Fontan, Single Ventricle
Conditions
Brief 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.
Detailed description
Carvedilol is a well studied heart failure medication in adult heart failure that has been shown to improve outcomes. However, it has not been studied in patients who have had a Fontan heart operation. Study participants will receive either placebo or carvedilol for 12 weeks, at the end of the 12 weeks participants will perform an exercise test. Then study participants will receive treatment with placebo or carvedilol for 12 weeks (opposite of what participants go the first 12 weeks) and will again perform an exercise test.
Interventions
DRUGCarvedilol
Carvedilol will be given for 12 weeks and then an exercise test will be performed
DRUGPlacebo
Placebo will be given for 12 weeks and then an exercise test will be performed
Sponsors
American Heart Association
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
10 Years to 35 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Peak Oxygen Uptake From Baseline Peak Oxygen Uptake | on week 12 and week 30 of the study | during exercise test on week 12 and week 30 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Peak Heart Rate | on week 12 and week 30 of the study | during exercise test on week 12 and week 30 |
| Change in Oxygen Uptake at Anaerobic Threshold | on week 12 and week 30 of the study | during exercise test on week 12 and week 30 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Since All Participants Would Be Randomized to Both Interventions, all Patients were Analyzed | 23 |
| Total | 23 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 14.9 years STANDARD_DEVIATION 2.8 |
| Race/Ethnicity, Customized Caucasian | 18 Participants |
| Race/Ethnicity, Customized Non-Caucasian | 5 Participants |
| Region of Enrollment United States | 23 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 24 |
| other Total, other adverse events | 4 / 25 | 0 / 24 |
| serious Total, serious adverse events | 0 / 25 | 0 / 24 |
Outcome results
Primary
Change in Peak Oxygen Uptake From Baseline Peak Oxygen Uptake
during exercise test on week 12 and week 30
Time frame: on week 12 and week 30 of the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carvedilol | Change in Peak Oxygen Uptake From Baseline Peak Oxygen Uptake | -2.01 ml/kg/min | Standard Deviation 3.57 |
| Placebo | Change in Peak Oxygen Uptake From Baseline Peak Oxygen Uptake | -1.01 ml/kg/min | Standard Deviation 3.36 |
Secondary
Change in Oxygen Uptake at Anaerobic Threshold
during exercise test on week 12 and week 30
Time frame: on week 12 and week 30 of the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carvedilol | Change in Oxygen Uptake at Anaerobic Threshold | -1.02 ml/kg/min | Standard Deviation 3.75 |
| Placebo | Change in Oxygen Uptake at Anaerobic Threshold | -1.78 ml/kg/min | Standard Deviation 4.55 |
Secondary
Change in Peak Heart Rate
during exercise test on week 12 and week 30
Time frame: on week 12 and week 30 of the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carvedilol | Change in Peak Heart Rate | -32.3 beats per minute | Standard Deviation 24.2 |
| Placebo | Change in Peak Heart Rate | 1.9 beats per minute | Standard Deviation 12.6 |