Ileus Study Group
• Journal: Annals of surgery (Ann Surg) Vol. 240 Issue 4 Pg. 728-34; discussion 734-5 (Oct 2004) ISSN: 0003-4932 [Print] United States
• PMID: 15383800 (Publication Type: Clinical Trial, Clinical Trial, Phase III, Comparative Study, Journal Article, Meta-Analysis, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Gastrointestinal Agents
• Piperidines
• Placebos
• Receptors, Opioid, mu
• alvimopan

Topics

• Adult
• Aged
• Aged, 80 and over
• Defecation (physiology)
• Double-Blind Method
• Female
• Gastrointestinal Agents (therapeutic use)
• Humans
• Hysterectomy
• Ileus (drug therapy)
• Intestine, Large (surgery)
• Intestine, Small (surgery)
• Laparotomy
• Male
• Middle Aged
• Patient Discharge
• Piperidines (therapeutic use)
• Placebos
• Postoperative Complications (drug therapy)
• Premedication
• Receptors, Opioid, mu (antagonists & inhibitors)
• Recovery of Function (physiology)
• Time Factors