Trial record 11 of 31 for:    "Hypoplastic left heart syndrome"

Sildenafil After the Fontan Operation (SAFO)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2009 by Children's Hospital of Philadelphia.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
The Mark H. and Blance M. Harrington Foundation
Information provided by:
Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT00507819
First received: July 25, 2007
Last updated: September 2, 2009
Last verified: September 2009
  Purpose

In this study, the investigators will evaluate the effect of sildenafil on exercise tolerance in patients with a single cardiac ventricle who have undergone the Fontan operation. The investigators will also evaluate echocardiographic measures of ventricular function and measure quality of life changes using two validated quality of life measures. The hypothesis is that sildenafil will result in increased exercise tolerance in patients who have had the Fontan operation as compared to placebo.


Condition Intervention Phase
Hypoplastic Left Heart Syndrome
Tricuspid Atresia
Drug: Sildenafil
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Sildenafil After Fontan Operation Study

Resource links provided by NLM:


Further study details as provided by Children's Hospital of Philadelphia:

Primary Outcome Measures:
  • Change in maximal oxygen consumption from baseline testing to post-medication/placebo testing [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Oxygen pulse [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ] [ Designated as safety issue: No ]
  • Ventricular function [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ] [ Designated as safety issue: No ]
  • Atrioventricular valvar regurgitation [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ] [ Designated as safety issue: No ]
  • Myocardial performance index [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ] [ Designated as safety issue: No ]
  • E:E (passive ventricular inflow/diastolic myocardial velocity) [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ] [ Designated as safety issue: No ]
  • Fontan flow pattern [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ] [ Designated as safety issue: No ]
  • Mesenteric artery pulsatility index [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ] [ Designated as safety issue: No ]
  • PedsQL 4.0 - a generic quality of life assessment [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ] [ Designated as safety issue: No ]
  • PCQLI - a disease specific quality of life assessment [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: December 2007
Estimated Study Completion Date: July 2010
Estimated Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Sildenafil will be given at a dose of 20 mg three times-a-day for six weeks.
Drug: Sildenafil
One 20 mg capsule of sildenafil will be taken by mouth three times-a-day.
Other Names:
  • Revatio
  • Viagra
Placebo Comparator: 2
Placebo will be given three times-a-day for six weeks.
Drug: Placebo
One placebo capsule will be taken by mouth three times-a-day.

Detailed Description:

The Fontan physiology is the end result of staged reconstruction of the heart and the major blood vessels in patients who have a single ventricle. After completion of the reconstruction, the great veins which usually bring blood back to the heart are connected directly to the pulmonary arteries, allowing blood from the body to bypass the heart and flow directly into the lungs. In this system, blood flow through the lungs is passive (not pumped) and the efficiency of flow through the cardiovascular system is related to the resistance to blood flow in the vessels of the lungs.

There are two potential problems that arise in this scenario, as a result of the resistance to blood flow in the vessels of the lungs. First, the amount of blood flow returning to the heart from the lungs may not be sufficient to allow the heart to function at maximum efficiency, compromising the heart's ability to keep up with the demands of the body. Second, if the resistance to blood flow in the lungs is high, pressure may be transmitted back into the great veins themselves and secondarily into the organs of the body causing mild, or sometimes significant, organ dysfunction. Not all patients with the Fontan physiology develop these problems, but we know that even in patients without obvious problems, the ability to keep up with an increased metabolic demand, as during exercise, in compromised.

Improving the efficiency of blood flow through the lungs should improve the return of blood to the heart and thereby diminish the pressure transmitted back to the vessels which passively deliver blood to the lungs. We believe that this change may manifest as diminished symptoms in those patients with known difficulties, or may allow for an increased ability to walk, run, or participate in sports in those without any overt symptoms. Most importantly, we speculate that improved efficiency of flow through the lungs, and the resulting improved cardiac output (blood flow through the body) will make patients more energetic and will make them feel better.

Sildenafil is an oral medication that has been used to treat patients with pulmonary hypertension, a disease in which there is abnormally elevated pressure in the vessels of the lung. In this disease, the resistance in the lungs is abnormally high, severely limiting the ability of the heart to keep up with the demands of the body. Sildenafil lowers the resistance in the vessels of the lungs and has been shown to improve exercise performance in patients with this disease. We believe that Sildenafil may have a similar benefit for our patients after Fontan operation in whom cardiac output is also limited by resistance of the blood vessels in the lungs.

In our study, we will compare the exercise capacity, echocardiographic measures of cardiac function, and the overall quality of life in patients with the Fontan before and after a six-week period of sildenafil administration. As a control, the same group of patients will take a placebo for a six-week period, also with before and after testing. We hypothesize that oral sildenafil will result in significant improvements in exercise capacity, energy levels, and echocardiographic measures of cardiac function and output in our study participants. We are hopeful that the findings of this investigation will directly help children and young adults with Fontan physiology.

  Eligibility

Ages Eligible for Study:   8 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 8 years of age or older
  • All participants must have had Fontan completion

Exclusion Criteria:

  • Height less than 132 cm
  • Unable to participate in exercise testing due to medical restrictions or physical limitations
  • Fontan baffle obstruction or single lung physiology
  • Coarctation of the aorta or neo-aorta (BP gradient > 20 mmHg)
  • Severe ventricular dysfunction assessed qualitatively by echocardiography
  • Severe atrioventricular valvar regurgitation assessed qualitatively by echocardiography
  • Presence of electronic pacemaker
  • History of treatment with sildenafil in the six weeks prior to enrollment in study
  • Patients with severe renal impairment
  • Patients with severe hepatic impairment
  • Patients taking medications that inhibit or induce CYP3A4 (including grapefruit juice and St. John's Wort)
  • Patients taking alpha-blockers and nitrates
  • Parents/guardians or subjects who, in the opinion of the investigator, may be non-compliant with study schedules or procedures
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00507819

Sponsors and Collaborators
Children's Hospital of Philadelphia
The Mark H. and Blance M. Harrington Foundation
Investigators
Principal Investigator: Jack Rychik, MD Children's Hospital of Philadelphia
  More Information

No publications provided

Responsible Party: Jack Rychik,MD, Children's Hospital pf Philadelphia
ClinicalTrials.gov Identifier: NCT00507819     History of Changes
Other Study ID Numbers: IRB 2007-4-5034
Study First Received: July 25, 2007
Last Updated: September 2, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital of Philadelphia:
Other Single Ventricle Anatomy
Hypoplastic Left Heart Syndrome
Tricuspid Atresia

Additional relevant MeSH terms:
Hypoplastic Left Heart Syndrome
Tricuspid Atresia
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities
Heart Valve Diseases
Sildenafil
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on August 28, 2014