Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000464460
Ethics application status
Approved
Date submitted
30/04/2025
Date registered
15/05/2025
Date last updated
15/05/2025
Date data sharing statement initially provided
15/05/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
The role of pharmacological heart failure therapy in LV recovery following INDEX catheter ablation for patients with atrial fibrillation (AF) induced cardiomyopathy - the INDEX-AF Study
Scientific title
The role of pharmacological heart failure therapy in LV recovery following INDEX catheter ablation for patients with atrial fibrillation (AF) induced cardiomyopathy - the INDEX-AF Study
Secondary ID [1] 313761 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
atrial fibrillation 336362 0
heart failure 336363 0
Condition category
Condition code
Cardiovascular 332897 332897 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a randomised control trial for to explore whether patients with atrial fibrillation (AF) induced cardiomyopathy undergoing AF catheter ablation can avoid heart failure (HF) pharmacotherapy.

All patients will undergo early AF catheter ablation within 1 month of enrolment (left ventricular ejection fraction is less than or equal to 40% and there is absence of late gadolinium enhancement).

The intervention arm will be monitored following catheter ablation without the addition of anti HF pharmacotherapy through follow-up in hospital at 6 weeks, 3 months and 6 months post randomisation. Adherence to the intervention will be via participant self report.
Intervention code [1] 330342 0
Treatment: Other
Comparator / control treatment
The control (usual care) arm will receive anti-HF pharmacotherapy, which includes a HF specific beta blocker, mineralocorticoid receptor antagonist (MRA), Sodium-glucose cotransporter-2 (SGLT2) inhibitors and either angiotension receptor antagonists (ACE) inhibitors, angiotensin receptor blockers (ARBs) or angiotensin receptor blocker/neprilysin inhibitor (ARNI, Eg. Entresto). These will be commenced, with up-titration and monitoring as per standard care, and have follow-up at 6 weeks, 3 months and 6 months post randomisation.
Control group
Active

Outcomes
Primary outcome [1] 340425 0
The primary outcome will be change in left ventricular ejection fraction at 6 months post randomisation
Timepoint [1] 340425 0
6 months post randomisation
Secondary outcome [1] 444010 0
Change from baseline to follow-up in Quality of life
Timepoint [1] 444010 0
Baseline, 3 and 6 months post randomisation
Secondary outcome [2] 444011 0
Arrhythmia recurrence
Timepoint [2] 444011 0
6 months post randomisation
Secondary outcome [3] 444012 0
Change from baseline to follow-up in cardiac dimensions
Timepoint [3] 444012 0
baseline, 3 months and 6 months post randomisation
Secondary outcome [4] 444013 0
Change from baseline to follow-up in functional capacity
Timepoint [4] 444013 0
baseline and 6 months post randomisation
Secondary outcome [5] 444014 0
Change from baseline to follow-up in cardiac heart failure biomarkers (NT Pro BNP)
Timepoint [5] 444014 0
baseline and 6 months post randomisation
Secondary outcome [6] 444015 0
Composite of: overall mortality, cardiovascular mortality, unplanned heart failure hospitalisation, total hospitalisation. This will be assessed as a composite outcome
Timepoint [6] 444015 0
6 months post randomisation
Secondary outcome [7] 444021 0
Direct current cardioversion, re-do AF ablation, requirement of anti-arrhythmic medications. This will be assessed as a composite outcome.
Timepoint [7] 444021 0
6 months post randomisation
Secondary outcome [8] 447213 0
Arrhythmia burden
Timepoint [8] 447213 0
at 6 months post randomisation
Secondary outcome [9] 447214 0
overall mortality
Timepoint [9] 447214 0
6 months post randomisation
Secondary outcome [10] 447215 0
cardiovascular mortality
Timepoint [10] 447215 0
6 months post randomisation
Secondary outcome [11] 447216 0
unplanned heart failure hospitalisations
Timepoint [11] 447216 0
6 months post randomisation
Secondary outcome [12] 447217 0
total hospitalisation
Timepoint [12] 447217 0
6 months post randomisation
Secondary outcome [13] 447218 0
Direct current cardioversion
Timepoint [13] 447218 0
6 months post randomisation
Secondary outcome [14] 447219 0
re-do AF ablation
Timepoint [14] 447219 0
6 months post randomisation
Secondary outcome [15] 447220 0
requirement of anti-arrhythmic medications
Timepoint [15] 447220 0
6 months post randomisation

Eligibility
Key inclusion criteria
Inclusion criteria
Age>18 years
New diagnosis of suspected atrial fibrillation (AF) induced cardiomyopathy
- Left ventricular ejection fraction (LVEF) less than or equal to 40% within 3 months of AF diagnosis to allow for delays in EF evaluation
- Minimal/Absence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) (defined burden <5%)
- Elevated B-type natriuretic peptide (BNP) or N-terminal (NT)-proBNP
Able to consent
Willing to adhere to follow up requirements
Recovering LVEF 1 month after catheter ablation (defined as LVEF greater than or equal to 50% or LVEF improved greater than or equal to 10% from initial transthoracic echocardiogram (TTE))
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with known contributing cause of LV dysfunction
- Ischaemic cardiomyopathy
- Valvular heart disease
- Hypertrophic cardiomyopathy
- Uncontrolled alcohol intake
- Other cause of cardiomyopathy (e.g. thyroid disease)
- LBBB or QRSD>130ms
Very severe LVEF dysfunction (defined as <20% on CMR)
Contraindication to catheter ablation
Any condition with expected survival < 2 years
Unable to provide informed consent
Patients with a clear indication for elements of heart failure therapy for reasons other than heart failure where alternative agents are contra-indicated or inappropriate

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 concealment: clinicians referring participants for inclusion in the trial will not be aware, when this decision was made, to which group the subject will be allocated. Central randomisation by computer will be performed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patient meeting eligibility following baseline screening will undergo baseline assessments and will subsequently be computer randomised in a 1:1 fashion through simple randomisation using a randomisation table created by computer software.
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
We utilised the data from the CAMERA-MRI II trial for patients without LGE and baseline LVEF of 20-40, at 6-month follow up after catheter ablation with recovering LVEF. This included 27 patients with mean LVEF 58.15 ± (SD) 5.43%. To perform a power calculation for a non-inferior study (assumption of no worse between anti-failure therapy and no anti-failure therapy arm), we assumed an equivalence limit of 5% with an expected delta of zero. For non-inferiority testing (one-tailed), significance level was set to p <0.025. We assumed a one-tailed T-test given the expectation that avoiding pharmacological heart failure therapy will not lead to worse LV function compared to the anti-failure therapy arm, and the one-tailed T-test provides more power to detect an effect. For this two arm non-inferior study to provide a statistical power of 90% with the probability of type one error being 0.025, we require a sample size of 50 (25 in each arm). In addition we accounted for an up to 20% cross-over and drop out rate, leading to the final sample size calculation 80 (40 in each arm).


Data will be analysed using SPSSv.26 and R (2023.12.0+369). All analyses will be conducted on an intention to treat and per protocol basis using standard statistical methods for categorical and continuous data. Continuous data will be expressed as mean ± standard deviation if normally distributed (median and interquartile range if non-parametric data). Categorical data will be presented as numbers and percentages. Differences in variables between groups will be analysed using the chi square test for categorical data and the Student’s T-test or Mann Whitney U test for normally distributed and skewed continuous data respectively. The study will be a non-inferior study (assumption of no worse in left ventricular ejection fraction between anti-failure therapy and no anti-failure therapy arm), with an assumed equivalence limit of 5% with an expected delta of zero. For non-inferiority testing (one-tailed), Statistical significance is defined as a p value of <0.05 for two tailed tests and <0.025 for one-tailed tests.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
26/05/2025
Actual
Date of last participant enrolment
Anticipated
31/07/2026
Actual
Date of last data collection
Anticipated
31/07/2027
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 318222 0
Self funded/Unfunded
Name [1] 318222 0
Country [1] 318222 0
Primary sponsor type
Hospital
Name
Alfred Health
Address
Country
Australia
Secondary sponsor category [1] 320606 0
None
Name [1] 320606 0
Address [1] 320606 0
Country [1] 320606 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316865 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 316865 0
Ethics committee country [1] 316865 0
Australia
Date submitted for ethics approval [1] 316865 0
08/08/2024
Approval date [1] 316865 0
28/10/2024
Ethics approval number [1] 316865 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 139246 0
A/Prof Sandeep Prabhu
Address 139246 0
Department of Cardiology Alfred Hospital 55 Commercial Rd, Melbourne VIC 3004
Country 139246 0
Australia
Phone 139246 0
+61 390763522
Fax 139246 0
Email 139246 0
[email protected]
Contact person for public queries
Name 139247 0
Dr Kenneth Cho
Address 139247 0
Department of Cardiology Alfred Hospital 55 Commercial Rd, Melbourne VIC 3004
Country 139247 0
Australia
Phone 139247 0
+61 390762000
Fax 139247 0
Email 139247 0
[email protected]
Contact person for scientific queries
Name 139248 0
Dr Kenneth Cho
Address 139248 0
Department of Cardiology Alfred Hospital 55 Commercial Rd, Melbourne VIC 3004
Country 139248 0
Australia
Phone 139248 0
+61 390762000
Fax 139248 0
Email 139248 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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.