Fontan Udenafil Exercise Longitudinal Assessment Trial

NCT02741115 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: PHN-Udenafil-02U01HL068270
• Study Type: interventional
• Target: 400
• Locations: 3 countries
• Sites: 30

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 subjects who have undergone the Fontan procedure.

Conditions

Single Ventricle Heart Disease

Keywords

Fontan; Maximal Oxygen Consumption; Vascular Function; EndoPAT; Myocardial Performance

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline to 26 Weeks

Secondary Outcomes (22)

• Change in Myocardial Performance Index (MPI) From Baseline to Week 26

  Week 26

• Change in Log-transformed Reactive Hyperemia Index (InRH) From Baseline to Week 26

  Week 26

• Change in Serum Brain-type Natriuretic Peptide (BNP) From Baseline to Week 26.

  Week 26

• Change in VO2 at VAT

  26 Weeks

• Change in Work Rate at VAT From Baseline to Week 26 With LOCF

  26 Weeks

Study Arms (2)

Drug

EXPERIMENTAL

Udenafil. One tablet twice daily for 26 weeks

Drug: Udenafil

Placebo

EXPERIMENTAL

Placebo. One tablet twice daily for 26 weeks

Drug: Placebo

Interventions

Udenafil DRUG

Active drug

Drug

Placebo DRUG

Matching Placebo

Placebo

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Mezzion Pharma Co. Ltd: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (30)

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

Phoenix, Arizona, 85016, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Cedars/Sinai Heart Institute

Los Angeles, California, 90048, United States

Location

Rady Children's Hospital

San Diego, California, 92123, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Nemours Cardiac Center/Alfred I. duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20008, United States

Location

Johns Hopkins All Children's Heart Institute

St. Petersburg, Florida, 33701, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

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

Indianapolis, Indiana, 46201, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

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

Ann Arbor, Michigan, 48109-4204, United States

Location

Children's Mercy Hospital Kansas City

Kansas City, Missouri, 64108, United States

Location

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

St Louis, Missouri, 63110, United States

Location

University of Nebraska Children's Hospital and Medical Center

Omaha, Nebraska, 68114, United States

Location

Children's Hospital of New York

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hosptial

Columbus, Ohio, 43205, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

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

Salt Lake City, Utah, 84113, United States

Location

Seattle Children's Hosptial

Seattle, Washington, 98105, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Stollery Children's Hospital - University of Alberta

Edmonton, Alberta, T6G 2B7, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, ON M5G 1X8, Canada

Location

Sejong General Hospital

Bucheon-si, Gyeonggi-do, 14754, South Korea

Location

Seoul National University Children's Hospital

Seoul, 110-744, South Korea

Location

Related Publications (3)

• 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.

  PMID: 36378780 DERIVED

• 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.

  PMID: 31736357 DERIVED

• 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.

  PMID: 29910047 DERIVED

MeSH Terms

Interventions

udenafil

Results Point of Contact

• Title: Director of Clinical Trials
• Organization: Mezzion Pharmaceuticals, Inc

kelly.williams@mezzion.com

5734342579

Study Officials

• Steve Paridon, MD

  Children's Hospital of Phildelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2016
• First Posted: April 18, 2016
• Study Start: July 22, 2016
• Primary Completion: December 27, 2018
• Study Completion: April 30, 2019
• Last Updated: June 17, 2025
• Results First Posted: May 21, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); KR (2); US (26)