PHILADELPHIA, Nov. 17, 2019 /PRNewswire/ -- The
largest-ever clinical trial of a medication for pediatric
cardiology patients found that an oral drug significantly improved
exercise capacity in adolescent patients with severe, congenital
single ventricle heart defects. A study leader says the physiologic
benefits represent a milestone in the care of those who have
undergone the Fontan procedure, a palliative operation for
single-ventricle disease.
"Exercise capacity is a surrogate for morbidity and mortality
outcomes in children with single ventricle congenital heart
disease. It is our hope that an improvement in exercise capacity
will translate into better long-term outcomes," said pediatric
cardiologist David J. Goldberg, MD,
of the Cardiac Center at Children's Hospital of Philadelphia (CHOP) and co-principal
investigator of the multicenter Fontan Udenafil Exercise
Longitudinal Assessment Trial (FUEL). The principal investigator of
the trial, also from CHOP's Cardiac Center, was Stephen Paridon, MD.
Goldberg reported the FUEL Trial results today at the 2019
Scientific Sessions of the American Heart Association in
Philadelphia and was the lead
author of an article published concurrently in the journal
Circulation.
The Phase 3 randomized, double-blind, placebo-controlled
clinical trial, sponsored by Mezzion Pharma Co., Ltd., enrolled 400
male and female participants aged 12 to 18 years old from 30
centers in the United States,
Canada and South Korea within the Pediatric Heart
Network. "This study of udenafil provides the first evidence
of clinical benefit for a medication in this unique population of
children with single-ventricle heart disease," said Goldberg.
Patients born with single-ventricle heart defects have a
severely underdeveloped pumping chamber in their hearts. A series
of complex childhood surgeries culminating in the Fontan procedure
has greatly improved survival of patients with single-ventricle
disease. However, the surgical corrections do not provide normal
blood circulation, and survivors have low cardiac output and
long-term complications. Among those complications is exercise
intolerance, associated with increased morbidity and mortality.
The researchers reported that participants in the FUEL trial had
statistically significant improvements in oxygen consumption and
other measures of exercise capacity during moderate levels of
activity. There was also a numeric improvement in oxygen
consumption at peak exercise, although this did not achieve
statistical significance. "These benefits in exercise capacity
reflect better circulatory function, and should correlate with
better long-term circulatory health for patients who have undergone
the Fontan procedure," said Goldberg.
The patients who took udenafil tolerated the treatment well,
with side effects limited to those previously known from
phosphodiesterase type 5 inhibitors, more commonly including
headache, facial flushing, abdominal pain, nosebleed and erection
(among males).
A related trial, the FUEL Open-Label Extension (FUEL OLE) Trial
is currently proceeding, with the goal of measuring treatment
tolerability and safety over a longer period for this patient
population. In the meantime, added Goldberg, "For the many patients
with heart disease worldwide now living with Fontan physiology,
these trial results represent a big step in the right
direction."
In addition to sponsorship by Mezzion, other support came from
the National Heart, Lung and Blood Institute of the National
Institutes of Health (grant HL068270).
In addition to their CHOP titles, Goldberg and Paridon are on
the faculty of Perelman School of Medicine at the University of Pennsylvania and among the
co-inventors of patent US10137128B2.
Disclosure: Drs. Goldberg and Paridon both receive grant
support from Mezzion and are co-inventors of patent
US10137128B2 which is for the use of Udenafil in Fontan physiology.
CHOP holds these patent rights in conjunction with Mezzion.
David Goldberg et al, "Results of
the Fontan Udenafil Exercise Longitudinal (FUEL) Trial,"
Circulation, published Nov. 17,
2019. https://doi.org/10.1161/CIRCULATIONAHA.119.044352
About Children's Hospital of Philadelphia: Children's Hospital of
Philadelphia was founded in 1855
as the nation's first pediatric hospital. Through its long-standing
commitment to providing exceptional patient care, training new
generations of pediatric healthcare professionals, and pioneering
major research initiatives, Children's Hospital has fostered many
discoveries that have benefited children worldwide. Its
pediatric research program is among the largest in the
country. In addition, its unique family-centered care and
public service programs have brought the 564-bed hospital
recognition as a leading advocate for children and adolescents. For
more information, visit http://www.chop.edu
Contact: Natalie Solimeo
Children's Hospital of Philadelphia
Cell: (856) 261-8090
Solimeon@email.chop.edu
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SOURCE Children's Hospital of Philadelphia