Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients

Abstract

Background

Postoperative ileus is a significant clinical challenge lacking effective management strategies. Ghrelin-receptor stimulation has promotility effects in the upper and lower gastrointestinal tract.

Objective

This proof-of-concept, phase 2, randomized study evaluated the safety and efficacy of the ghrelin-receptor agonist ipamorelin in the treatment of postoperative ileus following abdominal surgery (ClinicalTrials.gov NCT00672074).

Design

The design was a multicenter, double-blind, placebo-controlled, clinical trial.

Settings

The settings include hospital inpatients.

Patients

The patients were adults undergoing small and large bowel resection by open or laparoscopic surgery.

Intervention

The intervention was intravenous infusions of 0.03-mg/kg ipamorelin vs placebo twice daily, on postoperative day 1 to 7 or hospital discharge.

Main outcome measures

Safety was assessed by monitoring adverse events and laboratory tests. The key efficacy endpoint was time from first dose of study drug to tolerance of a standardized solid meal.

Results

One hundred seventeen patients were enrolled, of whom 114 patients composed the safety and modified intent-to-treat populations. Demographic and disease characteristics were balanced between groups. Overall incidence of any treatment-emergent adverse events was 87.5 % in the ipamorelin group and 94.8 % in placebo group. Median time to first tolerated meal was 25.3 and 32.6 h in the ipamorelin and placebo groups, respectively (p = 0.15).

Limitations

This proof of concept study was small and enrolled patients with a broad range of underlying conditions.

Conclusions

Ipamorelin 0.03-mg/kg twice daily for up to 7 days was well tolerated. There were no significant differences between ipamorelin and placebo in the key and secondary efficacy analyses.

Appendix

Ipamorelin 201 study group investigators

Robert Beart, MD, University of Southern California/Norris Cancer Center, Los Angeles, CA; David Beck, MD, Ochsner Medical Center, New Orleans, LA; Roberto Bergamaschi, MD, Stony Brook University Medical Center, Stony Brook, NY; Sander Binderow, MD, Saint Joseph’s Hospital of Atlanta, GA; James Fleshman, MD, Barnes-Jewish West, Creve Coeur, MO; Phillip Fleshner, MD, Cedars Sinai Medical Center, Los Angeles, CA; Walter Koltun, MD, Pennsylvania State University, Hershey, PA; Martin McCarter, MD, University of Colorado Hospital, Aurora, CO; Christopher Raeburn, MD, Denver VA Hospital, Denver, CO; Janice Rafferty, MD, The Christ Hospital, Cincinnati, OH; Bruce Robb, MD, Indiana University Medical Center, Indianapolis, IN; Marc Singer, MD, University of Illinois at Chicago, Chicago, IL; Thomas Stahl, MD, Washington Hospital Center, Washington, DC; Brian Sweeney, MD, University of Massachusetts Memorial Healthcare, Worcester, MA; Theresa Terem, MD, St. Joseph Hospital Franciscan Research Center, Tacoma, WA; Harry Wasvary, MD, William Beaumont Hospital, Royal Oak, MI; Steven Wexner, MD, Cleveland Clinic of Weston, Weston, FL; Sherry Wren, MD, Palo Alto Veterans Hospital, Palo Alto, CA.