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

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.

Enteral Feeding Intolerance: Updates in Definitions and Pathophysiology

“…Even though a motilin‐agonist erythromycin is frequently administered, and also supported by recent guidelines, 34 its effect and usefulness for patient‐centered outcomes is not uniformly confirmed 35,36 . Other treatment modalities targeting hormonal pathways to accelerate gastric emptying were unable to inaugurate a new, efficient, and safe drug for clinical practice 37–39 . The limited efficacy of the pharmacological approach designed to manipulate hormonal pathways highlights the complexity and time‐varying pattern of EFI.…”

The Role of GI Peptides in Functional Dyspepsia and Gastroparesis: A Systematic Review

“…Subsequently, several ghrelin agonists have been studied, with a major focus on diabetic gastroparesis. The intravenously administered macrocylic peptidomimetic molecule ulimorelin, enhanced gastric emptying, and was subsequently mainly studied in critical care patients, with lack of differentiation from metoclopramide (50,51). The orally administered TZP-102 showed promising results in phase 2a, but this was not confirmed in phase 2b (52,53).…”

Oral Nutrition during and after Critical Illness: SPICES for Quality of Care!

“…According to preliminary studies in animals or some groups of patients, benefits could be multiple: improvement of food intake, but also the additional effect on the upregulation of the growth hormone axis, or the modulation of the inflammatory response [ 85 ]. Unfortunately, in a recent study in critically patients (although enterally fed), the ghrelin agonist ulimorelin failed to be superior to metoclopramide in term of gastric emptying [ 86 ]. More data are needed before ghrelin modulation could be implemented in clinical practice.…”