Effect of Tadalafil on Exercise Capacity in Pediatric Fontan Patients

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.

Study Overview

• Status: Completed
• Conditions: Single Ventricle
• Intervention / Treatment: Drug: Tadalafil Citrate; Drug: Sugar pill

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt lake City, Utah, United States, 84113
      • Primary Childrens Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tadalafil Citrate; 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; 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.; Other Names: Cialis
Placebo Comparator: Sugar pill; 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; 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; Other Names: Ora sweet

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Utah
• Investigators: Principal Investigator: Shaji C. Menon, MD, University of Utah

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: February 4, 2011
• First Submitted That Met QC Criteria: February 4, 2011
• First Posted (Estimate): February 7, 2011

Study Record Updates

• Last Update Posted (Actual): April 17, 2017
• Last Update Submitted That Met QC Criteria: April 14, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Fontan; Tadalafil; Exercise performance
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Heart Defects, Congenital; Cardiovascular Abnormalities; Univentricular Heart; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Tadalafil
• Other Study ID Numbers: IRB_00050085