Safety and efficacy of ulimorelin administered postoperatively to accelerate recovery of gastrointestinal motility following partial bowel resection: results of two randomized, placebo-controlled phase 3 trials.

BACKGROUND: Gastrointestinal recovery is a critical milestone after bowel resection with postoperative ileus resulting in increased risk of complications and prolonged hospitalization. OBJECTIVE: The aim of this study is to evaluate the efficacy and safety of ulimorelin, a ghrelin receptor agonist given postoperatively in 2 identically designed phase 3 studies (ClinicalTrials.gov NCT01285570 and NCT01296620). DESIGN: This investigation is designed as a multicenter, double-blind, randomized, parallel-group study. SETTINGS: This study involves hospital inpatients. PATIENTS: Adult patients undergoing partial bowel resection were included. INTERVENTION: Thirty-minute intravenous infusions (160 µg/kg, 480 µg/kg ulimorelin, or placebo) once daily were started within 60 minutes after the end of surgery and ended at the first of the following: primary efficacy end point fulfilled (defined below), hospital discharge, or 7 days treatment. MAIN OUTCOME MEASURES: The primary efficacy end point was the time from the end of surgery to the composite end point of the later of first bowel movement and tolerance of solid food. Safety was assessed with the use of standard assessments including adverse events and laboratory tests. RESULTS: Ulimorelin Study of Efficacy and Safety 007, n = 332 patients; Ulimorelin Study of Efficacy and Safety 008, n = 330 patients: in both studies, the primary efficacy end point and the secondary efficacy outcomes, which included postsurgical time to first bowel movement, tolerance of solid food, and discharge eligibility, did not differ significantly among patients treated with either dose of ulimorelin versus placebo. Rates of serious adverse events were comparable across all treatment groups. There was no statistically significant difference from placebo in regard to events of interest, namely nausea, vomiting, ileus as an adverse event, nasogastric tube reinsertion, anastomotic complications, and infections. LIMITATIONS: A possible limitation is the variance inherent in surgery and comorbidities. CONCLUSIONS: Although the efficacy of ulimorelin in reducing the duration of postoperative ileus was not demonstrated in these studies, intravenous ulimorelin at doses of 160 µg/kg and 480 µg/kg was generally well tolerated in postcolectomy patients. Similar to other promotility agents, ulimorelin may find an application in other indications better suited to its attributes.