Prospective, Randomized, Controlled, Proof-Of-Concept Study of the Ghrelin Mimetic Ipamorelin for the Management of Postoperative Ileus in Bowel Resection Patients

Int J Colorectal Dis. 2014 Dec;29(12):1527-34. doi: 10.1007/s00384-014-2030-8. Epub 2014 Oct 21.

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.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Double-Blind Method
  • Female
  • Gastrointestinal Agents / adverse effects
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Ileus / drug therapy*
  • Ileus / etiology
  • Intestines / surgery*
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Oligopeptides / adverse effects
  • Oligopeptides / therapeutic use*
  • Postoperative Complications / drug therapy*
  • Prospective Studies
  • Receptors, Ghrelin / agonists*
  • Vomiting / chemically induced

Substances

  • Gastrointestinal Agents
  • Oligopeptides
  • Receptors, Ghrelin
  • ipamorelin

Associated data

  • ClinicalTrials.gov/NCT00672074