ANZCTR - Registration

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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

2/07/2021

Date data sharing statement initially provided

9/11/2018

Date results provided

2/07/2021

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

Secondary ID [1]

None

Universal Trial Number (UTN)

U1111-1223-3918

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Critical Illness

Condition category

Condition code

Diet and Nutrition

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day 28, treating clinician feels that it is in the patient’s best interest to cease the study intervention, consent is withdrawn before day 28, oral nutrition is commenced, additional enteral nutrition supplements are commenced, patient dies prior to day 28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]

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day 28, treating clinician feels that it is in the patient’s best interest to cease the study intervention, consent is withdrawn before day 28, oral nutrition is commenced, additional enteral nutrition supplements are commenced, patient dies prior to day 28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]

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]

Daily during up to 28 days of intervention

Secondary outcome [1]

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]

Daily during up to 28 days of intervention

Secondary outcome [2]

Recruitment rate - time frame required to recruit 120 patients - Feasibility outcome of study process

Timepoint [2]

Time taken to recruit 120 patients

Secondary outcome [3]

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]

Completed on day 2 and day 7 of intervention

Secondary outcome [4]

Number of episodes of vomiting. Data will be collected from patients medical records - Feasibility outcome of study process

Timepoint [4]

Daily during up to 28 days of intervention

Secondary outcome [5]

Serum urea - when measured for clinical purposes and highest for calendar day - Feasibility outcome of study process

Timepoint [5]

Daily during up to 28 days of intervention

Secondary outcome [6]

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]

Daily during up to 28 days of intervention

Secondary outcome [7]

Incident gastrokinetic drug administration for enteral feed intolerance, assessed by viewing medical records for gastrokinetic drug administration - Feasibility outcome of study process

Timepoint [7]

Daily during up to 28 days of intervention

Secondary outcome [8]

Bowel dysfunction assessed by viewing medical records for number of bowel motions per day - Feasibility outcome of study process

Timepoint [8]

Daily during up to 28 days of intervention

Secondary outcome [9]

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]

Daily during up to 28 days of intervention

Secondary outcome [10]

Serum creatinine - when measured for clinical purposes and highest for calendar day

Timepoint [10]

Daily during up to 28 days of intervention

Secondary outcome [11]

Serum albumin - when measured for clinical purposes and lowest for calendar day

Timepoint [11]

Daily during up to 28 days of intervention

Secondary outcome [12]

Serum phosphate - when measured for clinical purposes and lowest for calendar day

Timepoint [12]

Daily on days 1 to 7 in which TARGET Protein EN is delivered

Secondary outcome [13]

Blood glucose (closest to 0800 h)

Timepoint [13]

Daily during up to 28 days of intervention

Secondary outcome [14]

Serum potassium - when measured for clinical purposes and lowest for calendar day

Timepoint [14]

Daily on days 1 to 7 in which TARGET Protein EN is delivered

Secondary outcome [15]

Serum magnesium - when measured for clinical purposes and lowest for calendar day

Timepoint [15]

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

Sex

Both males and females

Can healthy volunteers participate?

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

Completed

Date of first participant enrolment

Anticipated

1/02/2019

Actual

11/04/2019

Date of last participant enrolment

Anticipated

1/08/2019

Actual

3/07/2019

Date of last data collection

Anticipated

1/11/2019

Actual

1/10/2019

Sample size

Target

120

Accrual to date

Final

120

Recruitment in Australia

Recruitment state(s)

NSW,SA,VIC

Recruitment hospital [1]

The Alfred - Prahran

Recruitment hospital [2]

Austin Health - Austin Hospital - Heidelberg

Recruitment hospital [3]

Frankston Hospital - Frankston

Recruitment hospital [4]

The Royal Adelaide Hospital - Adelaide

Recruitment hospital [5]

Royal Melbourne Hospital - City campus - Parkville

Recruitment hospital [6]

The Queen Elizabeth Hospital - Woodville

Recruitment hospital [7]

Royal Prince Alfred Hospital - Camperdown

Recruitment postcode(s) [1]

3004 - Prahran

Recruitment postcode(s) [2]

3084 - Heidelberg

Recruitment postcode(s) [3]

3199 - Frankston

Recruitment postcode(s) [4]

5000 - Adelaide

Recruitment postcode(s) [5]

3050 - Parkville

Recruitment postcode(s) [6]

5011 - Woodville

Recruitment postcode(s) [7]

2050 - Camperdown

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Wellington Region

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

The Hospital Research Foundation, Royal Adelaide Hospital

Address [1]

Port Road, Adelaide, South Australia 5000

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Central Adelaide Local Health Network Human Research Ethics Committee

Ethics committee address [1]

L3 Roma Mitchell House, North Terrace, Adelaide, South Australia 5000

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

24/09/2018

Approval date [1]

09/11/2018

Ethics approval number [1]

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

A/Prof Adam Deane

Address

Intensive Care Unit, The Royal Melbourne Hospital – City Campus, Grattan Street, Parkville Victoria 3050

Country

Australia

Phone

+61 3 9342 9253

Fax

+61 3 9342 8812

[email protected]

Contact person for public queries

Name

Adam Deane

Address

Intensive Care Unit, The Royal Melbourne Hospital – City Campus, Grattan Street, Parkville Victoria 3050

Country

Australia

Phone

+61 3 9342 9253

Fax

+61 3 9342 8812

[email protected]

Contact person for scientific queries

Name

Adam Deane

Address

Intensive Care Unit, The Royal Melbourne Hospital – City Campus, Grattan Street, Parkville Victoria 3050

Country

Australia

Phone

+61 3 9342 9253

Fax

+61 3 9342 8812

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Study results article	Yes		Published 2 December 2020, Journal of Parenteral a... [More Details]	376300-(Uploaded-20-01-2021-15-55-14)-Journal results publication.pdf

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Use of a High-Protein Enteral Nutrition Formula to Increase Protein Delivery to Critically Ill Patients: A Randomized, Blinded, Parallel-Group, Feasibility Trial.	2021	https://dx.doi.org/10.1002/jpen.2059

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically