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Trial registered on ANZCTR


Registration number
ACTRN12619001393145
Ethics application status
Approved
Date submitted
17/09/2019
Date registered
11/10/2019
Date last updated
22/09/2021
Date data sharing statement initially provided
11/10/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Determining the effect of Dapagliflozin on preventing heart failure in patients with type 2 diabetes (The LEAVE-DM trial).
Scientific title
Does Dapagliflozin limit the progression of Echocardiographically-Assessed left Ventricular dysfunction in Diabetes Mellitus? (The LEAVE-DM trial).
Secondary ID [1] 298675 0
None
Universal Trial Number (UTN)
U1111-1236-7496
Trial acronym
LEAVE-DM
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 313582 0
Heart Failure 313583 0
Condition category
Condition code
Metabolic and Endocrine 312018 312018 0 0
Diabetes
Cardiovascular 312019 312019 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomised in a 1:1 ratio into two groups; intervention with dapagliflozin or placebo. Participants who are randomised into the dapagliflozin arm will receive the tablet at a dose of 10mg once daily. The total duration of treatment is 24 months. Adherence and compliance to the intervention will be evaluated at each follow-up visit.

Dapagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor and is used in the treatment of type 2 diabetes mellitus. In clinical trials it has been effective in reducing hospitalisation from heart failure and cardiac death. It's use in this study is to determine whether it can reduce the progression of heart failure in at-risk patients with type 2 diabetes.
Intervention code [1] 315080 0
Treatment: Drugs
Intervention code [2] 315081 0
Prevention
Intervention code [3] 315082 0
Diagnosis / Prognosis
Comparator / control treatment
A placebo drug will form the 'treatment' for the control group. Participants will be allocated a tablet that is similar in shape, colour and size to the intervention drug and administered once daily. The placebo tablet contains lactose monohydrate, microcrystalline cellulose, magnesium stearate and coating material (Opadryl(R) II).
Control group
Placebo

Outcomes
Primary outcome [1] 320808 0
Left ventricular function assessed on echocardiography.
Timepoint [1] 320808 0
6 and 24 months (primary end-point) post-initiation of treatment.
Secondary outcome [1] 372920 0
Six minute walk test (assessment of functional capacity).
Timepoint [1] 372920 0
6 and 24 months post-initiation of treatment.

Eligibility
Key inclusion criteria
Patients with type 2 diabetes aged over 65 years will be screened with an echocardiogram. Those with stage B heart failure will be included. Subclinical LV dysfunction on ECHO is defined as:
1. Global longitudinal strain (GLS) -16% or less; or
2. Borderline GLS (-18 to -16%) and impaired relaxation or left atrial (LA) enlargement); or
3. E/e' > 15; or
4. E/e' > 10 and LA enlargement; or
5. Abnormal relaxation and LA enlargement.
Minimum age
65 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Unable to provide written informed consent to participate in this study
- Participating in another clinical research trial where randomised treatment would be unacceptable
- History of >moderate valvular heart disease
- History of previous heart failure, hypertrophic cardiomyopathy
- Current therapy with SGLT2 inhibitors and GLP-1
- Systolic blood pressure (BP) <110mmHg
- Estimated glomerular filtration rate (eGFR) <45
- Baseline New York Heart Association (NYHA) classification >2
- Oncologic life expectancy < 12 months
- Inability to acquire interpretable images (identified from baseline echo)
- Pregnant or breast-feeding

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
After baseline testing, participants will be randomised in a 1:1 fashion to receive either treatment with dapagliflozin or placebo. The randomisation schedule will be entered through the REDCap database which will be used in this study. This database will also reveal which group the patient has been randomised too.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomly allocated by an independent researcher to ether the dapagliflozin or placebo group via a computer-generated random number generator. Information related to the allocation sequence and block sizes will be kept on a separate, password protected database accessible only to the independent research and the principal investigator.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
We will perform an intention-to-treat (ITT) analysis. In order to exclude bias from dropouts, we will also use a maximum likelihood estimation method using a linear mixed model, which treats the data as two observations on each subject, with the second observation at 24 months missing for some subjects. This allows us to account for covariates of “missingness” to be taken into account in analysis, as well as the intermediate time-point (6 month) exercise analysis. We also plan a per-protocol analysis.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
12/11/2020
Actual
12/11/2020
Date of last participant enrolment
Anticipated
28/02/2022
Actual
Date of last data collection
Anticipated
29/02/2024
Actual
Sample size
Target
400
Accrual to date
39
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 14298 0
Baker Heart and Diabetes Institute - Melbourne
Recruitment postcode(s) [1] 27296 0
3004 - Melbourne
Recruitment postcode(s) [2] 35363 0
3029 - Hoppers Crossing

Funding & Sponsors
Funding source category [1] 303215 0
Charities/Societies/Foundations
Name [1] 303215 0
AstraZeneca Pty Ltd
Country [1] 303215 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Baker Heart and Diabetes Institute
Address
75 Commercial Road, Melbourne, VIC 3004
Country
Australia
Secondary sponsor category [1] 303228 0
None
Name [1] 303228 0
Address [1] 303228 0
Country [1] 303228 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303772 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 303772 0
Level 5/553 St Kilda Road,
Melbourne
VIC 3004
Ethics committee country [1] 303772 0
Australia
Date submitted for ethics approval [1] 303772 0
29/08/2019
Approval date [1] 303772 0
05/09/2019
Ethics approval number [1] 303772 0
HREC/324-19/Alfred-2019

Summary
Brief summary
Heart failure is a common and serious problem in our community. It is unclear whether preventative treatment in people at high risk of heart failure, such as those with type 2 diabetes mellitus, works. Dapagliflozin is an anti-diabetic medication that has been shown to be effective in treating heart failure and reducing death. We are trying to determine whether using dapagliflozin in people with early features of heart failure prevents the progression of the condition.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94746 0
Prof Thomas Marwick
Address 94746 0
Baker Heart and Diabetes Institute,
75 Commercial Road,
Melbourne, VIC, 3004
Country 94746 0
Australia
Phone 94746 0
+61 3 8532 1550
Fax 94746 0
Email 94746 0
[email protected]
Contact person for public queries
Name 94747 0
Seyma Mulayim
Address 94747 0
Baker Heart and Diabetes Institute,
75 Commercial Road,
Melbourne, VIC, 3004
Country 94747 0
Australia
Phone 94747 0
+61 3 8532 1511
Fax 94747 0
Email 94747 0
[email protected]
Contact person for scientific queries
Name 94748 0
Thomas Marwick
Address 94748 0
Baker Heart and Diabetes Institute,
75 Commercial Road,
Melbourne, VIC, 3004
Country 94748 0
Australia
Phone 94748 0
+61 3 8532 1550
Fax 94748 0
Email 94748 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identifed (re-identifable) data will only be shared. Requests for data will be assessed as per each individual request by the PI and will be released at the PI's discretion.
When will data be available (start and end dates)?
Data will be available upon the initial date of publication of the findings on a request basis. There will be no stated end date of data availability as requests will be assessed individually by the PI.
Available to whom?
Data will be available to any researcher or clinician that submits a reasonable request to the PI of the study.
Available for what types of analyses?
De-identifed (re-identifable) data will be available for analyses. No specific analyses criteria will be used for this study, however all data requests will be reviewed by the PI and data will be released on an individual request basis.
How or where can data be obtained?
Requests for data, analytic methods, and study materials should be sent to the PI who will consider all
reasonable requests.
PI - Prof Thomas Marwick
Email: [email protected]


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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