Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients
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Postoperative ileus is a significant clinical challenge lacking effective management strategies. Ghrelin-receptor stimulation has promotility effects in the upper and lower gastrointestinal tract.
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).
The design was a multicenter, double-blind, placebo-controlled, clinical trial.
The settings include hospital inpatients.
The patients were adults undergoing small and large bowel resection by open or laparoscopic surgery.
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.
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).
This proof of concept study was small and enrolled patients with a broad range of underlying conditions.
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.
KeywordsAbdominal surgery Ghrelin-receptor agonist Gastrointestinal Ileus Medication Postoperative management Prokinetic
The authors thank the patients and all of the Investigators and study staff who participated in this study. Support for developing this manuscript was provided by Helsinn Therapeutics (US), Inc. (Bridgewater, NJ), and copyediting, editorial assistance, and production assistance were provided by The Curry Rockefeller Group, LLC (Tarrytown, NY).
Conflicts of interest and source of funding
This study was supported by Helsinn Therapeutics (US), Inc. The authors’ institutions received grants from Helsinn Therapeutics (US), Inc., to conduct the study. The authors declare no financial or proprietary conflicts of interest.
Conception and design: DEB, WBS; data collection: DEB, WBS, MDM; data analysis: DEB; data interpretation: DEB; drafting of manuscript: DEB, WBS, MDM; critical revision: DEB, WBS, MDM; final approval: DEB, WBS, MDM.
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