Faculty Collaboration Database

Design and rationale of the Fontan Udenafil Exercise Longitudinal (FUEL) trial. Am Heart J 2018 Jul;201:1-8

Date

06/19/2018

Pubmed ID

29910047

Pubmed Central ID

PMC6010060

DOI

10.1016/j.ahj.2018.03.015

Scopus ID

2-s2.0-85046490446 (requires institutional sign-in at Scopus site)   22 Citations

Abstract

The Fontan operation creates a circulation characterized by elevated central venous pressure and low cardiac output. Over time, these characteristics result in a predictable and persistent decline in exercise performance that is associated with an increase in morbidity and mortality. A medical therapy that targets the abnormalities of the Fontan circulation might, therefore, be associated with improved outcomes. Udenafil, a phosphodiesterase type 5 inhibitor, has undergone phase I/II testing in adolescents who have had the Fontan operation and has been shown to be safe and well tolerated in the short term. However, there are no data regarding the long-term efficacy of udenafil in this population. The Fontan Udenafil Exercise Longitudinal (FUEL) Trial is a randomized, double-blind, placebo-controlled phase III clinical trial being conducted by the Pediatric Heart Network in collaboration with Mezzion Pharma Co, Ltd. This trial is designed to test the hypothesis that treatment with udenafil will lead to an improvement in exercise capacity in adolescents who have undergone the Fontan operation. A safety extension trial, the FUEL Open-Label Extension Trial (FUEL OLE), offers the opportunity for all FUEL subjects to obtain open-label udenafil for an additional 12 months following completion of FUEL, and evaluates the long-term safety and tolerability of this medication. This manuscript describes the rationale and study design for FUEL and FUEL OLE. Together, these trials provide an opportunity to better understand the role of medical management in the care of those who have undergone the Fontan operation.

Author List

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

Author

Peter C. Frommelt MD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Exercise
Exercise Therapy
Fontan Procedure
Heart Defects, Congenital
Humans
Longitudinal Studies
Phosphodiesterase 5 Inhibitors
Postoperative Care
Pyrimidines
Randomized Controlled Trials as Topic
Sulfonamides