Common complications of sickle cell disease include severe pain episodes, recurrent lung infections, persistant leg ulsers, chronic anemia and pulmonary hypertension. Nearly one-third of sickle cell paintes develop some form of pulmonary hypertension. The object is of this multi-center study is to demonstrate if bosentan improves pulmonary vascular resistance (PVR) in patients with symptomatic pulmonary arterial hypertension (PAH) and symptomatic pulmonary hypertension (PA) associated with sickle cell disease. The study population will include male and female patients with sickle cell disease (SS, S-beta-Thalassemia) age 16 and above who have pulmonary arterial hypertension or pulmonary hypertension. The secondary objectives are to evaluate the effect of bosentan on the time to clinical worsening in patients with symptomatic PH and PAH associated with SCD and to evaluate the safety and tolerability of bosentan in this patient population. During the screening for this study, subjects will undero pulmonary function testing, 6-minute walk, an echocardiogram and a heart catheterization. Patients will be randomized to receive either placebo or bosentan if they meet all the inclusion criteria and not of the exclusion criteria. Those subjects with PAH will be assigned to ASSET 1 and those with PH will be assigned to ASSET 2. The treatment medication or placebo will be administered for 4 weeks and then the dose will increase for the remaining 12 weeks. Study participants will return to the clinic once a month for safety tests and to measure 6-minute walk distance. Once a subject completes either ASSET 1 or ASSET 2 they will have the option of enrolling in the open-label study (ASSET 3) if treatment with bosentan could be beneficial. The object of ASSET 3 is to assess long-term safety, tolerability and efficacy of bosentan. Patients who meet all the inclusion criteria and not of the exclusion criteria will be started on 62.5 mg bid for 4 weeks and then start the maintenance dose of 125 mg bid (or stay on 62.5 mg is their weight is less than 40kg/90lbs). Patient will be divided into two groups. Group A will consist of patients who begin this study within 4 weeks of completing ASSET 1 or ASSET 2. Group B will consist of patients who begin this study longer than 4 weeks after completing ASSET 1 or ASSET 2. Patients will remain on drug until the FDA approves the drug for use in patients with pulmonary hypertension or until the sponsor decides to stop the study. We have enrolled 2 subjects on ASSET 1; 1 subject on ASSET 2; and 1 subject on the open-labe study (ASSET 3).
