Single Ventricle Heart DiseasePhase 3FALDNCT03430583

Evaluation of Fontan-associated Hepatic Stiffness and the Efficacy of Udenafil in Reducing Liver Stiffness

A Phase 3 study testing Udenafil in people with Single Ventricle Heart Disease, run by Mezzion Pharma Co. Ltd at 17 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

A study to evaluate the efficacy of MZ101 therapy in reducing liver stiffness. Read more about this study

Who is it for?: Ages 12 years and older
Conditions the study is for: Single Ventricle Heart Disease
What is being tested?: Udenafil
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 88 participants
Where: 17 sitesin 2 countries
Study dates: 20 Feb 2018to 16 Sep 2020
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 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Enrollment in on-going Phase 3 Open-Label Safety Study
Informed assent from subject, informed consent from parent/legal guardian as appropriate

Who cannot join

Non-enrollment in the on-going Phase 3 Open-Label Study
Subjects with contra-indications for MRI (these subjects will be excluded from the MRI component of this study)
Other exclusionary criteria will match those used for the Open-Label Safety Study

Trial locations and contacts

17 sites in 2 countries.

Country

City, postcode or hospital

17 sites in 2 countries

United States16 sites

University of Michigan Congenital Heart Center
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
Children's Mercy Hospital
Kansas City, Kansas, 64108
Children's Mercy Hospital Kansas City
Kansas City, Missouri, 64108
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
University of Nebraska Children's Hospital and Medical Center
Omaha, Nebraska, 68114
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Primary Children's Medical Hospital/Dept. of Pediatric Cardiology
Salt Lake City, Utah, 84113
Children's National Medical Center
Washington D.C., District of Columbia, 20008
Nemours Cardiac Center/Alfred I. duPont Hospital for Children
Wilmington, Delaware, 19803

Other trials in United States

Canada1 site

The Hospital for Sick Children
Toronto, Ontario, ON M5G 1X8

Other trials in Canada

About this study

Official title: Imaging and Biomarker Evaluation of Hepatic Stiffness in Children Enrolled in the Fontan Udenafil Exercise Longitudinal Study

A study to evaluate the efficacy of MZ101 therapy in reducing liver stiffness.

Read the detailed description

This is open-label, long-term prospective study in a cohort of Fontan subjects taking drug daily for one year. The study will determine the scope of hepatic stiffness in the cohort by ultrasound and magnetic resonance imaging elastography and evaluate MZ101 pharmacotherapy as a potentially efficacious treatment to reduce liver stiffness.

Conditions: Single Ventricle Heart Disease
Being tested: Udenafil
Keywords: Fontan, Ultrasound Shear Wave Elastography, Magnetic Resonance Imaging Elastography

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

UdenafilDrug
Open-label extension with Udenafil 87.5 mg BID treatment for 52 weeks.

Study groups in NCT03430583
Study group	Role	What they receive
Udenafil Continuation (U+)	Experimental	Subjects who were receiving Udenafil 87.5 mg BID in FUEL study prior to enrolling to this study (FALD). Receives: Drug: Udenafil
Udenafil Naive (U-)	Experimental	Subjects who were receiving Placebo BID in FUEL study prior to enrolling to this study (FALD). Receives: Drug: Udenafil

What is being measured

The primary outcome is the main question the study is designed to answer.

Effect of Udenafil 87.5 mg BID Treatment on Liver Stiffness in Udenafil Continuation and Naive Groups After 52 Weeks, as Determined by Ultrasound Shear Wave Elastography
Liver stiffness was measured at baseline and 52 weeks using Ultrasound Shear Wave Elastography (USWE) separately in Udenafil Continuation (U+) and Udenafil Naive (U-) groups. A decrease in value indicates a decrease in liver stiffness.
Measured: 52 weeks
Effect of Udenafil 87.5 mg BID Treatment on Liver Stiffness in Udenafil Continuation and Naive Groups After 52 Weeks, as Determined by Magnetic Resonance Elastography
Liver stiffness was measured at baseline and 52 weeks using Magnetic Resonance Elastography (MRE) separately in Udenafil Continuation (U+) and Udenafil Naive (U-) groups. A decrease in value indicates a decrease in liver stiffness.
Measured: 52 weeks

Secondary outcomes (2)

Effect of Udenafil 87.5 mg BID on Enhanced Liver Fibrosis (ELF) Score After 52 Weeks of Treatment
Overall ELF score. ELF score is based on the serum levels of hyaluronic acid (HA), amino-terminal propeptide of type III collagen (PIIINP), and tissue inhibitor of metalloproteinase-1 (TIMP-1), and calculated using the following formula: ELF score= 2.494+0.846 In(CHA)+0.391 In(CPIIINP)+0.391 In(CTIMP-1). The levels of each component were as assessed individually and as part of the calculated ELF score as continuous variables. The normal range in healthy subjects ≤20 years of age is 6.9 - 8.8. Correlations between ELF and the degree of liver fibrosis have not been established in patients with Fontan circulation, however, a decrease in ELF score is associated with improved liver health in other disease states.
Measured: 52 weeks
Effect of Udenafil 87.5 mg BID on Brain Natriuretic Peptide After 52 Weeks of Treatment
Brain Natriuretic Peptide (BNP) was measured at baseline and 52 weeks of treatment. BNP is a biomarker of overall cardiac function across a variety of disease states. A decrease in value is associated with improved cardiac function.
Measured: 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Feb 201816 Sep 2020

First posted13 Feb 2018
Study start20 Feb 2018
Primary completion15 Sep 2020
Study completion16 Sep 2020

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.
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: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 88 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03430583
Sponsor's protocol ID: PHN-Udenafil-04
Other IDs: U01HL068270
Acronym: FALD
Status last verified: Sep 2025
First submitted: 22 Jan 2018
Last updated: 14 Oct 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Trial of the F2 Filter and Delivery System for Embolic Protection During TAVR
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Effect and Safety of Flecainide and Metoprolol Versus Metoprolol Alone to Suppress Ventricular Arrhythmias in Arrhythmic Mitral Valve Prolapse
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IMProving DRug Dosing and Outcomes for Single VEntricle Patients With Fontan Associated Liver Disease
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Target Value Study to Evaluate the Safety and Efficacy of the Taurus NXT® Transcatheter Aortic Valve System for the Treatment of Severe Calcific Aortic Stenosis
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All Single Ventricle Heart Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Imaging and Biomarker Evaluation of Hepatic Stiffness in Children Enrolled in the Fontan Udenafil Exercise Longitudinal Study
ClinicalTrials.gov ID: NCT03430583
Acronym / sponsor ID: FALD / PHN-Udenafil-04
Conditions: Single Ventricle Heart Disease
Keywords: Fontan, Ultrasound Shear Wave Elastography, Magnetic Resonance Imaging Elastography
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 88 participants (actual)
Lead sponsor: Mezzion Pharma Co. LtdIndustry (pharma, biotech, devices)
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
Study start: 20 Feb 2018 (actual)
Primary completion: 15 Sep 2020 (actual)
Study completion: 16 Sep 2020 (actual)
First posted: 13 Feb 2018 (actual)
Results: Posted 18 Sep 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

A study to evaluate the efficacy of MZ101 therapy in reducing liver stiffness.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Udenafil Continuation (U+)	Experimental	Drug: UdenafilSubjects who were receiving Udenafil 87.5 mg BID in FUEL study prior to enrolling to this study (FALD).
Udenafil Naive (U-)	Experimental	Drug: UdenafilSubjects who were receiving Placebo BID in FUEL study prior to enrolling to this study (FALD).

Who may qualify

Ages: 12 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (2 listed)

Enrollment in on-going Phase 3 Open-Label Safety Study
Informed assent from subject, informed consent from parent/legal guardian as appropriate

Key exclusion criteria (3 listed)

Non-enrollment in the on-going Phase 3 Open-Label Study
Subjects with contra-indications for MRI (these subjects will be excluded from the MRI component of this study)
Other exclusionary criteria will match those used for the Open-Label Safety Study

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
UdenafilOpen-label extension with Udenafil 87.5 mg BID treatment for 52 weeks.	Drug	Udenafil Continuation (U+), Udenafil Naive (U-)

Primary outcome

Effect of Udenafil 87.5 mg BID Treatment on Liver Stiffness in Udenafil Continuation and Naive Groups After 52 Weeks, as Determined by Ultrasound Shear Wave Elastography
Time frame: 52 weeks
Liver stiffness was measured at baseline and 52 weeks using Ultrasound Shear Wave Elastography (USWE) separately in Udenafil Continuation (U+) and Udenafil Naive (U-) groups. A decrease in value indicates a decrease in liver stiffness.
Effect of Udenafil 87.5 mg BID Treatment on Liver Stiffness in Udenafil Continuation and Naive Groups After 52 Weeks, as Determined by Magnetic Resonance Elastography
Time frame: 52 weeks
Liver stiffness was measured at baseline and 52 weeks using Magnetic Resonance Elastography (MRE) separately in Udenafil Continuation (U+) and Udenafil Naive (U-) groups. A decrease in value indicates a decrease in liver stiffness.

2 secondary outcomes

Effect of Udenafil 87.5 mg BID on Enhanced Liver Fibrosis (ELF) Score After 52 Weeks of Treatment
Time frame: 52 weeks
Effect of Udenafil 87.5 mg BID on Brain Natriuretic Peptide After 52 Weeks of Treatment
Time frame: 52 weeks

Results and safety

Results posted to the registry on 18 Sep 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Udenafil Continuation (U+)	36	33
Udenafil Naive (U-)	52	45

Primary outcome: Effect of Udenafil 87.5 mg BID Treatment on Liver Stiffness in Udenafil Continuation and Naive Groups After 52 Weeks, as Determined by Ultrasound Shear Wave Elastography

Time frame: 52 weeks. Mean (Standard Deviation). Unit: meters per second

Measure	Udenafil Continuation (U+) n = 33	Udenafil Naive (U-) n = 42	Total Udenafil n = 75
Baseline	1.91 (0.380)	2.02 (0.450)	1.97 (0.422)
Week 52	1.86 (0.288)	1.96 (0.349)	1.92 (0.325)

Population analysed: Only participants with paired data points were included in the analysis population.

Primary outcome: Effect of Udenafil 87.5 mg BID Treatment on Liver Stiffness in Udenafil Continuation and Naive Groups After 52 Weeks, as Determined by Magnetic Resonance Elastography

Time frame: 52 weeks. Mean (Standard Deviation). Unit: kiloPascal (kPa)

Measure	Udenafil Continuation (U+) n = 21	Udenafil Naive (U-) n = 17	Total Udenafil n = 38
Baseline	5.26 (0.927)	5.26 (1.453)	5.26 (1.173)
Week 52	4.95 (1.080)	5.50 (1.550)	5.20 (1.322)

Population analysed: Only participants with paired data points were included in the analysis population.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Not applicable, as all safety information was collected in the Study PHN-Udenafil-03 (parent study) and will be reported as part of the results from that study. All-Cause Mortality, Serious, and Other (Not Including Serious) Adverse Events were not monitored/assessed as part of Study PHN-Udenafil-04.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Udenafil 87.5 mg BID	0 of 0	0 of 0	0

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Single Ventricle Heart Disease

Recruiting
Trial of the F2 Filter and Delivery System for Embolic Protection During TAVR
Aortic Stenosis Treated With TAVI, Aortic Diseases
Active, not recruitingPhase 3
Effect and Safety of Flecainide and Metoprolol Versus Metoprolol Alone to Suppress Ventricular Arrhythmias in Arrhythmic Mitral Valve Prolapse
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RecruitingPhase 1
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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.

David J Goldberg, MD principal investigator

Children's Hospital of Philadelphia

Kurt R Schumacher, MD principal investigator

University of Michigan Congenital Heart Center/C.S. Mott Children's Hospital

17 sites in 2 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 17 sites in 2 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 2 inclusion and 3 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 14 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States, 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 18 Sep 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?

Effect of Udenafil 87.5 mg BID Treatment on Liver Stiffness in Udenafil Continuation and Naive Groups After 52 Weeks, as Determined by Ultrasound Shear Wave Elastography (time frame: 52 weeks). The study lists 2 primary outcomes in all. 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 NCT03430583.

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 14 Oct 2025.