Clinical Trial: Sildenafil After the Fontan Operation

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: The Sildenafil After Fontan Operation Study

Brief Summary: In this study, the investigators will evaluate the effect of sildenafil on exercise tolerance in patients with a single cardiac ventricle who have undergone the Fontan operation. The investigators will also evaluate echocardiographic measures of ventricular function and measure quality of life changes using two validated quality of life measures. The hypothesis is that sildenafil will result in increased exercise tolerance in patients who have had the Fontan operation as compared to placebo.

Detailed Summary:

The Fontan physiology is the end result of staged reconstruction of the heart and the major blood vessels in patients who have a single ventricle. After completion of the reconstruction, the great veins which usually bring blood back to the heart are connected directly to the pulmonary arteries, allowing blood from the body to bypass the heart and flow directly into the lungs. In this system, blood flow through the lungs is passive (not pumped) and the efficiency of flow through the cardiovascular system is related to the resistance to blood flow in the vessels of the lungs.

There are two potential problems that arise in this scenario, as a result of the resistance to blood flow in the vessels of the lungs. First, the amount of blood flow returning to the heart from the lungs may not be sufficient to allow the heart to function at maximum efficiency, compromising the heart's ability to keep up with the demands of the body. Second, if the resistance to blood flow in the lungs is high, pressure may be transmitted back into the great veins themselves and secondarily into the organs of the body causing mild, or sometimes significant, organ dysfunction. Not all patients with the Fontan physiology develop these problems, but we know that even in patients without obvious problems, the ability to keep up with an increased metabolic demand, as during exercise, in compromised.

Improving the efficiency of blood flow through the lungs should improve the return of blood to the heart and thereby diminish the pressure transmitted back to the vessels which passively deliver blood to the lungs. We believe that this change may manifest as diminished symptoms in those patients with known difficulties, or may allow for an increased ability to walk, run, or participate in sports in those without any overt symptoms. Most importantly, we specula
Sponsor: Children's Hospital of Philadelphia

Current Primary Outcome: Change From Baseline in Mean Oxygen Consumption (mL/kg/Min) at 6 Weeks [ Time Frame: Baseline and 6 Weeks ]

Original Primary Outcome: Change in maximal oxygen consumption from baseline testing to post-medication/placebo testing. [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ]

Current Secondary Outcome:

• Change From Baseline in Mean Heart Rate (Bpm) at 6 Weeks [ Time Frame: Baseline and 6 Weeks ]
  Heart rate was measured at peak exercise. Subjects were exercised to maximal volition with an electronically braked cycle ergometer. The protocol consisted of 3 minutes of pedaling in an unloaded state followed by a ramp increase in work rate (watts) to maximal exercise. Metabolic and ventilatory data were obtained throughout the exercise study and for the first 2 minutes of recovery on a breath-by-breath basis with a metabolic cart.
• Change From Baseline in Mean Respiratory Rate (Breaths/Min) at 6 Weeks [ Time Frame: Baseline and 6 Weeks ]
  Respiratory rate was measured at peak exercise. Subjects were exercised to maximal volition with an electronically braked cycle ergometer. The protocol consisted of 3 minutes of pedaling in an unloaded state followed by a ramp increase in work rate (watts) to maximal exercise. Metabolic and ventilatory data were obtained throughout the exercise study and for the first 2 minutes of recovery on a breath-by-breath basis with a metabolic cart.
• Change From Baseline in Mean Minute Ventilation (L/Min) at 6 Weeks [ Time Frame: Baseline and 6 Weeks ]
  Minute ventilation measurements were taken at peak exercise. Subjects were exercised to maximal volition with an electronically braked cycle ergometer. The protocol consisted of 3 minutes of pedaling in an unloaded state followed by a ramp increase in work rate (watts) to maximal exercise. Metabolic and ventilatory data were obtained throughout the exercise study and for the first 2 minutes of recovery on a breath-by-breath basis with a metabolic cart.

Original Secondary Outcome:

• Oxygen pulse [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ]
• Ventricular function [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ]
• Atrioventricular valvar regurgitation [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ]
• Myocardial performance index [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ]
• E:E (passive ventricular inflow/diastolic myocardial velocity) [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ]
• Fontan flow pattern [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ]
• Mesenteric artery pulsatility index [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ]
• PedsQL 4.0 - a generic quality of life assessment [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ]
• PCQLI - a disease specific quality of life assessment [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ]

Dates:
Date Received: July 25, 2007
Date Started: December 2007
Date Completion:
Last Updated: May 4, 2015
Last Verified: May 2015