Results of the FUEL Trial-Reference-Cited by-同舟云学术

Results of the FUEL Trial

Published:2020-02-25 Issue:8 Volume:141 Page:641-651
ISSN:0009-7322
Container-title:Circulation
language:en
Short-container-title:Circulation

Author:

Goldberg David J.¹,Zak Victor²,Goldstein Bryan H.³,Schumacher Kurt R.⁴,Rhodes Jonathan⁵,Penny Daniel J.⁶,Petit Christopher J.⁷,Ginde Salil⁸,Menon Shaji C.⁹,Kim Seong-Ho¹⁰,Kim Gi Beom¹¹,Nowlen Todd T.¹²,DiMaria Michael V.¹³,Frischhertz Benjamin P.¹⁴,Wagner Jonathan B.¹⁵,McHugh Kimberly E.¹⁶,McCrindle Brian W.¹⁷,Shillingford Amanda J.¹⁸,Sabati Arash A.¹⁹,Yetman Anji T.²⁰,John Anitha S.²¹,Richmond Marc E.²²,Files Matthew D.²³,Payne R. Mark²⁴,Mackie Andrew S.²⁵,Davis Christopher K.²⁶,Shahanavaz Shabana²⁷,Hill Kevin D.²⁸,Garg Ruchira²⁹,Jacobs Jeffrey P.³⁰,Hamstra Michelle S.³,Woyciechowski Stacy¹,Rathge Kathleen A.³,McBride Michael G.¹,Frommelt Peter C.⁸,Russell Mark W.⁴,Urbina Elaine M.³,Yeager James L.³¹,Pemberton Victoria L.³²,Stylianou Mario P.³²,Pearson Gail D.³²,Paridon Stephen M.¹,

Affiliation:

1. Division of Cardiology, The Children’s Hospital of Philadelphia, Perelman School of Medicine, PA (D.J.G., S.W., M.G.M., S.M.P.).

2. New England Research Institutes, Watertown, MA (V.Z.).

3. Division of Cardiology, Cincinnati Children’s Hospital Medical Center, OH (B.H.G., M.S.H., K.A.R., E.M.U.).

4. Division of Cardiology, C.S. Mott Children’s Hospital, Ann Arbor, MI (K.R.S., M.W.R.).

5. Department of Cardiology, Children’s Hospital Boston, MA (J.R.).

6. Division of Cardiology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX (D.J.P.).

7. Emory University School of Medicine, Children’s Healthcare of Atlanta, GA (C.J.P.).

8. Division of Cardiology, Medical College of Wisconsin, Children’s Hospital of Wisconsin, Milwaukee (S.G., P.C.F.).

9. Division of Pediatric Cardiology, University of Utah, Salt Lake City (S.C.M.).

10. Department of Pediatrics, Sejong General Hospital, Bucheon-Si, South Korea (S.-H.K.).

11. Seoul National University School of Medicine, Seoul National University Children’s Hospital, South Korea (G.B.K.).

12. Heart Center, Phoenix Children’s Hospital, AZ (T.T.N.).

13. Department of Pediatrics, Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora (M.V.D.).

14. Division of Cardiology, Vanderbilt University School of Medicine, Nashville, TN (B.P.F.).

15. Divisions of Cardiology and Clinical Pharmacology, Children’s Mercy Kansas City, MO (J.B.W.).

16. Division of Pediatric Cardiology, Medical University of South Carolina, Charleston (K.E.M.).

17. Division of Cardiology, The Hospital for Sick Children, University of Toronto, Ontario (B.W.M.).

18. Nemours Cardiac Center, Nemours/Alfred I. DuPont Hospital for Children, Wilmington, DE (A.J.S.).

19. Los Angeles Children’s Hospital, Division of Cardiology, CA (A.A.S.).

20. Children’s Hospital and Medical Center, University of Nebraska, Omaha (A.T.Y.).

21. Division of Cardiology, Children’s National Health System, Washington, DC (A.S.J.).

22. Division of Pediatric Cardiology, Morgan Stanley Children’s Hospital, Columbia University Medical Center, New York, NY (M.E.R.).

23. Division of Cardiology, Seattle Children’s Hospital, WA (M.D.F.).

24. Division of Cardiology, Riley Hospital for Children, Indianapolis, IN (R.M.P.).

25. Division of Cardiology, Stollery Children’s Hospital, Edmonton, Alberta, Canada (A.S.M.).

26. Division of Cardiology, Rady Children’s Hospital, San Diego, CA (C.K.D.).

27. Division of Cardiology, St Louis Children’s Hospital, MO (S.S.).

28. Duke Children’s Pediatric and Congenital Heart Center, Durham, NC (K.D.H.).

29. Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA (R.G.).

30. Johns Hopkins All Children’s Hospital, Department of Surgery, St Petersburg, FL (J.P.J.).

31. Consultant to Mezzion Pharma Co Ltd, Mezzion Pharma Co Ltd, Seoul, South Korea (J.L.Y.).

32. Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (V.L.P., M.P.S., G.D.P.).

Abstract

Background: The Fontan operation creates a total cavopulmonary connection, a circulation in which the importance of pulmonary vascular resistance is magnified. Over time, this circulation leads to deterioration of cardiovascular efficiency associated with a decline in exercise performance. Rigorous clinical trials aimed at improving physiology and guiding pharmacotherapy are lacking. Methods: The FUEL trial (Fontan Udenafil Exercise Longitudinal) was a phase III clinical trial conducted at 30 centers. Participants were randomly assigned udenafil, 87.5 mg twice daily, or placebo in a 1:1 ratio. The primary outcome was the between-group difference in change in oxygen consumption at peak exercise. Secondary outcomes included between-group differences in changes in submaximal exercise at the ventilatory anaerobic threshold, the myocardial performance index, the natural log of the reactive hyperemia index, and serum brain-type natriuretic peptide. Results: Between 2017 and 2019, 30 clinical sites in North America and the Republic of Korea randomly assigned 400 participants with Fontan physiology. The mean age at randomization was 15.5±2 years; 60% of participants were male, and 81% were white. All 400 participants were included in the primary analysis with imputation of the 26-week end point for 21 participants with missing data (11 randomly assigned to udenafil and 10 to placebo). Among randomly assigned participants, peak oxygen consumption increased by 44±245 mL/min (2.8%) in the udenafil group and declined by 3.7±228 mL/min (–0.2%) in the placebo group ( P =0.071). Analysis at ventilatory anaerobic threshold demonstrated improvements in the udenafil group versus the placebo group in oxygen consumption (+33±185 [3.2%] versus –9±193 [–0.9%] mL/min, P =0.012), ventilatory equivalents of carbon dioxide (–0.8 versus –0.06, P =0.014), and work rate (+3.8 versus +0.34 W, P =0.021). There was no an improvement in myocardial performance index (–0.02 vs 0.01, P =0.030), but no change in reactive hyperemia index, or serum brain-type natriuretic peptide level. Conclusions: In the FUEL trial, treatment with udenafil (87.5 mg twice daily) was not associated with an improvement in oxygen consumption at peak exercise but was associated with improvements in multiple measures of exercise performance at the ventilatory anaerobic threshold. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02741115.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

Reference45 articles.

1. Surgical repair of tricuspid atresia

2. An operation for the correction of tricuspid atresia

3. Failure of the Fontan Circulation

4. Hemodynamics of Fontan Failure

5. The Fontan circulation: who controls cardiac output?

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