The Effects of Eplerenone on Markers of Myocardial Fibrosis in Adult Congenital Heart Disease

Study Overview
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Brief Summary
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Hypothesis: By blocking aldosterone signaling in patients with Tetralogy of Fallot, Transposition of the great vessels with a prior atrial switch, and single ventricle Fontan patients, incident heart failure will be delayed, symptoms of heart failure ameliorated, and risk of arrhythmias decreased through decreases in myocardial fibrosis. Half of enrolled patients will complete an SF-36 quality of life questionnaire, perform a 6 minute walk, and have blood drawn for biomarker analysis at enrollment, again after 3 months without therapy, after 6 months on therapy, then finally after 12 months of eplerenone therapy. Half of enrolled patients will have the 3 month drug free period at the end of 12 months on therapy. Patients will be randomly assigned to drug free period up front versus at the conclusion of the trial period. Eplerenone will be started at a dose of 25mg and titrated up to 50mg at 4 weeks if tolerated. Blood will be drawn for basic metabolic panel analysis at enrollment, 3 months, 4 months to allow for dose titration, and at 6 and 12 months for monitoring.

Official Title
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Eplerenone to Prevent Myocardial Fibrosis in Congenital Heart Disease

Conditions
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Tetralogy of Fallot, Transposition of the Great Vessels With an Arterial Switch, Single Ventricle With a Fontan Palliation

Intervention / Treatment
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* Drug: Eplerenone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Established diagnosis of tetralogy of Fallot, transposition of the great vessels with a systemic right ventricle, or Fontan type palliation Patient followed regularly at Washington University-affiliated institution If female, willing to use 2 forms of contraception including one barrier method during protocol Exclusion Criteria: GFR <30 ml/min Potassium >5.0 mmol/L Unable or unwilling to comply with study protocol Use of potassium sparing diuretics Use of an aldosterone blocker currently or previously Known intolerance of eplerenone or aldosterone blockade Pregnant, breastfeeding, or actively trying to get pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Eplerenone after drug free period<br>Patients will be given eplerenone 50mg for 12 months after an initial 3 month drug free period | Drug: Eplerenone<br> <br> * Other names: Inspra;|
| Other: Eplerenone before drug free period<br>Patients will be given eplerenone 50mg for 12 months, followed by a 3 month drug free period | Drug: Eplerenone<br> <br> * Other names: Inspra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Procollagen N-terminal Peptide 1 |  | Baseline, 6 months and 12 months from eplerenone administration | 
| Procollagen III N-Terminal Peptide |  | Baseline, 6 months and 12 months from eplerenone administration | 
| Galectin 3 |  | Baseline, 6 months and 12 months from eplerenone administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 Minute Walk |  | Baseline, 6 months, 12 months from eplerenone administration | 
| Quality of Life | Rand 36-item Short Score Physical Domain Scale (SF-36) Range: 0-100, Higher scores suggest better function | Baseline, 6 months, 12 months from eplerenone administration |