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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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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DOI: https://doi.org/10.1007/s00464-005-0104-y