ANZCTR - Registration

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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]

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

Hyperglycemia

Condition category

Condition code

Metabolic and Endocrine

Other metabolic disorders

Diet and Nutrition

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]

Treatment: Other

Comparator / control treatment

Standard feed of carbohydrate content of 142g/L

Control group

Active

Outcomes

Primary outcome [1]

Units of insulin administered over 48 hours.

Timepoint [1]

48 hours after commencement of the feed.

Secondary outcome [1]

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]

48 hours after commencement of the feed.

Secondary outcome [2]

Mortality

Timepoint [2]

28 days after commencement of the feed.

Secondary outcome [3]

Readmission to ICU and length of stay.

Timepoint [3]

Within 28 days after initial ICU discharge.

Secondary outcome [4]

Length of mechanical ventilation

Timepoint [4]

Within 48 hours of commencement of feed.

Secondary outcome [5]

Ability to meet protein and energy requirements

Timepoint [5]

Within 48 hours of commencement of feed.

Secondary outcome [6]

Incidence of diarrhoea

Timepoint [6]

Within 48 hours of commencement of feed.

Secondary outcome [7]

Requirement for prokinetic medications

Timepoint [7]

Within 48 hours of commencement of feed.

Secondary outcome [8]

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]

At baseline and 48 hours post commencement of feed

Secondary outcome [9]

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]

Assessed during the course of the study

Secondary outcome [10]

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]

Assessed during the course of the study

Secondary outcome [11]

Recruitment rates to assess number of eligible patients accounting for consent.

Timepoint [11]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

QLD

Recruitment hospital [1]

Mater Adult Hospital - South Brisbane

Recruitment hospital [2]

Mater Private Hospital - South Brisbane

Recruitment postcode(s) [1]

4101 - South Brisbane

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Mater Foundation and Mater Research Institute

Address [1]

Raymond Terrace, South Brisbane, QLD 4101

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Mater Health Services Human Research Ethics Committee

Ethics committee address [1]

Aubigny Place, Raymond Terrace, South Brisbane, Qld 4101

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

28/02/2014

Approval date [1]

Ethics approval number [1]

Ethics committee name [2]

The University of Queensland - Instituitional Human Research Ethics Approval

Ethics committee address [2]

UQ Research and Innovation, The University of Queensland, Cumbrae-Stewart Building #72, Brisbane, Queensland, 4072, Australia

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

01/10/2014

Approval date [2]

22/10/2014

Ethics approval number [2]

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

Mrs Ra'eesa Doola

Address

Allied Health reception, Level 3
Salmon Building, Mater Health
Raymond Terrace
South Brisbane, QLD
4101

Country

Australia

Phone

+61731636000

Fax

raeesa.doola@mater.uq.edu.au

Contact person for public queries

Name

Ra'eesa Doola

Address

Allied Health reception, Level 3
Salmon Building, Mater Health
Raymond Terrace
South Brisbane, QLD
4101

Country

Australia

Phone

+61731636000

Fax

raeesa.doola@mater.uq.edu.au

Contact person for scientific queries

Name

Ra'eesa Doola

Address

Allied Health reception, Level 3
Salmon Building, Mater Health
Raymond Terrace
South Brisbane, QLD
4101

Country

Australia

Phone

+61731636000

Fax

raeesa.doola@mater.uq.edu.au

No information has been provided regarding IPD availability

What supporting documents are/will be available?

Current supporting documents:

Updated to:

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
24409	Other	Doola R, Deane AM, Tolcher DM, et al. The effect of a low carbohydrate formula on glycaemia in critically ill enterally-fed adult patients with hyperglycaemia: A blinded randomised feasibility trial. Clin Nutr ESPEN. 2019;31:80-87. doi:10.1016/j.clnesp.2019.02.013

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.	Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
4454	Study results article	Yes		Doola R, et.al. The effect of a low carbohydrate f... [More Details]

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	The effect of a low carbohydrate formula on glycaemia in critically ill enterally-fed adult patients with hyperglycaemia: A blinded randomised feasibility trial.	2019	https://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.

Trial Review

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Documents added manually

Documents added automatically