(Completed Recruiting)

About This Study

In the FUEL study, we will learn whether taking a medication called udenafil or taking a placebo for 6 months helps improve heart function in children who had a Fontan operation. After taking the medication for 6 months, participants will be invited to join the FUEL OLE study and take udenafil (no placebo) for an additional 12 months. In FALD, we will study how the liver is affected by taking udenafil. In FUEL PERCEPTIONS, participants and their families are invited to complete a questionnaire about their experiences being in the FUEL studies.

Study Locations

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The Fontan operation has been a wonderful success for children born with congenital heart disease, yet it is not a cure. Within decades after the Fontan operation, individuals can develop many health issues including a decline in cardiovascular function and progressive liver disease that can result in liver failure. Udenafil is a medication that might be useful for adolescents who have had the Fontan operation. Through FUEL, FUEL-OLE, FALD, and FUEL Perceptions, we will learn more about the possible benefit of Udenafil for those who have had the Fontan operation.

Over time it becomes harder for children and young adults who have had a Fontan operation to exercise. Currently, there are no approved medications that have proven helpful in preventing this decline. However, results from several small studies (including the PHN Udenafil study) have shown that a medicine like udenafil (a phosphodiesterase type 5 [PDE5] inhibitor), may help children who have had Fontan surgery to exercise better. The drug works by making it easier for blood to flow through the lungs and back to the heart. The drug may also improve other parts of the circulation including function of the blood vessels to key organs like the liver and heart.

FALD stands for Fontan-associated liver disease. Every person who has had a Fontan operation develops scarring in their liver over time. This scarring can eventually result in liver cirrhosis or liver failure. We believe that congestion of the blood vessels in the liver is part of the cause of this scarring. Udenafil may decrease the congestion in the blood vessels and slow progression of the liver disease.

Male or females ages 12 to 18 who had Fontan surgery.

The study will be explained to you in detail by one of the study investigators. Once your questions have been answered, you will be asked to sign an informed consent form/Assent form to enter the study.

In the FUEL study, each individual will be randomly given either udenafil or placebo pills that they will take twice a day, every day for six months. We will also obtain blood, physical measurements, measurements of blood vessel function (EndoPAT), echocardiograms and ECGs, and exercise function tests at the beginning and end of the study. Some individuals in the study will also have their heart rhythm monitored before starting the study and again a few weeks after starting the study.

In the FUEL OLE study, each individual will take udenafil pills twice a day, every day, for one year. We will also obtain blood, physical measurements, measurements of vascular function (EndoPAT), echocardiograms and ECGs, and exercise function tests at the beginning and end of the study. If you were enrolled in the FUEL study and you are joining the FUEL OLE study, you will not have to repeat any of the assessments that were done at the end of the FUEL study for the beginning of the FUEL OLE study.

In both studies, we will also collect questionnaires about your quality of life.

In the FALD study, participants in FUEL OLE are asked to have an ultrasound and an MRI (if available at your center) of the liver at the first and last visit.

In FUEL Perceptions, participants in the FUEL and FUEL OLE studies and their parents are invited to complete a single questionnaire about their experiences in the studies.

You will be in the FUEL study for six months.
You will be in the FUEL OLE study for one year.
You will be in the FALD study at the same time at FUEL OLE, for one year.
You will be in the FUEL Perceptions study until you finish the questionnaires for FUEL and FUEL OLE. Both questionnaires will be done at the last study visit for each study.

It is possible that your child’s ability to exercise will improve while taking udenafil. However, your child may not benefit from taking part in this research study. The information we learn from this study may help improve the care of other children.

  • As with any drug, an allergic reaction can occur.
  • Udenafil has been studied in a limited number of children with Fontan physiology. In general, the side effects were mild to moderate and temporary. The most common side effect is flushing of the cheeks. Less common side effects include headache, stomach discomfort, nausea or stuffy nose. Other mild and rare side effects include hives or itchiness, fatigue, numbness or tingling, thirst, unusual tear production and toothache. A severe but rare side effect is changing in hearing or vision.
  • There are restrictions for some medications while your child is in the study. The study doctor and a member of the research team will review your child’s medication history throughout study participation.
  • The effect of udenafil on an embryo or fetus (developing baby still in the womb) is unknown and may be harmful. Because of these unknown risks, women cannot take part in this study if they are pregnant or trying to become pregnant.
  • Risks associated with drawing blood from a vein include momentary discomfort and/or bruising. Applying a numbing cream to the skin may be helpful in to lessen the discomfort of a blood draw.
  • There are no risks associated with physical examination.
  • The blood pressure cuff used during the EndoPAT vascular function test will cause a squeezing sensation in the arm, which can cause mild pain, numbness and/or tingling.
  • Some minor skin irritation may occur from the sticky patches placed on the chest for the echocardiogram and ECG. There may be some mild discomfort related to the pressure of the probe used in the echocardiogram.
  • The exercise testing is part of the routine care of children and young adults who have had Fontan surgery. Participants are monitored throughout the test by a pediatric cardiologist who will stop the test if he or she feels it is not safe to continue.
  • There may be risks to being in this study that we don’t know about now.

There will be no extra costs to you when you join this study. You must pay for all other costs related to your normal medical care such as hospital stays, surgery, drugs, lab tests, and doctor’s fees which are thought to be standard medical care for patients with your condition.