Clinical trial NCT05918211: Fontan Udenafil Exercise Longitudinal Assessment Trial - 2
Official title: Fontan Udenafil Exercise Longitudinal Assessment Trial (FUEL-2)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Single Ventricle Heart Disease
Keywords: Fontan
Maximal Oxygen Consumption
Work Rate
VO2 at VAT
Ventilatory Efficiency
Lead sponsor: Mezzion Pharma Co. Ltd
Sponsor class: INDUSTRY
First posted: 2023-06-26
Enrollment: 436
Sex: ALL
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled safety and efficacy study of udenafil versus placebo of approximately 436 subjects enrolled equally between the two arms (udenafil and placebo)
Primary purpose: TREATMENT

Brief 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 who have had the Fontan procedure.

Detailed description: This study is a 26 week, prospective, multicenter, randomized, double-blinded, placebo-controlled safety and efficacy study of udenafil vs. placebo in adolescent subjects who have had the Fontan procedure. The primary efficacy endpoint will be change from baseline at 26 weeks in peak minute oxygen consumption (VO2 mL/kg/min) as measured by maximal cardiopulmonary exercise test (CPET) reading laboratory who will be blinded to treatment allocation.

Eligibility criteria: 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.
4. Current antiplatelet 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 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. Failure to achieve maximal exertion (defined as RER \< 1.10) on screening/baseline exercise test.
10. Peak minute oxygen consumption (VO2) less than 45% or ≥ 80% of predicated for age and gender at enrollment.
11. Severe ventricular dysfunction assessed qualitatively by clinical echocardiography within 6 months prior to enrollment.
12. Severe valvar regurgitation, ventricular outflow obstruction, or severe aortic arch obstruction assessed by clinical echocardiography within six months prior to enrollment.
13. 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.
14. Inability to complete exercise testing at baseline screening.
15. Subjects with a pacemaker whose heart rate at peak exercise is controlled by the extrinsic pacemaker as opposed to a native atrial rhythm.
16. History of PDE-5 inhibitor use within 12 months prior to enrollment. (Treatment is defined as chronic therapy as opposed to a single dose.)
17. History of any other medication for treatment of pulmonary hypertension within 3 months before study onset.
18. Known intolerance to oral udenafil.
19. Frequent use of medications or other substances that inhibit or induce CYP3A4.
20. Current use of alpha-blockers or nitrates.
21. Ongoing or planned participation in another research protocol that would either prevent successful completion of planned study testing or invalidate its results.
22. Noncardiac medical, psychiatric, and/or social disorder that would prevent successful completion of planned study testing or would invalidate its results.
23. Cardiac care, ongoing or planned, at a non-study center that would impede study completion.
24. 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.
25. Unable to abstain or limit intake of grapefruit juice and grapefruit containing drinks during the duration of the trial.
26. Refusal to provide written informed consent/assent.
27. In the opinion of the investigator, the subject is likely to be non-compliant with the study protocol.
28. 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.
29. Coronavirus disease 2019 (COVID-19) vaccination or symptoms of COVID-19 infection within 7 days of Visit 1.
30. Not taking antiplatelet or anticoagulant therapy.

Primary outcomes:
measure: Change in Exercise Capacity
timeFrame: Baseline to 26 Weeks
Secondary outcomes:
measure: Change in VO2 at the ventilatory anaerobic threshold (VAT)
timeFrame: Baseline to 26 weeks
measure: Change in Enhanced Liver Fibrosis (ELF) Score
timeFrame: Baseline to 26 weeks
measure: Work rate (watts) at ventilatory anaerobic threshold (VAT)
timeFrame: Baseline to 26 weeks
measure: Change in ventilatory efficiency (VE/VCO2) at ventilatory anaerobic threshold
timeFrame: Baseline to 26 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's
state: Arkansas
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospital
state: California
city: Denver
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Wilmington
country: United States
facility: Nemours Children's Hospital
state: Delaware
city: Washington
country: United States
facility: Childrens National Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: UF Health Shands Hospital
state: Florida
city: Hollywood
country: United States
facility: Joe DiMaggio Children's Hospital
state: Florida
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Augusta
country: United States
facility: Children's Hospital of Georgia
state: Georgia
city: Chicago
country: United States
facility: Lurie Children's Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
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
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Children's Hospital and Medical Center
state: Nebraska
city: New York
country: United States
facility: Mt. Sinai Children's Hospital
state: New York
city: New York
country: United States
facility: New York-Presbyterian Children's Hospital
state: New York
city: Charlotte
country: United States
facility: Dana.Amaro@atriumhealth.org
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: MUSC Pediatric Research Group
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Medical Center
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Bucheon
country: Korea, Republic of
facility: Sejong General Hospital
state: Gyeonggi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Children's Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei Severance Hospital
Study officials:
affiliation: Mezzion Pharma Co. Ltd
name: WG Kim
role: STUDY_DIRECTOR
References: