A multicenter, randomized, double-blind study of ulimorelin and metoclopramide in the treatment of critically ill patients with enteral feeding intolerance: PROMOTE trial

Intensive Care Med. 2019 May;45(5):647-656. doi: 10.1007/s00134-019-05593-2. Epub 2019 May 6.

Abstract

Purpose: Enteral feeding intolerance (EFI) is a frequent problem in the intensive care unit (ICU), but current prokinetic agents have uncertain efficacy and safety profiles. The current study compared the efficacy and safety of ulimorelin, a ghrelin agonist, with metoclopramide in the treatment of EFI.

Methods: One hundred twenty ICU patients were randomized 1:1 to ulimorelin or metoclopramide for 5 days. EFI was diagnosed by a gastric residual volume (GRV) ≥ 500 ml. A volume-based feeding protocol was employed, and enteral formulas were standardized. The primary end point was the percentage daily protein prescription (%DPP) received by patients over 5 days of treatment. Secondary end points included feeding success, defined as 80% DPP; gastric emptying, assessed by paracetamol absorption; incidences of recurrent intolerance (GRV ≥ 500 ml); vomiting or regurgitation; aspiration, defined by positive tracheal aspirates for pepsin; and pulmonary infection.

Results: One hundred twenty patients were randomized and received the study drug (ulimorelin 62, metoclopramide 58). Mean APACHE II and SOFA scores were 21.6 and 8.6, and 63.3% of patients had medical reasons for ICU admission. Ulimorelin and metoclopramide resulted in comparable %DPPs over 5 days of treatment (median [Q1, Q3]: 82.9% [38.4%, 100.2%] and 82.3% [65.6%, 100.2%], respectively, p = 0.49). Five-day rates of feeding success were 67.7% and 70.6% when terminations unrelated to feeding were excluded, and there were no differences in any secondary outcomes or adverse events between the two groups.

Conclusions: Both prokinetic agents achieved similar rates of feeding success, and no safety differences between the two treatment groups were observed.

Keywords: Enteral feeding intolerance; Gastric residual volume; Metoclopramide; PROMOTE; Ulimorelin; Volume-based feeding.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • APACHE
  • Adult
  • Aged
  • Antiemetics / standards
  • Antiemetics / therapeutic use
  • Canada
  • Critical Illness / therapy
  • Double-Blind Method
  • Enteral Nutrition / methods
  • Enteral Nutrition / standards*
  • Enteral Nutrition / statistics & numerical data
  • Female
  • Gastric Emptying / drug effects
  • Gastric Emptying / physiology
  • Humans
  • Intensive Care Units / organization & administration
  • Intensive Care Units / statistics & numerical data
  • Macrocyclic Compounds / standards*
  • Macrocyclic Compounds / therapeutic use
  • Male
  • Metoclopramide / standards*
  • Metoclopramide / therapeutic use
  • Middle Aged
  • Netherlands
  • Organ Dysfunction Scores
  • Spain
  • United States

Substances

  • Antiemetics
  • Macrocyclic Compounds
  • Metoclopramide
  • ulimorelin