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

Primary Purpose

Atrial Fibrillation

Status
Unknown status
Phase
Phase 2
Locations
Singapore
Study Type
Interventional
Intervention
Spironolactone 25mg
Placebo oral tablet
Sponsored by
National University Hospital, Singapore
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Atrial Fibrillation

Eligibility Criteria

21 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • National University HospitalRecruiting
  • Tan Tock Seng Hospital
  • Changi General Hospital
  • Ng Teng Fong General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Active

Control

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Development of persistent AF (defined as the first episode of sustained AF lasting for more than 7 days)
Development of persistent AF (defined as the first episode of sustained AF lasting for more than 7 days)

Secondary Outcome Measures

Percentage of total time in AF.
Percentage of total time in AF.
Number of AF episodes
Number of AF episodes > 5 minutes duration recorded on pacemaker
Number of symptomatic AF episodes
Number of symptomatic AF episodes
Number of admissions for AF
Number of admissions for AF
Change in LA volumes in millimetre
Change in LA volumes in millimetre assessed by echo scan
Change in LV volumes in millimetre
Change in LV volumes in millimetre assessed by echo scan
Change in systolic and diastolic function
Change in systolic and diastolic function assessed by echo scan
Change in cardiac and systemic markers
Change in cardiac and systemic markers of stretch assessed by biomarkers blood tests - NT-proBNP
Change in cardiac and systemic markers of inflammation
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
Change in cardiac and systemic markers of fibrosis assessed by biomarkers blood tests - PIIP, type 1 and II procollagen

Full Information

First Posted
June 12, 2019
Last Updated
March 30, 2020
Sponsor
National University Hospital, Singapore
Collaborators
University of Otago
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1. Study Identification

Unique Protocol Identification Number
NCT04327232
Brief Title
Mineralocorticoid Antagonism to Stop Progression of Atrial Fibrillation (MONITOR-AF) Study
Official Title
Mineralocorticoid Antagonism to Stop Progression of Atrial Fibrillation (MONITOR-AF) Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2019
Overall Recruitment Status
Unknown status
Study Start Date
May 23, 2018 (Actual)
Primary Completion Date
May 31, 2022 (Anticipated)
Study Completion Date
May 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National University Hospital, Singapore
Collaborators
University of Otago

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
184 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active
Arm Type
Experimental
Arm Description
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.
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Spironolactone 25mg
Intervention Description
Mineralocorticoid Receptor Antagonists
Intervention Type
Drug
Intervention Name(s)
Placebo oral tablet
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Development of persistent AF (defined as the first episode of sustained AF lasting for more than 7 days)
Description
Development of persistent AF (defined as the first episode of sustained AF lasting for more than 7 days)
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Percentage of total time in AF.
Description
Percentage of total time in AF.
Time Frame
18 months
Title
Number of AF episodes
Description
Number of AF episodes > 5 minutes duration recorded on pacemaker
Time Frame
18 months
Title
Number of symptomatic AF episodes
Description
Number of symptomatic AF episodes
Time Frame
18 months
Title
Number of admissions for AF
Description
Number of admissions for AF
Time Frame
18 months
Title
Change in LA volumes in millimetre
Description
Change in LA volumes in millimetre assessed by echo scan
Time Frame
18 months
Title
Change in LV volumes in millimetre
Description
Change in LV volumes in millimetre assessed by echo scan
Time Frame
18 months
Title
Change in systolic and diastolic function
Description
Change in systolic and diastolic function assessed by echo scan
Time Frame
18 months
Title
Change in cardiac and systemic markers
Description
Change in cardiac and systemic markers of stretch assessed by biomarkers blood tests - NT-proBNP
Time Frame
18 months
Title
Change in cardiac and systemic markers of inflammation
Description
Change in cardiac and systemic markers of inflammation assessed by biomarkers blood tests - hsCRP, myeloperoxidase, ST-2, GD-15, Galectin-3
Time Frame
18 months
Title
Change in cardiac and systemic markers of fibrosis
Description
Change in cardiac and systemic markers of fibrosis assessed by biomarkers blood tests - PIIP, type 1 and II procollagen
Time Frame
18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pipin Kojodjojo
Phone
(+65) 67725286
Email
pipin_kojodjojo@nuhs.edu.sg
Facility Information:
Facility Name
National University Hospital
City
Singapore
ZIP/Postal Code
119074
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pipin Kojodjojo
Email
pipin_kojodjojo@nuhs.edu.sg
Facility Name
Tan Tock Seng Hospital
City
Singapore
ZIP/Postal Code
308433
Country
Singapore
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wee Kian Kenny Tan
Email
Kenny_WK_TAN@ttsh.com.sg
Facility Name
Changi General Hospital
City
Singapore
ZIP/Postal Code
529889
Country
Singapore
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vern Hsen Tan
Email
tan.vern.hsen@singhealth.com.sg
Facility Name
Ng Teng Fong General Hospital
City
Singapore
ZIP/Postal Code
609606
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pipin Kojodjojo
Email
pipin_kojodjojo@nuhs.edu.sg

12. IPD Sharing Statement

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

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