Role of Eplerenone in Reducing Recurrence of Atrial Fibrillation in Patient With Structural Heart Disease

The aim of this study is to study synergistic effect of eplerenone as Selective aldosterone receptor antagonist with amiodarone compared with amiodarone only in reducing recurrence of atrial fibrillation in patient with structural heart disease

Study Overview

• Status: Not yet recruiting
• Conditions: Paroxysmal Atrial Fibrillation
• Intervention / Treatment: Drug: Eplerenone

Detailed Description

Atrial fibrillation is the most common sustained arrhythmia, with a rising prevalence that substantially increases the risk of stroke and heart failure (1,2), The rate of recurrences without antiarrhythmic treatment is 71%-84%, and it can be reduced to 44%-67% with antiarrhythmic drug therapy(3) Mineralocorticoid receptor blockers (MRBs) are beneficial in systolic HF[ 4,5,6]. Specifically, the MRB eplerenone (EPL) has been shown to reduce new onset AF and recurrent AF in HF patients (7). Both angiotensin II and aldosterone elevations may lead to atrial fibrosis and contribute to human AF (8). Experimental results suggest that aldosterone may cause a substrate for atrial fibrosis and AF (9). Aldosterone increases the expression of 11β-hydroxysteroid dehydrogenase type 2 (11b-HSD2) leading to up-regulation of profibrotic mediators and collagen synthesis, which is prevented by MRBs (10).

The European Society of Cardiology (ESC) guidelines identify AF as secondary to Structural heart diseases (SHDs)when a left ventricle (LV) systolic or diastolic dysfunction is demonstrated or LV hypertrophy, valvular disease, and/or other SHDs are documented [11].currently, SHD includes: (a) heart failure with reduced ejection fraction (HFrEF, previously severe or moderate LV systolic dysfunction); (b) heart failure with preserved ejection fraction (HFpEF, previously LV diastolic dysfunction); (c) valvular heart disease (VHD) and (d) specific cardiomyopathies, such as hypertrophic cardiomyopathy (HCM) [12].

Electrical remodelling is the first mechanism that occurs at the onset of AF and promotes AF through a re-entry-prone substrate. Changes in atrial frequency are determined by changes in the physiology of ion channel activation[13] Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias,it blocks the channels that are upregulated by remodelling such as inward-rectifying K1 current (IK1) or by stimulation of the sympathetic nervous system.[14]

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Walid Abdellah; Phone Number: 01158931616; Email: walidshehata573@gmail.com
• Study Contact Backup: Name: Hatem Helmy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- paroxysmal AF who reverted to sinus rhythm either medically or electrically without appropriate secondary cause of primary AF

•AF attack should be documented with ECG

Exclusion Criteria:

• 1-patients are currently on eplerenone or spironolactone 2-hyperkalemia 3-impaired renal function(if CrCl <50ml/min or serum creatinine>2 mg/dl) 4-patient on beta blocker and calcium channel blocker (non- dihydropyridine) 5-prosthetic valve 6-severe mitral stenosis 7-thyroid dysfunction 8-WPW 9-severe liver disease 10-persistent or permanent AF 11-pregnancy or breast feeding 12-LV EF<50% 13-known hypersensitivity or drug reaction to amiodarone 14-acute coronary syndrome 15-refusal of consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Amiodarone as comparison; 50 patients >>Amiodarone +other treatmen	Drug: Eplerenone; Amiodarone vs eplerenone in AF
Experimental: Eplerenone plus amiodarone; 50 patients >>Amiodarone +other treatmen	Drug: Eplerenone; Amiodarone vs eplerenone in AF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Role of eplerenone in reducing recurrence of atrial fibrillation in patient with structural heart disease	decrease recurrence of paroxysmal AF in patient of structural heart disease	Baseline

Collaborators and Investigators

• Sponsor: Assiut University

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): September 29, 2026
• Study Completion (Estimated): May 20, 2027

Study Registration Dates

• First Submitted: December 5, 2023
• First Submitted That Met QC Criteria: December 5, 2023
• First Posted (Actual): December 13, 2023

Study Record Updates

• Last Update Posted (Actual): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Disease Attributes; Arrhythmias, Cardiac; Heart Diseases; Atrial Fibrillation; Recurrence; Physiological Effects of Drugs; Antihypertensive Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Eplerenone
• Other Study ID Numbers: Eplerenone in AF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No