Single Ventricle Heart DiseasePhase 3FUELNCT02741115
Fontan Udenafil Exercise Longitudinal Assessment Trial
A Phase 3 study testing Udenafil in people with Single Ventricle Heart Disease, run by Mezzion Pharma Co. Ltd at 30 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 12 to 18 years
- Conditions the study is for
- Single Ventricle Heart Disease
- What is being tested?
- Udenafil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 400 participants
- Where
- 30 sitesin 3 countries
- Study dates
- 22 Jul 2016to 30 Apr 2019
- 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 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
Who cannot join
- Weight < 40 kg
- Height < 132 cm.
- 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.
Show all 25Show fewer
- 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.
- VO2 less than 50%
- 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 (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.
- Inability to complete exercise testing at baseline screening.
- History of PDE-5 inhibitor use within 3 months before study onset.
- 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 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.
Trial locations and contacts
30 sites in 3 countries.
30 sites in 3 countries
United States26 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
Nationwide Children's Hosptial
Columbus, Ohio, 43205
Duke University Medical Center
Durham, North Carolina, 27710
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
Children's Hospital Los Angeles
Los Angeles, California, 90027
Cedars/Sinai Heart Institute
Los Angeles, California, 90048
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Children's Hospital of New York
New York, New York, 10032
University of Nebraska Children's Hospital and Medical Center
Omaha, Nebraska, 68114
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
Canada2 sites
Stollery Children's Hospital - University of Alberta
Edmonton, Alberta, T6G 2B7
The Hospital for Sick Children
Toronto, Ontario, ON M5G 1X8
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: Fontan Udenafil Exercise Longitudinal Assessment Trial (FUEL)
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.
Read the detailed 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).
- Conditions
- Single Ventricle Heart Disease
- Being tested
- Udenafil, Placebo
- Keywords
- Fontan, Maximal Oxygen Consumption, Vascular Function, EndoPAT, Myocardial Performance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UdenafilDrug
Active drug
PlaceboDrug
Matching Placebo
| Study group | Role | What they receive |
|---|---|---|
| Drug | Experimental | Udenafil. One tablet twice daily for 26 weeks Receives: Drug: Udenafil |
| Placebo | Experimental | Placebo. One tablet twice daily for 26 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Maximal VO2 From Baseline to Week 26 Using Last Observation Carried Forward (LOCF)
The change in exercise capacity (as measured by peak VO2 at maximum exercise effort) from baseline to 26 weeks
Measured: Baseline to 26 Weeks
Secondary outcomes (22)
Change in Myocardial Performance Index (MPI) From Baseline to Week 26
Change in the myocardial performance index (MPI) from baseline to 26 weeks is determined by velocities from blood pool Doppler of the inflow and outflow tract of the dominant ventricle. The measure is the ratio of the sum of isovolumetric contraction time and isovolumetric relaxation time, divided by ventricular ejection time. A lower value is consistent with a more efficient ventricle (better function). A value of zero indicates that there is no isovolumetric contraction or relaxation and, while physiologically implausible, would be consistent with a perfectly efficient ventricle. The mean left ventricular MPI in healthy people without heart disease is approximately 0.35 while the mean right ventricular MPI is approximately 0.1 due to the reduced ventricular afterload of the pulmonary circulation. In general, a decrease in the MPI corresponds to more efficient (better) ventricular function, while an increase in MPI corresponds to less efficient (worse) ventricular function.
Measured: Week 26
Change in Log-transformed Reactive Hyperemia Index (InRH) From Baseline to Week 26
Endothelial pulse amplitude tonometry (Endo-PAT) is a technique for the non-invasive assessment of peripheral vascular function. In adults, Endo-PAT has been demonstrated to identify those with coronary artery dysfunction and to correlate with brachial artery reactivity testing. Endo-PAT use in children has been more limited, but has shown excellent reproducibility. Reactive hyperemia index, a measure of the hyperemic response adjusted for baseline blood flow, is a measure of vascular function. A higher value denotes better, or more healthy, vascular (endothelial) function.
Measured: Week 26
Change in Serum Brain-type Natriuretic Peptide (BNP) From Baseline to Week 26.
BNP is a hormone produced when the heart is enlarged or has to work harder to pump blood to the body. Higher levels of BNP can be a sign of heart failure.
Measured: Week 26
Change in VO2 at VAT
This outcome measures the change in milliliters of oxygen consumption (VO2) per minute at the ventilatory anaerobic threshold (VAT) between Week 26 and Baseline Visits using last observation carried forward (ITT Population). The anaerobic threshold is the period in exercise when metabolism switches from aerobic to anaerobic. This is an useful measure of submaximal exercise capacity particularly in the single ventricle population.
Measured: 26 Weeks
Change in Work Rate at VAT From Baseline to Week 26 With LOCF
This outcome measures the change in work (measured in Watts) at the ventilatory anaerobic threshold (VAT) between Week 26 and Baseline Visits using last observation carried forward (ITT Population). The anaerobic threshold is the period in exercise when metabolism switches from aerobic to anaerobic. This is an useful measure of submaximal exercise capacity particularly in the single ventricle population.
Measured: 26 Weeks
Change in VE/VCO2 at VAT From Baseline to Week 26
This measure is a ratio of the amount of inspired air required to clear a given volume of CO2 from the circulation at the ventilatory anaerobic threshold (VAT). This measurement is made during exercise stress testing. Decreases in this ratio may reflect an improvement in ventilatory efficiency or an improvement in cardiac function.
Measured: 26 Weeks
Change in Respiratory Rate at Maximal Exercise Effort From Baseline to Week 26 Using LOCF
Measured: Week 26
Change in Minute Oxygen Consumption at Maximal Exercise Effort From Baseline to Week 26
The amount of air that enters the lungs per minute at maximal exercise effort.
Measured: Week 26
Change in Work Rate at Maximal Exercise Effort Between Baseline and Week 26 Using LOCF
Change in power at maximal exercise effort.
Measured: Week 26
Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Physical Functioning Subscale (Child Reported)
The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Measured: 26 weeks
Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Physical Functioning Subscale (Parent Reported)
The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Measured: 26 weeks
Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Psychosocial Health Subscale (Child Reported)
The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Measured: 26 weeks
Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Psychosocial Health Subscale (Parent Reported)
The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Measured: 26 weeks
Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Treatment II Subscale (Child-reported)
The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Measured: 26 weeks
Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Perceived Physical Appearance Subscale
The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Measured: 26 weeks
Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Treatment Anxiety Subscale
The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Measured: 26 weeks
Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Cognitive Problems Subscale
The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Measured: 26 weeks
Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Communication Problems Subscale
The PedsQL is a short questionnaire that has been used in multiple studies, including a previous study of Fontan patients. A 5-point Likert response scale (0-4) is used. This score was linearly transformed on a scale of 0-100 (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0). For an individual, a higher score is associated with a higher reported healthcare-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 week. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Measured: 26 weeks
Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 8 to 12 (Child Reported)
The PCLQI is a disease-specific measure of health-related quality of life for children and adolescents with congenital or acquired heart disease. The PCQLI score is calculated by adding together the scores from the two subscales: Disease Impact and Psychosocial Impact. Each subscale can score a maximum of 50 points, resulting in a total score with a maximum of 100. Higher scores indicate better perceived health-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Measured: 26 weeks
Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 8 to 12 (Parent Reported)
The PCLQI is a disease-specific measure of health-related quality of life for children and adolescents with congenital or acquired heart disease. The PCQLI score is calculated by adding together the scores from the two subscales: Disease Impact and Psychosocial Impact. Each subscale can score a maximum of 50 points, resulting in a total score with a maximum of 100. Higher scores indicate better perceived health-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Measured: 26 weeks
Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 13 to 18 (Child Reported)
The PCLQI is a disease-specific measure of health-related quality of life for children and adolescents with congenital or acquired heart disease. The PCQLI score is calculated by adding together the scores from the two subscales: Disease Impact and Psychosocial Impact. Each subscale can score a maximum of 50 points, resulting in a total score with a maximum of 100. Higher scores indicate better perceived health-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Measured: 26 weeks
Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 13 to 18 (Parent Reported)
The PCLQI is a disease-specific measure of health-related quality of life for children and adolescents with congenital or acquired heart disease. The PCQLI score is calculated by adding together the scores from the two subscales: Disease Impact and Psychosocial Impact. Each subscale can score a maximum of 50 points, resulting in a total score with a maximum of 100. Higher scores indicate better perceived health-related quality of life. For each population (treatment and placebo), population means were calculated at baseline and 26 weeks. The outcome measure is the difference between week 26 and baseline (week 26 - baseline).
Measured: 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2016 (estimated)
- Study start22 Jul 2016
- Primary completion27 Dec 2018
- Study completion30 Apr 2019
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 (3)Papers the sponsor has linked to this study.
- Other trials for 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 400 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 Phildelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02741115
- Sponsor's protocol ID
- PHN-Udenafil-02
- Other IDs
- U01HL068270
- Acronym
- FUEL
- Status last verified
- May 2025
- First submitted
- 10 Apr 2016
- Last updated
- 17 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Di Maria MV, Goldberg DJ, Zak V, Hu C, Lubert AM, Dragulescu A, Mackie AS, McCrary A, Weingarten A, Parthiban A, Goot B, Goldstein BH, Taylor C, Lindblade C, Petit CJ, Spurney C, Harrild DM, Urbina EM, Schuchardt E, Beom Kim G, Kyoung Yoon J, Colombo JN, Files MD, Schoessling M, Ermis P, Wong PC, Garg R, Swanson SK, Menon SC, Srivastava S, Thorsson T, Johnson TR, Krishnan US, Paridon SM, Frommelt PC; Pediatric Heart Network. Impact of Udenafil on Echocardiographic Indices of Single Ventricle Size and Function in FUEL Study Participants. Circ Cardiovasc Imaging. 2022 Nov;15(11):e013676. doi: 10.1161/CIRCIMAGING.121.013676. Epub 2022 Nov 15.
PubMed 36378780Goldberg DJ, Zak V, Goldstein BH, Schumacher KR, Rhodes J, Penny DJ, Petit CJ, Ginde S, Menon SC, Kim SH, Kim GB, Nowlen TT, DiMaria MV, Frischhertz BP, Wagner JB, McHugh KE, McCrindle BW, Shillingford AJ, Sabati AA, Yetman AT, John AS, Richmond ME, Files MD, Payne RM, Mackie AS, Davis CK, Shahanavaz S, Hill KD, Garg R, Jacobs JP, Hamstra MS, Woyciechowski S, Rathge KA, McBride MG, Frommelt PC, Russell MW, Urbina EM, Yeager JL, Pemberton VL, Stylianou MP, Pearson GD, Paridon SM; Pediatric Heart Network Investigators. Results of the FUEL Trial. Circulation. 2020 Feb 25;141(8):641-651. doi: 10.1161/CIRCULATIONAHA.119.044352. Epub 2019 Nov 17.
PubMed 31736357Goldberg 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 17 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fontan Udenafil Exercise Longitudinal Assessment Trial (FUEL)
- ClinicalTrials.gov ID
- NCT02741115
- Acronym / sponsor ID
- FUEL / PHN-Udenafil-02
- Conditions
- Single Ventricle Heart Disease
- Keywords
- Fontan, Maximal Oxygen Consumption, Vascular Function, EndoPAT, Myocardial Performance
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 400 participants (actual)
- Lead sponsor
- Mezzion Pharma Co. LtdIndustry (pharma, biotech, devices)
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 22 Jul 2016 (actual)
- Primary completion
- 27 Dec 2018 (actual)
- Study completion
- 30 Apr 2019 (actual)
- First posted
- 18 Apr 2016 (estimated)
- Results
- Posted 21 May 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 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.
Detailed 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Drug | Experimental | Drug: UdenafilUdenafil. One tablet twice daily for 26 weeks |
| Placebo | Experimental | Drug: PlaceboPlacebo. One tablet twice daily for 26 weeks |
Who may qualify
- Ages
- 12 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (25 listed)
- Weight < 40 kg
- Height < 132 cm.
- 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 |
| PlaceboMatching Placebo | Drug | Placebo |
Primary outcome
Change in Maximal VO2 From Baseline to Week 26 Using Last Observation Carried Forward (LOCF)
Time frame: Baseline to 26 Weeks
The change in exercise capacity (as measured by peak VO2 at maximum exercise effort) from baseline to 26 weeks
22 secondary outcomes
Change in Myocardial Performance Index (MPI) From Baseline to Week 26
Time frame: Week 26
Change in Log-transformed Reactive Hyperemia Index (InRH) From Baseline to Week 26
Time frame: Week 26
Change in Serum Brain-type Natriuretic Peptide (BNP) From Baseline to Week 26.
Time frame: Week 26
Change in VO2 at VAT
Time frame: 26 Weeks
Change in Work Rate at VAT From Baseline to Week 26 With LOCF
Time frame: 26 Weeks
Change in VE/VCO2 at VAT From Baseline to Week 26
Time frame: 26 Weeks
Change in Respiratory Rate at Maximal Exercise Effort From Baseline to Week 26 Using LOCF
Time frame: Week 26
Change in Minute Oxygen Consumption at Maximal Exercise Effort From Baseline to Week 26
Time frame: Week 26
Change in Work Rate at Maximal Exercise Effort Between Baseline and Week 26 Using LOCF
Time frame: Week 26
Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Physical Functioning Subscale (Child Reported)
Time frame: 26 weeks
Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Physical Functioning Subscale (Parent Reported)
Time frame: 26 weeks
Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Psychosocial Health Subscale (Child Reported)
Time frame: 26 weeks
Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Psychosocial Health Subscale (Parent Reported)
Time frame: 26 weeks
Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Treatment II Subscale (Child-reported)
Time frame: 26 weeks
Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Perceived Physical Appearance Subscale
Time frame: 26 weeks
Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Treatment Anxiety Subscale
Time frame: 26 weeks
Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Cognitive Problems Subscale
Time frame: 26 weeks
Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Communication Problems Subscale
Time frame: 26 weeks
Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 8 to 12 (Child Reported)
Time frame: 26 weeks
Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 8 to 12 (Parent Reported)
Time frame: 26 weeks
Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 13 to 18 (Child Reported)
Time frame: 26 weeks
Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 13 to 18 (Parent Reported)
Time frame: 26 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36378780Di Maria MV, Goldberg DJ, Zak V, Hu C, Lubert AM, Dragulescu A, Mackie AS, McCrary A, Weingarten A, Parthiban A, Goot B, Goldstein BH, Taylor C, Lindblade C, Petit CJ, Spurney C, Harrild DM, Urbina EM, Schuchardt E, Beom Kim G, Kyoung Yoon J, Colombo JN, Files MD, Schoessling M, Ermis P, Wong PC, Garg R, Swanson SK, Menon SC, Srivastava S, Thorsson T, Johnson TR, Krishnan US, Paridon SM, Frommelt PC; Pediatric Heart Network. Impact of Udenafil on Echocardiographic Indices of Single Ventricle Size and Function in FUEL Study Participants. Circ Cardiovasc Imaging. 2022 Nov;15(11):e013676. doi: 10.1161/CIRCIMAGING.121.013676. Epub 2022 Nov 15.
- Derived from this study: PubMed 31736357Goldberg DJ, Zak V, Goldstein BH, Schumacher KR, Rhodes J, Penny DJ, Petit CJ, Ginde S, Menon SC, Kim SH, Kim GB, Nowlen TT, DiMaria MV, Frischhertz BP, Wagner JB, McHugh KE, McCrindle BW, Shillingford AJ, Sabati AA, Yetman AT, John AS, Richmond ME, Files MD, Payne RM, Mackie AS, Davis CK, Shahanavaz S, Hill KD, Garg R, Jacobs JP, Hamstra MS, Woyciechowski S, Rathge KA, McBride MG, Frommelt PC, Russell MW, Urbina EM, Yeager JL, Pemberton VL, Stylianou MP, Pearson GD, Paridon SM; Pediatric Heart Network Investigators. Results of the FUEL Trial. Circulation. 2020 Feb 25;141(8):641-651. doi: 10.1161/CIRCULATIONAHA.119.044352. Epub 2019 Nov 17.
- 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 Phildelphia
30 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 Single Ventricle Heart Disease, run by Mezzion Pharma Co. Ltd at 30 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 3 inclusion and 25 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 17 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, Canada, South Korea. 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 21 May 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?
Change in Maximal VO2 From Baseline to Week 26 Using Last Observation Carried Forward (LOCF) (time frame: Baseline to 26 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 NCT02741115, which also lists 3 linked publications.
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 17 Jun 2025.