Ipamorelin did not significantly shorten time to first meal in postoperative ileus patients

Postoperative ileus is a common and significant complication following abdominal surgery, characterized by a temporary impairment of gastrointestinal motility. It leads to patient discomfort, delayed recovery, and increased hospital stays, but currently lacks effective management strategies. The endogenous hormone ghrelin is known to stimulate gastrointestinal motility through the ghrelin receptor (growth hormone secretagogue receptor, GHSR). Therefore, stimulating this receptor with an agonist has been proposed as a therapeutic strategy to accelerate the recovery of bowel function. Ipamorelin, a selective ghrelin-receptor agonist, was investigated in this context for its potential promotility effects in both the upper and lower gastrointestinal tract to address this clinical challenge.

This was a phase 2, multicenter, double-blind, placebo-controlled, proof-of-concept clinical trial (NCT00672074). The study enrolled 117 adult hospital inpatients undergoing small or large bowel resection via open or laparoscopic surgery. Patients were randomized to receive either intravenous infusions of 0.03 mg/kg ipamorelin or placebo, administered twice daily. Treatment started on the first postoperative day and continued for up to 7 days or until hospital discharge. The primary efficacy endpoint was the time from the first dose of the study drug to the tolerance of a standardized solid meal. Safety was the main outcome measure, monitored via adverse events and laboratory tests.

Ipamorelin was found to be well tolerated, with a lower overall incidence of treatment-emergent adverse events in the ipamorelin group (87.5%) compared to the placebo group (94.8%). The study's modified intent-to-treat population consisted of 114 patients. The primary efficacy endpoint was not met; there was no significant difference between the groups. The median time to the first tolerated meal was 25.3 hours in the ipamorelin group and 32.6 hours in the placebo group, a difference that was not statistically significant (p = 0.15). Secondary efficacy analyses also showed no significant differences between ipamorelin and placebo.

The median time to first tolerated meal was reduced by 7.3 hours with ipamorelin (25.3h vs 32.6h), but this effect failed to reach statistical significance (p = 0.15).

This indicates that while there was a trend toward faster recovery of gut function, the study did not provide definitive evidence of ipamorelin's efficacy for this indication at the dose tested.