Study of Effects of Sildenafil on Patients With Fontan Heart Circulation

Single Ventricle Heart Disease After Fontan Surgery Clinical Trial

Official title:

Response to Sildenafil in Patients With Fontan Physiology, A Pressure-volume Loop Analysis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01815502
• Other study ID #: PVL Fontan
• Secondary ID: AHA
• Status: Completed
• Phase: Phase 4
• Start date: February 2013
• Est. completion date: December 2014

Study information

• Verified date: November 2018
• Source: Medical University of South Carolina
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will investigate the cardiovascular effects of sildenafil on patients with Fontan circulation. Recent studies suggest that sildenafil may improve exercise in patients with Fontan circulation. However, why this occurs is not known. The study will used specialized catheters to measure pressure and volume. The measure of pressure and volume leads to more detailed analysis of heart function. Patients will receive either sugar pill or sildenafil prior to catheterization. It is believed that sildenafil will improve relaxation and contraction of the heart.

Description:

Modifications to surgical procedures and medical treatment have led to a rapidly declining mortality rates in patients with single-ventricle heart disease (SV). However, SV patients still suffer from lower quality of life, decreased exercise capacity, worse neurodevelopmental outcomes and many other morbidities. While patients with SV circulation only make a small portion of all congenital heart diseases, 2-4 %, they require a great deal of resource utilization.

Standard medical treatments for adult heart failure have not had the same success in the SV population. Phosphodiesterase 5 (PDE5) inhibitors have recently become a frequently used medication class in patients with SV heart disease to treat pulmonary hypertension, heart failure, as well as "Fontan" failure (i.e., plastic bronchitis and protein-losing enteropathy). While there have been findings of improved measures of exercise capacity and some reports of improved symptoms of heart failure, the physiologic mechanisms behind these findings are not completely understood. There have been reports, indicating that the phosphodiesterase five inhibitors improve ventricular function in biventricular circulation patients and animal models. The aim of our study was to investigate the effect of acute PDE5 inhibition on ventricular function in SV patients after the final palliative surgery, the Fontan procedure.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 40 Years

Eligibility

Inclusion Criteria:

• Presence of a congenital heart defect that leads to single ventricle physiology

• Previously performed Fontan surgery

Exclusion Criteria:

• The use of phosphodiesterase type 5 (PDE5) inhibitors at the time of catheterization of within 1 month of catheterization

• Unstable arrhythmia at the time of catheterization

• History of unstable arrhythmia within 2 months of catheterization

• Venous, arterial or cardiac malformation that precludes the proper placement of a microconductance catheter

• Allergy to sildenafil or previous significant adverse reaction to sildenafil (e.g. hypotension)

Related Conditions & MeSH terms

• Heart Diseases
• Single Ventricle Heart Disease After Fontan Surgery

Intervention

Diagnostic Test:
• Cardiac catheterization
All patients will receive a dobutamine infusion during catheterization. Patients were 1:1 randomized to a single dose of 1 mg/kg of sildenafil (max dose of 20 mg) or placebo 30-90 min prior to beginning of catheterization.

Locations

Country	Name	City	State
United States	Medical University of South Carolina	Charleston	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of South Carolina	American Heart Association

Country where clinical trial is conducted

United States, 

References & Publications (2)

Goldberg DJ, French B, McBride MG, Marino BS, Mirarchi N, Hanna BD, Wernovsky G, Paridon SM, Rychik J. Impact of oral sildenafil on exercise performance in children and young adults after the fontan operation: a randomized, double-blind, placebo-controlled, crossover trial. Circulation. 2011 Mar 22;123(11):1185-93. doi: 10.1161/CIRCULATIONAHA.110.981746. Epub 2011 Mar 7. — View Citation

Goldberg DJ, French B, Szwast AL, McBride MG, Marino BS, Mirarchi N, Hanna BD, Wernovsky G, Paridon SM, Rychik J. Impact of sildenafil on echocardiographic indices of myocardial performance after the Fontan operation. Pediatr Cardiol. 2012 Jun;33(5):689-96. doi: 10.1007/s00246-012-0196-9. Epub 2012 Feb 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Ventricular-arterial Coupling	Ventricular-arterial coupling is a measure of efficiency of ventricular work in response to the work created by the vascular tree	10 minutes after imitation of dobutamine
Other	Preload Augmentation	Preload augmentation is a measure of how quickly the heart fills with blood during exercise	10 minutes after imitation of dobutamine
Primary	End-systolic Elastance	end-systolic elastance (often abbreviated Ees or ESPVR) is a measure of contractility (systolic function)	10 minutes after imitation of dobutamine
Secondary	End-diastolic Pressure Volume Relationship	End-diastolic pressure volume relationship (EDPVR) is a measure of diastolic (relaxation) heart function	10 minutes after imitation of dobutamine