Treatment of Pulmonary Hypertension and Sickle Cell Disease With Sildenafil Therapy

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:

1. 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.
2. 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.
3. 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.