Fontan Udenafil Exercise Longitudinal Assessment Trial

Single Ventricle Heart Disease Clinical Trial

— FUEL  

Official title:

Fontan Udenafil Exercise Longitudinal Assessment Trial (FUEL)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02741115
• Other study ID #: PHN-Udenafil-02
• Secondary ID: U01HL068270
• Status: Completed
• Phase: Phase 3
• Start date: July 22, 2016
• Est. completion date: April 30, 2019

Study information

• Verified date: January 2020
• Source: Mezzion Pharma Co. Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 400
• Est. completion date: April 30, 2019
• Est. primary completion date: December 27, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Heart Diseases
• Single Ventricle Heart Disease

Intervention

Drug:
• Udenafil
Active drug
• Placebo
Matching Placebo

Locations

Country	Name	City	State
Canada	Stollery Children's Hospital - University of Alberta	Edmonton	Alberta
Canada	The Hospital for Sick Children	Toronto	Ontario
Korea, Republic of	Sejong General Hospital	Bucheon-si	Gyeonggi-do
Korea, Republic of	Seoul National University Children's Hospital	Seoul
United States	University of Michigan Congenital Heart Center/C.S. Mott Children's Hospital	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Nationwide Children's Hosptial	Columbus	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Texas Children's Hospital	Houston	Texas
United States	Riley Hospital for Children/Herman B. Wells Center for Pediatric Research	Indianapolis	Indiana
United States	Children's Mercy Hospital Kansas City	Kansas City	Missouri
United States	Cedars/Sinai Heart Institute	Los Angeles	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Children's Hospital of New York	New York	New York
United States	University of Nebraska Children's Hospital and Medical Center	Omaha	Nebraska
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital/Children's Heart Center at Phoenix Children's Hospital	Phoenix	Arizona
United States	Washington University St. Louis/St.Louis Children's Hospital	Saint Louis	Missouri
United States	Johns Hopkins All Children's Heart Institute	Saint Petersburg	Florida
United States	Primary Children's Medical Hospital/Dept. of Pediatric Cardiology	Salt Lake City	Utah
United States	Rady Children's Hospital	San Diego	California
United States	Seattle Children's Hosptial	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia
United States	Nemours Cardiac Center/Alfred I. duPont Hospital for Children	Wilmington	Delaware

Sponsors (2)

Lead Sponsor	Collaborator
Mezzion Pharma Co. Ltd	National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Canada,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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