Fontan Udenafil Exercise Longitudinal Assessment Trial (FUEL)

Mezzion Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Single Ventricle Heart Disease

Treatments: Drug: Udenafil; Drug: Placebo

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT02741115

U01HL068270 (U.S. NIH Grant/Contract)

PHN-Udenafil-02

Details and patient eligibility

About

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.

Full description

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).

Enrollment: 400 patients

Sex: All

Ages: 12 to 18 years old

Volunteers: No Healthy Volunteers

Inclusion 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

Exclusion criteria

1. Weight < 40 kg
2. Height < 132 cm.
3. Hospitalization for acute decompensated heart failure within the last 12 months.
4. Current intravenous inotropic drugs.
5. Undergoing evaluation for heart transplantation or listed for transplantation.
6. Diagnosis of active protein losing enteropathy or plastic bronchitis within the last 3 years, or a history of liver cirrhosis.
7. 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.
8. Single lung physiology with greater than 80% flow to one lung.
9. VO2 less than 50%
10. Severe ventricular dysfunction assessed qualitatively by clinical echocardiography within six months prior to enrollment.
11. Severe valvar regurgitation, ventricular outflow obstruction, or aortic arch obstruction assessed by clinical echocardiography within six months prior to enrollment.
12. 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.
13. Inability to complete exercise testing at baseline screening.
14. History of PDE-5 inhibitor use within 3 months before study onset.
15. History of any other medication for treatment of pulmonary hypertension within 3 months before study onset.
16. Known intolerance to oral udenafil.
17. Frequent use of medications or other substances that inhibit or induce CYP3A4.
18. Current use of alpha-blockers or nitrates.
19. Ongoing or planned participation in another research protocol that would either prevent successful completion of planned study testing or invalidate its results.
20. Noncardiac medical, psychiatric, and/or social disorder that would prevent successful completion of planned study testing or would invalidate its results.
21. Cardiac care, ongoing or planned, at a non-study center that would impede study completion.
22. 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.
23. Unable to abstain or limit intake of grapefruit juice during the duration of the trial.
24. Refusal to provide written informed consent/assent.
25. In the opinion of the primary care physician, the subject is likely to be non-compliant with the study protocol.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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400 participants in 2 patient groups

Drug

Experimental group

Description:

Udenafil. One tablet twice daily for 26 weeks

Treatment:

Drug: Udenafil

Placebo

Experimental group

Description:

Placebo. One tablet twice daily for 26 weeks

Treatment:

Drug: Placebo