Study of Effects of Sildenafil on Patients With Fontan Heart Circulation

NCT ID: NCT01815502

Last Updated: 2018-12-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2014-12-31

Brief 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.

Detailed 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.

Conditions

Single Ventricle Heart Disease After Fontan Surgery

Keywords

Single ventricle; Fontan; Sildenafil; Pressure-Volume Loops

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Dobutamine + Sildenafil

Sildenafil will be given an one time dose 30 to 90 minutes prior to cardiac catheterization. Sildenafil will be given at a dose 1 milligram per kilogram with a maximum of 20 milligrams. During the catheterization patients will have specialized catheter placed in the heart that measures pressure and volume simultaneously. The patients will undergo an infusion of dobutamine up to 10 micrograms per kilogram per minute to mimic exercise for up to ten minutes..

Group Type: EXPERIMENTAL

Cardiac catheterization

Intervention Type: DIAGNOSTIC_TEST

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.

Dobutamine + placebo

Patients will be given a one time dose of sugar pill 30 to 90 minutes prior to cardiac catheterization.During the catheterization patients will have specialized catheter placed in the heart that measures pressure and volume simultaneously. The patients will undergo an infusion of dobutamine up to 10 micrograms per kilogram per minute to mimic exercise for up to ten minutes..

Group Type: PLACEBO_COMPARATOR

Cardiac catheterization

Intervention Type: DIAGNOSTIC_TEST

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.

Interventions

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.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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)

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Heart Association

OTHER

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ryan Butts, M.D.

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Andrew M Atz, MD

Role: STUDY_CHAIR

Medical University of South Carolina

Locations

Medical University of South Carolina

Charleston, South Carolina, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 21382896 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22331056 (View on PubMed)

Butts RJ, Chowdhury SM, Baker GH, Bandisode V, Savage AJ, Atz AM. Effect of Sildenafil on Pressure-Volume Loop Measures of Ventricular Function in Fontan Patients. Pediatr Cardiol. 2016 Jan;37(1):184-91. doi: 10.1007/s00246-015-1262-x. Epub 2015 Sep 26.

Reference Type: DERIVED

PMID: 26409473 (View on PubMed)

Other Identifiers

AHA

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

PVL Fontan

Identifier Type: -

Identifier Source: org_study_id