Effect of Carvedilol on Exercise Performance in Fontan Patients

• ClinicalTrials.gov Identifier: NCT02946892
• Recruitment Status: Completed
• First Posted: October 27, 2016
• Results First Posted: January 22, 2021
• Last Update Posted: January 22, 2021
• Sponsor: University of Texas Southwestern Medical Center
• Collaborator: American Heart Association
• Information provided by (Responsible Party): Ryan Butts, University of Texas Southwestern Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Single Ventricle; Fontan	Drug: Carvedilol; Drug: Placebo	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect of Carvedilol on Exercise Performance in Fontan Patients
• Actual Study Start Date: November 2016
• Actual Primary Completion Date: December 2019
• Actual Study Completion Date: January 2020

Arms and Interventions

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 Name: 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 Name: Carvedilol Placebo

Outcome Measures

Primary Outcome Measures :

1. Change in Peak Oxygen Uptake From Baseline Peak Oxygen Uptake [ Time Frame: on week 12 and week 30 of the study ]
   during exercise test on week 12 and week 30

Secondary Outcome Measures :

1. Change in Peak Heart Rate [ Time Frame: on week 12 and week 30 of the study ]
   during exercise test on week 12 and week 30
2. Change in Oxygen Uptake at Anaerobic Threshold [ Time Frame: on week 12 and week 30 of the study ]
   during exercise test on week 12 and week 30

Eligibility Criteria

• Ages Eligible for Study: 10 Years to 35 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Texas

University of Texas Southwestern

Dallas, Texas, United States, 75390

Sponsors and Collaborators

University of Texas Southwestern Medical Center

American Heart Association

  Study Documents (Full-Text)

Documents provided by Ryan Butts, University of Texas Southwestern Medical Center:

Study Protocol and Statistical Analysis Plan  [PDF] March 2, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Ryan Butts, ASSOC PROFESSOR, PD-Cardiology, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT02946892
• Other Study ID Numbers: 062016-101
• First Posted: October 27, 2016
• Results First Posted: January 22, 2021
• Last Update Posted: January 22, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Univentricular Heart; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Carvedilol; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Antihypertensive Agents; Antioxidants; Protective Agents; Calcium Channel Blockers; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Vasodilator Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists