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Trial registered on ANZCTR


Registration number
ACTRN12614000166673
Ethics application status
Approved
Date submitted
4/02/2014
Date registered
11/02/2014
Date last updated
2/03/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Diabetes specific formulae versus standard formulae as enteral nutrition to treat hyperglycaemia in critically ill patients: study protocol for a randomised controlled feasibility trial
Scientific title
A randomised controlled feasibility trial to determine the efficacy of diabetes specific formulae to reduce exogenous insulin doses required to obtain acceptable glycaemic control when compared to the standard nutritional formula in critically ill tube fed patients
Secondary ID [1] 284029 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Critically ill tube fed ICU patients 291078 0
Hyperglycemia 291101 0
Condition category
Condition code
Metabolic and Endocrine 291422 291422 0 0
Other metabolic disorders
Diet and Nutrition 291423 291423 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following consent participants will be randomised to the control (CHO 142g/L; 1.28kcal/mL), or the intervention, which is a low carbohydrate, low glycaemic index diabetes-specific formula (CHO 75g/L; 1kcal/mL), Once treatment allocation has occurred, participants will remain on treatment as long as tube feeding continues in ICU or as per the treating physician. All investigators and the participant will be blinded to treatment allocation. Nutritional requirements will be calculated by providing an average of 100-125kJ/kg body weight or adjusted ideal body weight (BW / AIBW) and 1.2-1.5g protein/kg BW/AIBW as per current practice.
For the purpose of a biomarker sub-study, a second intervention arm using a different low glycaemic index diabetes specific formula will be used (CHO 113g/L; 1kcal/mL). Randomisation to this arm will be ceased once blood and urine samples are available for the first 10-12 participants in each group. These samples will be collected from all patients at randomisation and 48 hours later. Once this has been achieved, randomisation will revert to control and intervention groups only. Collection of urine and blood samples for biomarker assay will also be discontinued at this point.
Intervention code [1] 288720 0
Treatment: Other
Comparator / control treatment
Standard feed of carbohydrate content of 142g/L
Control group
Active

Outcomes
Primary outcome [1] 291410 0
Units of insulin administered over 48 hours.
Timepoint [1] 291410 0
48 hours after commencement of the feed.
Secondary outcome [1] 306705 0
Glycaemic variability as defined by the coefficient of variation (%) which is = (standard deviation of blood glucose levels/mean of blood glucose levels) X 100
Timepoint [1] 306705 0
48 hours after commencement of the feed.
Secondary outcome [2] 306706 0
Mortality
Timepoint [2] 306706 0
28 days after commencement of the feed.
Secondary outcome [3] 306707 0
Readmission to ICU and length of stay.
Timepoint [3] 306707 0
Within 28 days after initial ICU discharge.
Secondary outcome [4] 306708 0
Length of mechanical ventilation
Timepoint [4] 306708 0
Within 48 hours of commencement of feed.
Secondary outcome [5] 306709 0
Ability to meet protein and energy requirements
Timepoint [5] 306709 0
Within 48 hours of commencement of feed.
Secondary outcome [6] 306710 0
Incidence of diarrhoea
Timepoint [6] 306710 0
Within 48 hours of commencement of feed.
Secondary outcome [7] 306711 0
Requirement for prokinetic medications
Timepoint [7] 306711 0
Within 48 hours of commencement of feed.
Secondary outcome [8] 306712 0
Oxidative stress and antioxidant capacity as well as acute and chronic inflammatory markers (plasma inflammatory cytokine panel, CRP, Advanced Glycation End (AGE) products and soluble receptor for AGE (sRAGE))
Timepoint [8] 306712 0
At baseline and 48 hours post commencement of feed
Secondary outcome [9] 333397 0
The sufficiency of the current eligibility criteria to ensure patients are appropriately screened, consented and recruited. Investigators will be contacted by staff members identifying eligible patients. These patients will then be assessed by investigators as to whether they are appropriate prior to consent being sought. The inclusion and exclusion criteria will be considered successful if 95% of patients are identified appropriately.
Timepoint [9] 333397 0
Assessed during the course of the study
Secondary outcome [10] 333398 0
To assess if a minimum pre-defined period of time expected on nutrition support should be included as a component of the inclusion criteria. This will be assessed by the proportion of patients reaching the 48 hour mark on nutrition support. The expectation is that at least 80% of patients will remain on exclusive tube fed nutrition for 48 hours post randomisation for the current process to be considered successful
Timepoint [10] 333398 0
Assessed during the course of the study
Secondary outcome [11] 333399 0
Recruitment rates to assess number of eligible patients accounting for consent.
Timepoint [11] 333399 0
Assessed during the course of the study

Eligibility
Key inclusion criteria
A patient is receiving exclusive enteral nutrition and requires an insulin infusion. Patients with two consecutive blood glucose levels > 10mmol/L are likely to commence on an insulin infusion based on the units’ glucose management protocol.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
The exclusion criteria for this study include patients <18, declined consent by patient/ legally authorised representative, or if recruitment to the study is deemed clinically inappropriate by the treating physician.

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 is a prospective randomised control trial of a minimum of 54 ICU patients. Randomisation between three arms will be performed initially by a computer generated sequence which will then be put into sequentially numbered envelopes. Block randomisation will be used. Envelopes will be prepared by a non-investigator to include the treatment arm (denoted as Feed A, Feed B or Feed C). Once 10 patients have been recruited to the second intervention arm (CHO 113g/L; 1kcal/mL), further recruitment to this treatment will cease, and the trial continue with the remaining interventional arm (74g/L; 1kcal/mL), and the control arm (142 g/L; 1.28kcal/mL)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Allocations to groups will be generated through a randomisation table created by computer software (i.e. simple randomisation, computerised sequence generation). Group allocations will be allocated and concealed sequentially by a non-instigator independent of the study.
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
Two arms - a control and interventional arm form the primary study with ~21 patients per arm. A third arm (2nd interventional) of ~12 patients will be recruited as part of a nested cohort study.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Nineteen patients per study arm (two arms) are required to detect a statistically significant difference (alpha 0.05) with a power of 80%. This is based on a median difference of 21.5 units of insulin per day and standard deviation of 22.5 units (Mesejo (2003). Additionally, 10 patients will be randomised to a third arm for a sub-study investigating relevant biomarkers. A 10% buffer of two patients per arm has been added to the estimated sample size to account for patients lost to follow up or retracted consent.

Analysis will be performed using R commander software or equivalent. Descriptive statistics such as frequency, means and standard deviations, medians, interquartile ranges and full ranges will be calculated for demographic and baseline variables as well as for trial endpoints. Linear and logistic analyses will be performed using relevant data, returning point estimates of effect with associated 95% confidence intervals. Cross sectional analyses in cohort study data with equal follow-up time per subject will be analysed with linear (for continuous outcomes) or logistic models (for categorical outcomes).
Linear regression analyses will be used to analyse results from the nested cohort study to determine the contribution of AGE intake, AGE output and insulin dose on sRAGE levels.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
5/01/2015
Actual
30/01/2015
Date of last participant enrolment
Anticipated
31/03/2018
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
54
Accrual to date
53
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 2049 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [2] 2050 0
Mater Private Hospital - South Brisbane
Recruitment postcode(s) [1] 7738 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 288657 0
Charities/Societies/Foundations
Name [1] 288657 0
Mater Foundation and Mater Research Institute
Country [1] 288657 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Mater Foundation and Mater Research Institute
Address
Raymond Terrace, South Brisbane, QLD 4101
Country
Australia
Secondary sponsor category [1] 287368 0
None
Name [1] 287368 0
Address [1] 287368 0
Country [1] 287368 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290509 0
Mater Health Services Human Research Ethics Committee
Ethics committee address [1] 290509 0
Aubigny Place, Raymond Terrace, South Brisbane, Qld 4101
Ethics committee country [1] 290509 0
Australia
Date submitted for ethics approval [1] 290509 0
28/02/2014
Approval date [1] 290509 0
Ethics approval number [1] 290509 0
Ethics committee name [2] 297342 0
The University of Queensland - Instituitional Human Research Ethics Approval
Ethics committee address [2] 297342 0
UQ Research and Innovation, The University of Queensland, Cumbrae-Stewart Building #72, Brisbane, Queensland, 4072, Australia
Ethics committee country [2] 297342 0
Australia
Date submitted for ethics approval [2] 297342 0
01/10/2014
Approval date [2] 297342 0
22/10/2014
Ethics approval number [2] 297342 0
2014001353

Summary
Brief summary
This is a prospective, blinded, randomised controlled feasibility trial of critically ill tube fed ICU patients looking at the effectiveness of diabetes specific nutritional formula in managing stress hyperglycaemia. The primary aim of this study is to determine whether the administration of a diabetes specific formula, when compared to standard enteral formula, reduces insulin use over a 48 hour period. Secondary outcomes include both clinical endpoints and assessment of the feasibility of study processes to inform a potential multi-site RCT.

A sub-study will also be incorporated to determine if altered carbohydrate, is associated with a change in oxidative stress markers, as well acute and chronic inflammatory biomarkers.
Trial website
N/A
Trial related presentations / publications
N/A
Public notes
Nil

Contacts
Principal investigator
Name 46014 0
Mrs Ra'eesa Doola
Address 46014 0
Allied Health reception, Level 3
Salmon Building, Mater Health
Raymond Terrace
South Brisbane, QLD
4101
Country 46014 0
Australia
Phone 46014 0
+61731636000
Fax 46014 0
Email 46014 0
[email protected]
Contact person for public queries
Name 46015 0
Ra'eesa Doola
Address 46015 0
Allied Health reception, Level 3
Salmon Building, Mater Health
Raymond Terrace
South Brisbane, QLD
4101
Country 46015 0
Australia
Phone 46015 0
+61731636000
Fax 46015 0
Email 46015 0
[email protected]
Contact person for scientific queries
Name 46016 0
Ra'eesa Doola
Address 46016 0
Allied Health reception, Level 3
Salmon Building, Mater Health
Raymond Terrace
South Brisbane, QLD
4101
Country 46016 0
Australia
Phone 46016 0
+61731636000
Fax 46016 0
Email 46016 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Current supporting documents:


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23315Study protocol https://www.researchprotocols.org/2018/4/e90/citations 

Results publications and other study-related documents

Documents added manually
Current Study Results
No documents have been uploaded by study researchers.

Update to Study Results
Doc. No.TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
4454Study results articleYes Doola R, et.al. The effect of a low carbohydrate f... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseThe effect of a low carbohydrate formula on glycaemia in critically ill enterally-fed adult patients with hyperglycaemia: A blinded randomised feasibility trial.2019https://dx.doi.org/10.1016/j.clnesp.2019.02.013
N.B. These documents automatically identified may not have been verified by the study sponsor.