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Trial registered on ANZCTR


Registration number
ACTRN12617000116325
Ethics application status
Approved
Date submitted
21/12/2016
Date registered
23/01/2017
Date last updated
28/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Victorian study of Echocardiographic detection of Left ventricular dysFunction (Vic-ELF)
Scientific title
Use of advanced echocardiographic techniques to select asymptomatic subjects at risk of heart failure for spironolactone therapy to reduce progression to heart failure
Secondary ID [1] 290799 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
VicELF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
heart failure 301447 0
atrial fibrillation 301448 0
Condition category
Condition code
Cardiovascular 301164 301164 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will be randomised into two possible strategies of screening: Advanced imaging vs conventional imaging.

Advanced cardiac imaging will involve inclusion of global longitudinal strain and diastolic dysfunction evaluation. The test will be performed by a qualified clinician (usually a sonographer), and the procedure will take about 30 minutes.

Individuals in either imaging group who are identified as having Stage B heart failure will be treated with spironolactone as an oral tablet (25mg) daily for 12 months.

Adherence to spironolactone will be monitored by tablet count from empty drug packet return.
Intervention code [1] 296714 0
Early detection / Screening
Intervention code [2] 296715 0
Prevention
Intervention code [3] 296937 0
Treatment: Drugs
Comparator / control treatment
Conventional imaging- limited to evaluation of Ejection Fraction and valve disease. The test will be performed by a qualified clinician (usually a sonographer), and the procedure will take about 30 minutes.
Control group
Active

Outcomes
Primary outcome [1] 300579 0
Recognition of incident symptomatic heart failure at clinic review by a physician applying Framingham criteria..
Timepoint [1] 300579 0
At 24 months post randomization.
Primary outcome [2] 300580 0
New LV dysfunction, defined on the basis of 3D echo.
Timepoint [2] 300580 0
At 24 months post randomization.
Secondary outcome [1] 330350 0
Change in 6 minute walk.
Timepoint [1] 330350 0
at 24 months post randomization.
Secondary outcome [2] 330351 0
Diagnosed atrial fibrillation from medical records and multiple daily ECG acquisitions (usually 4/day) using a handheld single-lead monitoring device.
Timepoint [2] 330351 0
At 24 months post randomization.

Eligibility
Key inclusion criteria
Aged >65 years with any of;
-Diabetes (T2DM), based on self-report including medical management
-Obesity (body mass index [BMI] greater than or equal to 30)
-High blood pressure (blood pressure greater than 140/90 mmHg, self-reported, including anti-hypertensive medication)
-Known non-ischaemic cardiac disease (but not existing heart failure)
Minimum age
65 Years
Maximum age
No limit
Gender
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 randomized treatment would be unacceptable
-History of >moderate valvular heart disease
-History of previous heart failure, hypertrophic cardiomyopathy
-Current therapy, contraindications, intolerance to mineralocorticoid inhibition
-Systolic blood pressure (BP) <110mmHg
-Estimated glomerular filtration rate (eGFR) <60
- Baseline New York Heart Association (NYHA) classification >2
- Oncologic life expectancy < 12 months
- Inability to acquire interpretable images (identified from baseline echo)

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)
At risk subjects will be identified by cardiologists, study nurses, general practitioners, or self-referred. We plan to compare 400 subjects with strain vs 400 controls.

Clinical evaluation: All subjects will undertake a clinical history and answer questionnaires on general health status (EQ5D), activity (DASI), heart failure symptoms (MLHFQ) and performed a 6 minute walk test. All will undergo a screening echo for valvular disease. If these results are abnormal, subjects will be excluded.

Study protocol: A central (web-based) randomization program will be used to allocate patients to advanced vs conventional imaging only after the patient is enrolled. This allocation concealment will prevent the person performing recruitment from knowing the allocated group at the time of inclusion. Subsequent management decisions are not based on randomization and will occur as a "usual care' response to data provided from imaging.

Patients will be randomized to two possible strategies of screening: advanced imaging vs conventional imaging.
1) Conventional imaging- Limited to evaluation of EF and valve disease.
2) Advanced cardiac imaging- Inclusion of global longitudinal strain and diastolic dysfunction evaluation. Presence of a global strain <16% or raised filling pressure at diastolic function evaluation will provoke initiation of treatment
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be performed using a randomisation table created by computer software (i.e. computerised sequence generation).
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
1) Primary outcome- The 800 recruited subjects will be randomized into 400 studies with advanced echo and 400 with standard echo. Assuming subclinical cardiac dysfunction in 60%, we would expect 240 patients with myocardial dysfunction identified by imaging in each arm, This group will only be identifiable (and therefore treated) in the advanced echo arm. With an annualized event rate of 12% in patients with subclinical dysfunction (5% in those without), and an average follow-up of 4 years, we expect events in 40% and 15% in control and treatment groups, respectively. A comparison of 206 patients would provide an 80% power to identify the difference in the incident of HF a p<0.05. To allow for 15% loss to follow-up, we will study 240/group.

2) Secondary outcome- functional capacity: Assuming a similar 6-minute walk to previous work in patients with a similar risk profile to be 525+/-113m, so a 5% change could be identified with 297 patients per group at a power of 80%, at a p<0.05.

Both calculations were performed using statistics software ‘SPSS Sample Power 2.0’, using respectively survival and t-test modules.
The initial step will be a standard questionnaire for all subjects, to identify and exclude persons who have some problem (identified or otherwise) that makes them ineligible. We will also use the same equipment to screen for impaired EF (<40%) or moderate or worse valve disease.

Outcomes of patients will be compared with survival analysis (heart failure) and t-test (change in 6-minute walk test). Multivariable models (respectively Cox regression and linear) will be developed to identify effect size, and will be extremely important if groups are mismatched despite randomization. All analyses will be performed on an intention to treat basis.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 295223 0
Other
Name [1] 295223 0
Baker IDI Heart & Diabetes Institute
Address [1] 295223 0
75 Commercial Rd
Prahran
Victoria 3004
Country [1] 295223 0
Australia
Primary sponsor type
Other
Name
Baker IDI Heart and Diabetes Institute
Address
75 Commercial Rd
Melbourne VIC 3004
Country
Australia
Secondary sponsor category [1] 294051 0
Charities/Societies/Foundations
Name [1] 294051 0
Ian Potter Foundation
Address [1] 294051 0
Level 3
111 Collins St
Melbourne VIC 3000
Country [1] 294051 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296567 0
Bellberry Limited
Ethics committee address [1] 296567 0
129 Glen Osmond Road
Eastwood South
SA 5063
Ethics committee country [1] 296567 0
Australia
Date submitted for ethics approval [1] 296567 0
04/10/2016
Approval date [1] 296567 0
08/12/2016
Ethics approval number [1] 296567 0
2016-10-727

Summary
Brief summary
Heart failure (HF) is a problem that is assuming epidemic proportions, especially among the elderly. Unfortunately, its clinical diagnosis is associated with late-stage disease, which has a poor prognosis and responds poorly to medical therapy. At present, there is no effective strategy for identifying and preventing HF, with the result that patients present late in the course of the disease where hospitalisation is inevitable and treatment responses are poor.

The Vic-ELF study (Victorian Study of Echocardiographic detection of Left ventricular dysfunction) study is a randomised trial to explore the benefits of screening selected patients at risk of developing heart failure. We will do this with a special new imaging technique (strain imaging), in which we at Baker IDI Heart and Diabetes Institute have special expertise. Screening of "at risk" patients with a combination of clinical scores and echo imaging is able to identify patients who are liable to develop HF.
The question that now needs to be answered is whether surveillance with GLS could change HF outcomes in at risk patients. We anticipate that the prompt initiation of therapy in these patients that are recognized to have the earliest phase of HF will result in improvement in their functional capacity, and arrest in the subsequent progression to HF.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 71318 0
Prof Tom Marwick
Address 71318 0
Baker Heart and Diabetes Institute
75 Commercial Rd
Prahran
Victoria 3004
Country 71318 0
Australia
Phone 71318 0
+61 3 8532 1550
Fax 71318 0
Email 71318 0
tom.marwick@bakeridi.edu.au
Contact person for public queries
Name 71319 0
Miss Joanne Harris
Address 71319 0
Baker Heart and Diabetes Institute
Level 4, 99 Commercial Rd
Prahran
Victoria 3004
Country 71319 0
Australia
Phone 71319 0
+61 3 8532 1511
Fax 71319 0
Email 71319 0
jasmine.prichard@bakeridi.edu.au
Contact person for scientific queries
Name 71320 0
Prof Tom Marwick
Address 71320 0
Baker Heart and Diabetes Institute
75 Commercial Rd
Prahran
Victoria 3004
Country 71320 0
Australia
Phone 71320 0
+61 3 8532 1550
Fax 71320 0
Email 71320 0
tom.marwick@bakeridi.edu.au

No information has been provided regarding IPD availability
Summary results
No Results