Effect of Carvedilol on Exercise Performance in Fontan Patients

• Sponsor: University of Texas Southwestern Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02946892
• Collaborator: American Heart Association (Other)
• Enrollment: 26
• Location: 1
• Arms: 2
• Actual Duration (Months): 38
• Patients Per Site Per Month: 0.7

Study Details

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
• 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: Nov 1, 2016
• Actual Primary Completion Date: Dec 1, 2019
• Actual Study Completion Date: Jan 1, 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 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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Change in Peak Heart Rate [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 [on week 12 and week 30 of the study]

   during exercise test on week 12 and week 30

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 35 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas Southwestern	Dallas	Texas	United States	75390

Sponsors and Collaborators

• University of Texas Southwestern Medical Center
• American Heart Association

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 2, 2018

More Information

Publications

None provided.

• 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: Oct 27, 2016
• Last Update Posted: Jan 22, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Univentricular Heart; Carvedilol

Study Results

Participant Flow

Arm/Group Title	Carvedilol First, Then Placebo	Placebo First, Then Carvedilol
Arm/Group Description	Study participants will receive carvedilol for 12 weeks, washout for 6 weeks, then placebo for 12 weeks	Study participants will receive placebo (sugar pill) for 12 weeks, then washout for 6 weeks, then carvedilol for 12 weeks
Period Title: First Intervention (12 Weeks)
STARTED	11	15
COMPLETED	11	14
NOT COMPLETED	0	1
Period Title: First Intervention (12 Weeks)
STARTED	11	14
COMPLETED	9	14
NOT COMPLETED	2	0
Period Title: First Intervention (12 Weeks)
STARTED	9	14
COMPLETED	9	14
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Since All Participants Would Be Randomized to Both Interventions, all Patients were Analyzed
Overall Participants	23
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.9 (2.8)
Sex: Female, Male (Count of Participants)
Female	6 26.1%
Male	17 73.9%
Race/Ethnicity, Customized (Count of Participants)
Non-Caucasian	5 21.7%
Caucasian	18 78.3%
Region of Enrollment (participants) [Number]
United States	23 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Carvedilol	Placebo
Arm/Group Description	Study participants will receive carvedilol for 12 weeks Carvedilol: Carvedilol will be given for 12 weeks and then an exercise test will be performed	Study participants will receive placebo (sugar pill) for 12 weeks Placebo: Placebo will be given for 12 weeks and then an exercise test will be performed
Measure Participants	23	23
Mean (Standard Deviation) [ml/kg/min]	-2.01 (3.57)	-1.01 (3.36)

2. Secondary Outcome

Title	Change in Peak Heart Rate
Description	during exercise test on week 12 and week 30
Time Frame	on week 12 and week 30 of the study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Carvedilol	Placebo
Arm/Group Description	Study participants will receive carvedilol for 12 weeks Carvedilol: Carvedilol will be given for 12 weeks and then an exercise test will be performed	Study participants will receive placebo (sugar pill) for 12 weeks Placebo: Placebo will be given for 12 weeks and then an exercise test will be performed
Measure Participants	23	23
Mean (Standard Deviation) [beats per minute]	-32.3 (24.2)	1.9 (12.6)

3. Secondary Outcome

Title	Change in Oxygen Uptake at Anaerobic Threshold
Description	during exercise test on week 12 and week 30
Time Frame	on week 12 and week 30 of the study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Carvedilol	Placebo
Arm/Group Description	Study participants will receive carvedilol for 12 weeks Carvedilol: Carvedilol will be given for 12 weeks and then an exercise test will be performed	Study participants will receive placebo (sugar pill) for 12 weeks Placebo: Placebo will be given for 12 weeks and then an exercise test will be performed
Measure Participants	23	23
Mean (Standard Deviation) [ml/kg/min]	-1.02 (3.75)	-1.78 (4.55)

Adverse Events

Time Frame	36 weeks
Adverse Event Reporting Description	AE were classified as serious or non-serious also related to study drug or unrelated to study drug at the time of the study visit.
Arm/Group Title	Carvedilol		Placebo
Arm/Group Description	Study participants will receive carvedilol for 12 weeks Carvedilol: Carvedilol will be given for 12 weeks and then an exercise test will be performed		Study participants will receive placebo (sugar pill) for 12 weeks Placebo: Placebo will be given for 12 weeks and then an exercise test will be performed
All Cause Mortality
	Carvedilol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/24 (0%)
Serious Adverse Events
	Carvedilol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Carvedilol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/25 (16%)		0/24 (0%)
Cardiac disorders
Bradycardia	4/25 (16%)	4	0/24 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.