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Trial registered on ANZCTR


Registration number
ACTRN12621001340820
Ethics application status
Approved
Date submitted
1/10/2021
Date registered
6/10/2021
Date last updated
28/07/2024
Date data sharing statement initially provided
6/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A Clinical Trial of Insulin Therapy for Dexamethasone Induced Hyperglycaemia amongst Diabetes Patients with COVID-19
Scientific title
Cluster Randomised Trial of Isophane Insulin Therapy on Glucose Levels for Dexamethasone Induced Hyperglycaemia amongst Diabetes Patients with COVID-19 (CRITICal)
Secondary ID [1] 305451 0
None
Universal Trial Number (UTN)
Trial acronym
CRITICal
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 323826 0
Type 2 diabetes 323827 0
Steroid induced hyperglycaemia 323828 0
Condition category
Condition code
Metabolic and Endocrine 321334 321334 0 0
Diabetes
Infection 321335 321335 0 0
Other infectious diseases
Respiratory 321355 321355 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Regimen of morning subcutaneous administration of Isophane insulin with basal bolus insulin (BBI). Isophane will be added to a BBI regimen at 20% of the calculated total daily dose (TDD) if the highest blood glucose (BG) is 12-16 mmol/L or 30% of TDD if highest BG is >16 mmol/L. The TDD will be determined on the basis of pre-existing insulin therapy. Participants not on pre-existing insulin (BBI or premixed) will receive BBI at a TDD of 0.5 units/kg or 0.3 units/kg if BG 12-16 mmol/L, age greater than or equal to 70, or chronic kidney disease stage 3.

The intervention will commence from the time of recognition of hyperglycaemia following commencement of dexamethasone therapy, until one of the following occurs: cessation of dexamethasone, change to a different diabetes medication regimen (based on clinical decision), discharge from hospital, transfer to the intensive care unit, decision for palliation.

Insulin administration will be recorded for the purpose of monitoring adherence to the protocol and insulin usage as a result of the protocol.
Intervention code [1] 321849 0
Treatment: Drugs
Comparator / control treatment
Subcutaneous administration of basal bolus insulin (BBI) alone. Participants on pre-existing insulin therapy will have their total daily dose (TDD) increased by 20% if the highest blood glucose (BG) is 12-16 mmol/L or 30% if the highest BG is >16 mmol/L. Participants not on BBI or premixed insulin will receive BBI at a TDD of 0.5 units/kg or 0.3 units/kg if BG 12-16 mmol/L, age greater than or equal to 70, or chronic kidney disease stage 3.

The intervention will commence from the time of recognition of hyperglycaemia following commencement of dexamethasone therapy, until one of the following occurs: cessation of dexamethasone, change to a different diabetes medication regimen (based on clinical decision), discharge from hospital, transfer to the intensive care unit, decision for palliation.

Insulin administration will be recorded for the purpose of monitoring adherence to the protocol and insulin usage as a result of the protocol.
Control group
Active

Outcomes
Primary outcome [1] 329119 0
The primary outcome is the mean daily glucose level during the course of the trial. This will be calculated from glucose readings taken from before and after meals. Both formal venous and fingerprick glucose measurements will be accepted.
Timepoint [1] 329119 0
Daily pre and post meals, from the day of randomisation to the final day that the patient is in the trial.
Secondary outcome [1] 401531 0
Mean premeal glucose levels. This will be calculated from glucose readings taken before meals. Both formal venous and fingerprick glucose measurements will be accepted.
Timepoint [1] 401531 0
Daily premeal, from the day of randomisation to the final day that the patient is in the trial.
Secondary outcome [2] 401532 0
Mean glucose levels. This will be calculated from glucose readings taken after meals. Both formal venous and fingerprick glucose measurements will be accepted
Timepoint [2] 401532 0
Daily postmeals, from the day of randomisation to the final day that the patient is in the trial.
Secondary outcome [3] 401533 0
Mean glucose levels. This will be calculated from glucose readings taken before and after meals. Both formal venous and fingerprick glucose measurements will be accepted
Timepoint [3] 401533 0
On day 3 of the patient's participation in the trial (where day 1 is the first day)
Secondary outcome [4] 401534 0
Proportion of glucose readings in target. Both formal venous and fingerprick glucose measurements will be accepted
Timepoint [4] 401534 0
Daily pre and post meals, from the day of randomisation to the final day that the patient is in the trial.
Secondary outcome [5] 401535 0
Proportion of glucose readings in target. Both formal venous and fingerprick glucose measurements will be accepted.
Timepoint [5] 401535 0
Daily premeals, from the day of randomisation to the final day that the patient is in the trial.
Secondary outcome [6] 401536 0
Proportion of glucose readings in target. Both formal venous and fingerprick glucose measurements will be accepted.
Timepoint [6] 401536 0
Daily postmeals, from the day of randomisation to the final day that the patient is in the trial.
Secondary outcome [7] 401537 0
Length of hospital stay from time of commencement of dexamethasone, based on review of medical record
Timepoint [7] 401537 0
Discharge from hospital (index admission only)
Secondary outcome [8] 401538 0
Secondary infections, based on review of medical records
Timepoint [8] 401538 0
At any time during index hospital admission following the commencement of the participant's involvement in the trial.

Eligibility
Key inclusion criteria
1) have a confirmed diagnosis of COVID-19
2) are in a non-ICU ward, and are not imminently to be admitted to ICU or discharged
3) have known diabetes or newly diagnosed diabetes (diagnosed on an HbA1c >=6.5 mmol/L)
4) have had at least one fingerprick glucose level >=12 mmol/L since the commencement of dexamethasone.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) pregnant
2) type 1 diabetes
3) eGFR <30

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)
Allocation not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
This is a cluster randomised trial with wards re-randomised on a 2 weekly basis. Each cluster is therefore a ward and a time period. There will be 6 wards initially so we will randomise each ward using a permuted block of 6 across wards and a permuted block of 2 across time periods ensuring balance across wards and time periods. It is unclear how many time periods will be required so we kept the block sizes to 2 to optimise balance. There is the possibility of 2 more wards so an additional permuted block of size 2 across 2 wards will be generated for all the time periods in case these wards are implemented. The randomisation list will be generated by the study statistician using RandomiseR in R.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
We have powered our study to detect a 1.5 mmol/L difference between the 2 groups with a liberal within group standard deviation (SD) of mean glucose of 3.0 mmol/L..

Intraclass correlation coefficients range from 0.02 to 0.1 in various settings. Assuming an intraclass correlation of 0.05 and 5 patients per ward at each time point we need a sample size of 77 subjects in each arm to give 80% power to detect a difference in mean glucose of 1.5 mmol/L, at a significance level of 0.05. We will cease recruitment when both groups have had 80 subjects complete the study.

The primary analysis will be to assess the intervention effect on mean glucose levels using a mixed model adjusting for baseline HbA1c and with time period as a fixed effect to allow for the potential of time trends and room as a random effect. The study will be analysed on an intention to treat basis.

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
7/10/2021
Actual
10/11/2021
Date of last participant enrolment
Anticipated
31/12/2022
Actual
6/10/2022
Date of last data collection
Anticipated
31/01/2023
Actual
24/10/2022
Sample size
Target
160
Accrual to date
Final
40
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 20649 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 35439 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 309807 0
Hospital
Name [1] 309807 0
Dept of Diabetes & Endocrinology, Westmead Hospital
Country [1] 309807 0
Australia
Primary sponsor type
Individual
Name
Prof NW Cheung
Address
Dept of Diabetes & Endocrinology,
Hawkesbury Rd
Westmead Hospital
Westmead NSW 2145
Country
Australia
Secondary sponsor category [1] 310840 0
None
Name [1] 310840 0
Address [1] 310840 0
Country [1] 310840 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309554 0
Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 309554 0
Ethics committee country [1] 309554 0
Australia
Date submitted for ethics approval [1] 309554 0
09/09/2021
Approval date [1] 309554 0
30/09/2021
Ethics approval number [1] 309554 0
2021/ETH11485

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

Contacts
Principal investigator
Name 114570 0
Prof Ngai Wah Cheung
Address 114570 0
Dept of Diabetes & Endocrinology
Westmead Hospital
Hawkesbury Rd
Westmead NSW 2145
Country 114570 0
Australia
Phone 114570 0
+61 0288906796
Fax 114570 0
Email 114570 0
wah.cheung@sydney.edu.au
Contact person for public queries
Name 114571 0
Ngai Wah Cheung
Address 114571 0
Dept of Diabetes & Endocrinology
Westmead Hospital
Hawkesbury Rd
Westmead NSW 2145
Country 114571 0
Australia
Phone 114571 0
+61 0288906796
Fax 114571 0
Email 114571 0
wah.cheung@sydney.edu.au
Contact person for scientific queries
Name 114572 0
Ngai Wah Cheung
Address 114572 0
Dept of Diabetes & Endocrinology
Westmead Hospital
Hawkesbury Rd
Westmead NSW 2145
Country 114572 0
Australia
Phone 114572 0
+61 0288906796
Fax 114572 0
Email 114572 0
wah.cheung@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
deidentified unit data of glucose levels used for analysis in the study, and descriptive details of participants.
When will data be available (start and end dates)?
Following publication of the trial for a period of 7 years.
Available to whom?
Reputable academic organisations subject upon reasonable request with a sound proposal, and subject to appropriate ethics approvals.
Available for what types of analyses?
Meta-analysis.
How or where can data be obtained?
Contact the principal investigator. Email: wah.cheung@sydney.edu.au


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.