Fontan Udenafil Exercise Longitudinal Assessment Trial

NCT ID: NCT02741115

Last Updated: 2025-06-17

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-07-22

Study Completion Date

2019-04-30

Brief Summary

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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

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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

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Single Ventricle Heart Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Drug

Udenafil. One tablet twice daily for 26 weeks

Group Type EXPERIMENTAL

Udenafil

Intervention Type DRUG

Active drug

Placebo

Placebo. One tablet twice daily for 26 weeks

Group Type EXPERIMENTAL

Placebo

Intervention Type DRUG

Matching Placebo

Interventions

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Udenafil

Active drug

Intervention Type DRUG

Placebo

Matching Placebo

Intervention Type DRUG

Eligibility Criteria

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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

Exclusion Criteria

1. Weight \< 40 kg
2. Height \< 132 cm.
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. VO2 less than 50%
10. Severe ventricular dysfunction assessed qualitatively by clinical echocardiography within six months prior to enrollment.
11. Severe valvar regurgitation, ventricular outflow obstruction, or aortic arch obstruction assessed by clinical echocardiography within six months prior to enrollment.
12. 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.
13. Inability to complete exercise testing at baseline screening.
14. History of PDE-5 inhibitor use within 3 months before study onset.
15. History of any other medication for treatment of pulmonary hypertension within 3 months before study onset.
16. Known intolerance to oral udenafil.
17. Frequent use of medications or other substances that inhibit or induce CYP3A4.
18. Current use of alpha-blockers or nitrates.
19. Ongoing or planned participation in another research protocol that would either prevent successful completion of planned study testing or invalidate its results.
20. Noncardiac medical, psychiatric, and/or social disorder that would prevent successful completion of planned study testing or would invalidate its results.
21. Cardiac care, ongoing or planned, at a non-study center that would impede study completion.
22. 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.
23. Unable to abstain or limit intake of grapefruit juice during the duration of the trial.
24. Refusal to provide written informed consent/assent.
25. In the opinion of the primary care physician, the subject is likely to be non-compliant with the study protocol.
Minimum Eligible Age

12 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Mezzion Pharma Co. Ltd

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Steve Paridon, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Phildelphia

Locations

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Phoenix Children's Hospital/Children's Heart Center at Phoenix Children's Hospital

Phoenix, Arizona, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Cedars/Sinai Heart Institute

Los Angeles, California, United States

Site Status

Rady Children's Hospital

San Diego, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Nemours Cardiac Center/Alfred I. duPont Hospital for Children

Wilmington, Delaware, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Johns Hopkins All Children's Heart Institute

St. Petersburg, Florida, United States

Site Status

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Site Status

Riley Hospital for Children/Herman B. Wells Center for Pediatric Research

Indianapolis, Indiana, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

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

Ann Arbor, Michigan, United States

Site Status

Children's Mercy Hospital Kansas City

Kansas City, Missouri, United States

Site Status

Washington University St. Louis/St.Louis Children's Hospital

St Louis, Missouri, United States

Site Status

University of Nebraska Children's Hospital and Medical Center

Omaha, Nebraska, United States

Site Status

Children's Hospital of New York

New York, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Nationwide Children's Hosptial

Columbus, Ohio, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Texas Children's Hospital

Houston, Texas, United States

Site Status

Primary Children's Medical Hospital/Dept. of Pediatric Cardiology

Salt Lake City, Utah, United States

Site Status

Seattle Children's Hosptial

Seattle, Washington, United States

Site Status

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Stollery Children's Hospital - University of Alberta

Edmonton, Alberta, Canada

Site Status

The Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Sejong General Hospital

Bucheon-si, Gyeonggi-do, South Korea

Site Status

Seoul National University Children's Hospital

Seoul, , South Korea

Site Status

Countries

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United States Canada South Korea

References

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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.

Reference Type DERIVED
PMID: 36378780 (View on PubMed)

Goldberg 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.

Reference Type DERIVED
PMID: 31736357 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29910047 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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U01HL068270

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PHN-Udenafil-02

Identifier Type: -

Identifier Source: org_study_id

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