n-(3-fluorophenyl)-1-((4-(((3s)-3-methyl-1-piperazinyl)methyl)phenyl)acetyl)-4-piperidinamine and Critical-Illness

Camicinal is a novel, nonmacrolide, motilin receptor agonist that accelerates gastric emptying in critically ill patients with established feed intolerance. The primary question was whether the preemptive administration of camicinal increased the provision of enteral nutrition (EN) to critically ill patients with risk factors that predisposed to feed intolerance.. This was an international, multicenter, parallel-group, blinded, randomized controlled trial. Patients at risk for feed intolerance, defined as receiving moderate to high doses of vasopressors or opiates, or admitted because of multiple traumatic injuries or with brain injury, received either enteral camicinal 50 mg or placebo daily for a maximum of 7 days, along with EN administered according to a standardized feeding protocol. The primary outcome was the daily adequacy of enteral feed delivered, as assessed by percentage of goal volume (delivered/prescribed × 100) before development of intolerance.. Eighty-four patients participated. The administration of camicinal did not result in a statistically significant clinical difference in the daily average percentage goal volume delivered (camicinal vs placebo: 77% [95% confidence interval: 71, 83] vs 68% (58, 78); mean difference 9% [-5, 23]; P = 0.21). Similarly, there were no differences in the percentage goal calories (76% [65, 88] vs 68% [60, 77]) and protein (76% [66, 86] vs 70% [61, 80]) administered, or the incidence of feed intolerance (15% vs 14%).. The incidence of feed intolerance was low in both groups. In this cohort the preemptive administration of enteral camicinal did not significantly augment the provision of goal EN.

Topics: Adult; Aged; Critical Illness; Dietary Proteins; Double-Blind Method; Energy Intake; Enteral Nutrition; Female; Food Intolerance; Gastric Emptying; Humans; Intubation, Gastrointestinal; Male; Middle Aged; Nutritional Requirements; Piperazines; Piperidines; Placebos; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide; Risk Factors; Treatment Outcome

The promotility agents currently available to treat gastroparesis and feed intolerance in the critically ill are limited by adverse effects. The aim of this study was to assess the pharmacodynamic effects and pharmacokinetics of single doses of the novel gastric promotility agent motilin agonist camicinal (GSK962040) in critically ill feed-intolerant patients.. A prospective, randomized, double-blind, parallel-group, placebo-controlled, study was performed in mechanically ventilated feed-intolerant patients [median age 55 (19-84), 73 % male, APACHE II score 18 (5-37) with a gastric residual volume ≥200 mL]. Gastric emptying and glucose absorption were measured both pre- and post-treatment after intragastric administration of 50 mg (n = 15) camicinal and placebo (n = 8) using the (13)C-octanoic acid breath test (BTt1/2), acetaminophen concentrations, and 3-O-methyl glucose concentrations respectively.. Following 50 mg enteral camicinal, there was a trend to accelerated gastric emptying [adjusted geometric means: pre-treatment BTt1/2 117 minutes vs. post- treatment 76 minutes; 95 % confidence intervals (CI; 0.39, 1.08) and increased glucose absorption (AUC240min pre-treatment: 28.63 mmol.min/L vs. post-treatment: 71.63 mmol.min/L; 95 % CI (1.68, 3.72)]. When two patients who did not have detectable plasma concentrations of camicinal were excluded from analysis, camicinal accelerated gastric emptying (adjusted geometric means: pre-treatment BTt1/2 121 minutes vs. post-treatment 65 minutes 95 % CI (0.32, 0.91) and increased glucose absorption (AUC240min pre-treatment: 33.04 mmol.min/L vs. post-treatment: 74.59 mmol.min/L; 95 % CI (1.478, 3.449). In those patients receiving placebo gastric emptying was similar pre- and post-treatment.. When absorbed, a single enteral dose of camicinal (50 mg) accelerates gastric emptying and increases glucose absorption in feed-intolerant critically ill patients.. The study protocol was registered with the US NIH clinicaltrials.gov on 23 December 2009 (Identifier NCT01039805 ).

Topics: Adult; Aged; Aged, 80 and over; Critical Illness; Double-Blind Method; Enteral Nutrition; Feeding and Eating Disorders; Female; Gastric Absorption; Gastric Emptying; Gastrointestinal Motility; Glucose; Humans; Intensive Care Units; Male; Middle Aged; Piperazines; Piperidines; Placebos; Prospective Studies; South Australia