Spironolactone in Adult Congenital Heart Disease

Heart Failure in Congenital Heart Disease: the Role of Myocardial Fibrosis. Treatment Sub-Study: Spironolactone vs. Placebo

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Congenital Heart Disease; Endomyocardial Fibrosis
• Intervention / Treatment: Other: Placebo; Drug: Spironolactone 25mg

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Patients will receive placebo	Other: Placebo; Placebo daily for 12 months
Experimental: Spironolactone; Spironolactone 25 mg daily	Drug: Spironolactone 25mg; Spironolactone 25 mg daily for 12 months; Other Names: Aldactone 25 mg daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extracellular Volume Fraction	extracellular volume fraction measured by T1 mapping with MRI	12 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-minute Walk Distance	distance walked recorded in meters after 6 minutes on flat ground	12 month
Procollagen 3 NT Peptide		12 months

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Oregon Clinical and Translational Research Institute
• Investigators: Principal Investigator: Craig Broberg, MD, Oregon Health and Science University

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: February 16, 2010
• First Submitted That Met QC Criteria: February 16, 2010
• First Posted (Estimate): February 17, 2010

Study Record Updates

• Last Update Posted (Actual): August 21, 2019
• Last Update Submitted That Met QC Criteria: July 30, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Congenital Abnormalities; Cardiomyopathies; Cardiovascular Abnormalities; Fibrosis; Heart Failure; Heart Diseases; Heart Defects, Congenital; Endomyocardial Fibrosis; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Spironolactone
• Other Study ID Numbers: eIRB 5845; K23HL093024-01A1 (U.S. NIH Grant/Contract)