Sildenafil in Single Ventricle Patients

NCT01169519 | Completed Phase 1 Results DMC

• 1 other identifier: Pro00025220
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Disease

Keywords

Hypoplastic left heart syndrome; Hypoplastic right heart syndrome; Superior cavopulmonary anastomosis; Total cavopulmonary anastomosis; Children with single ventricle anatomy

Outcome Measures

Primary Outcomes (1)

• Maximum Sildenafil Plasma Concentration

  Assessment of peak sildenafil plasma concentration.

  5 minutes after completion of sildenafil infusion

Secondary Outcomes (1)

• Hemodynamic Safety and Efficacy

  10 minutes after completion of sildenafil infusion

Study Arms (1)

Sildenafil

ACTIVE COMPARATOR

Pharmacokinetic and hemodynamic evaluation following sildenafil administration

Drug: Sildenafil by injection

Interventions

Sildenafil by injection DRUG

Sildenafil 0.125mg/kg injection over 20min

Also known as: Revatio

Sildenafil

Eligibility Criteria

• Age: 3 Months - 120 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Sepsis.
• 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.

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (2)

• 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.

  PMID: 23823195 RESULT

• 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.

  PMID: 24201857 DERIVED

MeSH Terms

Conditions

Heart Diseases; Hypoplastic Left Heart Syndrome

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Cardiovascular Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Kevin Hill
• Organization: Duke University Medical Center

kevin.hill@duke.edu

919-668-8305

Study Officials

• Kevin D Hill, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2010
• First Posted: July 26, 2010
• Study Start: April 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: December 5, 2013
• Results First Posted: December 5, 2013

Record last verified: 2012-11

Locations

US (1)