Study of Effects of Sildenafil on Patients With Fontan Heart Circulation

Medical University of South Carolina (MUSC)

Status and phase: Completed; Phase 4

Conditions: Single Ventricle Heart Disease After Fontan Surgery

Treatments: Diagnostic Test: Cardiac catheterization

Study type: Interventional

Funder types: Other

Identifiers

NCT01815502

AHA

PVL Fontan

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 3 to 40 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

20 participants in 2 patient groups, including a placebo group

Dobutamine + Sildenafil

Experimental group

Description:

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..

Treatment:

Diagnostic Test: Cardiac catheterization

Dobutamine + placebo

Placebo Comparator group

Description:

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..

Treatment:

Diagnostic Test: Cardiac catheterization