Fibrosis and the Fontan

Part of paid clinical trials in Philadelphia, Pennsylvania.

Sponsor
Children's Hospital of Philadelphia
Study ID
NCT04901975
Phase
PHASE1/PHASE2
Status
Recruiting
Apply to this trial

Conditions

  • Single-ventricle

Eligibility Criteria

Sex
ALL
Age
1 Year - 6 Years
Healthy Volunteers
Not accepted

Interventions

  • Spironolactone — DRUG
    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, the aldosterone antagonist to be utilized in Specific Aim 2 of this study, is FDA approved, has been on the market for many years and is routinely administered to all types of children with congenital heart disease including SV patients. The choice of which patient this should be administered to is up to the clinician and their patients and therefore, not all SV patients are on this medication.

Study Details

The purpose of this study is to non-invasively characterize the fibrotic consequences of single ventricle 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 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.

Key Dates

Start date
Feb 11, 2021
Status verified
Jun 2025
Primary completion
Jun 30, 2026
Completion
Jun 30, 2026

Study Design

Enrollment
145 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Spironolactone
    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.
  • No Intervention: Observational
    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).
  • No Intervention: Control
    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.
  • No Intervention: Observational - 1A
    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).
  • No Intervention: Observational - 1B
    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).

Primary Outcome Measure

Liver elastography by MRE prior to and after Fontan [ Time Frame: up to 1 year ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Children's Hospital of PhiladelphiaPhiladelphiaPennsylvania19130
Mark Fogel, MD
[email protected]
215-590-4040
Cassandra L Giner, MS
[email protected]
915-503-3642

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