Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001484831
Ethics application status
Approved
Date submitted
23/09/2021
Date registered
1/11/2021
Date last updated
26/11/2023
Date data sharing statement initially provided
1/11/2021
Date results information initially provided
18/09/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
TARGET Protein: The effect of augmented administration of enteral protein to critically ill adults on clinical outcomes: A cluster randomised, cross-sectional double cross-over, registry-embedded, pragmatic clinical trial
Scientific title
TARGET Protein: The effect of augmented administration of enteral protein to critically ill adults on out of hospital survival: A cluster randomised, cross-sectional double cross-over, registry-embedded, pragmatic clinical trial
Secondary ID [1] 305402 0
None
Universal Trial Number (UTN)
U1111-1269-7646
Trial acronym
TARGET Protein
Linked study record
Nil

Health condition
Health condition(s) or problem(s) studied:
Critical Illness 323767 0
Condition category
Condition code
Diet and Nutrition 321285 321285 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention enteral nutrition (EN) - ‘Nutrison Protein Intense’ 1.26 kcal/ml and 100g protein per 1000 ml delivered via naso-enteric tube, delivered daily for up to 90 days.

The goal rate for enteral nutrition will be as per usual site processes with the maximum goal rate of the enteral nutrition for both groups of 1 ml/kg ideal body weight (IBW / hour), delivered over 24 hours/day. This will ensure participant safety with no participant receiving excess protein, calories or volume.
Intervention code [1] 321809 0
Treatment: Other
Comparator / control treatment
Control enteral nutrition (EN) - ‘Nutrison Protein Plus’ 1.25 kcal/ml and 63g protein per 1000ml delivered via naso-enteric tube, delivered daily for up to 90 days.

The goal rate for enteral nutrition will be as per usual site processes with the maximum goal rate of the enteral nutrition for both groups of 1 ml/kg ideal body weight (IBW / hour), delivered over 24 hours/day. This will ensure participant safety with no participant receiving excess protein, calories or volume.
Control group
Active

Outcomes
Primary outcome [1] 329060 0
Days free of the index hospital and alive at day-90

(Calculated as 90 and subtracting all days in hospital during the index hospital admission plus any readmissions to the index hospital within 90 days for which the patient remains in-hospital at 2400 h. Patients will be considered alive if they are alive at discharge from the index-hospital and there is no evidence of death before day 90 and after hospital death from the national death index. All deaths up to day 90 counted as zero days free of index hospital and alive at day-90).
Timepoint [1] 329060 0
Censored at 90 days following commencement of enteral nutrition (intervention EN or control EN)
Secondary outcome [1] 401313 0
All-cause mortality
Timepoint [1] 401313 0
At day 90 following commencement of enteral nutrition (intervention EN or control EN)
Secondary outcome [2] 401314 0
Duration of invasive ventilation, assessed by data linkage to medical records
Timepoint [2] 401314 0
At ICU discharge
Secondary outcome [3] 401317 0
Duration of admission to ICU, assessed by data linkage to medical records
Timepoint [3] 401317 0
At ICU discharge
Secondary outcome [4] 401318 0
Duration of admission to hospital, assessed by data linkage to medical records
Timepoint [4] 401318 0
At hospital discharge
Secondary outcome [5] 401319 0
Incidence of tracheostomy insertion, assessed by data linkage to medical records
Timepoint [5] 401319 0
During ICU stay
Secondary outcome [6] 401320 0
Incidence of renal replacement therapy, assessed by data linkage to medical records
Timepoint [6] 401320 0
During ICU stay
Secondary outcome [7] 401321 0
Discharge destination, assessed by data linkage to medical records
Timepoint [7] 401321 0
On hospital discharge
Secondary outcome [8] 409815 0
Alive at day-90, assessed by data linkage to medical records
Timepoint [8] 409815 0
At day 90 following commencement of enteral nutrition (intervention EN or control EN)
Secondary outcome [9] 409816 0
Days free of the index hospital at day-90 in survivors

(survivor only analysis calculated as 90 and subtracting all days in hospital during the index hospital admission plus any readmissions to the index hospital within 90 days for which the patient remains in-hospital at 2400 h).
Timepoint [9] 409816 0
At day 90 following commencement of enteral nutrition (intervention EN or control EN)

Eligibility
Key inclusion criteria
1) About to commence enteral nutrition
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. The treating clinician considers the study formulae to be contraindicated
2. The patient has previously participated in TARGET Protein Trial

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
All patients in a given ICU (cluster) who meet eligibility criteria will receive the same enteral nutrition (intervention EN or control EN) across a 3-month period. The enteral nutrition assigned to the ICU (cluster) for that period is the variable randomised. This allows the enteral nutrition (intervention EN or control EN) to be delivered as if it were usual care, which increases the efficiency of data collection and reduces the burden on participating sites. After a 3-month period, the ICU will then administer the alternative enteral nutrition for all patient admissions over the next 3 months. Participants will continue to receive the enteral nutrition that they were originally assigned if they remain in the ICU during a crossover period. The process is then repeated so each ICU (cluster) crosses over twice

Following the treating clinician’s decision to commence EN, the participant will receive the enteral nutrition (intervention EN or control EN) to which the ICU is currently randomised.

All aspects of nutrition management, other than the choice of enteral nutrition, will be according to individual unit practice. The rate at which enteral nutrition is commenced and incremented, and strategies to increase nutrient delivery (e.g. pro-kinetic drugs, post-pyloric tubes) in both treatment groups, will be at the discretion of the treating team usual unit nutrition protocol. It is recommended that goal rate is achieved within 48 hours of the commencement of enteral nutrition.

Enteral nutrition will be administered when clinically indicated until either the patient reaches day 90, is discharged from ICU, or dies. Patients discharged and readmitted to the ICU within 90 days of study enrolment still requiring EN will be recommenced on enteral nutrition as per the previous treatment allocation.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The main analyses will be conducted on an intention to treat basis. Descriptive statistics will be presented at the ICU level by the allocated treatment sequence and for patient characteristics by allocation sequence and treatment period. The primary analysis will be using generalised estimating equations with an exchangeable working correlation matrix and robust standard errors using the ICU as the clustering unit. The appropriate link function will be used for each outcome. The extent and pattern of missing data will be reported, and a sensitivity analysis will be performed to investigate the impact of different missing data assumptions on the results. The protocol and statistical analysis plan will be publicly available prior to the database being locked and any analysis conducted.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
23/05/2022
Actual
23/05/2022
Date of last participant enrolment
Anticipated
23/08/2023
Actual
23/08/2023
Date of last data collection
Anticipated
3/12/2023
Actual
Sample size
Target
3000
Accrual to date
Final
3399
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 20594 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 20595 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [3] 20596 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [4] 20598 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [5] 20599 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [6] 20600 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [7] 22403 0
Sunshine Hospital - St Albans
Recruitment postcode(s) [1] 35386 0
5000 - Adelaide
Recruitment postcode(s) [2] 35387 0
3084 - Heidelberg
Recruitment postcode(s) [3] 35388 0
3050 - Parkville
Recruitment postcode(s) [4] 35390 0
5011 - Woodville
Recruitment postcode(s) [5] 35391 0
2050 - Camperdown
Recruitment postcode(s) [6] 35392 0
3220 - Geelong
Recruitment postcode(s) [7] 37568 0
3021 - St Albans
Recruitment outside Australia
Country [1] 24147 0
New Zealand
State/province [1] 24147 0
Wellington Region

Funding & Sponsors
Funding source category [1] 309765 0
Other Collaborative groups
Name [1] 309765 0
Central Adelaide Local Health Network
Country [1] 309765 0
Australia
Funding source category [2] 311474 0
Government body
Name [2] 311474 0
Medical Research Future Fund - Rare Cancers Rare Diseases and Unmet Need - Streams
Country [2] 311474 0
Australia
Funding source category [3] 311475 0
Charities/Societies/Foundations
Name [3] 311475 0
The Australian and New Zealand Intensive Care Foundation
Country [3] 311475 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Central Adelaide Local Health Network
Address
Royal Adelaide Hospital, Port Road, Adelaide, SA 5000
Country
Australia
Secondary sponsor category [1] 310791 0
None
Name [1] 310791 0
NA
Address [1] 310791 0
NA
Country [1] 310791 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309522 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 309522 0
Level 3 Roma Mitchell House, North Terrace, Adelaide, South Australia 5000
Ethics committee country [1] 309522 0
Australia
Date submitted for ethics approval [1] 309522 0
30/07/2021
Approval date [1] 309522 0
03/09/2021
Ethics approval number [1] 309522 0
HREC reference number: 2021/HRE00248

Summary
Brief summary
An intensive care unit (ICU) stay is associated with significant muscle wasting in up to 80% of critically ill patients. This muscle wasting results in ‘ICU-acquired weakness’ that is associated with slower weaning from ventilator support, longer time to discharge alive from ICU and hospital, higher in-hospital costs which persist well after discharge from the acute care setting. Nutrition therapy, delivered as liquid nutrition via a tube into the stomach, forms usual care for critically ill patients. The provision of additional protein has the potential to attenuate muscle atrophy, and hence improve outcomes following critical illness. Current international guidelines recommend delivery of protein prescription of 1.2 - 2.0 g/kg/day or higher, but this is based on very low quality of evidence, and there is observational evidence to support both benefit and harm of augmented protein prescription. Therefore, there is a need for a high-quality randomised controlled trial of differing protein prescriptions. We propose a cluster randomised clinical trial with the aim of evaluating the effect of higher dietary protein delivery on outcomes of critically ill adult patients when compared to usual care. In this study each ICU will be randomised to one of the two study formulae for 3 months and then crosses over to the other study formulae for 3 months, which is then repeated, with each site participating for 12 months. Each eligible patient admitted to the ICU during these 3-month periods will receive the same study formula.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 114446 0
A/Prof Adam Deane
Address 114446 0
Intensive Care Unit, The Royal Melbourne Hospital – City Campus, Grattan Street, Parkville Victoria 3050
Country 114446 0
Australia
Phone 114446 0
+61 3 9342 9253
Fax 114446 0
+61 3 9342 8812
Email 114446 0
[email protected]
Contact person for public queries
Name 114447 0
A/Prof Adam Deane
Address 114447 0
Intensive Care Unit, The Royal Melbourne Hospital – City Campus, Grattan Street, Parkville Victoria 3050
Country 114447 0
Australia
Phone 114447 0
+61 3 9342 9253
Fax 114447 0
+61 3 9342 8812
Email 114447 0
[email protected]
Contact person for scientific queries
Name 114448 0
A/Prof Adam Deane
Address 114448 0
Intensive Care Unit, The Royal Melbourne Hospital – City Campus, Grattan Street, Parkville Victoria 3050
Country 114448 0
Australia
Phone 114448 0
+61 3 9342 9253
Fax 114448 0
+61 3 9342 8812
Email 114448 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual participant data will not specially be available. Results of the study will be published in a medical journal as combined results of the entire study population in a de-identified manner.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEditorial: Personalized nutrition therapy in critical illness and convalescence: Moving beyond one-size-fits-All to phenotyping and endotyping.2023https://dx.doi.org/10.1097/MCC.0000000000001060
N.B. These documents automatically identified may not have been verified by the study sponsor.