Sildenafil After the Fontan Operation
Information source: Children's Hospital of Philadelphia
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hypoplastic Left Heart Syndrome; Tricuspid Atresia
Intervention: Sildenafil (Drug); Placebo (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Children's Hospital of Philadelphia Official(s) and/or principal investigator(s): Jack Rychik, MD, Principal Investigator, Affiliation: Children's Hospital of Philadelphia
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.
Clinical Details
Official title: The Sildenafil After Fontan Operation Study
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Change From Baseline in Mean Oxygen Consumption (mL/kg/Min) at 6 Weeks
Secondary outcome: Change From Baseline in Mean Heart Rate (Bpm) at 6 WeeksChange From Baseline in Mean Respiratory Rate (Breaths/Min) at 6 Weeks Change From Baseline in Mean Minute Ventilation (L/Min) at 6 Weeks
Detailed description:
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 speculate that improved efficiency of flow through the lungs, and the
resulting improved cardiac output (blood flow through the body) will make patients more
energetic and will make them feel better.
Sildenafil is an oral medication that has been used to treat patients with pulmonary
hypertension, a disease in which there is abnormally elevated pressure in the vessels of the
lung. In this disease, the resistance in the lungs is abnormally high, severely limiting
the ability of the heart to keep up with the demands of the body. Sildenafil lowers the
resistance in the vessels of the lungs and has been shown to improve exercise performance in
patients with this disease. We believe that Sildenafil may have a similar benefit for our
patients after Fontan operation in whom cardiac output is also limited by resistance of the
blood vessels in the lungs.
In our study, we will compare the exercise capacity, echocardiographic measures of cardiac
function, and the overall quality of life in patients with the Fontan before and after a
six-week period of sildenafil administration. As a control, the same group of patients will
take a placebo for a six-week period, also with before and after testing. We hypothesize
that oral sildenafil will result in significant improvements in exercise capacity, energy
levels, and echocardiographic measures of cardiac function and output in our study
participants. We are hopeful that the findings of this investigation will directly help
children and young adults with Fontan physiology.
Eligibility
Minimum age: 8 Years.
Maximum age: 40 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- 8 years of age or older
- All participants must have had Fontan completion
Exclusion Criteria:
- Height less than 132 cm
- Unable to participate in exercise testing due to medical restrictions or physical
limitations
- Fontan baffle obstruction or single lung physiology
- Coarctation of the aorta or neo-aorta (BP gradient > 20 mmHg)
- Severe ventricular dysfunction assessed qualitatively by echocardiography
- Severe atrioventricular valvar regurgitation assessed qualitatively by
echocardiography
- Presence of electronic pacemaker
- History of treatment with sildenafil in the six weeks prior to enrollment in study
- Patients with severe renal impairment
- Patients with severe hepatic impairment
- Patients taking medications that inhibit or induce Cytochrome P450 3A4 (CYP3A4)
(including grapefruit juice and St. John's Wort)
- Patients taking alpha-blockers and nitrates
- Parents/guardians or subjects who, in the opinion of the investigator, may be
non-compliant with study schedules or procedures
Locations and Contacts
Additional Information
Starting date: December 2007
Last updated: May 4, 2015
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