Effect of Tadalafil on Exercise Capacity in Pediatric Fontan Patients

Study Overview
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Brief Summary
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This pilot study is aimed at assessing the short-term effects of Tadalafil on the hemodynamic response to exercise and exercise capacity in patients with Fontan circulation. Data regarding effect size and drug tolerability will be used in the design of a randomized multicenter trial. The long-term goal of this investigation is to systematically evaluate the effect of tadalafil therapy on exercise performance, quality of life, and delay of functional deterioration in patients with single ventricle physiology.

Official Title
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Effect of Tadalafil on Exercise Capacity in Pediatric Fontan Patients

Conditions
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Single Ventricle

Intervention / Treatment
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* Drug: Tadalafil Citrate
* Drug: Sugar pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have undergone the Fontan procedure (regardless of type of Fontan connection or presence or absence of a fenestration) Age 8.0 to 35.0 years Stable clinical condition over the last 3 months (i.e. No change in medication, treatments, or development of new symptoms) Ability to perform exercise testing Consent and assent (as appropriate to participate in the study after receiving information concerning procedures, risks, and possible clinical benefits) o Patients will be enrolled without regard to gender, race, and ethnicity. All patients meeting study eligibility will be approached for consent. Exclusion Criteria: Severe heart failure (New York Heart Association functional class III or IV) Presence of liver or renal dysfunction based on the latest lab test results Presence of hearing or visual deficit Transcutaneous arterial blood oxygen saturation (SaO2) <80% at rest History of echocardiographic, MRI, or angiographic evidence of Fontan pathway obstruction History of exercise-induced life-threatening arrhythmias or unstable rhythm(i.e. atrial flutter) Known or suspected pregnancy. Females in the reproductive age group will be screened for pregnancy using serum beta hCG prior to administering study drug. Patients on open label sildenafil or tadalafil

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 35 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tadalafil Citrate<br>The study subjects will be given Tadalfil citrate, encapsulated, 0.8-1 mg/kg/day in 1 dose orally. Max dose 40 mg. All patients will receive either study drug or placebo for a total of 20 days. | Drug: Tadalafil Citrate<br>* If allocated to the treatment arm, the patient will be given tadalfil citrate, 0.8-1 mg/kg/day in 1 daily dose. Maximum dose 40 mg. All patients will receive either study drug or placebo for a total of 20 days.<br>* Other names: Cialis;|
| Placebo Comparator: Sugar pill<br>If allocated to the placebo arm, the child will be given a similar appearing medication; the placebo will be a sugar pill. All patients will receive either study drug or placebo for a total of 20 days. | Drug: Sugar pill<br>* If allocated to the placebo arm, the child will be given a similar appearing medication; the placebo will be a mixture of Ora-Sweet® and Ora-Plus® in a 1:1 ratio. All patients will receive drug for 20 days<br>* Other names: Ora sweet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the effects of Tadalafil versus placebo on exercise capacity (maximal oxygen consumption: VO2 max) for patients (8-35 years)with the Fontan circulation (8 -18 years). | Short-term treatment with Tadalafil will augment cardiac output and improve exercise capacity (maximal oxygen consumption: VO2 max) in patients with the Fontan circulation. Primary outcome variables include the change in peak exercise capacity (VO2 max), using cycle ergometry after one week of tadalafil therapy | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the adverse effects of Tdalafil in patients (8-35 years)with the Fontan circulation and compare with the placebo group. | Hypothesis: Short-term treatment with Tadalafil will be well tolerated by children with the Fontan circulation. Adverse effect forms will be used to compare the side effects between Tadalafil and treatment group. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fontan, Tadalafil, Exercise performance