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

Phase 4

Terminated

• Conditions: Transposition of the Great Vessels With an Arterial Switch; Single Ventricle With a Fontan Palliation; Tetralogy of Fallot
• Interventions: Drug: Eplerenone

• Registration Number: NCT01971593
• Lead Sponsor: Washington University School of Medicine

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-08
• Study First Submitted: 2013-10-23
• Study First Submitted QC: 2013-10-23
• Study First Posted: 2013-10-29
• Primary Completion: 2016-03
• Study Completion: 2016-06
• Results First Submitted: 2018-01-25
• Status Verified: 2018-04
• Results First Submitted QC: 2018-04-03
• Last Update Submitted: 2018-04-03
• Results First Posted: 2018-05-04
• Last Update Posted: 2018-05-04

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 26

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Eplerenone after drug free period	Eplerenone	Patients will be given eplerenone 50mg for 12 months after an initial 3 month drug free period
Eplerenone before drug free period	Eplerenone	Patients will be given eplerenone 50mg for 12 months, followed by a 3 month drug free period

Primary Outcome Measures

Name	Time	Method
Procollagen N-terminal Peptide 1	Baseline, 6 months and 12 months from eplerenone administration
Galectin 3	Baseline, 6 months and 12 months from eplerenone administration
Procollagen III N-Terminal Peptide	Baseline, 6 months and 12 months from eplerenone administration

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States