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Trial registered on ANZCTR


Registration number
ACTRN12623000940673
Ethics application status
Approved
Date submitted
14/08/2023
Date registered
31/08/2023
Date last updated
21/01/2024
Date data sharing statement initially provided
31/08/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A pilot trial of Dapagliflozin in patients at risk of acute kidney injury who are admitted to the intensive care unit
Scientific title
Dapagliflozin in Patients at Risk of Acute Kidney Injury (AKI) Admitted to Intensive Care: A Pilot, Single-Centre, Efficacy, Feasibility, Safety, Randomised, Placebo-Controlled Trial
Secondary ID [1] 310383 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes 331126 0
Acute kidney injury 331227 0
Condition category
Condition code
Metabolic and Endocrine 327909 327909 0 0
Diabetes
Renal and Urogenital 327989 327989 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Dapagliflozin 10 milligram tablet, administered orally, once daily, from the day of enrolment for a maximum of 28 days while the patient is admitted to the intensive care with adherence monitored via medical record audit.
Intervention code [1] 326786 0
Treatment: Drugs
Comparator / control treatment
Placebo microcellulose tablet, administered orally, once daily, from the day of enrolment for a maximum of 28 days while the patient is admitted to the intensive care with adherence monitored via medical record audit..
Control group
Placebo

Outcomes
Primary outcome [1] 335761 0
Mean daily insulin units administered while in the intensive care unit assessed from patient medical records
Timepoint [1] 335761 0
Daily dose of insulin units administered from the day of enrolment until intensive care unit discharge.
Secondary outcome [1] 425491 0
Feasibility outcome of an eligibility to screening ratio
Timepoint [1] 425491 0
Review of eligibility screening logs assessed at the conclusion of the study.
Secondary outcome [2] 425492 0
Feasibility outcome of protocol compliance for the daily dosage of the study medication being administered to enrolled participants.
Timepoint [2] 425492 0
Review of medical record for dose administration from the day of enrolment until intensive care unit discharge for a maximum of 28-days for each enrolled participant.
Secondary outcome [3] 425493 0
Secondary physiological outcome of daily urinary outcome volumes between the two groups as assessed from patient medical records.
Timepoint [3] 425493 0
Medical record review of daily urinary volumes from the time of enrolment until discharge from the intensive care unit between the two groups.
Secondary outcome [4] 425494 0
Secondary physiological outcome of daily serum creatinine level occurring from the time of enrolment until discharge from the intensive care unit as assessed from patient medical records.
Timepoint [4] 425494 0
Medical record review of daily creatinine values from the time of enrolment until discharge from the intensive care unit between the two groups.
Secondary outcome [5] 425495 0
Secondary physiological outcome of glycaemic control occurring from the time of enrolment until discharge from the intensive care unit as assessed from patient medical records.
Timepoint [5] 425495 0
Medical record review of serum blood glucose levels as recording from the time of enrolment until discharge from the intensive care unit.
Secondary outcome [6] 425496 0
Secondary safety outcome on the incidence of ketoacidosis occurring from the time of enrolment until discharge from the intensive care unit.
Timepoint [6] 425496 0
Medical record review of the recorded episode of ketoacidosis defined as a ketone level of greater than 2 mmol/L and a pH of less than 7.3 occurring from the time of enrolment until discharge from the intensive care unit between the two groups.
Secondary outcome [7] 425497 0
Secondary safety outcome of incidence of hypovolaemia requiring fluid intervention in the intensive care unit.
Timepoint [7] 425497 0
Medical record review of the recorded episode of hypovolaemia requiring fluid intervention occurring from the time of enrolment until discharge from the intensive care unit between the two groups.
Secondary outcome [8] 425498 0
Secondary safety outcome of episode of hypovolaemia requiring vasopressor intervention in the intensive care unit.
Timepoint [8] 425498 0
Medical record review of the recorded episode of hypovolaemia requiring vasopressor intervention occurring from the time of enrolment until discharge from the intensive care unit between the two groups.

Eligibility
Key inclusion criteria
Adult aged 18 years or older
Admitted to the intensive care unit within the last 7 days
Expected to remain in intensive care until the day after tomorrow
Arterial or central venous catheter access in situ or planned
Central venous catheter access in situ or planned
Able to receive study treatment via the enteral route
At least one risk factor for AKI as defined below:
Pre-existing diagnosis of Type 2 Diabetes Mellitus (T2DM)
At least one of these two risk factors for Acute Kidney Injury (AKI):
- Required fluid resuscitation, defined as a bolus of fluid prescribed to be given over less than 1 hour to increase or maintain intravascular volume, in addition to maintenance fluids
- Being treated with continuous vasopressors or inotropes to maintain a systolic blood pressure (SBP) < 90 mmHg, or mean arterial blood pressure (MAP) > 60 mmHg or a MAP target set by the treating clinician to maintain perfusion
At least one of the following pre-morbid risk factors:
- Treatment for high blood pressure
- Treatment for Type 2 diabetes (minimum diet therapy)
- History of coronary artery disease
- History of heart failure
- Impaired renal function, defined as an estimated Glomerular Filtration rate (eGFR) of 60 ml/min/1.73m2 or greater
- Estimated body mass index (BMI) 30 kg/m2 or more
- Age 60 years or older
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Met all inclusion criteria >24 hours ago
History of Type-1 diabetes mellitus (T1DM)
Requiring renal replacement therapy for intoxication
Admission with urosepsis
eGFR less than 20 ml/min/1.73m2 at the time of assessment for enrolment
Known hypersensitivity to any SGLT2 inhibitor medication (dapagliflozin, canagliflozin, empagliflozin)
Solid organ transplantation with the last 12 months
Likely to be transferred to another hospital in the next 3 days
Known or suspected pregnancy
Death is deemed imminent or inevitable
Life expectancy is estimated to be less than 90 days
Patient or the treating clinician declines to participate
Enrolled in another interventional trial for which co-enrolment is not approved
Patient has previously been enrolled in the PREVENTS-AKI study

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)
opaque sealed envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
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
Phase
Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
11/09/2023
Actual
10/10/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 25378 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 41108 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 314583 0
Hospital
Name [1] 314583 0
Austin Health
Country [1] 314583 0
Australia
Primary sponsor type
Individual
Name
Prof Rinaldo Bellomo
Address
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country
Australia
Secondary sponsor category [1] 316618 0
Hospital
Name [1] 316618 0
Austin Health
Address [1] 316618 0
Office for Research
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country [1] 316618 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313618 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 313618 0
145 Studley Road
Heidelberg VIC 3084
Ethics committee country [1] 313618 0
Australia
Date submitted for ethics approval [1] 313618 0
26/06/2023
Approval date [1] 313618 0
14/08/2023
Ethics approval number [1] 313618 0
HREC/97929/Austin-2023

Summary
Brief summary
Over the last few years, evidence has emerged that Dapagliflozin, a blood sugar lowering drug that can be administered as a tablet, does not just return blood sugar levels toward normal with minimal or no side effects but also protects the kidney form injury.

This drug has also been shown to slow the progression of heart and kidney related complications of diabetes and heart failure patients. This makes treatment with Dapagliflozin potentially desirable in patients at risk of acute kidney injury who are admitted to the intensive care unit. However, the effect of Dapagliflozin in such patients, although logical, has not yet been studied.

For this reason, we are planning to perform a clinical research project, known as a randomised controlled trial. We aim to evaluate whether giving oral Dapagliflozin (10mg daily for up to 28-days while in ICU) compared to placebo (a dummy tablet) in ICU patients at risk of acute kidney injury (AKI) decreases the severity and risk of injury and maintains blood sugar levels while decreasing the use of insulin. We plan to study 40 patients at high risk of developing AKI.

If our findings demonstrate safety and potential benefit, they will allow this treatment to be studied in larger groups and, perhaps become a new effective treatment for these patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 128766 0
Prof Rinaldo Bellomo
Address 128766 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 128766 0
Australia
Phone 128766 0
+61394965992
Fax 128766 0
+61394963932
Email 128766 0
[email protected]
Contact person for public queries
Name 128767 0
Rinaldo Bellomo
Address 128767 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 128767 0
Australia
Phone 128767 0
+61394965992
Fax 128767 0
+61394963932
Email 128767 0
[email protected]
Contact person for scientific queries
Name 128768 0
Rinaldo Bellomo
Address 128768 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 128768 0
Australia
Phone 128768 0
+61394965992
Fax 128768 0
+61394963932
Email 128768 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.