Single Ventricle Heart Disease After Fontan SurgeryPhase 4NCT01815502
Study of Effects of Sildenafil on Patients With Fontan Heart Circulation
A Phase 4 study testing Cardiac catheterization in people with Single Ventricle Heart Disease After Fontan Surgery, run by Medical University of South Carolina at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 40 years
- Conditions the study is for
- Single Ventricle Heart Disease After Fontan Surgery
- What is being tested?
- Cardiac catheterization
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2013to Dec 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Presence of a congenital heart defect that leads to single ventricle physiology
- Previously performed Fontan surgery
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical University of South Carolina
Charleston, South Carolina, 29425
About this study
Official title: 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.
Read the 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.
- Being tested
- Cardiac catheterization
- Keywords
- Single ventricle, Fontan, Sildenafil, Pressure-Volume Loops
- Medical subject headings
- Univentricular Heart
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiac catheterizationDiagnostic test
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.
| Study group | Role | What they receive |
|---|---|---|
| Dobutamine + Sildenafil | Experimental | 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.. Receives: Diagnostic Test: Cardiac catheterization |
| Dobutamine + placebo | Placebo comparator | 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.. Receives: Diagnostic Test: Cardiac catheterization |
What is being measured
The primary outcome is the main question the study is designed to answer.
End-systolic Elastance
end-systolic elastance (often abbreviated Ees or ESPVR) is a measure of contractility (systolic function)
Measured: 10 minutes after imitation of dobutamine
Secondary outcomes (1)
End-diastolic Pressure Volume Relationship
End-diastolic pressure volume relationship (EDPVR) is a measure of diastolic (relaxation) heart function
Measured: 10 minutes after imitation of dobutamine
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2013 (estimated)
- Study startFeb 2013
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Single Ventricle Heart Disease After Fontan SurgeryStudies of the same condition, open and under way.
- More trials run by Medical University of South CarolinaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Collaborators
- American Heart Association
- Responsible party
- Sponsor
- Investigators
- Ryan Butts, M.D., Principal investigator, Medical University of South CarolinaAndrew M Atz, MD, Study chair, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01815502
- Sponsor's protocol ID
- PVL Fontan
- Other IDs
- AHA
- Status last verified
- Nov 2018
- First submitted
- 19 Mar 2013
- Last updated
- 7 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Goldberg DJ, French B, McBride MG, Marino BS, Mirarchi N, Hanna BD, Wernovsky G, Paridon SM, Rychik J. Impact of oral sildenafil on exercise performance in children and young adults after the fontan operation: a randomized, double-blind, placebo-controlled, crossover trial. Circulation. 2011 Mar 22;123(11):1185-93. doi: 10.1161/CIRCULATIONAHA.110.981746. Epub 2011 Mar 7.
PubMed 21382896Goldberg DJ, French B, Szwast AL, McBride MG, Marino BS, Mirarchi N, Hanna BD, Wernovsky G, Paridon SM, Rychik J. Impact of sildenafil on echocardiographic indices of myocardial performance after the Fontan operation. Pediatr Cardiol. 2012 Jun;33(5):689-96. doi: 10.1007/s00246-012-0196-9. Epub 2012 Feb 14.
PubMed 22331056Butts RJ, Chowdhury SM, Baker GH, Bandisode V, Savage AJ, Atz AM. Effect of Sildenafil on Pressure-Volume Loop Measures of Ventricular Function in Fontan Patients. Pediatr Cardiol. 2016 Jan;37(1):184-91. doi: 10.1007/s00246-015-1262-x. Epub 2015 Sep 26.
PubMed 26409473
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Response to Sildenafil in Patients With Fontan Physiology, A Pressure-volume Loop Analysis
- ClinicalTrials.gov ID
- NCT01815502
- Acronym / sponsor ID
- PVL Fontan
- Keywords
- Single ventricle, Fontan, Sildenafil, Pressure-Volume Loops
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Collaborators
- American Heart Association
- Study start
- Feb 2013
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 21 Mar 2013 (estimated)
- Results
- Posted 7 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dobutamine + Sildenafil | Experimental | Diagnostic Test: Cardiac catheterizationSildenafil 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.. |
| Dobutamine + placebo | Placebo comparator | Diagnostic Test: Cardiac catheterizationPatients 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.. |
Who may qualify
- Ages
- 3 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- Presence of a congenital heart defect that leads to single ventricle physiology
- Previously performed Fontan surgery
Key exclusion criteria (5 listed)
- The use of phosphodiesterase type 5 (PDE5) inhibitors at the time of catheterization of within 1 month of catheterization
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cardiac catheterizationAll 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. | Diagnostic test | Dobutamine + Sildenafil, Dobutamine + placebo |
Primary outcome
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)
1 secondary outcome
End-diastolic Pressure Volume Relationship
Time frame: 10 minutes after imitation of dobutamine
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21382896Goldberg DJ, French B, McBride MG, Marino BS, Mirarchi N, Hanna BD, Wernovsky G, Paridon SM, Rychik J. Impact of oral sildenafil on exercise performance in children and young adults after the fontan operation: a randomized, double-blind, placebo-controlled, crossover trial. Circulation. 2011 Mar 22;123(11):1185-93. doi: 10.1161/CIRCULATIONAHA.110.981746. Epub 2011 Mar 7.
- Background: PubMed 22331056Goldberg DJ, French B, Szwast AL, McBride MG, Marino BS, Mirarchi N, Hanna BD, Wernovsky G, Paridon SM, Rychik J. Impact of sildenafil on echocardiographic indices of myocardial performance after the Fontan operation. Pediatr Cardiol. 2012 Jun;33(5):689-96. doi: 10.1007/s00246-012-0196-9. Epub 2012 Feb 14.
- Derived from this study: PubMed 26409473Butts RJ, Chowdhury SM, Baker GH, Bandisode V, Savage AJ, Atz AM. Effect of Sildenafil on Pressure-Volume Loop Measures of Ventricular Function in Fontan Patients. Pediatr Cardiol. 2016 Jan;37(1):184-91. doi: 10.1007/s00246-015-1262-x. Epub 2015 Sep 26.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ryan Butts, M.D. principal investigator
Medical University of South Carolina
Andrew M Atz, MD study chair
Medical University of South Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Cardiac catheterization in people with Single Ventricle Heart Disease After Fontan Surgery, run by Medical University of South Carolina at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
End-systolic Elastance (time frame: 10 minutes after imitation of dobutamine). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01815502, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2018.