Efficacy and Safety of Bosentan in Sickle Cell Disease (SCD) Patients With Pulmonary Arterial Hypertension (PAH)

Inclusion Criteria: Screening Criteria: 1. Males or females ≥ 12 years of age with a documented history of SCD 2. Patients with symptomatic PAH associated with shortness of breath 3. 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 4. 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: 1. Patients with hemoglobin (Hb) SS or Hb S/β0 genotype and with Hb A ≤ 10% 2. Six-minute walk test (6MWT) distance ≥ 150 m and ≤ 450 m 3. PAH 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) ≥ 25 mmHg * Pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg measured by RHC or left ventricular end diastolic pressure (LVEDP) ≤ 15 mmHg measured by left heart catheterization, if PCWP measurement is not reliable * Pulmonary vascular resistance (PVR) at rest ≥ 160 dyn.sec/cm5 4. 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: 1. Left ventricular ejection fraction \< 40% (echo/Doppler) 2. Systolic blood pressure \< 85 mmHg 3. Uncontrolled hypertension with systolic blood pressure \>160 mmHg and/or diastolic blood pressure \> 100 mmHg 4. Forced expiratory volume in 1 second divided by forced vital capacity (FEV1/FVC) \< 0.5 5. Total lung capacity (TLC) \< 50% of normal predicted value 6. Significant cardiac disease: ischemic, valvular, constrictive 7. Hemoglobin concentration \< 6.0 g/dL at the time of randomization 8. Acute liver disease 9. Evidence of cirrhosis or portal hypertension on a liver ultrasound or biopsy 10. ALT ≥ 2 times upper limit of normal (ULN) and/or albumin \< 2.8 g/dL 11. 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 12. 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 13. Blood transfusion within 4 weeks prior to randomization 14. Illness with a life expectancy shorter than 6 months 15. HIV with opportunistic infection 16. Psychotic, addictive, or other disorder limiting the ability to provide informed consent or to comply with study requirements 17. Pregnant or lactating women 18. Recently started (\< 8 weeks prior to randomization) or planned, exercise-based cardio-pulmonary rehabilitation program 19. Bone marrow transplantation 20. Treatment or planned treatment with another investigational drug within 3 months prior to randomization 21. 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 22. Treatment with calcineurin-inhibitors (e.g., cyclosporine A and tacrolimus), sirolimus, fluconazole, amiodarone, miconazole and glibenclamide (glyburide) within 1 week prior to randomization 23. Known hypersensitivity to bosentan or any of its excipients