Effect of Carvedilol on Exercise Performance in Fontan Patients

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.

Study Overview

• Status: Completed
• Conditions: Single Ventricle; Fontan
• Intervention / Treatment: Drug: Carvedilol; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 35 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Carvedilol; Study participants will receive carvedilol for 12 weeks	Drug: Carvedilol; Carvedilol will be given for 12 weeks and then an exercise test will be performed; Other Names: Coreg
EXPERIMENTAL: Placebo; Study participants will receive placebo (sugar pill) for 12 weeks	Drug: Placebo; Placebo will be given for 12 weeks and then an exercise test will be performed; Other Names: Carvedilol Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Peak Oxygen Uptake From Baseline Peak Oxygen Uptake	during exercise test on week 12 and week 30	on week 12 and week 30 of the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Peak Heart Rate	during exercise test on week 12 and week 30	on week 12 and week 30 of the study
Change in Oxygen Uptake at Anaerobic Threshold	during exercise test on week 12 and week 30	on week 12 and week 30 of the study

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: American Heart Association

Publications and helpful links

General Publications

• Butts R, Atz AM, BaezHernandez N, Sutcliffe D, Reisch J, Mahony L. Carvedilol Does Not Improve Exercise Performance in Fontan Patients: Results of a Crossover Trial. Pediatr Cardiol. 2021 Apr;42(4):934-941. doi: 10.1007/s00246-021-02565-6. Epub 2021 Feb 14.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2016
• Primary Completion (ACTUAL): December 1, 2019
• Study Completion (ACTUAL): January 1, 2020

Study Registration Dates

• First Submitted: September 23, 2016
• First Submitted That Met QC Criteria: October 25, 2016
• First Posted (ESTIMATE): October 27, 2016

Study Record Updates

• Last Update Posted (ACTUAL): January 22, 2021
• Last Update Submitted That Met QC Criteria: January 11, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Heart Defects, Congenital; Cardiovascular Abnormalities; Univentricular Heart; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Protective Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Antioxidants; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Carvedilol
• Other Study ID Numbers: 062016-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO