Sildenafil in Single Ventricle Patients

Study Overview
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Brief Summary
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Patients with single ventricle anatomy undergo staged surgical palliation. The result is an in series circulation with pulmonary blood flow and cardiac output directly related to pulmonary vascular resistance. While surgical outcomes have improved, the physiology of the single ventricle palliation results in continued long term attrition. Elevated pulmonary vascular resistance and impaired systemic ventricular function are important risk factors for failure of single ventricle palliation. Sildenafil is a pulmonary vasodilator and has been shown to improve cardiac contractility in the pressure overloaded right ventricle. The investigators will assess the safety, pharmacokinetics and hemodynamic efficacy of sildenafil in single ventricle patients following stage II and III surgical palliation.

Official Title
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Safety, Pharmacokinetics and Hemodynamic Efficacy of Sildenafil in Single Ventricle Patients

Conditions
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Heart Disease

Intervention / Treatment
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* Drug: Sildenafil by injection
* Drug: Sildenafil by injection
* Drug: Sildenafil by injection
* Drug: Sildenafil by injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 3 months; ≤120 months. History of congenital heart disease with severe hypoplasia of a right or left ventricle. Undergoing cardiac catheterization as part of standard clinical care. Availability and willingness of the parent/legally authorized representative to provide written informed consent. Exclusion Criteria: History of serious adverse event related to sildenafil administration. History of sildenafil exposure within 48 hours of the study. Presence of pulmonary venous obstruction. Treatment with organic nitrates or alpha blockade therapy. Contraindication to cardiac catheterization as determined by the attending cardiologist and including: Significant hemodynamic instability. Sepsis. Need for Extra-Corporeal Membrane Oxygenation (ECMO) support. Venous occlusion precluding adequate access. Recent systemic illness. Renal failure defined as serum creatinine > 2 times higher than the upper limit of normal. Liver dysfunction defined as alanine aminotransferase or aspartate aminotransferase > 3 times higher than the upper limit of normal. Thrombocytopenia defined as a platelet count < 50 000 cells/µL. Leukopenia defined as white blood cells < 2500 cells/µL.

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 120 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sildenafil<br>Pharmacokinetic and hemodynamic evaluation following sildenafil administration | Drug: Sildenafil by injection<br>* Sildenafil 0.125mg/kg injection over 20min<br>* Other names: Revatio;Drug: Sildenafil by injection<br>* Sildenafil 0.25mg/kg injection over 20min<br>* Other names: Revatio;Drug: Sildenafil by injection<br>* Sildenafil 0.35mg/kg by injection over 20min<br>* Other names: Revatio;Drug: Sildenafil by injection<br>* Sildenafil 0.45mg/kg by injection over 20min<br>* Other names: Revatio;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Sildenafil Plasma Concentration | Assessment of peak sildenafil plasma concentration. | 5 minutes after completion of sildenafil infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemodynamic Safety and Efficacy | Assessment of pulmonary vascular resistance | 10 minutes after completion of sildenafil infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypoplastic left heart syndrome, Hypoplastic right heart syndrome, Superior cavopulmonary anastomosis, Total cavopulmonary anastomosis, Children with single ventricle anatomy