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Trial registered on ANZCTR


Registration number
ACTRN12615000876594
Ethics application status
Approved
Date submitted
4/08/2015
Date registered
21/08/2015
Date last updated
15/02/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Targeted Full Energy and Protein Delivery in Critically Ill Patients: A Pilot Randomised Control Trial
Scientific title
Targeted Full Energy and Protein Delivery in Critically Ill Patients: A Pilot Randomised Control Trial
Secondary ID [1] 287217 0
nil
Universal Trial Number (UTN)
U1111-1172-8563
Trial acronym
FEED Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Critical illness 295813 0
Condition category
Condition code
Diet and Nutrition 296074 296074 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention group will receive their nutrition care based on the FEED protocol. This protocol has been devised in order to optimise both energy and protein delivery, in line with best practise guidelines. A high protein feed (Nutrison Protein plus 1.25kcal/ml) will be used in order to meet higher protein targets of 1.5g/kg/day IBW. A volume based approach will be used to deliver 25kcal/kg IBW. If the feeds are interrupted the feeding rate will be adjusted to ensure the target volume is delivered over a 24 hour period. Supplementary protein will be provided using Beneprotein, in 7g boluses, to ensure the patient meets a protein target of 1.5g/kg/day IBW. The intervention will be provided continuously over a 24 hour period, while the participant is receiving enteral feeds or up until day 15 of the ICU admission.
Intervention code [1] 292503 0
Treatment: Other
Comparator / control treatment
The control group will receive standard nutrition care, this will include commencing a standard 1.0kcal/ml enteral formula (Nutrison 1.0kcal). The feed will be commenced using the RMH ICU protocol and the target rate will be set at 25kcal/kg Ideal body weight (IBW), to avoid overfeeding. This is in line with international guidelines and is viewed as standard practice. Therefore it is expected that participants will be provided with 25kcal/kg IBW of energy and about 1.0g/kg IBW of protein. Enteral feed tolerance will be assessed as per the standard RMH ICU protocol.
Control group
Active

Outcomes
Primary outcome [1] 302311 0
The co-primary outcome is the average daily energy and protein delivery between the 2 groups
This will be determined by calculating the daily energy and protein delivered from all sources from the fluid balance charts
Timepoint [1] 302311 0
Daily from enrolment to study day 15
Secondary outcome [1] 316409 0
ICU Length of Stay, using hospital records
Timepoint [1] 316409 0
Day 60
Secondary outcome [2] 316410 0
28 day and 60 day mortality and discharge destination
Timepoint [2] 316410 0
Day 60
Secondary outcome [3] 335440 0
Muscle Strength - Using handgrip dynamometry and the Medical Research Council (MRC) scale
Timepoint [3] 335440 0
Baseline, Day 5 and Discharge or day 15
Secondary outcome [4] 335441 0
Muscle Mass - Using ultrasound to measure Quadriceps Muscle Layer Thickness (QMLT) bilaterally at two points; the midpoint between the Anterior Superior Iliac Spine (ASIS) and the upper pole of the patella and at the point 2/3 between the ASIS and the top of the patella
Timepoint [4] 335441 0
Baseline, day 5, day 10 and day 15 or discharge
Secondary outcome [5] 335442 0
Physical function - using the physical function in ICU test score
Timepoint [5] 335442 0
awakening and discharge or day 15
Secondary outcome [6] 335443 0
Incidence of ICU -AW (MRC score <48)
Timepoint [6] 335443 0
Discharge from ICU or study day 15

Eligibility
Key inclusion criteria
Adutls who are 18 years of Age and Mechanically ventilated for 48hrs, with no plans to extubate
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who have a contraindication to enteral feeding; A limit of medical treatment order in place; Pre-morbid disability causing inability to ambulate > 10m independently (+/- gait aid) Pregnancy; The attending physician does not support inclusion

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)
This study will take place in a single centre tertiary 24 bed ICU. Recruitment will only occur from Monday to Friday 8:00-17:00, over an 18 month period. Patients must be recruited within 48 hours of admission. Patients who meet the inclusion criteria will be invited to participate in the study. As the patients will be Mechanically ventilated they will be unable to consent themselves, therefore written informed consent will be obtained from the person responsible and continuation of consent will be obtained from the participant as soon as they are deemed competent.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
There will be a total of 60 participants, with 30 in each group, based on the primary outcome of average energy and protein delivery.
Sample size is based on observational data (Fetterplace et al abstract) Based on mean (SD) daily intake of 50.8 g (20.1 g) protein per day, 29 participants per group will provide 80% power (two-sided a 0.05) to detect a minimum difference of 15 g protein between groups
Then participants will be randomly assigned [1:1] to receive either standard care or the intervention using Simple randomisation. Opaque sealed envelopes, will be used, 30 envelopes will be allocated to group A (Standard Care) and 30 to group B (Feed Protocol). They will be shuffled and provided to independent research personnel with no involvement in the trial.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Due to the nature of the intervention, the dietitians and nursing staff cannot be blinded. The treating physicians will not be involved in the study, however they may be aware of the group allocations. However the physiotherapist involved in outcome measures of muscle strength and physical function will be blinded to the group allocations. This will be achieved by using a label over the feed product and by using a study folder at the bedside for nursing staff to follow. The data analysts will be blinded to group allocations.
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis
All analyses will use an intention-to-treat approach to identify the full analysis patient set. Baseline data in patient demographics, severity of illness, ICU length of stay, mortality and nutritional markers will be tabulated according to treatment group. Initial exploratory data analysis will involve calculation of summary statistics, and comparison between treatment groups using non-parametric (Wilcoxon), parametric (t-test) and Fisher exact tests as appropriate, as well as construction of trajectory plots according to treatment group. The co-primary outcomes of average daily energy consumption and delivered protein will be compared between treatment and control groups with two-sample unpaired t tests, with statistical significance for each set conservatively at two-sided values of 0.025 to limit the family-wise type 1 error for the two co-primary outcomes to less than 0.05 overall.

All secondary outcomes will be regarded as exploratory and hypothesis-generating, with no multiple comparison adjustment to conventional 5% type 1 error thresholds. Group differences for change from baseline at selected time points in continuous outcome variables, including QMLT, will be compared after adjustment for initial values using analysis of covariance (ANCOVA) regression models, initially unadjusted, and subsequently adjusted as described below for other regression models. Natural logarithmic transformations may be applied to stabilize variance within these or other linear models if appropriate. The relationships between calorie deficits using both prescribed calories (25kcal/kg) and MEE and protein adequacy and the outcome measures (QMLT change, muscle strength, diagnosis of ICU AW and physical function at ICU discharge) will be explored using linear or logistic regression analyses, with adjustment for likely confounders and any baseline variable found to show substantial imbalance between treatment groups. Finally, a population-averaged generalized linear model using a generalized estimating equation (GEE) approach with an unstructured working correlation matrix and robust standard error estimates adjusted for clustering within individual subjects will be applied to these longitudinal data to evaluate the overall associations of the vector of (untransformed or log transformed) outcome variables with treatment group across multiple time points. Multiple imputation for missing data may be used to support conclusions from other generalized linear models constructed without imputation of missing data. Data analysis will be carried out using the Statistical Package for the Social Sciences (SPSS) or Stata (Stata Corporation. Stata Statistical Software: Release 14.2. Release 14.2 ed. College Station, TX: StataCorp LP; 2016).

Recruitment
Recruitment status
Completed
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] 4135 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 10066 0
3050 - Royal Melbourne Hospital

Funding & Sponsors
Funding source category [1] 291789 0
Hospital
Name [1] 291789 0
Royal Melbourne Hospital Mary Elizabeth Watson Allied Health Fellowship
Address [1] 291789 0
Royal Melbourne Hospital, 300 Grattan Street Parkville, Victoria, 3050
Country [1] 291789 0
Australia
Primary sponsor type
Hospital
Name
Royal Melbourne Hospital
Address
300 Grattan St, Parkville, VIC, 3050
Country
Australia
Secondary sponsor category [1] 290451 0
University
Name [1] 290451 0
La Trobe University
Address [1] 290451 0
1 Kingsbury Dr, La Trobe University, Bundoora, VIC 3086
Country [1] 290451 0
Australia
Other collaborator category [1] 279591 0
University
Name [1] 279591 0
University of Melbourne
Address [1] 279591 0
Grattan Street, Parkville Victoria 3010
Country [1] 279591 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293307 0
Melbourne Health HREC
Ethics committee address [1] 293307 0
Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC, 3050
Ethics committee country [1] 293307 0
Australia
Date submitted for ethics approval [1] 293307 0
Approval date [1] 293307 0
11/06/2015
Ethics approval number [1] 293307 0
2015.048

Summary
Brief summary
Intensive care admissions, particularly for prolonged periods are often associated with muscle weakness, deconditioning, malnutrition and impaired long-term functional status. Nutrition is a potential modifiable factor to attenuate this deterioration. However defining what optimal nutrition is for critically ill patients in order to improve their outcomes remains controversial and needs further investigation. Despite feeding protocols, internationally and at the Royal Melbourne Hospital (RMH), patients continue to receive inadequate energy and protein compared to recommended targets. Results from our recently completed observational study in Intensive Care at RMH showed that accumulating an energy debt over an Intensive Care Unit (ICU) admission is associated with decreased muscle strength, physical function and the diagnosis of ICU Acquired Weakness (ICUAW). Patients with poorer strength and suboptimal physical function had a longer ICU length of stay and a higher requirement for inpatient rehabilitation, which is associated with increased health costs.

This pilot randomised controlled trial aims to determine if a feeding protocol based on energy and protein targets, using a volume approach decreases muscle wastage and improves muscle strength and functional outcomes at discharge from the ICU compared to standard care. Patients will be randomised to standard care or the targeted feeding protocol which aims to provide 25kcal per kilogram and 1.5g protein per kilogram, which is in line with international best practice guidelines. The study period is from day of enrolment until ICU day 15 or discharge from ICU. Data collection will be the same for both groups and will include demographic data, the amount of energy and protein delivered, nutritional markers; such as weight and nutritional status and outcome such as length of stay and length of mechanical ventilation. Muscle strength and physical function will be assessed by the physiotherapist using standardised methods, which have been validated in the ICU. Muscle mass will be measured using ultrasound, which is a non-invasive technique, which has been safely used in the ICU. Data from this study will assist in informing future research studies to answer important clinical questions, including; should higher protein recommendations be targeted and what are the effects of improved calorie and protein delivery on functional outcomes for patients. This study will provide feasibility data to inform large multicentre randomised control trials.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 59318 0
Miss Kate Fetterplace
Address 59318 0
Allied Health, Royal Melbourne Hospital, 300 Grattan St Parkville, VIC, 3050
Country 59318 0
Australia
Phone 59318 0
+61 3 93247440
Fax 59318 0
+61 3 93428440
Email 59318 0
Kate.fetterplace@mh.org.au
Contact person for public queries
Name 59319 0
Miss Kate Fetterplace
Address 59319 0
Allied Health, Royal Melbourne Hospital, 300 Grattan St Parkville, VIC, 3050
Country 59319 0
Australia
Phone 59319 0
+61 3 93247440
Fax 59319 0
Email 59319 0
Kate.fetterplace@mh.org.au
Contact person for scientific queries
Name 59320 0
Miss Kate Fetterplace
Address 59320 0
Allied Health, Royal Melbourne Hospital, 300 Grattan St Parkville, VIC, 3050
Country 59320 0
Australia
Phone 59320 0
+61 3 93247440
Fax 59320 0
Email 59320 0
Kate.fetterplace@mh.org.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary