Clinical trial NCT00313196 (phase 3, status: terminated)
Conditions: pulmonary hypertension
ICD codes: I27.0, I27.20, I27.21, I27.24, I27.29, P29.30, I27.22
Drugs: bosentan
SMILES: COC1=CC=CC=C1OC1=C(NS(=O)(=O)C2=CC=C(C=C2)C(C)(C)C)N=C(N=C1OCCO)C1=NC=CC=N1
Reason stopped: 
    slow enrollment
  
Eligibility criteria:

        Inclusion Criteria: Screening Criteria:

          1. Males or females > or = 12 years of age with a documented history of SCD

          2. Patients with symptomatic PH 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 < or = 10%

          2. Six-minute walk test (6MWT) distance > or = 150 m and < or = 450 m

          3. 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

          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 (SBP) < 85 mmHg

          3. Uncontrolled hypertension with SBP > 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. cirrhosis or portal hypertension

         10. ALT > or = 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