ANZICS CTG Endorsed Study
The augmented versus routine approach to giving energy trial
Although the importance of nutrition in critical illness is widely recognized, there remains uncertainty about the optimal target for caloric requirements. We plan to conduct a pivotal, 4000-patient, multicentre, double-blinded, randomised, controlled, parallel-group, phase III clinical trial to determine if the delivery of more calories improves survival following critical illness.
Aim: The primary aim of the study is to determine if augmentation of calorie delivery using energy dense enteral nutrition in mechanically ventilated patients improves 90 day survival when compared to routine care. A secondary aim is to determine if augmentation of calorie delivery using energy dense enteral nutrition in mechanically ventilated patients improves functional outcomes when compared to routine care. Primary Study Hypothesis: We hypothesise that, in mechanically ventilated patients, the enteral delivery of energy dense nutrition improves 90 day survival when compared to standard enteral care (which usually results in under-nutrition). Our secondary hypothesis is that enteral delivery of energy dense nutrition will also improve functional outcomes.
We have developed a simple & inexpensive strategy to deliver more calories safely & effectively via the enteral route. The strategy is to substitute standard formula (1.0 kcal/ml) with energy dense formula (1.5 kcal/ml) & deliver it at the same rate. This is a novel concept. Concentrated feed formulae are used in ICU feeding practice but are usually given at a reduced rate to patients who require fluid restriction. This is the first time that a concentrated formula has intentionally been given at full rate with the aim of increasing calorie delivery in the knowledge that over a 24 hour period the full target volume of feed is rarely given. We confirmed the safety & efficacy of this in a phase II multicentre, double-blind, randomised controlled trial, which has shown promising beneficial results. It is now logical, opportune & important to determine if this strategy can improve clinical outcomes including survival in a pivotal phase III double-blind, multicentre, randomised controlled trial.
The primary endpoint is survival at 90 days.
Secondary endpoints include: Death at ICU discharge, hospital discharge, 28 days, and 180 days; length of stay in ICU and hospital; ventilator free days, dialysis free days and inotrope free days, all to day 28; functional outcomes at, 180 day (EQ-5D-5L; Australian Work Force Survey; or WHODAS2.0 or Adelaide Activities Profile). All data will be analysed using the intention-to-treat principle.
Marianne Chapman (Co-Chair), Sandra Peake (Co-Chair), Rinaldo Bellomo, Andrew Davies, Adam Deane, Suzie Ferrie, Frank van Haren, Michael Horowitz, Sally Hurford (Project Manager), Theodore Iwashyna, Kylie Lange, Lorraine Little (Project Manager), Edward Litton, Diane Mackle (Project Manager), Stephanie O’Connor, Jeffrey Presneill, Emma Ridley, Vanessa Singh, Patricia Williams, and Paul Young.
ANZIC Research Centre, Monash University
The National Health & Medical Research Council – Centre of Research Excellence for the Translation of Nutritional Science into Good Health (NHMRC CREnutrition).
NHMRC Project Grant $3,534,236
Health Research Council of New Zealand NZ$1,200,000
Project Status as of June 2018
Recruitment completed 14 November 2017.
The data is being prepared for final analysis. Day 90 data lock is scheduled for 25 June 2018.
The Day 90 data will be presented at the ESICM Paris, October 2018 with a simultaneous publication in a peer review journal.
Full data lock is scheduled for 1st of August 2018 (all day 180 data completed).
Marianne Chapman (email)