Fontan Udenafil Exercise Longitudinal – FUEL/OLE (Udenafil vs Placebo Trial & Open Label Extension)

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 in the body and the heart itself. 

Udenafil has been approved in several countries to treat erectile dysfunction in adult men. It has not yet been approved by the United States (U.S.) Food and Drug Administration (FDA) or Health Canada for use in North America. This means that Udenafil can only be used in research studies. 

In the FUEL study, we will learn about the possible benefit of Udenafil in children who have had a Fontan operation over a 6 month treatment period. 

In the FUEL OLE study, we will ask the same individuals who participated in the FUEL study to take Udenafil for an additional 12 months, to learn more about the possible benefit of Udenafil in these children.

Who can be in the study?

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

What do we have to do to be in the study?

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 vascular 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.

How long will we be in the study?

You will be in the FUEL study for six months.
You will be in the FUEL OLE study for one year.

What are the possible benefits to being in this 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.

What are the possible risks to being in this study?

  • 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. Infection, excess bleeding, clotting, and fainting are also possible, although very unlikely. 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.
  • Your child may experience minor skin irritation from the sticky patches placed on his or her chest for the echocardiogram and ECG. He or she may also experience 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. Your child may feel uncomfortable during the test, and if this occurs your child may stop the test. Your child will be monitored throughout the test by a pediatric cardiologist who will stop the test if he or she feels it is not safe for your child to continue.
  • There may be risks to being in this study that we don't know about now.

What are the costs to me to be in the study? 

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.