Study of Tadalafil vs. Placebo for Improving Hemodynamics and End-Organ Dysfunction in Fontan Physiology

Study Overview
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Brief Summary
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The purpose of this study is to find out more about the effectiveness of Tadalafil in improving hemodynamic capabilities, endothelial function, and end-organ function in patients who have previously undergone a Fontan Palliation.

Official Title
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A Phase III, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy of Tadalafil Versus Placebo in Improving Hemodynamics and End-Organ Dysfunction in Fontan Physiology (TRIUMPH Trial)

Conditions
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Fontan Palliation

Intervention / Treatment
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* Drug: Tadalafil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 years old. Have previously undergone a Fontan Palliation. Able to exercise using a supine bike. Ability and willingness to provide written consent. Undergoing a clinically indicated Cardiac Catheterization Exclusion Criteria: Patients < 18 years old. Current intravenous inotropic drugs. Current use of alpha-blockers, pulmonary vasodilators, or nitrates. Unable to exercise. Pregnancy or lactating. Unable or unwilling to consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tadalafil Group<br>Study participants will receive 10 mg of Tadalafil daily for 1 week, then 20 mg daily for 1 week, and finally 40 mg daily for 50 weeks for a total therapy time of 52 weeks. Tadalafil will be taken orally in capsule form once daily. | Drug: Tadalafil<br>* 10 mg once daily orally week 1, 20 mg once daily orally during week 2, and 40 mg once daily orally during weeks 3 through 52<br>|
| Placebo Comparator: Placebo Group<br>Study participants will receive a placebo capsule that looks identical to the Tadalafil capsule. The placebo will be taken orally once daily for 52 weeks. | Drug: Placebo<br>* Looks exactly like the study drug, but it contains no active ingredient<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microvascular endothelial function | Measured by the reactive hyperemic index using peripheral artery tonometry (EndoPAT) | 52 weeks | 
| Pulmonary vascular reserve | The slope of mean pulmonary artery pressure / cardiac output (mPAP/CO) | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver stiffness | Liver magnetic resonance elastography (MRE) will be used to assess liver stiffness expressed in Pascals (Pa) | 52 weeks | 
| Renal function | Measured by the glomerular filtration rate | 52 weeks | 
| Exercise capacity | Assessed using peak VO2 (oxygen consumption) obtained from an upright treadmill or supine bike cardiopulmonary exercise test with echocardiogram | 52 weeks | 
| Patient reported quality of life | Measured by the Minnesota Living with Heart Failure Questionnaire that asks subjects to rate how much their heart failure (heart condition) has affected their life during the past month (4 weeks) on a scale of 0=no and 5=very much. | 52 weeks |