Sildenafil in Single Ventricle Patients
Condition: Heart Disease
MeSH terms: Heart Diseases; Univentricular Heart
Intervention: Sildenafil by injection; Sildenafil by injection; Sildenafil by injection; Sildenafil by injection
Intervention description: Sildenafil 0.125mg/kg injection over 20min; Sildenafil 0.25mg/kg injection over 20min; Sildenafil 0.35mg/kg by injection over 20min; Sildenafil 0.45mg/kg by injection over 20min
Intervention MeSH terms: Sildenafil Citrate
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 3 Months
Maximum age: 120 Months
Healthy volunteers: No
Keywords: Hypoplastic left heart syndrome; Hypoplastic right heart syndrome; Superior cavopulmonary anastomosis; Total cavopulmonary anastomosis; Children with single ventricle anatomy

Summary:

      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.
    

Eligibility criteria:

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