Congenital Heart Disease, Endomyocardial Fibrosis, Heart Failure
Conditions
Brief summary
The purpose of this study is to see if the study drug called spironolactone reduces fibrous (stiffening) in heart muscle tissue and improves heart function. Subjects from the study titled Heart Failure in Congenital Heart Disease: the role of myocardial fibrosis who have evidence of heart dysfunction and/or evidence of fibrosis (stiffening) in the heart muscle will be asked to take part in this study.
Detailed description
This study will include randomizing the subject to receive the study drug or placebo. Randomization will occur during visit 1. Visit 1 will include the following: * Subjects will answer questions about how well they can breathe. * An MRI. Dye called gadolinium will be injected into the subject's vein. * They will go to the Oregon Clinical and Translational Research Institute where 2 tablespoons of blood will be drawn from an intravenous (IV) catheter (tube). * They will do a 6 minute walk test.. * They will also have an echocardiogram, which is a test that looks at the movement of the subject's heart. A technician will place a cool jelly on their chest and use a small wand to take pictures through the skin. Subjects' will also have visits 3-6 weeks, 3, 6, 9 months, and 12 months after randomization. Visits 2-5 will include the following: * They will go to the Oregon Clinical and Translational Research Institute where 1/2 tablespoon of blood will be drawn. * They will do a 6 minute walk test. During this test, they will walk back and forth in a hallway. The goal is to walk as far as possible for 6 minutes. Subjects will probably get out of breath or become exhausted. If they do, they can slow down, stop, or rest as they need to. Blood pressure will be taken before the walk. * They will have a health review at 6 months. Visit 6 will be identical to visit 1 and include the following: * Subjects will answer questions about how well they can breathe. * An MRI. Dye called gadolinium will be injected into the subject's vein. * They will go to the Oregon Clinical and Translational Research Institute where 2 tablespoons of blood will be drawn from an intravenous (IV) catheter (tube). * They will do a 6 minute walk test.. * They will also have an echocardiogram, which is a test that looks at the movement of the subject's heart. A technician will place a cool jelly on their chest and use a small wand to take pictures through the skin. The investigators will compare the study drug, called spironolactone, to placebo with regard to any changes in heart stiffening and function of the heart.
Interventions
Spironolactone 25 mg daily for 12 months
OTHERPlacebo
Placebo daily for 12 months
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Oregon Clinical and Translational Research Institute
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Fibrosis index ≥29%, or 2. Evidence of cardiovascular dysfunction including any of the following: * Systemic ejection fraction \<55%, * NYHA 2-3 * 6-minute walk distance \<500 m. 3. Completion of Visit 1 of the study Heart Failure in Congenital Heart Disease: the role of myocardial fibrosis (eIRB # 3665) including meeting all inclusion for that study (Aged 18-80, Known congenital heart disease). 4. Tetralogy of Fallot, cyanotic congenital heart disease, or a systemic right ventricle.
Exclusion criteria
1. Patient currently taking spironolactone or previously taking spironolactone within the last 6 months. 2. Serum potassium ≥5.0 mmol/L at the initial visit, if not taking potassium supplements. Patients will be eligible if a repeat potassium is \<5.0 mmol/L after potassium supplements have been discontinued. 3. Moderate/severe systemic atrioventricular valve regurgitation, 4. Likely to undergo cardiac surgery, pacemaker implantation, or possible transplantation within one year (all self-reported), 5. Unwilling to commit to return visits including mandatory blood draws for potassium, 6. Renal insufficiency (estimated creatinine clearance \< 30 ml/min/1.73m2), 7. Positive urine pregnancy test. 8. Any contraindication to MRI.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Extracellular Volume Fraction | 12 month | extracellular volume fraction measured by T1 mapping with MRI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 6-minute Walk Distance | 12 month | distance walked recorded in meters after 6 minutes on flat ground |
| Procollagen 3 NT Peptide | 12 months | — |
Countries
United States
Participant flow
Recruitment details
Recruited at time of presentation for larger study. However, most did not meet enrollment criteria and could not be randomized.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients will receive placebo
Placebo: Placebo daily for 12 months | 8 |
| Spironolactone Spironolactone 25 mg daily
Spironolactone 25mg: Spironolactone 25 mg daily for 12 months | 7 |
| Total | 15 |
Baseline characteristics
| Characteristic | Placebo | Spironolactone | Total |
|---|---|---|---|
| Age, Continuous | 36 years STANDARD_DEVIATION 6 | 38 years STANDARD_DEVIATION 16 | 37 years STANDARD_DEVIATION 11 |
| Region of Enrollment United States | 8 participants | 7 participants | 15 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 8 | 0 / 7 |
| serious Total, serious adverse events | 0 / 8 | 0 / 7 |
Outcome results
Primary
Extracellular Volume Fraction
extracellular volume fraction measured by T1 mapping with MRI
Time frame: 12 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Extracellular Volume Fraction | 30.1 percentage of myocardium | Standard Deviation 3.8 |
| Spironolactone | Extracellular Volume Fraction | 25.3 percentage of myocardium | Standard Deviation 1.5 |
Secondary
6-minute Walk Distance
distance walked recorded in meters after 6 minutes on flat ground
Time frame: 12 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 6-minute Walk Distance | 516 meters | Standard Deviation 124 |
| Spironolactone | 6-minute Walk Distance | 492 meters | Standard Deviation 138 |
Secondary
Procollagen 3 NT Peptide
Time frame: 12 months
Population: Limited samples obtained from participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Procollagen 3 NT Peptide | 3 mcg/l | Standard Deviation 0.7 |
| Spironolactone | Procollagen 3 NT Peptide | 4.8 mcg/l | Standard Deviation 1.2 |