Effect of Carvedilol on Exercise Performance in Fontan Patients
Condition: Single Ventricle; Fontan
MeSH terms: Univentricular Heart
Intervention: Carvedilol; Placebo
Intervention description: Carvedilol will be given for 12 weeks and then an exercise test will be performed; Placebo will be given for 12 weeks and then an exercise test will be performed
Intervention MeSH terms: Carvedilol
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 26.0
Sex: All
Minimum age: 10 Years
Maximum age: 35 Years
Healthy volunteers: No

Summary:

      This study evaluates the effect of carvedilol in patients who have undergone a Fontan heart
      operation. All participants will receive carvedilol and placebo for 12 weeks. Exercise tests
      will be performed at the end of each 12 week period.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Informed consent of parent(s) or legal guardian; informed consent or assent of subject
             as applicable.

          2. Male or female children between the ages of 10 and 35 years with congenital heart
             disease that has been palliated with a Fontan circulation.

          3. Ability of perform a maximal exercise test as defined by a respiratory exchange ratio
             (RER) greater than 1.0 at the time of maximal exercise

        Exclusion Criteria:

          1. The use of beta blockers within 2 months of randomization

          2. Patients actively listed for transplantation at time of entry into the study or
             anticipated to undergo heart transplantation, interventional catheterization, or
             corrective cardiac surgery during the 7 months following entry into the study

          3. Sustained or symptomatic ventricular dysrhythmias uncontrolled by drug therapy or the
             use of an implantable defibrillator, and/or significant cardiac conduction defects,
             e.g., 2nd degree or 3rd degree AV block, or sick sinus syndrome, unless a functioning
             pacemaker is in place

          4. Uncorrected obstructive or severe regurgitant valve disease, nondilated
             cardiomyopathy, or significant systemic ventricular outflow obstruction

          5. Known renovascular hypertension or evidence of pulmonary hypertension (pulmonary
             vascular resistance > 6 Wood units) unresponsive to vasodilator agents such as oxygen,
             nitroprusside, or nitric oxide

          6. History or current clinical evidence of moderate-to-severe fixed obstructive pulmonary
             disease or severe reactive airway diseases (e.g., asthma) requiring hospitalization
             within the past 2 years or patient currently using long-term inhaled bronchodilators

          7. Renal, hepatic, gastrointestinal, or biliary disorder that could impair absorption,
             metabolism or excretion of orally administered medication

          8. Concurrent terminal illness or other severe disease (e.g., active neoplasm) or other
             significant laboratory value(s) which, in the opinion of the investigator, could
             preclude participation or survival

          9. Endocrine disorders such as primary aldosteronism, pheochromocytoma, hyper- or
             hypothyroidism, insulin-dependent diabetes mellitus

         10. Unwillingness or inability to cooperate, or for the parents or guardians to give
             consent, or for the child to give assent, or any condition of sufficient severity to
             impair cooperation in the study

         11. Pregnancy or possible pregnancy at time of randomization, or female of child bearing
             potential who are lactating, or sexually active and not taking adequate contraceptive
             precautions (e.g., intrauterine device or oral contraceptives for 3 months prior to
             entry into the study)

         12. Use of an investigational drug within 30 days of randomization, or within 5 half-lives
             of the investigational drug (the longer period will apply)

         13. History of drug sensitivity or allergic reaction to alpha-blockers or ß-blockers

         14. Use of any of the following medications within two weeks of randomization: MAO
             inhibitors, Calcium channel blockers, alpha blockers, beta blockers, disopyramide,
             flecainide, encainide, moricizine, propafenone, sotalol, or beta adrenergic agonists

         15. Hospital admission for protein losing enteropathy or plastic bronchitis within 3
             months of randomization

         16. Active and/or chronic protein losing enteropathy or plastic bronchitis (on inhaled
             medication to control the plastic bronchitis).

         17. Hypoalbuminemia defined as serum albumin <2.0g/dL

         18. Renal dysfunction defined as serum creatinine >2.0mg/dL

         19. Hepatic dysfunction defined as serum AST and/or ALT> 3 times upper limit of normal
             (approximately 120 IU/L however, will vary depending on age),

         20. Significant anemia or polycythemia defined as hemoglobin >18gm/dL or hemoglobin
             <7gm/dL

         21. Severely elevated serum BNP defined as BNP>300pg/ml