Sildenafil in Single Ventricle Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT01169519
First received: July 7, 2010
Last updated: October 10, 2013
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Heart Disease
Drug: Sildenafil by injection
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety, Pharmacokinetics and Hemodynamic Efficacy of Sildenafil in Single Ventricle Patients

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Maximum Sildenafil Plasma Concentration [ Time Frame: 5 minutes after completion of sildenafil infusion ] [ Designated as safety issue: No ]
    Assessment of peak sildenafil plasma concentration.


Secondary Outcome Measures:
  • Hemodynamic Safety and Efficacy [ Time Frame: 10 minutes after completion of sildenafil infusion ] [ Designated as safety issue: Yes ]
    Assessment of pulmonary vascular resistance


Enrollment: 21
Study Start Date: April 2011
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Sildenafil
Pharmacokinetic and hemodynamic evaluation following sildenafil administration
Drug: Sildenafil by injection
Sildenafil 0.125mg/kg injection over 20min
Other Name: Revatio
Drug: Sildenafil by injection
Sildenafil 0.25mg/kg injection over 20min
Other Name: Revatio
Drug: Sildenafil by injection
Sildenafil 0.35mg/kg by injection over 20min
Other Name: Revatio
Drug: Sildenafil by injection
Sildenafil 0.45mg/kg by injection over 20min
Other Name: Revatio

  Eligibility

Ages Eligible for Study:   3 Months to 120 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01169519

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Investigators
Principal Investigator: Kevin D Hill, MD Duke University
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT01169519     History of Changes
Other Study ID Numbers: Pro00025220
Study First Received: July 7, 2010
Results First Received: July 29, 2013
Last Updated: October 10, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Duke University:
Hypoplastic left heart syndrome
Hypoplastic right heart syndrome
Superior cavopulmonary anastomosis
Total cavopulmonary anastomosis
Children with single ventricle anatomy

Additional relevant MeSH terms:
Heart Diseases
Cardiovascular Diseases
Sildenafil
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on August 28, 2014