Indirect Calorimetry Guided Energy Provision in Critically Ill Patients With Obesity (DIRECT)

GuiDIng Energy Provision Using indiREct CalorimeTry: a Pilot Feasibility Randomised Controlled Trial in Critically Ill Adults With Obesity

The DIRECT trial is a prospective, multi-centre, two arm parallel feasibility pilot randomised controlled trial. The primary aim is to determine the feasibility of using repeat indirect calorimetry measurements to direct energy delivery in critically ill patients with obesity.

The trial will recruit 60 mechanically ventilated patients from 4-6 ICUs in Australia and New Zealand.

Study Overview

• Status: Completed
• Conditions: Obesity; Critical Illness
• Intervention / Treatment: Other: Indirect calorimetry; Other: Indirect calorimetry (Standard care nutrition arm)

Detailed Description

Indirect calorimetry is the current reference standard for measuring energy expenditure during critical illness, allowing for personalisation of energy delivery. Use of indirect calorimetry may be important in mitigating under- and overfeeding and associated adverse outcomes. This may be particularly important in patients with obesity, where energy expenditure is difficult to estimate, and limited data is available on the optimal nutritional management of this subgroup.

Although access to indirect calorimetry is gradually improving, it remains an underutilised tool and skills required to complete and interpret measurements are limited which may hinder use and integration into practice. There is a resulting knowledge gap on the impact of indirect calorimetry on outcomes in comparison to standard care predictive equations.

A definitive and pragmatic trial is needed to assess the impact of guiding energy delivery with indirect calorimetry on patient outcomes. Importantly, confirming the feasibility of using indirect calorimetry to guide energy delivery is needed to define optimal measurement protocols prior to completion of a larger trial.

The primary aim of the DIRECT trial is to determine the feasibility of using repeat indirect calorimetry measurements to direct energy delivery in critically ill patients with obesity. The secondary aim is to inform a larger trial by collecting process, nutrition, functional, clinical and safety outcomes.

The investigators will consider the main trial feasible to conduct if 2 of the following 3 feasibility criteria are achieved: (a) recruitment rate is ≥ 1 patient per calendar month; (b) between group separation of ≥20% in energy adequacy during ICU admission is achieved in relation to measured energy expenditure and; (c) the number of indirect calorimetry measurements completed/planned ≥60% during ICU admission.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Blacktown Hospital
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
  • Victoria
    • Ballarat Central, Victoria, Australia, 3550
      • Ballarat Base Hospital, Grampians Health
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• New Zealand
  • Auckland, New Zealand, 1023
    • Department of Critical Care Medicine, Auckland City Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult (≥ 18 years) patients
• Body mass index ≥30 kg/m2
• Between day 3 and 6 of index ICU admission
• Receiving invasive mechanical ventilation
• Receiving enteral or parenteral nutrition

Exclusion Criteria:

• Receiving extracorporeal membrane oxygenation support
• Major burns (≥20% total body surface area)
• Unable to perform indirect calorimetry within 24 hours of randomisation
• Known pregnancy
• Death is imminent
• Treating clinician believes the study is not in the best interest of the patient

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Individualised energy delivery; Energy delivery will be guided by indirect calorimetry, with the aim to meet 80-100% of the most recent energy expenditure measurement from day 4 to 28 of hospital admission.	Other: Indirect calorimetry; Weekly indirect calorimetry measurements using the Q-NRG+ device will be used to guide energy delivery up to day 28 of hospital admission.
Active Comparator: Standard care nutrition; Energy delivery will be according to predictive equation estimates and usual site practice from day 4 to 28 of hospital admission.	Other: Indirect calorimetry (Standard care nutrition arm); Weekly indirect calorimetry measurements using the Q-NRG+ device will be conducted up to day 28 of hospital admission. In the standard care nutrition arm, clinicians will be blinded to indirect calorimetry measurements.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility: Recruitment rate	Patients per site, per month	During ICU admission (up to day 28)
Feasibility: Treatment separation in energy adequacy	Energy adequacy % will be calculated as daily energy delivery (kcal)/ measured energy expenditure (kcal) and expressed as a percentage.	During ICU admission (up to day 28)
Feasibility: Protocol adherence	Number of indirect calorimetry measurements completed/planned.	During ICU admission (up to day 28)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment separation in energy adequacy	Energy adequacy % will be calculated as energy delivery (kcal)/ measured energy expenditure (kcal) and expressed as a percentage	Post-ICU period (up to day 28)
Protocol adherence	Number of indirect calorimetry measurements completed/ planned	Post-ICU period (up to day 28)
Reasons for indirect calorimetry measurement non-completion	Reported overall and separately for ventilated and canopy measurements	Up to day 28
Clinician acceptability relating to use of indirect calorimetry in routine clinical care (questionnaire)	Reported separately for ventilated and canopy measurements. A combination of yes/no, multiple-choice and Likert scale (1 (minimum) - 5 (maximum)) questions are included.	Up to day 28
Patient acceptability relating to use of indirect calorimetry in routine clinical care (questionnaire)	Reported for canopy measurements only. A combination of yes/no, multiple-choice and Likert scale (1 (minimum) - 5 (maximum)) questions are included.	Up to day 28
Cumulative difference in energy delivery compared to measured energy expenditure	kcal; reported overall and separately for ventilated and canopy measurements	Day 28
Cumulative difference in energy delivery compared to prescribed energy expenditure	kcal; reported overall and separately for ventilated and canopy measurements	Day 28
Nutritional status	Assessed using the Global Leadership Initiative on Malnutrition (GLIM) criteria where malnutrition diagnosis is based on meeting predefined phenotypic and etiologic criteria (PMID: 30181091). Severity of malnutrition (moderate or severe) is determined based on the phenotypic criterion related to severity of unintentional weight loss.	Baseline, ICU (up to day 28) and hospital discharge (up to day 28)
Handgrip strength	Measured using a hand dynamometer	Hospital discharge (up to day 28)
Duration of mechanical ventilation	Duration of mechanical ventilation (days)	Day 28
ICU length of stay	Duration of ICU stay (days)	Day 28
Hospital length of stay	Duration of hospital stay (days)	Day 28
Survival	ICU, in-hospital and 90 day mortality	ICU discharge (up to day 28), in-hospital (up to day 28) and 90 day
European Quality Of Life 5 Dimensions 5 Level (EQ5D-5L)	Health related quality of life assessment using EQ5D-5L. Each dimension has 5 levels ranging from no problems (1) to extreme problems (5), there is no overall score. It also has a visual analogue scale (VAS) ranging 0-100 with 0 being worst imaginable health state and 100 being best imaginable health state	Day 90
World Health Organization Disability Assessment Schedule 2.0 (WHODAS)	WHODAS is a 12 point disability assessment with a raw score range of 0-48. 0 is no disability and 48 being full disability	Day 90

Collaborators and Investigators

• Sponsor: Australian and New Zealand Intensive Care Research Centre

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2023
• Primary Completion (Actual): November 3, 2025
• Study Completion (Actual): February 1, 2026

Study Registration Dates

• First Submitted: August 21, 2023
• First Submitted That Met QC Criteria: September 21, 2023
• First Posted (Actual): September 25, 2023

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Indirect calorimetry; Critical care nutrition
• Additional Relevant MeSH Terms: Pathologic Processes; Nutrition Disorders; Disease Attributes; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Critical Illness; Investigative Techniques; Chemistry Techniques, Analytical; Calorimetry; Calorimetry, Indirect
• Other Study ID Numbers: ANZIC-RC/OT001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data sharing requests will be considered following publication of the primary trial data on an individual basis by the trial management committee (the data custodians). Data sharing will only be considered for investigator-initiated, independent researchers who provide a written data evaluation proposal that is judged to be methodologically sound. A data sharing agreement will be required to detail conditions under which data is shared and used. Resulting publications should appropriately cite and acknowledge the original data custodians. Requests for data sharing are to be made to anzicrc@monash.edu and the corresponding author, Dr Oana Tatucu; oana.tatucu@monash.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No