Sildenafil in Single Ventricle Patients

Heart Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01169519
• Other study ID #: Pro00025220
• Status: Completed
• Phase: Phase 1
• First received: July 7, 2010
• Last updated: October 10, 2013
• Start date: April 2011
• Est. completion date: December 2012

Study information

• Verified date: November 2012
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Months to 120 Months

Eligibility

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.

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heart Disease

Intervention

Drug:
• Sildenafil by injection
Sildenafil 0.125mg/kg injection over 20min
• Sildenafil by injection
Sildenafil 0.25mg/kg injection over 20min
• Sildenafil by injection
Sildenafil 0.35mg/kg by injection over 20min
• Sildenafil by injection
Sildenafil 0.45mg/kg by injection over 20min

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Country where clinical trial is conducted

United States, 

References & Publications (1)

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.0b013e31828a — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Sildenafil Plasma Concentration	Assessment of peak sildenafil plasma concentration.	5 minutes after completion of sildenafil infusion	No
Secondary	Hemodynamic Safety and Efficacy	Assessment of pulmonary vascular resistance	10 minutes after completion of sildenafil infusion	Yes