Clinical trial NCT01169519: Sildenafil in Single Ventricle Patients
Official title: Safety, Pharmacokinetics and Hemodynamic Efficacy of Sildenafil in Single Ventricle Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Heart Disease
Keywords: Hypoplastic left heart syndrome
Hypoplastic right heart syndrome
Superior cavopulmonary anastomosis
Total cavopulmonary anastomosis
Children with single ventricle anatomy
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2010-07-26
Enrollment: 21
Sex: ALL
Minimum age (years): 3
Maximum age (years): 120
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Maximum Sildenafil Plasma Concentration
timeFrame: 5 minutes after completion of sildenafil infusion
Secondary outcomes:
measure: Hemodynamic Safety and Efficacy
timeFrame: 10 minutes after completion of sildenafil infusion
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Kevin D Hill, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hill KD, Tunks RD, Barker PC, Benjamin DK Jr, Cohen-Wolkowiez M, Fleming GA, Laughon M, Li JS. Sildenafil exposure and hemodynamic effect after stage II single-ventricle surgery. Pediatr Crit Care Med. 2013 Jul;14(6):593-600. doi: 10.1097/PCC.0b013e31828aa5ee.
citation: Tunks RD, Barker PC, Benjamin DK Jr, Cohen-Wolkowiez M, Fleming GA, Laughon M, Li JS, Hill KD. Sildenafil exposure and hemodynamic effect after Fontan surgery. Pediatr Crit Care Med. 2014 Jan;15(1):28-34. doi: 10.1097/PCC.0000000000000007.