Indirect Calorimetry Guided Energy Provision in Critically Ill Patients With Obesity

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Critical Illness, Obesity

Intervention / Treatment
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* Other: Indirect calorimetry
* Other: Indirect calorimetry (Standard care nutrition arm)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A multi-centre, prospective, two arm parallel feasibility pilot randomised controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Individualised energy delivery<br>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<br>* Weekly indirect calorimetry measurements using the Q-NRG+ device will be used to guide energy delivery up to day 28 of hospital admission.<br>|
| Active Comparator: Standard care nutrition<br>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)<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Critical care nutrition, Indirect calorimetry