Sildenafil After the Fontan Operation

Brief Title

Sildenafil After the Fontan Operation

Official Title

The Sildenafil After Fontan Operation Study

Brief Summary

      In this study, the investigators will evaluate the effect of sildenafil on exercise tolerance
      in patients with a single cardiac ventricle who have undergone the Fontan operation. The
      investigators will also evaluate echocardiographic measures of ventricular function and
      measure quality of life changes using two validated quality of life measures. The hypothesis
      is that sildenafil will result in increased exercise tolerance in patients who have had the
      Fontan operation as compared to placebo.
    

Detailed Description

      The Fontan physiology is the end result of staged reconstruction of the heart and the major
      blood vessels in patients who have a single ventricle. After completion of the
      reconstruction, the great veins which usually bring blood back to the heart are connected
      directly to the pulmonary arteries, allowing blood from the body to bypass the heart and flow
      directly into the lungs. In this system, blood flow through the lungs is passive (not pumped)
      and the efficiency of flow through the cardiovascular system is related to the resistance to
      blood flow in the vessels of the lungs.

      There are two potential problems that arise in this scenario, as a result of the resistance
      to blood flow in the vessels of the lungs. First, the amount of blood flow returning to the
      heart from the lungs may not be sufficient to allow the heart to function at maximum
      efficiency, compromising the heart's ability to keep up with the demands of the body. Second,
      if the resistance to blood flow in the lungs is high, pressure may be transmitted back into
      the great veins themselves and secondarily into the organs of the body causing mild, or
      sometimes significant, organ dysfunction. Not all patients with the Fontan physiology develop
      these problems, but we know that even in patients without obvious problems, the ability to
      keep up with an increased metabolic demand, as during exercise, in compromised.

      Improving the efficiency of blood flow through the lungs should improve the return of blood
      to the heart and thereby diminish the pressure transmitted back to the vessels which
      passively deliver blood to the lungs. We believe that this change may manifest as diminished
      symptoms in those patients with known difficulties, or may allow for an increased ability to
      walk, run, or participate in sports in those without any overt symptoms. Most importantly, we
      speculate that improved efficiency of flow through the lungs, and the resulting improved
      cardiac output (blood flow through the body) will make patients more energetic and will make
      them feel better.

      Sildenafil is an oral medication that has been used to treat patients with pulmonary
      hypertension, a disease in which there is abnormally elevated pressure in the vessels of the
      lung. In this disease, the resistance in the lungs is abnormally high, severely limiting the
      ability of the heart to keep up with the demands of the body. Sildenafil lowers the
      resistance in the vessels of the lungs and has been shown to improve exercise performance in
      patients with this disease. We believe that Sildenafil may have a similar benefit for our
      patients after Fontan operation in whom cardiac output is also limited by resistance of the
      blood vessels in the lungs.

      In our study, we will compare the exercise capacity, echocardiographic measures of cardiac
      function, and the overall quality of life in patients with the Fontan before and after a
      six-week period of sildenafil administration. As a control, the same group of patients will
      take a placebo for a six-week period, also with before and after testing. We hypothesize that
      oral sildenafil will result in significant improvements in exercise capacity, energy levels,
      and echocardiographic measures of cardiac function and output in our study participants. We
      are hopeful that the findings of this investigation will directly help children and young
      adults with Fontan physiology.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Change From Baseline in Mean Oxygen Consumption (mL/kg/Min) at 6 Weeks

Secondary Outcome

 Change From Baseline in Mean Heart Rate (Bpm) at 6 Weeks

Condition

Hypoplastic Left Heart Syndrome

Intervention

Sildenafil

Study Arms / Comparison Groups

 Sildenafil, then Placebo
Description:  Sildenafil will be given at a dose of 20 mg three times-a-day for six weeks followed by a six week washout period followed by placebo for an additional six weeks.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

28

Start Date

December 2007

Completion Date

July 2009

Primary Completion Date

April 2009

Eligibility Criteria

        Inclusion Criteria:

          -  8 years of age or older

          -  All participants must have had Fontan completion

        Exclusion Criteria:

          -  Height less than 132 cm

          -  Unable to participate in exercise testing due to medical restrictions or physical
             limitations

          -  Fontan baffle obstruction or single lung physiology

          -  Coarctation of the aorta or neo-aorta (BP gradient > 20 mmHg)

          -  Severe ventricular dysfunction assessed qualitatively by echocardiography

          -  Severe atrioventricular valvar regurgitation assessed qualitatively by
             echocardiography

          -  Presence of electronic pacemaker

          -  History of treatment with sildenafil in the six weeks prior to enrollment in study

          -  Patients with severe renal impairment

          -  Patients with severe hepatic impairment

          -  Patients taking medications that inhibit or induce Cytochrome P450 3A4 (CYP3A4)
             (including grapefruit juice and St. John's Wort)

          -  Patients taking alpha-blockers and nitrates

          -  Parents/guardians or subjects who, in the opinion of the investigator, may be
             non-compliant with study schedules or procedures
      

Gender

All

Ages

8 Years - 40 Years

Accepts Healthy Volunteers

No

Contacts

Jack Rychik, MD, , 



Administrative Informations


NCT ID

NCT00507819

Organization ID

IRB 2007-4-5034


Responsible Party

Sponsor

Study Sponsor

Children's Hospital of Philadelphia

Collaborators

 The Mark H. and Blanche M. Harrington Foundation

Study Sponsor

Jack Rychik, MD, Principal Investigator, Children's Hospital of Philadelphia


Verification Date

May 2015