Study of Effects of Sildenafil on Patients With Fontan Heart Circulation

November 9, 2018 updated by: Medical University of South Carolina

Response to Sildenafil in Patients With Fontan Physiology, A Pressure-volume Loop Analysis

The study will investigate the cardiovascular effects of sildenafil on patients with Fontan circulation. Recent studies suggest that sildenafil may improve exercise in patients with Fontan circulation. However, why this occurs is not known. The study will used specialized catheters to measure pressure and volume. The measure of pressure and volume leads to more detailed analysis of heart function. Patients will receive either sugar pill or sildenafil prior to catheterization. It is believed that sildenafil will improve relaxation and contraction of the heart.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Modifications to surgical procedures and medical treatment have led to a rapidly declining mortality rates in patients with single-ventricle heart disease (SV). However, SV patients still suffer from lower quality of life, decreased exercise capacity, worse neurodevelopmental outcomes and many other morbidities. While patients with SV circulation only make a small portion of all congenital heart diseases, 2-4 %, they require a great deal of resource utilization.

Standard medical treatments for adult heart failure have not had the same success in the SV population. Phosphodiesterase 5 (PDE5) inhibitors have recently become a frequently used medication class in patients with SV heart disease to treat pulmonary hypertension, heart failure, as well as "Fontan" failure (i.e., plastic bronchitis and protein-losing enteropathy). While there have been findings of improved measures of exercise capacity and some reports of improved symptoms of heart failure, the physiologic mechanisms behind these findings are not completely understood. There have been reports, indicating that the phosphodiesterase five inhibitors improve ventricular function in biventricular circulation patients and animal models. The aim of our study was to investigate the effect of acute PDE5 inhibition on ventricular function in SV patients after the final palliative surgery, the Fontan procedure.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 40 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Presence of a congenital heart defect that leads to single ventricle physiology
  • Previously performed Fontan surgery

Exclusion Criteria:

  • The use of phosphodiesterase type 5 (PDE5) inhibitors at the time of catheterization of within 1 month of catheterization

    • Unstable arrhythmia at the time of catheterization
    • History of unstable arrhythmia within 2 months of catheterization
    • Venous, arterial or cardiac malformation that precludes the proper placement of a microconductance catheter
    • Allergy to sildenafil or previous significant adverse reaction to sildenafil (e.g. hypotension)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dobutamine + Sildenafil
Sildenafil will be given an one time dose 30 to 90 minutes prior to cardiac catheterization. Sildenafil will be given at a dose 1 milligram per kilogram with a maximum of 20 milligrams. During the catheterization patients will have specialized catheter placed in the heart that measures pressure and volume simultaneously. The patients will undergo an infusion of dobutamine up to 10 micrograms per kilogram per minute to mimic exercise for up to ten minutes..
Diagnostic test: Cardiac catheterization
All patients will receive a dobutamine infusion during catheterization. Patients were 1:1 randomized to a single dose of 1 mg/kg of sildenafil (max dose of 20 mg) or placebo 30-90 min prior to beginning of catheterization.
Placebo Comparator: Dobutamine + placebo
Patients will be given a one time dose of sugar pill 30 to 90 minutes prior to cardiac catheterization.During the catheterization patients will have specialized catheter placed in the heart that measures pressure and volume simultaneously. The patients will undergo an infusion of dobutamine up to 10 micrograms per kilogram per minute to mimic exercise for up to ten minutes..
Diagnostic test: Cardiac catheterization
All patients will receive a dobutamine infusion during catheterization. Patients were 1:1 randomized to a single dose of 1 mg/kg of sildenafil (max dose of 20 mg) or placebo 30-90 min prior to beginning of catheterization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
End-systolic Elastance
Time Frame: 10 minutes after imitation of dobutamine
end-systolic elastance (often abbreviated Ees or ESPVR) is a measure of contractility (systolic function)
10 minutes after imitation of dobutamine

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
End-diastolic Pressure Volume Relationship
Time Frame: 10 minutes after imitation of dobutamine
End-diastolic pressure volume relationship (EDPVR) is a measure of diastolic (relaxation) heart function
10 minutes after imitation of dobutamine

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ventricular-arterial Coupling
Time Frame: 10 minutes after imitation of dobutamine
Ventricular-arterial coupling is a measure of efficiency of ventricular work in response to the work created by the vascular tree
10 minutes after imitation of dobutamine
Preload Augmentation
Time Frame: 10 minutes after imitation of dobutamine
Preload augmentation is a measure of how quickly the heart fills with blood during exercise
10 minutes after imitation of dobutamine

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of South Carolina

Collaborators

American Heart Association

Investigators

  • Principal Investigator: Ryan Butts, M.D., Medical University of South Carolina
  • Study Chair: Andrew M Atz, MD, Medical University of South Carolina

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2013

Primary Completion (Actual)

December 1, 2014

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

March 19, 2013

First Submitted That Met QC Criteria

March 19, 2013

First Posted (Estimate)

March 21, 2013

Study Record Updates

Last Update Posted (Actual)

December 7, 2018

Last Update Submitted That Met QC Criteria

November 9, 2018

Last Verified

November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PVL Fontan
  • AHA (American Heart Association)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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