Sildenafil Therapy for Pulmonary Hypertension and Sickle Cell Disease
This study will examine whether the drug sildenafil can lower blood pressure in the pulmonary artery (the blood vessel that leads from the heart to the lungs) in patients with sickle cell disease and pulmonary hypertension (high blood pressure in the lungs). It will see if this treatment can reduce disease complications, such as shortness of breath, pain crisis, pneumonia, and increase survival.
Patients 12 years of age and older with sickle cell disease and pulmonary hypertension may be eligible for this study. Participants are randomly assigned to receive sildenafil or placebo (sugar pill) for 16 weeks. Before starting treatment, patients have baseline studies, including a pregnancy test for females of childbearing age; a chest x-ray; pulmonary function tests to measure how much air the patient can breathe in and out; an echocardiogram (heart ultrasound); a 6-minute walk test to measure exercise capacity; a quality-of-life assessment and a pain inventory. Patients with moderate to severe pulmonary hypertension undergo heart catheterization to evaluate the severity of hypertension before beginning sildenafil therapy.
During treatment, patients are monitored with the following:
- Blood tests: weeks 6, 10 and 16.
- Echocardiogram: weeks 6 and 16.
- 6-minute walk test: weeks 6, 10 and 16.
- Measurements of weight, blood pressure and heart rate: weeks 6, 10 and 16.
- Pregnancy test for women of childbearing age: weeks 6, 10 and 16.
- Pain questionnaire once a day for a week: weeks 6 and 1.0
- Quality-of-life questionnaire: week 16.
- Heart catheterization: week 16 for patients with moderate to severe hypertension.
At the end of the 16-week period, patients may opt to continue to receive sildenafil and monitoring in an open-label phase of the study for up to 1 year.
Sickle Cell Disease
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Treatment of Pulmonary Hypertension and Sickle Cell Disease With Sildenafil Therapy|
- Change in Exercise Capacity as Assessed by 6 Minute Walk. [ Time Frame: Baseline to week 16/Imputed last visit. ] [ Designated as safety issue: No ]The primary outcome measure was change in exercise capacity assessed by 6 minute walk distance in meters from baseline to 16 weeks. Subjects without a week 16 assessment had their last observation carried forward.
- Change From Baseline in Pulmonary Hypertension at Week 16 as Assessed by Tricuspid Regurgitant Jet Velocity [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]Secondary outcome measure was change from baseline in Pulmonary hypertension at week 16 as assessed by Tricuspid regurgitant jet velocity(TRV). Tricuspid regurgitant jet velocity was measured by transthoracic Doppler Echocardiography.
- Borg Dyspnea Score [ Time Frame: baseline to 16 weeks ] [ Designated as safety issue: No ]Borg dyspnea score was used to measure the level of severity of breathlessness perceived by the patient before and after 6 minute walk. The severity is measured on a 10 point scale with 0= nothing at all and 10=maximum severity of breathlessness.
- Brain Natriuretic Peptide(BNP)Levels. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||June 2007|
|Study Completion Date:||October 2009|
|Primary Completion Date:||September 2009 (Final data collection date for primary outcome measure)|
There was a balancing of treatment group assignment across Tricuspid Regurgitant Jet velocity(TRV)measured on Echo.
Oral Sildenafil 20mg three times daily for 6 weeks,followed by 40mg three times daily for 4 weeks followed by 80mg three times daily for 6 weeks.
Other Name: phosphodiesterase-5(PDE5) inhibitor
Placebo Comparator: Placebo
There was a balancing of treatment group assignment across Tricuspid Regurgitant Jet velocity(TRV)measured on Echo
Placebo 20mg three times daily for 6 weeks,followed by 40mg three times daily for 4 weeks followed by 80mg three times daily for 6 weeks.
Other Name: Sugar pill
Sickle cell disease (SCD) is an autosomal recessive disorder and the most common genetic disease affecting African-Americans. Approximately 0.15 percent of African-Americans are homozygous for sickle cell disease, and 8 percent have sickle cell trait. Acute pain crisis, acute chest syndrome (ACS), and pulmonary hypertension are common complications of sickle cell anemia. Pulmonary hypertension (PH) has now been identified as a marker of mortality in adults with sickle cell disease. Sildenafil has been proven beneficial in pulmonary hypertension (PH) and recent phase I/II studies from the intramural National Institutes of Health (NIH) suggest it is well tolerated and efficacious in the SCD population. Furthermore, a number of recent studies have suggested that nitric oxide (NO) based therapies may have a favorable impact on sickle red cells at the molecular level and could improve the abnormal microvascular perfusion that is characteristic of sickle cell anemia.
The project has 3 distinct components:
- Screening Phase. Approximately 1000 subjects with sickle cell disease will be screened. Assessments will include historical and laboratory data, Doppler echocardiogram, 6-minute walk test, plasma/serum, and DNA for banking.
- Main Interventional Trial. The randomized, double-blind, placebo controlled phase is designed to determine the effects of 16 weeks of Sildenafil therapy on exercise endurance, cardiopulmonary hemodynamic parameters and symptoms in this patient population. The open-label follow-up phase is designed to provide up to an additional year of Sildenafil therapy to subjects who completed the randomized, double-blind phase.
- Observational Follow-up Study. Screened patients who do not qualify for participation in the main interventional trial may be contacted every 6-12 months for up to 3 years to assess major disease-related complications, including mortality.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00492531
|United States, California|
|Children's Hospital, Oakland|
|Oakland, California, United States, 94609|
|United States, Colorado|
|University of Colorado|
|Denver, Colorado, United States, 80220-3706|
|United States, District of Columbia|
|Howard University Hospital|
|Washington, District of Columbia, United States, 20060|
|United States, Illinois|
|University of Illinois at Chicago|
|Chicago, Illinois, United States, 60612|
|United States, Maryland|
|Johns Hopkins University|
|Baltimore, Maryland, United States, 21205|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|United States, New York|
|Albert Einstein College of Medicine|
|Bronx, New York, United States, 10461|
|United States, Pennsylvania|
|Childrens Hospital, Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15213-2583|
|Imperial College London and Hammersmith Hospital|
|London, United Kingdom|
|Principal Investigator:||Mark T Gladwin, M.D||Professor of Medicine: Chief, Pulmonary, Allergy and Critical CRE Medicine: Director, Hemostasis and Vascular Biology Research Institute; University of Pittsburgh School of Medicine|