Mineralocorticoid Antagonism to Stop Progression of Atrial Fibrillation (MONITOR-AF) Study

Phase 2

• Conditions: Atrial Fibrillation
• Interventions: Drug: Spironolactone 25mg; Drug: Placebo oral tablet

• Registration Number: NCT04327232
• Lead Sponsor: National University Hospital, Singapore

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-05-23
• Status Verified: 2019-06
• Study First Submitted: 2019-06-12
• Study First Submitted QC: 2020-03-30
• Last Update Submitted: 2020-03-30
• Study First Posted: 2020-03-31
• Last Update Posted: 2020-03-31
• Primary Completion: 2022-05-31
• Study Completion: 2022-05-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 184

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active	Spironolactone 25mg	For patients randomized to active experimental arm: Spironolactone Patient will receive study drug for 18 months. Study drug dosages are 1 tablet alternate day, 1 tablet per day, or 2 tablets per day, with 1 tablet being 25mg spironolactone. Study drugs are titrated every 3 months based on patients' potassium and eGFR blood tests results.
Control	Placebo oral tablet	For patients randomized to control arm: Placebo Patient will receive placebo for 18 months. Placebo dosages are 1 tablet alternate day, 1 tablet per day, or 2 tablets per day. Placebo are titrated every 3 months based on patients' potassium and eGFR blood tests results.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Number of AF episodes	18 months	Number of AF episodes \> 5 minutes duration recorded on pacemaker
Number of admissions for AF	18 months	Number of admissions for AF
Change in LV volumes in millimetre	18 months	Change in LV volumes in millimetre assessed by echo scan
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
Number of symptomatic AF episodes	18 months	Number of symptomatic AF episodes
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.

Trial Locations

Locations (4)

Ng Teng Fong General Hospital; 🇸🇬 Singapore, Singapore

Changi General Hospital; 🇸🇬 Singapore, Singapore

Tan Tock Seng Hospital; 🇸🇬 Singapore, Singapore

National University Hospital; 🇸🇬 Singapore, Singapore