Fontan Udenafil Exercise Longitudinal Assessment Trial - 2

Eligibility Criteria

• 1. Males and females with Fontan physiology who are 12 to less than 19 years of age at enrollment.
• 2. Participant consent or parental/guardian consent and participant assent.
• 3. Participant fluency in primary language of country in which study is being conducted.
• 4. Current antiplatelet or anticoagulant therapy.
• 1. Height \< 132 cm.
• 2. Hospitalization for acute decompensated heart failure within the last 12 months.
• 3. Current intravenous inotropic drugs.
• 4. Undergoing evaluation for heart transplantation or listed for transplantation.
• 5. Diagnosis of active protein losing enteropathy or plastic bronchitis within the last 3 years, or a history of liver cirrhosis.
• 6. Known Fontan baffle obstruction, branch pulmonary artery stenosis, or pulmonary vein stenosis resulting in a mean gradient of \> 4 mmHg between the regions proximal and distal to the obstruction as measured by either catheterization or echocardiography, obtained prior to screening for the trial.
• 7. Single lung physiology with greater than 80% flow to one lung.
• 8. Peak minute oxygen consumption (VO2) less than 45% or ≥ 80% of predicated for age and gender at enrollment.
• 9. Severe ventricular dysfunction assessed qualitatively by clinical echocardiography within 6 months prior to enrollment.
• 10. Severe valvar regurgitation, ventricular outflow obstruction, or severe aortic arch obstruction assessed by clinical echocardiography within six months prior to enrollment.
• 11. History of significant renal (serum creatinine \> 2.0), hepatic (serum AST and/or ALT \> 3 times upper limit of normal), gastrointestinal or biliary disorders that could impair absorption, metabolism or excretion of orally administered medications.
• 12. Inability to complete exercise testing at baseline screening.
• 13. History of PDE-5 inhibitor use within 12 months prior to enrollment.
• 14. History of any other medication for treatment of pulmonary hypertension within 3 months before study onset.
• 15. Known intolerance to oral udenafil.
• 16. Frequent use of medications or other substances that inhibit or induce CYP3A4.
• 17. Current use of alpha-blockers or nitrates.
• 18. Ongoing or planned participation in another research protocol that would either prevent successful completion of planned study testing or invalidate its results.
• 19. Noncardiac medical, psychiatric, and/or social disorder that would prevent successful completion of planned study testing or would invalidate its results.
• 20. Cardiac care, ongoing or planned, at a non-study center that would impede study completion.
• 21. For females: Pregnancy at the time of screening, pregnancy planned before study completion, or refusal to use an acceptable method of contraception for study duration if sexually active.
• 22. Unable to abstain or limit intake of grapefruit juice and grapefruit containing drinks during the duration of the trial.
• 23. Refusal to provide written informed consent/assent.
• 24. In the opinion of the investigator, the subject is likely to be non-compliant with the study protocol.
• 25. History of clinically significant thromboembolic event, in the option of the site Principal Investigator, that may put the subject at increased risk of a subsequent event while participating in the study.
• 26. Coronavirus disease 2019 (COVID-19) vaccination or symptoms of COVID-19 infection within 7 days of Visit 1.
• 27. Not taking antiplatelet or anticoagulant therapy.