ANZCTR - Registration

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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]

Nil Known

Universal Trial Number (UTN)

Trial acronym

VicELF

Linked study record

Health condition

Health condition(s) or problem(s) studied:

heart failure

atrial fibrillation

Condition category

Condition code

Cardiovascular

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]

Early detection / Screening

Intervention code [2]

Prevention

Intervention code [3]

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]

Recognition of incident symptomatic heart failure at clinic review by a physician applying Framingham criteria..

Timepoint [1]

At 24 months post randomization.

Primary outcome [2]

New LV dysfunction, defined on the basis of 3D echo.

Timepoint [2]

At 24 months post randomization.

Secondary outcome [1]

Change in 6 minute walk.

Timepoint [1]

at 24 months post randomization.

Secondary outcome [2]

Diagnosed atrial fibrillation from medical records and multiple daily ECG acquisitions (usually 4/day) using a handheld single-lead monitoring device.

Timepoint [2]

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

Sex

Both males and females

Can healthy volunteers participate?

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

1/02/2017

Actual

13/04/2017

Date of last participant enrolment

Anticipated

1/02/2019

Actual

Date of last data collection

Anticipated

1/02/2021

Actual

Sample size

Target

800

Accrual to date

180

Final

Recruitment in Australia

Recruitment state(s)

VIC

Funding & Sponsors

Funding source category [1]

Other

Name [1]

Baker IDI Heart & Diabetes Institute

Address [1]

75 Commercial Rd
Prahran
Victoria 3004

Country [1]

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]

Charities/Societies/Foundations

Name [1]

Ian Potter Foundation

Address [1]

Level 3
111 Collins St
Melbourne VIC 3000

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Bellberry Limited

Ethics committee address [1]

129 Glen Osmond Road 
Eastwood South 
SA 5063

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

04/10/2016

Approval date [1]

08/12/2016

Ethics approval number [1]

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

Prof Tom Marwick

Address

Baker Heart and Diabetes Institute
75 Commercial Rd
Prahran
Victoria 3004

Country

Australia

Phone

+61 3 8532 1550

Fax

tom.marwick@bakeridi.edu.au

Contact person for public queries

Name

Joanne Harris

Address

Baker Heart and Diabetes Institute
Level 4, 99 Commercial Rd
Prahran
Victoria 3004

Country

Australia

Phone

+61 3 8532 1511

Fax

jasmine.prichard@bakeridi.edu.au

Contact person for scientific queries

Name

Tom Marwick

Address

Baker Heart and Diabetes Institute
75 Commercial Rd
Prahran
Victoria 3004

Country

Australia

Phone

+61 3 8532 1550

Fax

tom.marwick@bakeridi.edu.au

No information has been provided regarding IPD availability

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

Source	Title	Year of Publication	DOI
Embase	Associations of subclinical heart failure and atrial fibrillation with mild cognitive impairment: A cross-sectional study in a subclinical heart failure screening programme.	2021	https://dx.doi.org/10.1136/bmjopen-2020-045896
Embase	Machine Learning of ECG Waveforms to Improve Selection for Testing for Asymptomatic Left Ventricular Dysfunction.	2021	https://dx.doi.org/10.1016/j.jcmg.2021.04.020
Embase	Screening-guided spironolactone treatment of subclinical left ventricular dysfunction for heart failure prevention in at-risk patients.	2022	https://dx.doi.org/10.1002/ejhf.2428

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added manually

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