Teens with heart disease improve exercise capacity in large clinical trial

November 17, 2019

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."
-end-
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

Children's Hospital of Philadelphia

Related Clinical Trial Articles from Brightsurf:

Clinical trial investigates gabapentin for alcohol use disorder
This randomized clinical trial investigated if gabapentin, a drug often used to treat nerve pain, would be useful in the treatment of patients with alcohol use disorder (problem drinking that becomes severe) and a history of alcohol withdrawal symptoms.

Electrical stimulation helps treat constipation in clinical trial
Electrical stimulation benefited women with constipation in a recent clinical trial published in Alimentary Pharmacology & Therapeutics.

Treatment of migraine pain in randomized clinical trial
Adults experiencing a migraine of moderate or severe severity took the drug ubrogepant or placebo and reported if after two hours they were free of pain and of their most bothersome migraine-associated symptom in this randomized clinical trial.

First entirely digital clinical trial encourages physical activity
As little as a daily ping on your phone can boost physical activity, researchers from the Stanford University School of Medicine and their collaborators report in a new study.

HIV vaccine nears clinical trial following new findings
A promising vaccine that clears an HIV-like virus from monkeys is closer to human testing after a new, weakened version of the vaccine has been shown to provide similar protection as its original version.

Sickle cell drug showing promise in clinical trial
An investigational drug for the treatment of sickle cell disease is showing early promise in clinical trials for impacting biomarkers of the disease in patients, reported UConn School of Medicine researchers.

Meditation goes digital in new clinical trial
Scientists at UC San Francisco have developed a personalized digital meditation training program that significantly improved attention and memory in healthy young adults -- a group already at the peak of brain health -- in just six weeks.

Could blockchain ensure integrity of clinical trial data?
UC San Francisco researchers have created a proof-of-concept method for ensuring the integrity of clinical trials data with blockchain.

Eating crickets can be good for your gut, according to new clinical trial
A new clinical trial shows that consuming crickets can help support the growth of beneficial gut bacteria and that eating crickets is not only safe at high doses but may also reduce inflammation in the body.

Idera Pharmaceuticals presents clinical data from the ILLUMINATE-204 trial of the combination of tilsotolimod and ipilimumab for anti-PD-1 refractory metastatic melanoma at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting
Idera Pharmaceuticals Inc., a clinical-stage biopharmaceutical company developing toll-like receptor and RNA therapeutics for patients with rare cancers and rare diseases, announced results from the ongoing ILLUMINATE-204 trial investigating tilsotolimod, Idera's intratumorally-delivered Toll-like Receptor 9 agonist, in combination with ipilimumab (Yervoy®).

Read More: Clinical Trial News and Clinical Trial Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.