Title of Study:
Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (walk-PHaSST)
Study Sponsor: NHLBI
Start Date: 1/1/2008
End Date: December 2009
Treatment Trial? yes
Description:
Sickle cell disease (SCD) is an autosomal recessive disorder and the most common genetic disease affecting African-Americans. Approximately 0.15% of African-Americans are homozygous for sickle cell disease, and 8% 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 1 additional year of sildenafil therapy to subjects who completed the randomized, double-blind phase.
- Observational Follow-up Study. All patients who sign informed consent for the Screening Phase are also consenting to participate in the Observational Follow-up Study. Screened subjects will proceed into the Observational Follow-up Study if a) they do not qualify for -or choose not to participate in- the MIT; b) are discontinued for any reason during the MIT or the Open-label
Follow-up Phase; or c) complete the Open-label Follow-up Phase. Subjects
may be contacted every 6-12 months for up to 3 years to assess major disease- related complications, including mortality; subject follow-up during this study will be at the discretion of each clinical site.
Website for more information and study sites
