Fibrosis and the Fontan
Single-ventricle
About this trial
This is an interventional treatment trial for Single-ventricle
Eligibility Criteria
Inclusion Criteria:
- Single Ventricle (SV) Patients
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.
Controls
- Subjects between 1 and <6 years of age of either gender
- Subjects with normal ventricular function and normal livers who present to CMR for clinical indications and require anesthesia.
- Receiving contrast for clinical purposes. No control patient will receive contrast for research purposes.
- Parents signing informed consent.
Exclusion Criteria:
-
Cohort 1 (Observational Group - no study medication):
- Subjects with any condition judged by the patient's physician that would cause this trial to be detrimental to the patient.
- Any contradiction to a sedated CMR (i.e. presence of a pacemaker).
- Patient currently taking spironolactone or eplerenone
- Subjects in any study that would preclude participation in the study by altering results
Cohort 2 (Study Drug Group - Spironolactone):
- Subjects with any condition judged by the patient's physician that would cause this trial to be detrimental to the patient.
- Any contradiction to a sedated CMR (i.e. presence of a pacemaker).
- Patient currently taking spironolactone or eplerenone
- Subjects with hyperkalemia or Addison disease;
- Subjects on enalapril or other angiotensin receptor blockers
- Subjects with a history of hypersensitivity to spironolactone suspension or any component of the formulation
- Subjects with a clinically documented diagnosis of severe renal insufficiency (implying estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m2).
- Subjects in any study that would preclude participation in the study by altering results
Controls
- Any condition judged by the patient's physician that would cause this trial to be detrimental to the patient.
- Any contradiction to a sedated CMR (i.e. presence of a pacemaker).
- Patient currently taking spironolactone, eplerenone or an angiotensin converting the enzyme inhibitor/angiotensin receptor blocker.
Sites / Locations
- Children's Hospital of PhiladelphiaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
No Intervention
No Intervention
No Intervention
Spironolactone
Observational
Control
Observational - 1A
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.
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).
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.
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).