Fontan Udenafil Exercise Longitudinal Assessment Trial

Study Overview
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Brief Summary
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This study will evaluate the clinical efficacy and safety of udenafil, an orally administered, potent and selective inhibitor of PDE5, versus placebo for the treatment of adolescent subjects who have undergone the Fontan procedure.

Detailed Description
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This study is a randomized, double-blinded, efficacy trial of the effects of udenafil vs. placebo on the background of standard therapy on maximal VO2 (ml/kg/min) from baseline to six months in adolescent survivors of the Fontan procedure. . The target sample size is 400 subjects (200 per group).

Official Title
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Fontan Udenafil Exercise Longitudinal Assessment Trial (FUEL)

Conditions
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Single Ventricle Heart Disease

Intervention / Treatment
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* Drug: Udenafil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females with Fontan physiology who are 12 to less than 19 years of age at enrollment. Participant consent or parental/guardian consent and participant assent Participant fluency in primary language of country in which study is being conducted Exclusion Criteria: Weight < 40 kg Height < 132 cm. Hospitalization for acute decompensated heart failure within the last 12 months. Current intravenous inotropic drugs. Undergoing evaluation for heart transplantation or listed for transplantation. Diagnosis of active protein losing enteropathy or plastic bronchitis within the last 3 years, or a history of liver cirrhosis. 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. Single lung physiology with greater than 80% flow to one lung. VO2 less than 50% Severe ventricular dysfunction assessed qualitatively by clinical echocardiography within six months prior to enrollment. Severe valvar regurgitation, ventricular outflow obstruction, or aortic arch obstruction assessed by clinical echocardiography within six months prior to enrollment. 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, based on laboratory assessment six weeks prior to screening for the trial. Inability to complete exercise testing at baseline screening. History of PDE-5 inhibitor use within 3 months before study onset. History of any other medication for treatment of pulmonary hypertension within 3 months before study onset. Known intolerance to oral udenafil. Frequent use of medications or other substances that inhibit or induce CYP3A4. Current use of alpha-blockers or nitrates. Ongoing or planned participation in another research protocol that would either prevent successful completion of planned study testing or invalidate its results. Noncardiac medical, psychiatric, and/or social disorder that would prevent successful completion of planned study testing or would invalidate its results. Cardiac care, ongoing or planned, at a non-study center that would impede study completion. 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. Unable to abstain or limit intake of grapefruit juice during the duration of the trial. Refusal to provide written informed consent/assent. In the opinion of the primary care physician, the subject is likely to be non-compliant with the study protocol.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug<br>Udenafil. One tablet twice daily for 26 weeks | Drug: Udenafil<br>* Active drug<br>|
| Experimental: Placebo<br>Placebo. One tablet twice daily for 26 weeks | Drug: Placebo<br>* Matching Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Exercise Capacity | The change in exercise capacity (as measured by maximal VO2 at maximum exercise effort) from baseline to 26 weeks (or study completion) | Baseline to 26 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Myocardial Performance Index (MPI) | The change in the myocardial performance index (MPI) from baseline to 26 weeks determined by velocities obtained from blood pool Doppler assessment of the inflow and outflow tract of the dominant ventricle. | Baseline to 26 weeks | 
| Change in log-transformed reactive hyperemia index (InRH) | The change in log-transformed reactive hyperemia index (lnRHI) from baseline to 26 weeks as measured by pulse amplitude tonometry (PAT) testing using the EndoPAT® device. | Baseline to 26 weeks | 
| Change in Level of Serum serum brain-type natriuretic peptide BNP | Change in Level of Serum serum brain-type natriuretic peptide BNP from baseline to 26 weeks. | Baseline to 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fontan, Maximal Oxygen Consumption, Vascular Function, EndoPAT, Myocardial Performance