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Study of Effects of Sildenafil on Patients With Fontan Heart Circulation

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ClinicalTrials.gov Identifier: NCT01815502
Recruitment Status : Completed
First Posted : March 21, 2013
Results First Posted : December 7, 2018
Last Update Posted : December 7, 2018
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
Medical University of South Carolina

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Single Ventricle Heart Disease After Fontan Surgery Diagnostic Test: Cardiac catheterization Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Response to Sildenafil in Patients With Fontan Physiology, A Pressure-volume Loop Analysis
Study Start Date : February 2013
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 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


Other Outcome Measures:
  1. 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

  2. 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



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Ages Eligible for Study:   3 Years to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01815502


Locations
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United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Sponsors and Collaborators
Medical University of South Carolina
American Heart Association
Investigators
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Principal Investigator: Ryan Butts, M.D. Medical University of South Carolina
Study Chair: Andrew M Atz, MD Medical University of South Carolina
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT01815502    
Other Study ID Numbers: PVL Fontan
AHA ( Other Grant/Funding Number: American Heart Association )
First Posted: March 21, 2013    Key Record Dates
Results First Posted: December 7, 2018
Last Update Posted: December 7, 2018
Last Verified: November 2018
Keywords provided by Medical University of South Carolina:
Single ventricle
Fontan
Sildenafil
Pressure-Volume Loops
Additional relevant MeSH terms:
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Heart Diseases
Cardiovascular Diseases