Safety, Pharmacokinetics and Hemodynamic Efficacy of Sildenafil in Single Ventricle Patients
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Duke University
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- Maximum Sildenafil Plasma Concentration
Study Overview
Brief 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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 3 Months to 120 Months (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
- •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.
Arms & Interventions
Sildenafil
Pharmacokinetic and hemodynamic evaluation following sildenafil administration
Intervention: Sildenafil by injection (Drug)
Outcomes
Primary Outcomes
Maximum Sildenafil Plasma Concentration
Time Frame: 5 minutes after completion of sildenafil infusion
Assessment of peak sildenafil plasma concentration.
Secondary Outcomes
- Hemodynamic Safety and Efficacy(10 minutes after completion of sildenafil infusion)