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

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01971593
• Collaborator: Pfizer (Industry)
• Enrollment: 26
• Location: 1
• Arms: 2
• Duration (Months): 34
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Tetralogy of Fallot; Transposition of the Great Vessels With an Arterial Switch; Single Ventricle With a Fontan Palliation	Drug: Eplerenone	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Eplerenone to Prevent Myocardial Fibrosis in Congenital Heart Disease
• Study Start Date: Aug 1, 2013
• Actual Primary Completion Date: Mar 1, 2016
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Other: Eplerenone after drug free period Patients will be given eplerenone 50mg for 12 months after an initial 3 month drug free period	Drug: Eplerenone; Other Names: Inspra
Other: Eplerenone before drug free period Patients will be given eplerenone 50mg for 12 months, followed by a 3 month drug free period	Drug: Eplerenone; Other Names: Inspra

Outcome Measures

Primary Outcome Measures

1. Procollagen N-terminal Peptide 1 [Baseline, 6 months and 12 months from eplerenone administration]

2. Procollagen III N-Terminal Peptide [Baseline, 6 months and 12 months from eplerenone administration]

3. Galectin 3 [Baseline, 6 months and 12 months from eplerenone administration]

Secondary Outcome Measures

1. 6 Minute Walk [Baseline, 6 months, 12 months from eplerenone administration]

2. 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

Other Outcome Measures

1. Serum Creatinine [Baseline, 6 months, 12 months from eplerenone administration]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University School of Medicine	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine
• Pfizer

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ari Cedars, Assistant Professor of Medicine, Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT01971593
• Other Study ID Numbers: WI170964
• First Posted: Oct 29, 2013
• Last Update Posted: May 4, 2018
• Last Verified: Apr 1, 2018

• Additional relevant MeSH terms: Heart Diseases; Heart Defects, Congenital; Univentricular Heart; Tetralogy of Fallot; Transposition of Great Vessels; Eplerenone

Study Results

Participant Flow

Arm/Group Title	Eplerenone After Drug Free Period	Eplerenone Before Drug Free Period
Arm/Group Description	Patients will be given eplerenone 50mg for 12 months after an initial 3 month drug free period Eplerenone	Patients will be given eplerenone 50mg for 12 months, followed by a 3 month drug free period Eplerenone
Period Title: Overall Study
STARTED	14	12
COMPLETED	9	8
NOT COMPLETED	5	4

Baseline Characteristics

Arm/Group Title	Total Study Group
Arm/Group Description	Crossover study, all patients pooled for baseline analysis
Overall Participants	26
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	26 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	9 34.6%
Male	17 65.4%
Tetralogy of Fallot (Count of Participants)
Count of Participants [Participants]	12 46.2%
Patients with Transposition of the Great Vessels with a Systemic Right Ventricle (RV) (Count of Participants)
Count of Participants [Participants]	14 53.8%

Outcome Measures

1. Primary Outcome

Title	Procollagen N-terminal Peptide 1
Time Frame	Baseline, 6 months and 12 months from eplerenone administration

Outcome Measure Data

Analysis Population Description

Outcome analyzed only during the eplerenone period as specified in the protocol

Arm/Group Title	Total Study Group
Arm/Group Description	Change from baseline at time of drug initiation
Measure Participants	17
Baseline	45.1 (15.4)
6 Months	48.9 (20.3)
12 Months	42.7 (12.2)

2. Primary Outcome

Title	Procollagen III N-Terminal Peptide
Time Frame	Baseline, 6 months and 12 months from eplerenone administration

Outcome Measure Data

Analysis Population Description

Outcome analyzed only during the eplerenone period as specified in the protocol

Arm/Group Title	Total Study Group
Arm/Group Description	Change from baseline at time of drug initiation
Measure Participants	17
Baseline	4.6 (1.7)
6 Months	4.4 (1.5)
12 Months	4.4 (1.5)

3. Primary Outcome

Title	Galectin 3
Time Frame	Baseline, 6 months and 12 months from eplerenone administration

Outcome Measure Data

Analysis Population Description

Outcome analyzed only during the eplerenone period as specified in the protocol

Arm/Group Title	Total Study Group
Arm/Group Description	Change from baseline at time of drug initiation
Measure Participants	17
Baseline	10.0 (2.4)
6 Months	11.6 (2.9)
12 Months	11.2 (2.2)

4. Secondary Outcome

Title	6 Minute Walk
Time Frame	Baseline, 6 months, 12 months from eplerenone administration

Outcome Measure Data

Analysis Population Description

Outcome analyzed only during the eplerenone period as specified in the protocol

Arm/Group Title	Total Study Group
Arm/Group Description	Change from baseline at time of drug initiation
Measure Participants	17
Baseline	1629 (261)
6 Months	1630 (250)
12 Months	1680.2 (255)

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Outcome analyzed only during the eplerenone period as specified in the protocol

Arm/Group Title	Total Study Group
Arm/Group Description	Change from baseline at time of drug initiation
Measure Participants	17
Baseline	87.5
6 Months	90
12 Months	85

6. Other Pre-specified Outcome

Title	Serum Creatinine
Time Frame	Baseline, 6 months, 12 months from eplerenone administration

Outcome Measure Data

Analysis Population Description

Outcome analyzed only during the eplerenone period as specified in the protocol

Arm/Group Title	Total Study Group
Arm/Group Description	Change from baseline at time of drug initiation
Measure Participants	17
Baseline	0.9 (0.2)
6 Months	0.9 (0.2)
12 Months	0.9 (0.2)

Adverse Events

Time Frame	During 12 months while on eplerenone
Adverse Event Reporting Description	Adverse event data only collected during the eplerenone period
Arm/Group Title	Eplerenone Period
Arm/Group Description	Change from baseline at time of drug initiation
All Cause Mortality
	Eplerenone Period
	Affected / at Risk (%)	# Events
Total	0/26 (0%)
Serious Adverse Events
	Eplerenone Period
	Affected / at Risk (%)	# Events
Total	0/26 (0%)
Other (Not Including Serious) Adverse Events
	Eplerenone Period
	Affected / at Risk (%)	# Events
Total	6/26 (23.1%)
Cardiac disorders
chest pain	1/26 (3.8%)	1
hypotension	1/26 (3.8%)	1
Musculoskeletal and connective tissue disorders
Leg cramping	1/26 (3.8%)	1
Nervous system disorders
dizziness	1/26 (3.8%)	1
Renal and urinary disorders
hyperkalemia	1/26 (3.8%)	1
Skin and subcutaneous tissue disorders
edema	2/26 (7.7%)	2

Limitations/Caveats

Incomplete study enrollment led to inadequate power to derive reliable conclusions.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.