Functional Single Ventricle Heart DiseasePhase 3FUELExtenNCT03013751
A Extension Study of Udenafil in Adolescents
A Phase 3 study testing Udenafil in people with Functional Single Ventricle Heart Disease, run by Mezzion Pharma Co. Ltd at 24 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 18 years
- Conditions the study is for
- Functional Single Ventricle Heart Disease
- What is being tested?
- Udenafil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 301 participants
- Where
- 24 sitesin 3 countries
- Study dates
- 6 Feb 2017to 20 Dec 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
- Participant consent or parental/guardian consent and participant assent.
- Participant fluent in English, Spanish, or Korean.
- Current anti-platelet or anticoagulant therapy.
Who cannot join
- 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 three years, or a history of liver cirrhosis.
Show all 26Show fewer
- 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.
- Single lung physiology.
- Maximal VO2 less than 50% of predicted for age and gender at enrollment.
- Severe ventricular dysfunction assessed qualitatively by clinical echocardiography within six months prior to enrollment.
- Severe valvar regurgitation, ventricular outflow obstruction, or aortic arch obstruction assessed by clinical echocardiography within six months prior to enrollment.
- Significant renal, hepatic, gastrointestinal or biliary disorders that could impair absorption, metabolism or excretion of orally administered medications.
- Inability to complete exercise testing at baseline screening.
- History of PDE-5 inhibitor use (with the exception of FUEL participation) within 3 months before study onset.
- Use of any other drug to treat 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.
- Unable to abstain or limit intake of grapefruit juice during the duration of the trial.
- Refusal to provide written informed consent/assent.
- In the opinion of the primary care physician, the subject is likely to be non-compliant with the study protocol.
- History of clinically significant thromboembolic event, as adjudicated by study Investigators.
Trial locations and contacts
24 sites in 3 countries.
24 sites in 3 countries
United States21 sites
University of Michigan Congenital Heart Center/C.S. Mott Children's Hospital
Ann Arbor, Michigan, 48109-4204
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
Children's Hospital Colorado
Aurora, Colorado, 80045
Boston Children's Hospital
Boston, Massachusetts, 02115
Medical University of South Carolina
Charleston, South Carolina, 29425
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Texas Children's Hospital
Houston, Texas, 77030
Riley Hospital for Children/Herman B. Wells Center for Pediatric Research
Indianapolis, Indiana, 46201
Children's Mercy Hospital Kansas City
Kansas City, Missouri, 64108
Cedars/Sinai Heart Institute
Los Angeles, California, 90048
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Children's Hospital of New York
New York, New York, 10032
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Phoenix Children's Hospital/Children's Heart Center at Phoenix Children's Hospital
Phoenix, Arizona, 85016
Primary Children's Medical Hospital/Dept. of Pediatric Cardiology
Salt Lake City, Utah, 84113
Rady Children's Hospital
San Diego, California, 92123
Seattle Children's Hosptial
Seattle, Washington, 98105
Washington University St. Louis/St.Louis Children's Hospital
St Louis, Missouri, 63110
Johns Hopkins All Children's Heart Institute
St. Petersburg, Florida, 33701
Children's National Medical Center
Washington D.C., District of Columbia, 20008
Nemours Cardiac Center/Alfred I. duPont Hospital for Children
Wilmington, Delaware, 19803
South Korea2 sites
Sejong General Hospital
Bucheon-si, Gyeonggi-do, 14754
Seoul National University Children's Hospital
Seoul, 110-744
About this study
Official title: A Phase III Extension Study of Udenafil in Adolescents With Single Ventricle Physiology After Fontan Palliation
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.
Read the 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.
- Being tested
- Udenafil
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UdenafilDrug
Active drug
| Study group | Role | What they receive |
|---|---|---|
| Drug | Experimental | Udenafil administered for 52 weeks Receives: Drug: Udenafil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-Emergent Adverse Events
Summary of Treatment Emergent Adverse Events
Measured: 52 Weeks
Secondary outcomes (10)
Change in Maximal VO2
Change in Maximal VO2 from baseline to 52 weeks
Measured: 52 Weeks
Change in Log-transformed Reactive Hyperemia Index (lnRHI)
Change from baseline to 52 weeks in Log-transformed Reactive Hyperemia Index (lnRHI). The Reactive Hyperemia Index (RHI) is the ratio of the amount of blood flow after the release of a period of vessel occlusion relative to baseline amount of blood flow. Because the amount of blood does not decrease after release of vessel occlusion, the minimum value for the RHI is 1.0, which would indicate no change in blood flow. There is no upper limit for this ratio, and higher values are generally thought to represent a healthier endothelial response. In this study, as in other studies, we used the natural log of RHI (lnRHI) to normalize the data.
Measured: 52 Weeks
Change in Serum BNP
Change in Serum BNP from baseline to 52 weeks
Measured: 52 Weeks
Change in Myocardial Performance Index (MPI)
Change in Myocardial Performance Index from baseline to 52 weeks
Measured: 52 Weeks
Change in PedsQL Physical Functioning (Child Reported)
Change in PedsQL Physical Functioning (Child Reported) from baseline to 52 weeks. The Pediatric Quality of Life Inventory (PedsQL) - Physical Function Scale is calculated from a child's answers to a short questionnaire. The range of possible scores is 0-100, and higher scores indicate better reported physical function.
Measured: 52 Weeks
Change in PedsQL Physical Functioning (Parent Reported)
Change in PedsQL Physical Functioning (Parent Reported) from baseline to 52 weeks. The Pediatric Quality of Life Inventory (PedsQL) - Physical Function Scale is calculated from parent's answers to a short questionnaire. The range of possible scores is 0-100, and higher scores indicate better reported physical function.
Measured: 52 Weeks
Change in PedsQL Psychosocial Health Summary Score (Child Reported)
Change in PedsQL Psychosocial Health Summary Score (Child reported) from baseline to 52 weeks. The Pediatric Quality of Life Inventory (PedsQL) - Psychosocial Health Summary Scale is calculated from a child's answers to a short questionnaire. The range of possible scores is 0-100, and higher scores indicate better reported psychosocial health.
Measured: 52 Weeks
Change in PedsQL Psychosocial Health Summary Score (Parent Reported)
Change in PedsQL Psychosocial Health Summary Score (Parent reported) from baseline to 52 weeks. The Pediatric Quality of Life Inventory (PedsQL) - Psychosocial Health Summary Scale is calculated from parent's answers to a short questionnaire. The range of possible scores is 0-100, and higher scores indicate better reported psychosocial health.
Measured: 52 Weeks
Change in PedsQL Functional Health Status Score (Child Reported)
Change in PedsQL Functional Health Status Score (Child reported) from baseline to 52 weeks. The Pediatric Quality of Life Inventory (PedsQL) - Functional Health Status Score is calculated from a child's answers to a short questionnaire. The range of possible scores is 0-100, and higher scores indicate better functional health status.
Measured: 52 Weeks
Change in PedsQL Functional Health Status Score (Parent Reported)
Change in PedsQL Functional Health Status Score (Parent reported) from baseline to 52 weeks. The Pediatric Quality of Life Inventory (PedsQL) - Functional Health Status Score is calculated from parent's answers to a short questionnaire. The range of possible scores is 0-100, and higher scores indicate better functional health status.
Measured: 52 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2017 (estimated)
- Study start6 Feb 2017
- Primary completion30 Dec 2019
- Study completion20 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Functional Single Ventricle Heart DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 301 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mezzion Pharma Co. Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Steve Paridon, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03013751
- Sponsor's protocol ID
- PHN-Udenafil-03
- Other IDs
- U01HL068270
- Acronym
- FUELExten
- Status last verified
- Nov 2025
- First submitted
- 5 Jan 2017
- Last updated
- 9 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 29910047
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Extension Study of Udenafil in Adolescents With Single Ventricle Physiology After Fontan Palliation
- ClinicalTrials.gov ID
- NCT03013751
- Acronym / sponsor ID
- FUELExten / PHN-Udenafil-03
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 301 participants (actual)
- Lead sponsor
- Mezzion Pharma Co. LtdIndustry (pharma, biotech, devices)
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 6 Feb 2017 (actual)
- Primary completion
- 30 Dec 2019 (actual)
- Study completion
- 20 Dec 2022 (actual)
- First posted
- 6 Jan 2017 (estimated)
- Results
- Posted 9 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Drug | Experimental | Drug: UdenafilUdenafil administered for 52 weeks |
Who may qualify
- Ages
- 12 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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.
- Participant consent or parental/guardian consent and participant assent.
- Participant fluent in English, Spanish, or Korean.
- Current anti-platelet or anticoagulant therapy.
Key exclusion criteria (26 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UdenafilActive drug | Drug | Drug |
Primary outcome
Treatment-Emergent Adverse Events
Time frame: 52 Weeks
Summary of Treatment Emergent Adverse Events
10 secondary outcomes
Change in Maximal VO2
Time frame: 52 Weeks
Change in Log-transformed Reactive Hyperemia Index (lnRHI)
Time frame: 52 Weeks
Change in Serum BNP
Time frame: 52 Weeks
Change in Myocardial Performance Index (MPI)
Time frame: 52 Weeks
Change in PedsQL Physical Functioning (Child Reported)
Time frame: 52 Weeks
Change in PedsQL Physical Functioning (Parent Reported)
Time frame: 52 Weeks
Change in PedsQL Psychosocial Health Summary Score (Child Reported)
Time frame: 52 Weeks
Change in PedsQL Psychosocial Health Summary Score (Parent Reported)
Time frame: 52 Weeks
Change in PedsQL Functional Health Status Score (Child Reported)
Time frame: 52 Weeks
Change in PedsQL Functional Health Status Score (Parent Reported)
Time frame: 52 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29910047Goldberg 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steve Paridon, MD principal investigator
Children's Hospital of Philadelphia
24 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Udenafil in people with Functional Single Ventricle Heart Disease, run by Mezzion Pharma Co. Ltd at 24 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, South Korea, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment-Emergent Adverse Events (time frame: 52 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03013751, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2025.