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Trial registered on ANZCTR


Registration number
ACTRN12620001305910
Ethics application status
Approved
Date submitted
16/10/2020
Date registered
2/12/2020
Date last updated
2/12/2020
Date data sharing statement initially provided
2/12/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
ß-Hydroxy-ß-Methylbutrate (HMB) supplementation and functiOnal OutcomeS in multi-Trauma patients (BOOST TRIAL)
Scientific title
ß-Hydroxy-ß-Methylbutrate (HMB) supplementation and functional outcomes in multi-trauma patients: A feasibility and pilot randomised controlled trial
Secondary ID [1] 302530 0
Nil known
Universal Trial Number (UTN)
U1111-1259-5534
Trial acronym
BOOST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multi-trauma 319397 0
Critical Illness 319398 0
Condition category
Condition code
Injuries and Accidents 317366 317366 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention: 3 grams of Calcium ß-Hydroxy-ß-Methylbutrate (HMB-Ca) dissolved in either 150ml of orange juice for those allowed oral intake or 150ml of water for those being enterally fed.

The intervention/ control will be administered by a nurse once daily over hospital admission from day 1 post enrollment until day 28 or hospital discharge. Consumption of the intervention/placebo will be monitored daily through nursing administration records in the medication administration records.

In a sub-group of patients who do not meet additional exclusion criteria and whose medical treatment decision maker (MTDM) provide consent, a muscle biopsy and plasma sample will be collected on day 1 post enrollment and again at day 7 post enrollment.
Intervention code [1] 318816 0
Treatment: Other
Comparator / control treatment
Control: Either 150ml of orange juice for those allowed oral intake or 150ml of water for those being enterally fed.
The intervention/ control will be administered by a nurse once daily over hospital admission from day 1 post enrollment until day 28 or hospital discharge.
Control group
Placebo

Outcomes
Primary outcome [1] 325404 0
Successful blinding of the intervention determined through patient and clinician surveys.
Timepoint [1] 325404 0
Blinding surveys (patient and clinician) will be completed on day 1 and again at hospital discharge.
Primary outcome [2] 325717 0
Recruitment and retention rates will be analysed for patients who meet all inclusion and none of the exclusion criteria at completion of the study.
Timepoint [2] 325717 0
Recruitment and retention will be assessed once the last participant has completed the final outcome measure.
Primary outcome [3] 325718 0
The amount of HMB supplementation actually administered compared to the amount intended with full protocol compliance.
Timepoint [3] 325718 0
Assessed daily from via the medication administration record documented by nursing staff in the medical record from recruitment until hospital discharge or day 28 of the study.
Secondary outcome [1] 387795 0
Primary Outcome [4]:
Feasibility of administering the intervention or control will be declared if greater than 75% of eligible participants are able to consume 7 days of the intervention or the control (i.e have the potential to receive the minimum intervention dose for a biologically plausible effect).
Timepoint [1] 387795 0
Primary timepoint [4]
Consumption of the intervention/placebo will be assessed daily via the medication administration record documented by nursing staff in the medical record from recruitment until hospital discharge or day 28 of the study.
Secondary outcome [2] 387796 0
Primary Outcome [5]:
The extent of missing data, including death as a competing outcome, and the number of losses to follow up in survivors.
Timepoint [2] 387796 0
Primary timepoint [5]
Assessed at completions of the study.
Secondary outcome [3] 387797 0
Nutrition intake through dietitian analysis of protein and energy provision from enteral or parenteral nutrition documented in the fluid balance charts and/or from food consumption documented food record charts documented in the medial record.
Timepoint [3] 387797 0
From day of enrollment until ICU discharge and then for the first seven days post ICU discharge.
Secondary outcome [4] 387798 0
Patient-reported appetite assessed using a visual analogue scale (VAS).
Timepoint [4] 387798 0
Day of enrollment and then weekly until day 28 or hospital discharge whichever occurs first and again at day 90 post enrollment.
Secondary outcome [5] 387799 0
Muscle mass using ultrasound
Timepoint [5] 387799 0
Day of enrollment and then weekly until day 28 or hospital discharge whichever occurs first and again at day 90 post enrolment.
Secondary outcome [6] 387800 0
Muscle strength using hand grip dynamometry
Timepoint [6] 387800 0
Day of enrollment and then weekly until day 28 or hospital discharge whichever occurs first and again at day 90 post enrollment.
Secondary outcome [7] 387801 0
Physical Function using the ICU mobility scale (IMS).
Timepoint [7] 387801 0
ICU discharge and hospital discharge or day 28 post enrollment.
Secondary outcome [8] 387802 0
Physical function using the Physical Function ICU Test-scored (PFIT-s)
Timepoint [8] 387802 0
ICU discharge
Secondary outcome [9] 387803 0
Quality of life assessed using the EQ-5D-5L questionnaire
Timepoint [9] 387803 0
90 days post enrollment
Secondary outcome [10] 387804 0
(Sub-group) Plasma HMB concentration measured using high-performance liquid chromatography.
Timepoint [10] 387804 0
Baseline and 60 minutes post administration of the intervention/control on day 1 of enrolment
Secondary outcome [11] 387805 0
(Subgroup) Intramuscular HMB concentration and histological assessments from percutaneous muscle biopsy from the quadriceps (vastus lateralis muscle). Muscle HMB concentration and histologically determined quadriceps (vastus lateralis) myofibre cross-sectional area, markers of muscle proteolysis (ratio of protein to DNA), presence or absence of an inflammatory infiltrate, muscle necrosis and mitochondrial content will be examined.
Timepoint [11] 387805 0
Prior to commencement of the intervention (day 0 or 1) and on repeated on day 7 or prior to extubation (whichever occurs first).
Secondary outcome [12] 388793 0
Physical function using the Modified Iowa Level of Activity (mILOA)
Timepoint [12] 388793 0
ICU discharge and then hospital discharge or day 28 post enrollment.
Secondary outcome [13] 388903 0
Change in body weight using standing, chair or hoist scales.
Timepoint [13] 388903 0
Day of enrollment and then weekly until day 28 or hospital discharge whichever occurs first and again at day 90 post injury.
Secondary outcome [14] 388905 0
Malnutrition status using the Subjective Global Assessment (SGA)
Timepoint [14] 388905 0
Measured on the day of enrollment and then day 28 or hospital discharge whichever occurs first and again at day 90 post enrollment.

Eligibility
Key inclusion criteria
a. Adults, 18 years of age and older
b. Completed two full calendar days in ICU
c. The predominant reason for ICU admission was a traumatic injury
d. Allowed enteral/ oral nutrition at the time of randomization

Inclusion criteria for the muscle biopsy sub group as above.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
a. Death during ICU admission deemed to be inevitable
b. Bilateral above knee amputation
c. Patients assessed as requiring completely or predominantly parenteral nutrition
d. Pregnancy
e. Primary neuromuscular pathology present or strongly suspected this admission episode
f. Presumed transection of the spinal cord at any level
g. Medical decision treatment maker, participant or medical practitioner declined consent
h. Limited research availability over enrolment timeframe
I. Enrollment conflict with other research studies
j. Unlikely to be able to participate in long term follow up measures
k. Unable to obtain consent within 7 days from initial traumatic injury

Additional exclusion criteria for the muscle biopsy sub-group:
g. Not mechanically ventilated at the time of enrollment or predicted to be extubated within 48 hours of enrollment.
h. Present or strongly suspected disseminated cancer of any kind
i. Bleeding diathesis (corrected INR > 1.5 and/or APTT > 50 sec), or receiving any anticoagulant medication beyond that required for venous thromboembolism prophylaxis, or any antiplatelet drug other than low dose aspirin

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will involve contacting the suitably qualified person who is not involved in the study, located in an off site administration location and is the holder of the allocation schedule which is concealed in locked electronic file.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation to either the intervention or control group using a simple randomisation system in a [1:1] allocation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
A convenience sample has been used to determine the primary aim to estimate the feasibility of adequate recruitment and the ability to perform proposed outcome measures in this patient cohort.
Descriptive statistics and tables will be used to summarize relevant patient demographics and outcomes overall and according to the two treatment groups. Continuous data will be reported as means (with standard deviations) if approximately normally distributed, and medians (inter-quartile range) and full [range] otherwise. Categorial data will be reported as frequencies and summarized as proportions with 95% confidence intervals as appropriate.
Differences between the two treatment groups will be analysed using the two-sample unpaired t-test for approximately normal data, the Wilcoxon-rank sum test for substantially skew data and the Fisher’s exact test for categorical variables within contingency tables. Group differences for the change weight, muscle mass, and muscle strength from baseline to day 90 enrollment will be compared after adjustment for initial baseline values and other selected potentially relevant co-variables using linear regression (analysis of covariance, ANCOVA). Statistical significance will be set conventionally at a p value of 0.05. Given the clinical severity of the critical care trauma patients under study, deaths prior to recruitment and during the study are likely, both of which form of patient losses may influence the statistical validity of the observed outcomes in the study cohort. In the presence of sufficient data, exploratory time-to-event analyses in competing-risks regression models returning subhazard functions of failure events of primary interest while accounting for the competing outcome of death will be explored according to the method of Fine and Gray (1999). Multiplicity of testing will be acknowledged but multiple statistical tests will be otherwise unadjusted, consistent with the exploratory nature of this pilot study. Data analyses will be carried out using the Statistical Package for the Social Sciences (IBM® SPSS® Statistics Premium Grad Pack Version 25.0) or Stata Corporation (Stata Statistical Software: Release 16. College Station, TX: StataCorp LP; 2019).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 17817 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 31670 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 306966 0
Hospital
Name [1] 306966 0
The Royal Melbourne Hospital Mary Elizabeth Watson Early Career Research Fellowship
Address [1] 306966 0
The Royal Melbourne Hospital
300 Grattan Street,
Parkville, VIC 3050
Country [1] 306966 0
Australia
Primary sponsor type
Hospital
Name
The Royal Melbourne Hospital
Address
The Royal Melbourne Hospital
300 Grattan Street,
Parkville, VIC 3050
Country
Australia
Secondary sponsor category [1] 307529 0
None
Name [1] 307529 0
Address [1] 307529 0
Country [1] 307529 0
Other collaborator category [1] 281511 0
University
Name [1] 281511 0
The University of Melbourne
Address [1] 281511 0
The University of Melbourne
Grattan Street
Parkville, VIC 3010
Country [1] 281511 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307100 0
Melbourne Health HREC
Ethics committee address [1] 307100 0
The Royal Melbourne Hospital,
Level 2, South West Building,
300 Grattan Street,
Parkville, VIC 3050
Ethics committee country [1] 307100 0
Australia
Date submitted for ethics approval [1] 307100 0
27/11/2019
Approval date [1] 307100 0
03/02/2020
Ethics approval number [1] 307100 0
2019.358

Summary
Brief summary
Patients who survive ICU stay often develop important muscle weakness and rapid reduction in muscle mass. Furthermore, they often have notable deficits in nutritional intake. These changes in body composition and nutritional shortfalls may negatively impact long term outcomes and recovery. Therefore, ward based interventions or therapeutic agents which may slow muscle loss or aid in recovery from critical illness associated muscle loss have the potential to deliver clinical benefits.
This study aims to determine the feasibility of providing a nutrition intervention to critically ill multi-trauma populations throughout hospital admission at the Royal Melbourne Hospital. Secondly, we aim to describe nutrition related patient outcomes (including anthropometric changes, nutritional intake, muscle strength and physical function) in this group.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 106034 0
Ms Kym Wittholz
Address 106034 0
The Royal Melbourne Hospital
Level 4 Main building, Allied Health
300 Grattan Street,
Parkville, VIC 3050
Country 106034 0
Australia
Phone 106034 0
+61 3 9342 7440
Fax 106034 0
+61 3 9342 8440
Email 106034 0
kym.wittholz@mh.org.au
Contact person for public queries
Name 106035 0
Ms Kym Wittholz
Address 106035 0
The Royal Melbourne Hospital
Level 4 Main building, Allied Health
300 Grattan Street,
Parkville, VIC 3050
Country 106035 0
Australia
Phone 106035 0
+61 3 9342 7440
Fax 106035 0
+61 3 9342 8440
Email 106035 0
kym.wittholz@mh.org.au
Contact person for scientific queries
Name 106036 0
Ms Kym Wittholz
Address 106036 0
The Royal Melbourne Hospital
Level 4 Main building, Allied Health
300 Grattan Street,
Parkville, VIC 3050
Country 106036 0
Australia
Phone 106036 0
+61 3 9342 7440
Fax 106036 0
+61 3 9342 8440
Email 106036 0
kym.wittholz@mh.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No IDP data will be shared at this stage
What supporting documents are/will be available?
No other documents available
Summary results
No Results