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Trial registered on ANZCTR


Registration number
ACTRN12618001829202
Ethics application status
Approved
Date submitted
2/11/2018
Date registered
9/11/2018
Date last updated
17/05/2019
Date data sharing statement initially provided
9/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
TARGET Protein Feasibility Study: a prospective, blinded, parallel group, randomised controlled trial to assess the feasibility of conducting a phase III trial of protein targets in critically ill adults
Scientific title
TARGET Protein Feasibility Study: a prospective, blinded, parallel group, randomised controlled trial to assess the feasibility of conducting a phase III trial of protein targets in critically ill adults
Secondary ID [1] 296492 0
None
Universal Trial Number (UTN)
U1111-1223-3918
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Critical Illness 310273 0
Condition category
Condition code
Diet and Nutrition 309011 309011 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention enteral nutrition (EN) will be a higher protein formula produced by Nutricia with 1.25 kcal/ml and 100 g protein in 1000 ml bag. Study protocol EN will be delivered via naso-enteric tube for a maximum of 28 days. The goal rate for administration of protocol EN will be 1ml/kg of Ideal Body Weight (IBW)/hour, delivered over 24 hours/ day

The blinded protocol EN will cease if one of the following occur: cessation of EN by the treating clinicians before day 28, patient is discharged from the ICU before day 28, treating clinician feels that it is in the patient’s best interest to cease the study intervention, consent is withdrawn before day 28, oral nutrition is commenced, additional enteral nutrition supplements are commenced, patient dies prior to day 28

Intervention code [1] 312814 0
Treatment: Other
Comparator / control treatment
Standard care EN will be ‘Nutrison Protein Plus’ 1.25 kcal/ml and 63 g protein in 1000 ml bag. Study protocol EN will be delivered via naso-enteric tube for a maximum of 28 days. The goal rate for administration of protocol EN will be 1ml/kg of IBW/hour, delivered over 24 hours/ day

The blinded protocol EN will cease if one of the following occur: cessation of EN by the treating clinicians before day 28, patient is discharged from the ICU before day 28, treating clinician feels that it is in the patient’s best interest to cease the study intervention, consent is withdrawn before day 28, oral nutrition is commenced, additional enteral nutrition supplements are commenced, patient dies prior to day 28
Control group
Active

Outcomes
Primary outcome [1] 307968 0
Mean daily protein delivery (g/kg IBW/day) and group separation by study randomisation.
The overall protein delivery will be calculated as total intake divided by the number of days fed and expressed as intake per 24 h - feasibility outcome
Timepoint [1] 307968 0
Daily during up to 28 days of intervention
Secondary outcome [1] 353522 0
Number of days in which enrolled patients receive TARGET Protein Protocol EN. Data will be collected from medical records and electronic randomisation database - Feasibility outcome of study process
Timepoint [1] 353522 0
Daily during up to 28 days of intervention
Secondary outcome [2] 353523 0
Recruitment rate - time frame required to recruit 120 patients - Feasibility outcome of study process
Timepoint [2] 353523 0
Time taken to recruit 120 patients
Secondary outcome [3] 353524 0
Blinding of intervention - as evaluated by bedside nurse, treating dietitian and/or treating physician - composite secondary outcome. This will be assessed through a questionnaire designed specifically for this study - Feasibility outcome of study process
Timepoint [3] 353524 0
Completed on day 2 and day 7 of intervention
Secondary outcome [4] 353525 0
Number of episodes of vomiting. Data will be collected from patients medical records - Feasibility outcome of study process
Timepoint [4] 353525 0
Daily during up to 28 days of intervention
Secondary outcome [5] 353526 0
Serum urea - when measured for clinical purposes and highest for calendar day - Feasibility outcome of study process
Timepoint [5] 353526 0
Daily during up to 28 days of intervention
Secondary outcome [6] 353667 0
Need for cessation of EN for enteral feed intolerance, as assessed by viewing medical records for documented reasons for EN cessation - Feasibility outcome of study process
Timepoint [6] 353667 0
Daily during up to 28 days of intervention
Secondary outcome [7] 353668 0
Incident gastrokinetic drug administration for enteral feed intolerance, assessed by viewing medical records for gastrokinetic drug administration - Feasibility outcome of study process
Timepoint [7] 353668 0
Daily during up to 28 days of intervention
Secondary outcome [8] 353669 0
Bowel dysfunction assessed by viewing medical records for number of bowel motions per day - Feasibility outcome of study process
Timepoint [8] 353669 0
Daily during up to 28 days of intervention
Secondary outcome [9] 353670 0
Highest gastric residual volume in each 24 hour period assessed by viewing medical records for documented gastric residual volumes - Feasibility outcome of study process
Timepoint [9] 353670 0
Daily during up to 28 days of intervention
Secondary outcome [10] 353671 0
Serum creatinine - when measured for clinical purposes and highest for calendar day
Timepoint [10] 353671 0
Daily during up to 28 days of intervention
Secondary outcome [11] 353672 0
Serum albumin - when measured for clinical purposes and lowest for calendar day
Timepoint [11] 353672 0
Daily during up to 28 days of intervention
Secondary outcome [12] 353673 0
Serum phosphate - when measured for clinical purposes and lowest for calendar day
Timepoint [12] 353673 0
Daily on days 1 to 7 in which TARGET Protein EN is delivered
Secondary outcome [13] 353674 0
Blood glucose (closest to 0800 h)
Timepoint [13] 353674 0
Daily during up to 28 days of intervention
Secondary outcome [14] 353675 0
Serum potassium - when measured for clinical purposes and lowest for calendar day
Timepoint [14] 353675 0
Daily on days 1 to 7 in which TARGET Protein EN is delivered
Secondary outcome [15] 353676 0
Serum magnesium - when measured for clinical purposes and lowest for calendar day
Timepoint [15] 353676 0
Daily on days 1 to 7 in which TARGET Protein EN is delivered

Eligibility
Key inclusion criteria
1. Aged greater than or equal to 18 years old
2. Receiving invasive mechanical ventilation
3. About to commence EN or EN commenced within the previous 12 hours
4. Expected to be receiving EN in ICU beyond the calendar day following randomisation
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Expected to be receiving any oral nutrition before the calendar day following randomisation
2. Any EN or PN received for >12 hours in any ICU admission in this hospital episode
3. Previously enrolled in this study
4. Treating clinician considers the EN goal rate (i.e. 1ml/kg of ideal body weight (IBW) per hour) to be clinically contraindicated e.g. requirement for fluid restriction
5. Treating clinician considers that either dose of protein delivered in this study is unsuitable for the patient.
6. Requirement for specific nutritional therapy as determined by the treating doctor or dietitian i.e. protocol EN not considered to be in the best interest of the subject

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)
Central randomisation will be performed using a randomisation website (SPIRAL). Research and clinical staff will be blinded to treatment allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A permuted block randomisation method with variable block sizes, stratified by site will be used to allocate eligible patients to either standard or augmented protein delivery in a 1:1 ratio.
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
Both the high protein enteral nutrition (100 g protein in 1000 ml bag.) and the standard protein enteral nutrition (63 g protein in 1000 ml bag) will be administered in identical 500ml bottles. The formulations will be indistinguishable in color and packaging.
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The primary aim is to establish adequate treatment separation in terms of protein doses with ‘augmented protein’ providing a dose of protein that is within guideline recommendations and ‘control’ representing usual standard care. There will be a number of secondary outcomes (feasibility or study processes) that will provide information to optimise study design of a phase III RCT. Tertiary outcomes will also be reported for important clinical outcomes; e.g. death, duration of ICU admission (point estimate and 95% CI for all.).

The sample size is set at N=120 in order to allow for separation of the treatment groups, as well as establish feasibility of recruitment rate, consent rate, drop-out rates, and protocol adherence. Assuming equal group allocation and an a-level of 0.05, this number would achieve >95% power for group separation; based upon the use of enteral formula suitable for blinding and assuming feed rates equivalent to the TARGET feasibility study, with estimated standard group mean (SD) 0.92 (0.32) g/kg/day and intervention arm 1.46 (0.5) g/kg/day.

Recruitment
Recruitment status
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)
NSW,SA,VIC
Recruitment hospital [1] 12328 0
The Alfred - Prahran
Recruitment hospital [2] 12329 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [3] 12330 0
Frankston Hospital - Frankston
Recruitment hospital [4] 12331 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [5] 12332 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [6] 12333 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [7] 12334 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 24566 0
3004 - Prahran
Recruitment postcode(s) [2] 24567 0
3084 - Heidelberg
Recruitment postcode(s) [3] 24568 0
3199 - Frankston
Recruitment postcode(s) [4] 24569 0
5000 - Adelaide
Recruitment postcode(s) [5] 24570 0
3050 - Parkville
Recruitment postcode(s) [6] 24571 0
5011 - Woodville
Recruitment postcode(s) [7] 24572 0
2050 - Camperdown
Recruitment outside Australia
Country [1] 20985 0
New Zealand
State/province [1] 20985 0
Wellington Region

Funding & Sponsors
Funding source category [1] 301079 0
Hospital
Name [1] 301079 0
The Hospital Research Foundation, Royal Adelaide Hospital
Address [1] 301079 0
Port Road, Adelaide, South Australia 5000
Country [1] 301079 0
Australia
Primary sponsor type
Individual
Name
Professor Marianne Chapman
Address
Intensive Care Unit, Royal Adelaide Hospital, Port Road, Adelaide, South Australia SA 5000
Country
Australia
Secondary sponsor category [1] 300689 0
None
Name [1] 300689 0
NA
Address [1] 300689 0
NA
Country [1] 300689 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301832 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 301832 0
L3 Roma Mitchell House, North Terrace, Adelaide, South Australia 5000
Ethics committee country [1] 301832 0
Australia
Date submitted for ethics approval [1] 301832 0
24/09/2018
Approval date [1] 301832 0
09/11/2018
Ethics approval number [1] 301832 0
HREC reference number: HREC/18/CALHN/658

Summary
Brief summary
An 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, usually delivered to ICU patients as liquid feed via a tube into the stomach. The provision of additional protein has the potential to improve at least part of the significant muscle atrophy that occurs, and hence enhance functional recovery from critical illness. A number of observational research studies have reported that a large proportion of ICU patients do not meet prescribed protein targets, with protein delivered closer to prescribed targets associated with reduced mortality, ventilation and ICU and hospital length of stay. Currently guidelines recommend delivery of protein doses of 1.2 - 2.0 g/kg/day or higher, but this is based on very low quality of evidence. Therefore, there is a need for high-quality randomised controlled trials of differing protein doses.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 88258 0
A/Prof Adam Deane
Address 88258 0
Intensive Care Unit, The Royal Melbourne Hospital – City Campus, Grattan Street, Parkville Victoria 3050
Country 88258 0
Australia
Phone 88258 0
+61 3 9342 9253
Fax 88258 0
+61 3 9342 8812
Email 88258 0
adam.deane@mh.org.au
Contact person for public queries
Name 88259 0
A/Prof Adam Deane
Address 88259 0
Intensive Care Unit, The Royal Melbourne Hospital – City Campus, Grattan Street, Parkville Victoria 3050
Country 88259 0
Australia
Phone 88259 0
+61 3 9342 9253
Fax 88259 0
+61 3 9342 8812
Email 88259 0
adam.deane@mh.org.au
Contact person for scientific queries
Name 88260 0
A/Prof Adam Deane
Address 88260 0
Intensive Care Unit, The Royal Melbourne Hospital – City Campus, Grattan Street, Parkville Victoria 3050
Country 88260 0
Australia
Phone 88260 0
+61 3 9342 9253
Fax 88260 0
+61 3 9342 8812
Email 88260 0
adam.deane@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
What supporting documents are/will be available?
No other documents available
Summary results
No Results