Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001467729
Ethics application status
Approved
Date submitted
1/11/2022
Date registered
18/11/2022
Date last updated
20/02/2024
Date data sharing statement initially provided
18/11/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating the effect of a new agent on heart disease and kidney function in people who have recovered from acute kidney injury
Scientific title
carDIovaScular and renal outCOmes in patients recoVERed from acute kidney injury
Secondary ID [1] 308079 0
Protocol number: GI-RM-3472
Universal Trial Number (UTN)
N/A
Trial acronym
DISCOVER
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart disease 327774 0
Acute kidney injury 327775 0
Condition category
Condition code
Cardiovascular 324844 324844 0 0
Coronary heart disease
Renal and Urogenital 324845 324845 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomised to dapagliflozin. Participants will receive 10 mg dapagliflozin, in one oral tablet form, each day for 84 days (12 weeks) from the date of randomisation.

Adherence will be assessed at 6 weeks (self-reported) and 12 weeks (returned tablet count by study coordinator).
Intervention code [1] 324527 0
Treatment: Drugs
Comparator / control treatment
Matched placebo composed of a gelatin capsule and microcrystalline cellulose
Control group
Placebo

Outcomes
Primary outcome [1] 332657 0
Feasibility, i.e. the ability to recruit and retain participants in the trial until completion. This will be assessed by sites maintaining screening and recruitment logs throughout the duration of the trial
Timepoint [1] 332657 0
At completion of the trial
Primary outcome [2] 332742 0
Feasibility, as determined by compliance with the protocol. This includes out of window trial visits as assessed by reviewing protocol deviation records, the number of withdrawals from the trial as assessed by auditing trial consent and withdrawal forms, and reviewing adherence to taking the trial intervention as assessed by participant self-reporting with use of a trial diary along with returned tablet count at the end of the intervention period.
Timepoint [2] 332742 0
At 42, 84 and 112 days post-randomisation
Primary outcome [3] 332885 0
Changes in albuminuria levels from baseline assessed by measuring urinary albumin-creatinine ratio (UACR) levels
Timepoint [3] 332885 0
At baseline, 42, 84 and 112 days post-randomisation
Secondary outcome [1] 414288 0
Safety events will be assessed by the incidence of adverse events. This includes, but is not limited to, 1) hypotension assessed by measuring blood pressure using a sphygmomanometer, 2) dehydration assessed by fluid balance as indicated in the participants medical records, and 3) diabetic ketoacidosis assessed by physical examination of the participant, e.g. dryness of the skin and mouth, muscle stiffness, tiredness, nausea/vomiting, and blood tests, in particular by measuring plasma glucose and bicarbonate levels
Timepoint [1] 414288 0
At baseline, 42, 84 and 112 days post-randomisation
Secondary outcome [2] 414291 0
Incidence of death from renal causes, as assessed by review of medical records
Timepoint [2] 414291 0
At baseline, 42, 84 and 112 days post-randomisation
Secondary outcome [3] 415819 0
Incidence of death from cardiovascular causes, as assessed by review of medical records
Timepoint [3] 415819 0
At baseline, 42, 84 and 112 days post-randomisation
Secondary outcome [4] 415820 0
All-cause mortality, as assessed by review of medical records
Timepoint [4] 415820 0
At baseline, 42, 84 and 112 days post-randomisation
Secondary outcome [5] 415821 0
Incidence of hospitalisation for heart failure, as assessed by review of medical records
Timepoint [5] 415821 0
At baseline, 42, 84 and 112 days post-randomisation
Secondary outcome [6] 415822 0
Incidence of end-stage kidney disease, determined by review of medical records for details of maintenance dialysis for at least 28 days, kidney transplantation, or an estimated glomerular filtration rate (eGFR) of less than 15ml per min
Timepoint [6] 415822 0
At baseline, 42, 84 and 112 days post-randomisation

Eligibility
Key inclusion criteria
1) Adult participants at least 18 years of age
2) Pre-existing diagnosis of albuminuria (defined as urine albumin-creatinine ratio (UACR) greater than or equal to 30 mg/g)
3) Recovered from the previous acute kidney injury (AKI) within the last 30 days. AKI recovery is defined as:
• Complete if the estimated glomerular filtration rate (eGFR) level, at the time of screening for the DISCOVER trial, has returned to within 20% of baseline levels as assessed by the median eGFR level during the 12 months prior to the recent AKI episode, and excluding eGFR values during other instances of AKI
• Complete if the serum creatinine (SCr) level, at the time of screening for the DISCOVER trial, has returned to within 20% of baseline levels as assessed by the median SCr level during the 12 months prior to the recent AKI episode, and excluding SCr values during other instances of AKI
• Partial if there is a fall in the Kidney Disease Improving Global Outcomes (KDIGO) AKI stage classification by at least one stage (e.g., from stage 3 to stage 2 AKI, or from stage 2 to stage 1 AKI) when a baseline eGFR and/or SCr value is not available during the 12 months prior to the recent AKI episode
4) Recently discharged from hospital or seen in the renal outpatient clinic
5) Stable eGFR defined as within 20% of the hospital discharge level or increasing (greater than 20% of discharge levels)
6) Expected to be under the care of the participating renal unit for the next 6 months
7) The treating physician has equipoise on the balance of risk and benefit for the participant in either arm of the study and is willing to randomise participants
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Diagnosis of type-1 diabetes mellitus (T1DM)
2) Current use of a sodium glucose cotransporter 2 (SGLT2) inhibitor at the time of screening for the DISCOVER trial
3) Documented SGLT2 inhibitor intolerance
4) Current or ongoing use of contraindicated concomitant medications
5) Severe hepatic impairment, defined as Child-Pugh class C hepatic failure
6) Pregnancy, including breast feeding
7) Patients with diabetic ketoacidosis
8) Advanced CKD with an estimated glomerular filtration rate (eGFR) of less than 25 ml/min/1.73m2
9) Solid organ transplant recipients
10) Participants with cognitive impairment

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 is concealed by central randomisation using the REDCap database. The randomisation allocation code will not be released until the participant has been recruited into the trial
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Consented participants will be randomised equally on a 1:1 basis, using permuted blocks stratified by trial site
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
Intervention assignment
Parallel
Other design features
N/A
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Summary statistics will be used to describe the feasibility and clinical data and presented as mean ± standard deviation (SD), median with interquartile range (IQR) and percentages, as appropriate. Chi-squared analysis with Fisher’s exact test (when appropriate), and Student’s t-test (Mann Whitney U test for non-normal distributions) will be used to compare data between the active treatment group and the control group. Safety analyses will be performed on all adverse events occurring before or at the trial closure visit.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
5/06/2023
Actual
1/11/2023
Date of last participant enrolment
Anticipated
31/03/2024
Actual
Date of last data collection
Anticipated
31/07/2024
Actual
Sample size
Target
60
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 23330 0
Concord Repatriation Hospital - Concord
Recruitment hospital [2] 23331 0
Prince of Wales Hospital - Randwick
Recruitment postcode(s) [1] 38705 0
2031 - Randwick
Recruitment postcode(s) [2] 38704 0
2139 - Concord

Funding & Sponsors
Funding source category [1] 312333 0
Charities/Societies/Foundations
Name [1] 312333 0
National Heart Foundation of Australia
Country [1] 312333 0
Australia
Funding source category [2] 312390 0
Other
Name [2] 312390 0
The George Institute for Global Health
Country [2] 312390 0
Australia
Primary sponsor type
Other
Name
The George Institute for Global Health
Address
Level 18, International Towers 3, 300 Barangaroo Avenue, Barangaroo NSW 2000
Country
Australia
Secondary sponsor category [1] 313962 0
None
Name [1] 313962 0
Address [1] 313962 0
Country [1] 313962 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311700 0
Sydney Local Health District HREC - Royal Prince Alfred
Ethics committee address [1] 311700 0
Level 11
KGV Building
Missenden Road
Camperdown
NSW 2050
Ethics committee country [1] 311700 0
Australia
Date submitted for ethics approval [1] 311700 0
29/11/2022
Approval date [1] 311700 0
03/02/2023
Ethics approval number [1] 311700 0
HREC Protocol Number: X22-0389

Summary
Brief summary
BACKGROUND:- Acute kidney injury (AKI) is a potentially life-threatening condition caused by unsafe levels of fluid and waste products accumulating in the body due to kidneys not working correctly. This can be associated with increased levels of albumin (a blood protein) within urine (called albuminuria). AKI can occur in when a person is already unwell with another health condition, and so is more common in people who are in hospital. AKI can increase the risk of heart events, further kidney disease and death.

Dapagliflozin is a mediciation that is used to treat people with diabetes, heart disease and kidney disease. Recent studies have shown dapagliflozin to reduce albuminuria, but this has not been shown in people with albuminuria who have recently recovered from AKI.

AIM:- To determine if giving dapagliflozin (10mg in one tablet per day) compared to placebo (a tablet that looks and smells identical but has no active ingredients) reduces kidney injury in people with albuminuria, who have recently recovered from AKI. This is a feasibility trial to show whether this trial will be successful before expanding to a larger trial.

DESIGN:- The trial will enrol 60 participants from 2 hospitals with in NSW. Participants will be randomised (randomly assigned; like tossing a coin) by a computer to receive either dapagliflozin or placebo for a maximum of 84 days (12 weeks) and followed up for a total of 112 days (16 weeks). This trial is 'double-blinded' which means the doctor and treating team, nor the participant will know which treatment that are receiving.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 122050 0
A/Prof Amanda Ying Wang
Address 122050 0
The George Institute for Global Health
PO Box M201
Missenden Road
Camperdown
NSW 2050
Country 122050 0
Australia
Phone 122050 0
+61 2 8052 4573
Fax 122050 0
Email 122050 0
awang@georgeinstitute.org.au
Contact person for public queries
Name 122051 0
A/Prof Amanda Ying Wang
Address 122051 0
The George Institute for Global Health
PO Box M201
Missenden Road
Camperdown
NSW 2050
Country 122051 0
Australia
Phone 122051 0
+61 2 8052 4573
Fax 122051 0
Email 122051 0
awang@georgeinstitute.org.au
Contact person for scientific queries
Name 122052 0
A/Prof Amanda Ying Wang
Address 122052 0
The George Institute for Global Health
PO Box M201
Missenden Road
Camperdown
NSW 2050
Country 122052 0
Australia
Phone 122052 0
+61 2 8052 4573
Fax 122052 0
Email 122052 0
awang@georgeinstitute.org.au

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?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
17289Study protocol  awang@georgeinstitute.org.au The protocol will made publicly available once fin... [More Details]
17290Statistical analysis plan  awang@georgeinstitute.org.au The statistical analysis plan made publicly availa... [More Details]
17291Informed consent form  awang@georgeinstitute.org.au
17292Ethical approval  awang@georgeinstitute.org.au



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.