Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000859886
Ethics application status
Approved
Date submitted
12/05/2021
Date registered
2/07/2021
Date last updated
13/04/2024
Date data sharing statement initially provided
2/07/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
REDuced CARBohydrate enteral formula compared to standard care in hyperglycaemic critically ill tube fed patients – a randomised controlled phase II trial
Scientific title
REDuced CARBohydrate enteral formula compared to standard care to improve glycaemic control in critically ill tube fed patients – a randomised controlled phase II trial
Secondary ID [1] 304065 0
None
Universal Trial Number (UTN)
Trial acronym
REDCARB
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hyperglycaemia 321710 0
Condition category
Condition code
Diet and Nutrition 319454 319454 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
• The intervention EN formula, a reduced carbohydrate formula (Glucerna Select®) will be commenced, with a target rate which is calorically equivalent to the amount that was being provided or targeted while the patient received routine clinical care.
• All other aspects of nutrition and blood glucose management (e.g. gastric residual volume management, prokinetic use, cessation for procedures, insulin dose) remain as per routine clinical practice.
• Intervention formula use will continue for the duration enteral feeding is clinically required in ICU.
• Medical records will be used to assess to nutrition delivery, glycaemic control and clinical outcome measures
Intervention code [1] 320387 0
Treatment: Other
Comparator / control treatment
•Enteral nutrition will be provided as per each site’s standard nutrition protocol or as per routine clinical practice.
Control group
Active

Outcomes
Primary outcome [1] 327324 0
Units of insulin administered as per daily ICU records
Timepoint [1] 327324 0
Daily, to a maximum of 7 days post randomisation
Secondary outcome [1] 394603 0
Glycaemic variability using recorded blood glucose levels from patients' medical records
Timepoint [1] 394603 0
From the point of randomisation to a maximum of 7 days thereafter
Secondary outcome [2] 394604 0
Mean blood glucose levels recorded as measured in routine clinical practice (arterial blood gases, glucometer readings using arterial blood or finger prick tests) and recorded within patients' medical records
Timepoint [2] 394604 0
From the point of randomisation to a maximum of 7 days thereafter
Secondary outcome [3] 394605 0
Time within target blood glucose range, defined as 6-10mmol/L, extracted from patient medical records
Timepoint [3] 394605 0
From the point of randomisation to a maximum of 7 days thereafter
Secondary outcome [4] 394606 0
Frequency of hypoglycaemic episodes extracted from patient medical records
Timepoint [4] 394606 0
From the point of randomisation to a maximum of 7 days thereafter
Secondary outcome [5] 394607 0
Number of insulin free days extracted from patient medical records
Timepoint [5] 394607 0
From the point of randomisation to a maximum of 7 days thereafter
Secondary outcome [6] 394608 0
Caloric and protein intake based on volume delivered as per patients' medical records
Timepoint [6] 394608 0
From the point of randomisation to a maximum of 7 days thereafter
Secondary outcome [7] 394609 0
Incidence of diarrhoea extracted from patient medical records
Timepoint [7] 394609 0
From the point of randomisation to a maximum of 7 days thereafter
Secondary outcome [8] 394610 0
Prescription of prokinetic medications (metoclopramide or erythromycin) during the study period extracted from patient medical records
Timepoint [8] 394610 0
From the point of randomisation to a maximum of 7 days thereafter
Secondary outcome [9] 394611 0
Positive blood cultures extracted from patient medical records
Timepoint [9] 394611 0
From the point of randomisation up to 48 hours post cessation of enteral feeding in ICU, censored at day 28
Secondary outcome [10] 394612 0
Ventilator free days extracted from patient medical records
Timepoint [10] 394612 0
From randomisation to Day 28 (censored at Day 28)
Secondary outcome [11] 394613 0
ICU-free days extracted from patient medical records
Timepoint [11] 394613 0
From randomisation to Day 28 (censored at Day 28)
Secondary outcome [12] 394614 0
Hospital-free days extracted from patient medical records
Timepoint [12] 394614 0
From randomisation to Day 28 (censored at Day 28)
Secondary outcome [13] 394615 0
In-hospital mortality
Timepoint [13] 394615 0
From randomisation to Day 28 (censored at Day 28)
Secondary outcome [14] 394616 0
Feasibility measure: Ability to deliver the intervention formula extracted from patient medical records
Timepoint [14] 394616 0
From randomisation to point of feed cessation or Day 28 (censored at Day 28) , whichever occurs first
Secondary outcome [15] 395366 0
Exploratory outcome: Change in plasma and urine inflammatory markers over time
Timepoint [15] 395366 0
Randomisation, D3, D6 and D7 unless enteral feeds ceased prior at which point a sample will be taken at that time

Eligibility
Key inclusion criteria
• Admission to ICU
• Aged =18 years old
• Receiving or able to receive enteral nutrition within the next 24 hours
• In the last 24 hours, has received insulin for glycaemic control as per local protocol OR has had two consecutive blood glucose levels > 10mmol/L
• EN remains indicated and is expected to continue until at least the day after tomorrow
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Patient has been enterally fed for =72hrs during this admission episode
• Treating clinician deems study formula to be clinically contraindicated
• Patient expected to receive parenteral nutrition (total or supplemental)
• Futility of care or death was imminent
• Patient unlikely to regain capacity to consent and patient has no surrogate decision maker
• Previously enrolled in REDCARB study or co-enrolment in other nutrition or glycaemic management intervention studies

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)
Randomisation sequences for each stratum will be generated by an independent statistician using a computer system.
This sequence will be made available to sites via an electronic platform at time of randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be allocated in a 1:1 ratio to control and intervention groups using random permuted block randomisation with block sizes of 2 and 4 and stratified by study site and presence of pre-admission diabetes (yes/no). Randomisation sequences for each stratum will be generated by an independent statistician. The number of patients at each site will not be fixed in advance but rather recruitment will finish when the total number of patients reaches 160
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample Size and Statistical Power

The sample size calculation is based on the primary outcome total daily insulin dose and an expected average study length of 3 days. As the outcome is both continuous and measured longitudinally, we used the sample size calculation suggested by Diggle et al., 2002. Assuming a significance level of 0.05 (Z_(a/2)=1.96), 80% power (Z_ß=0.84), a mean total insulin dose of 54 units/day in the control group, a pooled standard deviation of 50 units, a moderately strong within-subject correlation (?=0.5), an average of three time points (t=3) and an anticipated drop-out rate of 15% (r=0.15), 79 patients ( in each group) would be required to detect a 40% reduction (21.6 units) in mean total daily insulin dose. This was based on the phase I pilot trial carried out by members of the REDCARB management committee. We will aim to recruit 80 patients per arm.

Data Analysis Plan
Patient characteristics will be summarised using frequency and percent for categorical variables and mean (SD) or median (IQR) for continuous variables. Differences between intervention and control groups for repeated measures including cumulative total daily insulin dose and average daily blood glucose will be examined using linear mixed effects models with a random intercept at the level of each patient and a restricted maximum likelihood approach. Repeated binary categorical outcomes such as probability of blood glucose outside of target range will be analysed using binary logistic mixed effects models. Two sample t-tests will be used to assess differences between groups for continuous outcomes that are approximately normally distributed and not repeated. This includes glycaemic variability summarised as the coefficient of variation, total carbohydrate from feed and patients' ability to meet protein and energy requirements. Pearson’s chi-squared tests or Fisher's exact tests for tables with small expected cell counts will be used to compare categorical outcomes that are not repeated including tolerance of nutrition, incidence of infectious complications and mortality at 28 days between intervention and control groups. Duration of ventilation, ICU length of stay and hospital length of stay are expected to be skewed and will be analysed using a Mann-Whitney U test. Sensitivity analyses accounting for stratification by site and pre-existing diabetes will be conducted. All data analysis will be completed using Stata Statistical Software version 15.1 or R: A Language and Environment for Statistical computing. The level of statistical significance will be set at 0.05.

Planned sub-group analysis
We intend to perform analyses by diabetes status (yes/no) for all primary and secondary outcome measures.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
30/07/2021
Actual
15/02/2022
Date of last participant enrolment
Anticipated
27/12/2024
Actual
Date of last data collection
Anticipated
30/01/2025
Actual
Sample size
Target
160
Accrual to date
108
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 19204 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [2] 19205 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [3] 19206 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [4] 19207 0
The Prince Charles Hospital - Chermside
Recruitment hospital [5] 19208 0
Logan Hospital - Meadowbrook
Recruitment hospital [6] 19209 0
Redcliffe Hospital - Redcliffe
Recruitment hospital [7] 19210 0
Caboolture Hospital - Caboolture
Recruitment hospital [8] 26401 0
Ipswich Hospital - Ipswich
Recruitment postcode(s) [1] 33776 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 33777 0
4101 - South Brisbane
Recruitment postcode(s) [3] 33778 0
4029 - Herston
Recruitment postcode(s) [4] 33779 0
4032 - Chermside
Recruitment postcode(s) [5] 33780 0
4131 - Meadowbrook
Recruitment postcode(s) [6] 33781 0
4020 - Redcliffe
Recruitment postcode(s) [7] 33782 0
4510 - Caboolture
Recruitment postcode(s) [8] 42377 0
4305 - Ipswich

Funding & Sponsors
Funding source category [1] 308449 0
Other Collaborative groups
Name [1] 308449 0
Metro South Study, Education and Research Trust Account
Country [1] 308449 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
St Lucia QLD 4072
Country
Australia
Secondary sponsor category [1] 309284 0
Hospital
Name [1] 309284 0
Princess Alexandra Hospital
Address [1] 309284 0
199 Ipswich Road
Woolloongabba, QLD, 4102
Country [1] 309284 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308402 0
Metro South HREC
Ethics committee address [1] 308402 0
Ethics committee country [1] 308402 0
Australia
Date submitted for ethics approval [1] 308402 0
12/05/2021
Approval date [1] 308402 0
19/07/2021
Ethics approval number [1] 308402 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110594 0
Dr Ra'eesa Doola
Address 110594 0
Department of Nutrition and Dietetics
Ground floor, Building 15,
Princess Alexandra Hospital
199 Ipswich Road,
Woolloongabba, QLD, 4102
Country 110594 0
Australia
Phone 110594 0
+61 7 3176 7938
Fax 110594 0
+61 7 3176 5619
Email 110594 0
[email protected]
Contact person for public queries
Name 110595 0
Ra'eesa Doola
Address 110595 0
Department of Nutrition and Dietetics
Ground floor, Building 15,
Princess Alexandra Hospital
199 Ipswich Road,
Woolloongabba, QLD, 4102
Country 110595 0
Australia
Phone 110595 0
+61 7 3176 7938
Fax 110595 0
+61 7 3176 5619
Email 110595 0
[email protected]
Contact person for scientific queries
Name 110596 0
Ra'eesa Doola
Address 110596 0
Department of Nutrition and Dietetics
Ground floor, Building 15,
Princess Alexandra Hospital
199 Ipswich Road,
Woolloongabba, QLD, 4102
Country 110596 0
Australia
Phone 110596 0
+61 7 3176 7938
Fax 110596 0
+61 7 3176 5619
Email 110596 0
[email protected]

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 Supporting Document Provided



Results publications and other study-related documents

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

Documents added automatically
No additional documents have been identified.