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Trial registered on ANZCTR


Registration number
ACTRN12622001465741
Ethics application status
Approved
Date submitted
9/11/2022
Date registered
18/11/2022
Date last updated
26/11/2023
Date data sharing statement initially provided
18/11/2022
Date results information initially provided
26/11/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Muscle mass and functional outcomes in critically Ill patients receiving augmented enteral protein – The MAINTAIN study
Scientific title
Muscle mass and functional outcomes in critically Ill patients receiving augmented enteral protein – The MAINTAIN study
Secondary ID [1] 308377 0
None
Universal Trial Number (UTN)
Trial acronym
The MAINTAIN study
Linked study record
'This record is a sub-study of ACTRN12621001484831

Health condition
Health condition(s) or problem(s) studied:
Critical Illness 328175 0
Condition category
Condition code
Diet and Nutrition 325229 325229 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] 324827 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] 333072 0
Change in ultrasound-derived quadricep muscle layer thickness (QMLT)
Timepoint [1] 333072 0
Assessed within 48 hours of commencement of enteral nutrition and at day 7 post-commencement of enteral nutrition
Secondary outcome [1] 415707 0
Change in functional status assessed using the Barthel Index
Timepoint [1] 415707 0
ICU discharge
Secondary outcome [2] 415708 0
Muscle strength assessed using a hand grip dynamometer
Timepoint [2] 415708 0
ICU dischagre
Secondary outcome [3] 415709 0
Rate of ICU-acquired weakness, as defined by a score of less than 48 on the Medical Research Council Sum Score
Timepoint [3] 415709 0
ICU discharge
Secondary outcome [4] 415710 0
Physical function assessed using the World Health Organisation Disability Assessment Schedule (WHODAS) 2.0 questionnaire
Timepoint [4] 415710 0
Day 90 post commencement of enteral nutrition
Secondary outcome [5] 415711 0
Quality of life assessed using the EuroQol five dimension five-level (EQ-5D-5L)
Timepoint [5] 415711 0
Day 90 post commencement of enteral nutrition

Eligibility
Key inclusion criteria
Patients admitted to ICU and commence enteral nutrition
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Expected to require <48 hrs of enteral nutrition in ICU
Bilateral quadriceps not accessible and unable to complete study measure e.g. burns, femoral shaft fractures, above knee amputations, prone ventilated
Pregnant
Unable to complete baseline measurement within 48h of enteral nutrition commencement
Expected death, or expected palliative care prior to day 7

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
Efficacy
Statistical methods / analysis
The primary analysis will be the difference in the change in ultrasound-derived QMLT from baseline to day 7 between groups that received standard protein enteral formula or high protein enteral formula. For secondary analysis, protein delivery will be dichotomized into participants that receive <1.2g of protein/kg of body weight/day and participants that received >1.2g of protein/kg of body weight/day over the first 7 days i.e. achieving protein doses recommended in international critical care nutrition guidelines. Differences in the primary outcome will be tested via analysis of covariance (ANCOVA) with protein treatment and baseline MLT included as fixed effects. The first ultrasound measure available for each participant will serve as baseline measure. Change in the ultrasound measurements at day 7 will be performed using a mixed effects model with fixed effects for time, protein treatment groups and the time by treatment group interaction. Difference between treatment groups and muscle strength, physical function and quality of life will be tested with independent samples t-tests and Mann-Whitney rank sum tests for continuous variables, and chi-square tests for categorical variables. Correlations between QMLT and strength/function will be assessed by Pearson correlation or spearman rank correlation for parametric or nonparametric data respectively

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
23/11/2022
Actual
25/11/2022
Date of last participant enrolment
Anticipated
23/05/2023
Actual
24/05/2023
Date of last data collection
Anticipated
23/08/2023
Actual
23/08/2023
Sample size
Target
100
Accrual to date
Final
59
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 23526 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 38939 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 25116 0
New Zealand
State/province [1] 25116 0
Wellington Region

Funding & Sponsors
Funding source category [1] 312623 0
Government body
Name [1] 312623 0
Medical Research Future Fund - Rare Cancers Rare Diseases and Unmet Need - Streams
Country [1] 312623 0
Australia
Funding source category [2] 312625 0
Charities/Societies/Foundations
Name [2] 312625 0
The Australian and New Zealand Intensive Care Foundation
Country [2] 312625 0
Australia
Funding source category [3] 312942 0
Charities/Societies/Foundations
Name [3] 312942 0
AuSPEN Novice Investigator Grant.
Country [3] 312942 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] 314234 0
None
Name [1] 314234 0
NA
Address [1] 314234 0
NA
Country [1] 314234 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311942 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 311942 0
Level 3 Roma Mitchell House, North Terrace, Adelaide, South Australia 5000
Ethics committee country [1] 311942 0
Australia
Date submitted for ethics approval [1] 311942 0
12/08/2022
Approval date [1] 311942 0
28/09/2022
Ethics approval number [1] 311942 0
2022/HRE00202

Summary
Brief summary
Patients admitted to the Intensive Care Unit (ICU) are the most acutely unwell in hospital, and those that survive experience significant muscle wasting and poor functional outcomes. Nutrition therapy, usually delivered to ICU patients as liquid formula via a tube into the stomach, has the potential to improve at least part of the significant muscle atrophy that occurs, and hence enhance functional recovery from critical illness. Current international guidelines recommend delivery of protein doses of 1.2 - 2.0 g/kg bodyweight/day or higher, but this is based on very low quality of evidence. It has been reported in observational studies that a large proportion of ICU patients do not meet these prescribed protein targets. The TARGET Protein study is a large randomised controlled trial comparing augmented protein doses recommended in international guidelines to current standard care (ACTRN12621001484831). Augmenting dietary protein has the capability to achieve these recommended protein targets, yet it is unknown whether meeting protein targets improves muscle mass or functional outcomes following critical illness. We propose undertaking a prospective sub-study within a large randomised controlled trial to measure muscle mass, strength and physical function in critically ill patients receiving high protein protein doses compared to standard care.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 122918 0
Mr Matthew Summers
Address 122918 0
ICU Research, Royal Adelaide Hospital, Port Road, ADELAIDE SA 5000
Country 122918 0
Australia
Phone 122918 0
+61 870741765
Fax 122918 0
Email 122918 0
matthew.summers@sa.gov.au
Contact person for public queries
Name 122919 0
Mr Matthew Summers
Address 122919 0
ICU Research, Royal Adelaide Hospital, Port Road, ADELAIDE SA 5000
Country 122919 0
Australia
Phone 122919 0
+61 870741765
Fax 122919 0
Email 122919 0
matthew.summers@sa.gov.au
Contact person for scientific queries
Name 122920 0
Mr Matthew Summers
Address 122920 0
ICU Research, Royal Adelaide Hospital, Port Road, ADELAIDE SA 5000
Country 122920 0
Australia
Phone 122920 0
+61 870741765
Fax 122920 0
Email 122920 0
matthew.summers@sa.gov.au

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
No additional documents have been identified.