A phase 2 liver trial where the add-on drug didn't help — and the base drug quietly did
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Study wrapper · #202

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

Beck DE, Sweeney WB, McCarter MD, et al. International journal of colorectal disease. 2014.
ContradictedRCTMentions: Ipamorelin

Editor's note

This is the strongest study in the batch by design: a multicentre, double-blind, placebo-controlled Phase 2 randomised trial (NCT00672074) of intravenous ipamorelin for postoperative ileus in 114 adults after bowel resection. It is a genuine efficacy trial, not a mention — and the result was negative. Median time to tolerating a solid meal was 25.3 hours on ipamorelin versus 32.6 hours on placebo, but the difference was not statistically significant (p=0.15), and no secondary efficacy endpoint separated from placebo either. On the safety side, treatment-emergent adverse events were common in both arms (87.5% ipamorelin vs 94.8% placebo), and the authors reported ipamorelin was well tolerated at this dose and duration. Weigh this carefully: a ghrelin-receptor agonist has a mechanistically plausible promotility rationale, and the numeric trend favoured ipamorelin, but this adequately blinded trial did not demonstrate benefit. It stands as a rare controlled human dataset for ipamorelin and a useful counterweight to mechanistic optimism from rodent ileus models.

Plain-language abstract

Postoperative ileus — a temporary shutdown of normal gut movement after abdominal surgery — has few good treatments. Because the ghrelin receptor helps drive gut motility, researchers tested ipamorelin, a drug that activates that receptor, in a well-designed clinical trial. This was a multicentre, randomised, double-blind, placebo-controlled Phase 2 study: neither patients nor doctors knew who got the drug. 117 adults having small or large bowel removal were enrolled (114 analysed), receiving intravenous ipamorelin (0.03 mg/kg) or placebo twice daily for up to 7 days. The main measure was how long until a patient could tolerate a normal solid meal. Patients on ipamorelin reached that point at a median of 25.3 hours versus 32.6 hours on placebo — a difference that was not statistically significant (p=0.15). No other efficacy measure showed a clear advantage. Side effects were common in both groups (87.5% with ipamorelin, 94.8% with placebo), and the drug was reported as well tolerated at this dose. The authors noted the study was small with a varied patient mix. Bottom line: this trial did not show that ipamorelin worked better than placebo for this use.