Efficacy of Aldosterone Antagonist Therapy for Prevention of New Atrial Fibrillation

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to accurately determine, using an implantable rhythm monitor, the long-term incidence of new atrial fibrillation after ablation of atrial flutter in those treated with spironolactone compared with standard medical therapy.

Detailed Description
-----------------
Catheter ablation of the cavotricuspid isthmus (CTI) is an effective and safe procedure in patients with atrial flutter (AFL) with excellent long-term results in preventing AFL recurrences. However, new-onset atrial fibrillation (AF) commonly develops after this procedure and has important clinical implications for patient management. Few studies have assessed the long-term incidence and prevalence of AF after CTI ablation via intensive continuous rhythm monitoring with an implantable cardiac monitor. Furthermore, whether the development of AF can be impacted beneficially by adjunctive therapeutic approaches is not known. The co-primary objectives of this pilot study in patients with typical atrial flutter (AFL) but no previously detected AF are: 1) to accurately determine the long-term incidence of new-onset AF after CTI ablation using an implantable rhythm monitor; 2) to compare the rates of new onset AF in subjects randomized to standard, usual-care, medical therapy following CTI ablation compared with those randomized to treatment with an aldosterone antagonist (spironolactone) in addition to their usual care medications. The patient population will be subjects with typical atrial flutter and a history of hypertension or heart failure, but no known AF episodes, scheduled to undergo catheter ablation of the CTI for treatment of AFL. Patients will be randomized to remain on their standard, usual-care. medications or to take oral spironolactone (a standard, FDA-approved medication used in the treatment of hypertension and heart failure) starting after their ablation procedure. The primary study endpoint will be any atrial tachyarrhythmia episode (AF, AFL or atrial tachycardia) lasting greater than one minute detected via the implanted cardiac monitor after CTI ablation during long-term follow-up. The incidence of new-onset AF after CTI ablation will be compared between subjects randomized to be treated with usual care vs. those treated with usual care plus spironolactone on an intention to treat basis.

Official Title
-----------------
A Randomized Prospective Pilot Study to Evaluate Efficacy of Aldosterone Antagonist Therapy for Prevention of New Atrial Fibrillation (AF) in Patients With Atrial Flutter (AFL), But no Previously Detected AF, Undergoing caVOtricuspID Isthmus Ablation

Conditions
-----------------
AFib

Intervention / Treatment
-----------------
* Drug: Spironolactone
* Drug: No Spironolactone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: diagnosis of typical AFL confirmed by 12-lead ECG no documented AF on ECG, ambulatory monitor, pacemaker or ICD at any time scheduled to undergo catheter ablation of the CTI for treatment of AFL history of hypertension (HTN) or heart failure (HF) (reduced or preserved systolic function) Exclusion Criteria: history of known AF episodes previous CTI or PVI ablation procedure other SVT mechanisms demonstrated (AVNRT, AVRT or accessory pathways) amiodarone usage within the past 3 months, unwillingness to participate or undergo insertable monitor implantation hyperkalemia (potassium > 5.0 mEq/L) severe renal disease (Cr >2.5 mg/dL [men], >2.0 mg/dL [women, GFR < 30 mL/min/1.73 m2) life expectancy < 18 months prior intolerance to treatment with an aldosterone antagonist current treatment with an aldosterone antagonist need for treatment with a class I or III AAD for another indication operative AFL (occurring within 30 days of surgery) that is expected to resolve presence of a cardiac rhythm device (pacemaker or ICD) capable of AF monitoring currently pregnant or nursing a child unwilling not to become pregnant and to use birth control while taking spironolactone

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, pilot study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Therapy<br>subjects undergoing CTI ablation | Drug: No Spironolactone<br>* no spironolactone treatment<br>|
| Experimental: Interventional Therapy<br>subjects treated with an aldosterone antagonist after CTI ablation | Drug: Spironolactone<br>* receive spironolactone treatment after CTI ablation<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long-Term incidence of new-onset AF after CTI ablation | 1. To accurately determine the long-term incidence of new-onset AF after CTI ablation using an implantable rhythm monitor | 24 months | 
| Rates of new-onset AF between standard therapy and spironolactone | 2. To compare the rates of new onset AF in subjects randomized to standard medical therapy following CTI ablation compared with those randomized to treatment with an aldosterone antagonist (spironolactone) | 24 months |