Clinical trial NCT03013751: A Extension Study of Udenafil in Adolescents
Official title: A Phase III Extension Study of Udenafil in Adolescents With Single Ventricle Physiology After Fontan Palliation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Functional Single Ventricle Heart Disease
Lead sponsor: Mezzion Pharma Co. Ltd
Sponsor class: INDUSTRY
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2017-01-06
Enrollment: 300
Sex: ALL
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a 12-month (52 week) safety extension study to supplement the FUEL Phase III clinical trial to provide safety information regarding the long-term use of udenafil in adolescents with single ventricle congenital heart disease.

Detailed description: This will be an open-label extension study. All enrolled subjects will be provided with udenafil for the duration of the study. Subjects completing the Phase III FUEL study will be eligible for recruitment. Additional subjects will be recruited as needed to ensure a minimum of 300 total subjects enroll. Safety, pharmacodynamic and quality of life data will be collected and analyzed.

Eligibility criteria: Inclusion Criteria:

1. Males and females with Fontan physiology who participated in the FUEL trial or, if they did not participate in FUEL, those who are 12 to less than 19 years of age at enrollment.
2. Participant consent or parental/guardian consent and participant assent.
3. Participant fluent in English, Spanish, or Korean.
4. Current anti-platelet or anticoagulant therapy.

Exclusion Criteria:

1. Height \< 132 cm.
2. Weight \< 40 kg.
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 three 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 mm Hg between the regions proximal and distal to the obstruction as measured by either catheterization or echocardiography.
8. Single lung physiology.
9. Maximal VO2 less than 50% of predicted for age and gender at enrollment.
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, hepatic, gastrointestinal or biliary disorders that could impair absorption, metabolism or excretion of orally administered medications.
13. Inability to complete exercise testing at baseline screening.
14. History of PDE-5 inhibitor use (with the exception of FUEL participation) within 3 months before study onset.
15. Use of any other drug to treat 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.
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.
26. History of clinically significant thromboembolic event, as adjudicated by study Investigators.

Primary outcomes:
measure: Safety (Adverse Events)
timeFrame: 52 Weeks
Secondary outcomes:
measure: Exercise (Change in maximal oxygen consumption)
timeFrame: 52 Weeks
measure: Echo (Change in myocardial performance Index)
timeFrame: 52 Weeks
measure: Endothelial function (Change in log-transformed Reactive Hyperemia Index)
timeFrame: 52 Weeks
measure: Function Health Status (Change in full scale Peds QL)
timeFrame: 52 Weeks
measure: Biomarkers (Change in serum BNP level)
timeFrame: 52 Weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital/Children's Heart Center at Phoenix Children's Hospital
state: Arizona
city: Los Angeles
country: United States
facility: Cedars/Sinai Heart Institute
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Wilmington
country: United States
facility: Nemours Cardiac Center/Alfred I. duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Heart Institute
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Indianapolis
country: United States
facility: Riley Hospital for Children/Herman B. Wells Center for Pediatric Research
state: Indiana
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Congenital Heart Center/C.S. Mott Children's Hospital
state: Michigan
city: Kansas City
country: United States
facility: Children's Mercy Hospital Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Washington University St. Louis/St.Louis Children's Hospital
state: Missouri
city: New York
country: United States
facility: Children's Hospital of New York
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Medical Hospital/Dept. of Pediatric Cardiology
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hosptial
state: Washington
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Bucheon-si
country: Korea, Republic of
facility: Sejong General Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Children's Hospital
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Steve Paridon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Goldberg DJ, Zak V, Goldstein BH, McCrindle BW, Menon SC, Schumacher KR, Payne RM, Rhodes J, McHugh KE, Penny DJ, Trachtenberg F, Hamstra MS, Richmond ME, Frommelt PC, Files MD, Yeager JL, Pemberton VL, Stylianou MP, Pearson GD, Paridon SM; Pediatric Heart Network Investigators. Design and rationale of the Fontan Udenafil Exercise Longitudinal (FUEL) trial. Am Heart J. 2018 Jul;201:1-8. doi: 10.1016/j.ahj.2018.03.015. Epub 2018 Apr 3.