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Mineralocorticoid Receptor Antagonist

Spironolactone for Single Ventricle Heart Condition

Phase 1 & 2

Recruiting

Led By Mark Fogel, MD

Research Sponsored by Children's Hospital of Philadelphia

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Cohort 1 (Observational Group - no study medication): Subjects between 1 and ≤ 6 years of age of either gender. Either single left or single right ventricle. Subjects who are scheduled to undergo a Fontan operation at CHOP. Parents signing informed consent.

Cohort 2 (study drug Group - spironolactone): Subjects between 1 and ≤ 6 years of age of either gender. Either single left or single right ventricle. Subjects who are scheduled to undergo a Fontan operation at CHOP. Parents signing informed consent.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial is investigating the effect of Fontan hemodynamics on the interrelationship between liver and cardiac fibrosis/dysfunction and lymphatic congestion. A pilot trial of the antifibrotic agent, spironolactone, will be conducted to prevent these consequences and to determine if MRI can discern these differences.

Who is the study for?

This trial is for children aged 1 to less than 6 with a single ventricle heart defect, scheduled for Fontan surgery at CHOP. It includes those who agree to MRI scans under sedation and whose parents consent. Excluded are kids already on spironolactone or similar drugs, with severe kidney issues, hyperkalemia, Addison disease, or conditions making the trial harmful.

What is being tested?

The study tests if spironolactone can prevent heart and liver fibrosis in kids with single ventricle hearts facing Fontan surgery. It uses MRIs and blood markers to track changes non-invasively. Participants will be observed before and after starting the medication.

What are the potential side effects?

Spironolactone may cause electrolyte imbalances like high potassium levels (hyperkalemia), hormonal changes leading to breast enlargement in males (gynecomastia), stomach issues, dizziness, or skin rashes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I am between 1 and 6 years old, scheduled for a Fontan operation at CHOP, and my parents have agreed.

Select...

I am between 1 and 6 years old, scheduled for a Fontan operation at CHOP, and my parents have agreed.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Heart

Heart tissue characterization prior to and after Fontan

Liver

+1 more

Secondary study objectives

Lymphatic dysfunction T1rho prior to and after Fontan

Lymphatic dysfunction by MRE prior to and after Fontan

Serum biomarkers of fibrosis

Side effects data

From 2022 Phase 4 trial • 79 Patients • NCT02169089

Hypotension

Hyperkalemia

Infection

Diabetes related

Surgical

Chest pain/discomfort

Breast tenderness/Gynecomastia

100%

80%

60%

40%

20%

Study treatment Arm

Spironolactone

Placebo

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Active Control

Group I: SpironolactoneExperimental Treatment1 Intervention

Children will undergo characterization and measurement of liver and cardiac fibrosis with MRI and cardiac magnetic resonance (CMR) as well as serum biomarkers immediately prior to the Fontan operation. All SV children will undergo characterization and measurement of liver and cardiac fibrosis with MRI and cardiac magnetic resonance (CMR) as well as serum biomarkers \~1 year after the Fontan operation. Spironolactone is a mild diuretic. Drug dosage will be those used clinically and per the CHOP formulary: 3 mg/kg/day in divided doses every 6-24 hours; the drug will be weight adjusted every \~0.5 kg with a maximum dosage of 200 mg/24 hours. Maximum single dose is 100 mg. Spironolactone administration will begin after the Fontan procedure in the hospital prior to discharge or at the first outpatient visit \~ 2 weeks after discharge.

Group II: ObservationalActive Control1 Intervention

Children will undergo characterization and measurement of liver and cardiac fibrosis with MRI and cardiac magnetic resonance (CMR) as well as serum biomarkers immediately prior to the Fontan operation. All SV children, whether they received spironolactone or not, will undergo characterization and measurement of liver and cardiac fibrosis with MRI and cardiac magnetic resonance (CMR) as well as serum biomarkers \~1 year after the Fontan operation. Demographics and medical history will be collected again along with adverse events. Children will also undergo CMR for evaluation of hemodynamics, ventricular function (including strain), computational modeling and lymphatic abnormalities. A few of these patients will be undergoing CMR for clinical reasons and study CMR related and study MRI related imaging and blood draws will be performed in coordination with their clinical care (ie these sequences will be added on to their clinical sequences).

Group III: ControlActive Control1 Intervention

The purpose of this study is to non-invasively characterize the fibrotic consequences of SV physiology, its possible solution and effect on lymphatics. This project investigates the response to acute imposition of Fontan hemodynamics by examining the interrelationship between liver and cardiac fibrosis/dysfunction and lymphatic congestion (figure 1) along with a pilot trial of the antifibrotic agent, spironolactone, to prevent these consequences and to determine if MRI can discern these differences. The combination of serum biomarkers and MRI form a powerful non-invasive tool in putting together this complicated web of dysfunction. Control subjects who are non-SV patients but who have normal heart function who are undergoing CMR for evaluation (eg patients undergoing CMR for vascular ring evaluation, family history of congenital heart disease but found to be normal, etc) will have study related MRI and CMR sequences performed.

Group IV: Observational - 1AActive Control1 Intervention

Subjects who were enrolled in this study in Spironolactone arm and patient's family would like to continue participation. All SV children, whether they received spironolactone or not, will undergo characterization and measurement of liver and cardiac fibrosis with MRI and cardiac magnetic resonance (CMR) as well as serum biomarkers \~1 year after the Fontan operation. Demographics and medical history will be collected again along with adverse events. Children will also undergo CMR for evaluation of hemodynamics, ventricular function (including strain), computational modeling and lymphatic abnormalities. A few of these patients will be undergoing CMR for clinical reasons and study CMR related and study MRI related imaging and blood draws will be performed in coordination with their clinical care (ie these sequences will be added on to their clinical sequences).

Group V: Observational - 1BActive Control1 Intervention

Subjects who were enrolled in other studies with intervention. All SV children, whether they received spironolactone or not, will undergo characterization and measurement of liver and cardiac fibrosis with MRI and cardiac magnetic resonance (CMR) as well as serum biomarkers \~1 year after the Fontan operation. Demographics and medical history will be collected again along with adverse events. Children will also undergo CMR for evaluation of hemodynamics, ventricular function (including strain), computational modeling and lymphatic abnormalities. A few of these patients will be undergoing CMR for clinical reasons and study CMR related and study MRI related imaging and blood draws will be performed in coordination with their clinical care (ie these sequences will be added on to their clinical sequences).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Spironolactone

2005

Completed Phase 4

~14570

0 / 2Eligibility criteria met