Atrial Fibrillation
Conditions
Brief summary
This proposal details the implementation of an international (Singapore and New Zealand) multi-centre study to test a novel therapeutic strategy aimed at reducing the burden of atrial fibrillation - an important medical condition with major healthcare implications. Unique aspects of this study include i) a non-arrhythmic treatment target (mineralocorticoid receptor antagonism) -targeting the arrhythmogenic substrate of AF before it becomes permanently established, ii) the use of pacemaker monitoring capability to accurately document AF burden, thus increasing the power of the study and iii) multi-national collaborative, double blind design.
Interventions
Mineralocorticoid Receptor Antagonists
DRUGPlacebo oral tablet
Placebo
Sponsors
University of Otago
National University Hospital, Singapore
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Age \> 21 years (without child-bearing potential for women); * With a permanent pacemaker capable of AF monitoring; * Device documented AF in the last 12 months; Defined as: i. atrial high rate events (AHRE) \> 220 bpm for \>1% of the time; or ii. \> 6 mins on at least one occasion
Exclusion criteria
* Persistent (defined as sustained AF lasting continuously for 7 or more days) * History of heart failure with indication for MRAs * Any existing clinical indication for MRA or K+ sparing diuretic such as uncontrolled hypertension or oedema * Contraindication to MRA * Severe renal dysfunction (eGFR \<30ml/min by CKD-Epi) * Sustained hyperkalaemia (defined as K+ \>5mmol/L in the absence of reversible cause) * Receiving AF suppression pacing * Women of child bearing potential * Patients taking medications which may interact with the study drug or increase the level of potassium in the blood, include lithium, amiloride, cyclosporine, eplerenone, tacrolimus, and triamterene.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Development of persistent AF (defined as the first episode of sustained AF lasting for more than 7 days) | 18 months | Development of persistent AF (defined as the first episode of sustained AF lasting for more than 7 days) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of AF episodes | 18 months | Number of AF episodes \> 5 minutes duration recorded on pacemaker |
| Number of symptomatic AF episodes | 18 months | Number of symptomatic AF episodes |
| Number of admissions for AF | 18 months | Number of admissions for AF |
| Change in LA volumes in millimetre | 18 months | Change in LA volumes in millimetre assessed by echo scan |
| Percentage of total time in AF. | 18 months | Percentage of total time in AF. |
| Change in systolic and diastolic function | 18 months | Change in systolic and diastolic function assessed by echo scan |
| Change in cardiac and systemic markers | 18 months | Change in cardiac and systemic markers of stretch assessed by biomarkers blood tests - NT-proBNP |
| Change in cardiac and systemic markers of inflammation | 18 months | Change in cardiac and systemic markers of inflammation assessed by biomarkers blood tests - hsCRP, myeloperoxidase, ST-2, GD-15, Galectin-3 |
| Change in cardiac and systemic markers of fibrosis | 18 months | Change in cardiac and systemic markers of fibrosis assessed by biomarkers blood tests - PIIP, type 1 and II procollagen |
| Change in LV volumes in millimetre | 18 months | Change in LV volumes in millimetre assessed by echo scan |
Countries
Singapore
Contacts
Primary ContactPipin Kojodjojo
Outcome results
None listed