Fontan Udenafil Exercise Longitudinal Assessment Trial - 2
- Registration Number
- NCT05918211
- Lead Sponsor
- Mezzion Pharma Co. Ltd
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 436
- 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.
- Current antiplatelet or anticoagulant therapy.
- Height < 132 cm.
- Weight < 40 kg.
- 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.
- Failure to achieve maximal exertion (defined as RER < 1.10) on screening/baseline exercise test.
- Peak minute oxygen consumption (VO2) less than 45% or ≥ 80% of predicated for age and gender at enrollment.
- Severe ventricular dysfunction assessed qualitatively by clinical echocardiography within 6 months prior to enrollment.
- Severe valvar regurgitation, ventricular outflow obstruction, or severe aortic arch obstruction assessed by clinical echocardiography within six months prior to enrollment.
- 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.
- Inability to complete exercise testing at baseline screening.
- Subjects with a pacemaker whose heart rate at peak exercise is controlled by the extrinsic pacemaker as opposed to a native atrial rhythm.
- History of PDE-5 inhibitor use within 12 months prior to enrollment. (Treatment is defined as chronic therapy as opposed to a single dose.)
- 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 and grapefruit containing drinks during the duration of the trial.
- Refusal to provide written informed consent/assent.
- In the opinion of the investigator, the subject is likely to be non-compliant with the study protocol.
- 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.
- Coronavirus disease 2019 (COVID-19) vaccination or symptoms of COVID-19 infection within 7 days of Visit 1.
- Not taking antiplatelet or anticoagulant therapy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Drug Udenafil Approximately 218 subjects dosed with udenafil will be enrolled at approximately 30 sites. Placebo Placebo Approximately 218 subjects dosed with matching placebo will be enrolled at approximately 30 sites.
- Primary Outcome Measures
Name Time Method Change in Exercise Capacity Baseline to 26 Weeks The change in exercise capacity (as measured by maximal VO2 at maximum exercise effort) from baseline to 26 weeks (or study completion)
- Secondary Outcome Measures
Name Time Method Change in VO2 at the ventilatory anaerobic threshold (VAT) Baseline to 26 weeks Change in peak oxygen consumption (VO2) from baseline to Week 26 as measured by maximal central cardiopulmonary exercise test (CPET) reading laboratory.
Change in Enhanced Liver Fibrosis (ELF) Score Baseline to 26 weeks Change from baseline to Week 26 in the Enhanced Liver Fibrosis (ELF) Score calculated by the change in the following biomarkers: hyaluronic acid, amino-terminal propeptide of type III collagen, and tissue inhibitor of metalloproteinase-1. subjects with scores of \<7.7 were assigned to the no or mild fibrosis group; 7.7 to 9.8 to the moderate fibrosis group, and \>9.8 to the severe fibrosis group.
Work rate (watts) at ventilatory anaerobic threshold (VAT) Baseline to 26 weeks Change from baseline to 26 weeks in work rate in watts at the ventilatory anaerobic threshold as measured by the central cardiopulmonary exercise test reading laboratory.
Change in ventilatory efficiency (VE/VCO2) at ventilatory anaerobic threshold Baseline to 26 weeks Change from baseline to Week 26 in ventilatory efficiency calculated by ventilatory efficiency divided by minute carbon dioxide production at the ventilatory anaerobic threshold (VE/VCO2 at VAT).
Trial Locations
- Locations (80)
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Arkansas Children's
🇺🇸Little Rock, Arkansas, United States
Children's Hospital of Los Angeles
🇺🇸Los Angeles, California, United States
Children's Hospital of Colorado
🇺🇸Denver, Colorado, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Rady Children's Hospital
🇺🇸San Diego, California, United States
UCSF Benioff Children's Hospital
🇺🇸San Francisco, California, United States
Childrens National Medical Center
🇺🇸Washington, District of Columbia, United States
Yale School of Medicine
🇺🇸New Haven, Connecticut, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Nemours Children's Hospital
🇺🇸Wilmington, Delaware, United States
Johns Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
UF Health Shands Hospital
🇺🇸Gainesville, Florida, United States
Joe DiMaggio Children's Hospital
🇺🇸Hollywood, Florida, United States
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
Children's Hospital of Georgia
🇺🇸Augusta, Georgia, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Lurie Children's Hospital
🇺🇸Chicago, Illinois, United States
Children's Mercy Hospital Kansas City
🇺🇸Kansas City, Missouri, United States
Mt. Sinai Children's Hospital
🇺🇸New York, New York, United States
New York-Presbyterian Children's Hospital
🇺🇸New York, New York, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
University of Nebraska Children's Hospital and Medical Center
🇺🇸Omaha, Nebraska, United States
Dana.Amaro@atriumhealth.org
🇺🇸Charlotte, North Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Cincinnati Childrens Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
MUSC Pediatric Research Group
🇺🇸Charleston, South Carolina, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Sejong General Hospital
🇰🇷Bucheon, Gyeonggi, Korea, Republic of
Seoul National University Children's Hospital
🇰🇷Seoul, Korea, Republic of
Yonsei Severance Hospital
🇰🇷Seoul, Korea, Republic of
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Arkansas Children's
🇺🇸Little Rock, Arkansas, United States
Children's Hospital of Los Angeles
🇺🇸Los Angeles, California, United States
Rady Children's Hospital
🇺🇸San Diego, California, United States
UCSF Benioff Children's Hospital
🇺🇸San Francisco, California, United States
Children's Hospital of Colorado
🇺🇸Denver, Colorado, United States
Yale School of Medicine
🇺🇸New Haven, Connecticut, United States
Nemours Children's Hospital
🇺🇸Wilmington, Delaware, United States
Childrens National Medical Center
🇺🇸Washington, District of Columbia, United States
UF Health Shands Hospital
🇺🇸Gainesville, Florida, United States
Joe DiMaggio Children's Hospital
🇺🇸Hollywood, Florida, United States
Johns Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
Children's Hospital of Georgia
🇺🇸Augusta, Georgia, United States
Lurie Children's Hospital
🇺🇸Chicago, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Children's Mercy Hospital Kansas City
🇺🇸Kansas City, Missouri, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
University of Nebraska Children's Hospital and Medical Center
🇺🇸Omaha, Nebraska, United States
Mt. Sinai Children's Hospital
🇺🇸New York, New York, United States
New York-Presbyterian Children's Hospital
🇺🇸New York, New York, United States
Dana.Amaro@atriumhealth.org
🇺🇸Charlotte, North Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Cincinnati Childrens Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
MUSC Pediatric Research Group
🇺🇸Charleston, South Carolina, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Sejong General Hospital
🇰🇷Bucheon, Gyeonggi, Korea, Republic of
Seoul National University Children's Hospital
🇰🇷Seoul, Korea, Republic of
Yonsei Severance Hospital
🇰🇷Seoul, Korea, Republic of