Efficacy and Safety of Bosentan in Sickle Cell Disease (SCD) Patients Diagnosed With Pulmonary Hypertension (PH) (ASSET-2)

Inclusion Criteria: Screening Criteria: Males or females > or = 12 years of age with a documented history of SCD Patients with symptomatic PH associated with shortness of breath Patients with tricuspid regurgitation jet (TRJ) velocity of > 2.9 m/sec based on echo/Doppler conducted within 6 months prior to randomization and not during SCD crisis Signed written informed consent is obtained from the patient or patient's parent/ legal representative prior to initiation of any study related procedure Inclusion Criteria: Patients with hemoglobin (Hb) SS or Hb S/β0 genotype and with Hb A < or = 10% Six-minute walk test (6MWT) distance > or = 150 m and < or = 450 m Pulmonary hypertension confirmed by right heart catheterization (RHC) performed at the study site within 3 months of the randomization visit and defined as: Mean pulmonary arterial pressure (mPAP) > or - 25 mmHg Pulmonary capillary wedge pressure (PCWP) measured by right heart catheterization or left ventricular end diastolic pressure (LVEDP) measured by left heart catheterization, if PCWP measurement is not reliable. Two subsets of patients will be considered for this study: PCWP < or = 15 mm Hg, if PVR at rest < 160 dyn.sec/cm5 PCWP of 16-25 mm Hg with any PVR value Women of childbearing potential must have a negative result on their serum pregnancy test and use reliable methods of contraception during study treatment and for 3 months after study treatment termination Exclusion Criteria: Left ventricular ejection fraction < 40% (echo/Doppler) Systolic blood pressure (SBP) < 85 mmHg Uncontrolled hypertension with SBP > 160 mmHg and/or diastolic blood pressure > 100 mmHg Forced expiratory volume in 1 second divided by forced vital capacity (FEV1/FVC) < 0.5 Total lung capacity (TLC) < 50% of normal predicted value Significant cardiac disease: ischemic, valvular, constrictive Hemoglobin concentration < 6.0 g/dL at the time of randomization Acute liver disease cirrhosis or portal hypertension ALT > or = 2 times upper limit of normal (ULN) and/or albumin < 2.8 g/dL Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements (in particular with 6MWT), e.g., angina pectoris, intermittent claudication, symptomatic hip osteonecrosis Vaso-occlusive crisis (VOC) or acute chest syndrome (ACS) within 2 weeks of randomization or more than 12 VOC and/or ACS within the last 12 months Blood transfusion within 4 weeks prior to randomization Illness with a life expectancy shorter than 6 months HIV with opportunistic infection Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements Pregnant or lactating women Recently started (< 8 weeks prior to randomization) or planned, exercise-based cardio-pulmonary rehabilitation program Bone marrow transplantation Treatment or planned treatment with another investigational drug within 3 months prior to randomization Treatment for pulmonary hypertension with an endothelin receptor antagonist, a phosphodiesterase-5 inhibitor, prostanoids (excluding acute administration during a catheterization procedure to test vascular reactivity) within 3 months prior to randomization or with L-arginine within 1 week prior to randomization Treatment with calcineurin-inhibitors (e.g., cyclosporine A and tacrolimus), sirolimus, fluconazole, amiodarone, miconazole and glibenclamide (glyburide) within 1 week prior to randomization Known hypersensitivity to bosentan or any of its excipients