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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

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An Erratum to this article was published on 14 February 2006

Abstract

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 ≥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.

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Acknowledgments

Grateful appreciation is extended to Jeanne Fisher and Jennifer Lessin, clinical nurse coordinators. Their assistance made this study possible.

The following investigators and institutions participated in the Alvimopan Postoperative Ileus Study Group for study 14CL308 (listed alphabetically by last name of the PIs):

Paul Baron, Discovery Alliance, Inc., Mt. Pleasant, SC, USA

James Barone, The Stamford Hospital, Stamford, CT, USA

Maria Bell, South Dakota Health Research Foundation, Sioux Falls, SD, USA

Eric Bieber, Geisinger Medical Center, Danville, PA, USA

Lance Bruck, Jacobi Medical Center, Bronx, NY, USA

Thomas Cataldo, Cooper Health System/University Medical Center, Camden, NJ, USA

Gene Coppa, Staten Island University Hospital, Staten Island, NY, USA

Daniel Dempsey, Temple University Hospital, Philadelphia, PA, USA

Daniel Dent, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

Samir Fakhry, INOVA Fairfax Hospital, Falls Church, VA, USA

Linda Farkas, UPMC Cancer Pavilion, Pittsburgh, PA, USA

Stephanie Fine, West Jordan, UT, USA

Philip Fleshner, Cedars-Sinai Medical Center, Los Angeles, CA, USA

Susan Galandiuk, University of Louisville, Louisville, KY, USA

Gary Gecelter, North Shore–Long Island Jewish Health System, New Hyde Park, NY, USA

Bimal Ghosh, New York Harbor Healthcare System–Brooklyn Campus, Brooklyn, NY, USA

Matthew Indeck, Geisinger Medical Center, Danville, PA, USA

Ivan Kangrga, Washington University Medical Center, St. Louis, MO, USA

Andrea Kurz, Washington University Medical Center, St. Louis, MO, USA

Edward Lee, Albany Medical College, Albany, NY, USA

Warren Lichliter, Sammons Cancer Center, Dallas, TX, USA

Kirk Ludwig, Duke University Medical Center, Durham, NC, USA

Robert Martindale, Medical College of Georgia, Augusta, GA, USA

Martin McCarter, Denver, CO, USA

Fabrizio Michelasi, University of Chicago Medical Center, Chicago, IL, USA

Brent Miedema, Columbia, MO, USA

Deborah Nagle, Graduate Hospital, Philadelphia, PA, USA

Mark Pello, Cooper Health System, Camden, NJ, USA

Alexander Pue, Sharp Mary Birch Hospital for Women, San Diego, CA, USA

Jebadurai Ratnaraj, Washington University Medical Center, St. Louis, MO, USA

Thanjuvar Ravikumar, Montefiore Medical Center, Bronx, NY, USA

Harry Reynolds, University Hospitals of Cleveland, Cleveland, OH, USA

Steven Schechter, Rhode Island Colorectal Clinic, Providence, RI, USA

Kurt Stockamp, Pensacola, FL, USA

Anthony Vernava, Colon/Rectal Surgery, Cleveland Clinic, Naples, FL, USA

Eugene Viscusi, Thomas Jefferson University Hospitals, Philadelphia, PA, USA

Harry Wasvary, Oakland Colon and Rectal Associates, Royal Oaks, MI, USA

Carl Westcott, Wake Forest University School of Medicine, Winston-Salem, NC, USA

Steven Wexner, Cleveland Clinic, Weston, FL, USA

Sherry Wren, Palo Alto Veterans Health Care System, Palo Alto, CA, USA

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Correspondence to E. R. Viscusi.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s00464-006-3025-5.

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Viscusi, E.R., Goldstein, S., Witkowski, T. et al. Alvimopan, a peripherally acting mu-opioid receptor antagonist, compared with placebo in postoperative ileus after major abdominal surgery. Surg Endosc 20, 64–70 (2006). https://doi.org/10.1007/s00464-005-0104-y

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