Please select the eligibility criteria that correspond to the clinical trial below.
Title: Prospective, Randomized, Placebo-controlled, Double-blind, Multicenter, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of Bosentan in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
Brief Summary: The present trial investigates a possible use of oral bosentan, which is currently approved for the treatment of symptoms of pulmonary arterial hypertension (PAH), to patients suffering from inoperable chronic thromboembolic pulmonary hypertension (CTEPH) because of (i) peripheral localization of thrombotic material or (ii) persistent or recurrent pulmonary hypertension after pulmonary endarterectomy.


Options:
A: Inclusion Criteria:

* Symptomatic pulmonary hypertension in modified NYHA functional class II to IV due to CTEPH as demonstrated by ventilation/perfusion lung scanning and pulmonary angiography.
* CTEPH judged inoperable because of peripheral localization of thrombotic material or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy (PEA) with no evidence of recurrent thromboembolism and not amenable to repeated surgery.
* 6-minute walk test (6MWT) distance \< 450 m.
* Hemodynamic evaluation showing: Mean pulmonary arterial pressure (mPAP) \>= 25 mmHg; Pulmonary capillary wedge pressure (PCWP) \< 15 mmHg; Pulmonary vascular resistance (PVR) at rest \>= 300 dyn×sec/cm5
* For patients who underwent PEA, hemodynamic evaluation must have been performed more than 6 months after PEA.
* For all patients, hemodynamic evaluation must have been performed with the 3 months immediately preceding inclusion.
* Men or women \>= 18 and =\< 80 years of age (Women of childbearing potential must have a negative pre-treatment pregnancy test and use a reliable method of contraception).
* Anticoagulants at efficacious dose for at least 3 months prior to randomization.
* Signed informed consent prior to initiation of any study-mandated procedure.

Exclusion Criteria:

* Other forms of pulmonary hypertension including pulmonary hypertension related to sickle cell disease.
* Obstructive lung disease: FEV1/FVC \< 0.5 after bronchodilator.
* Severe restrictive lung disease: Total Lung Capacity \< 60% of predicted value.
* 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 pulmonary embolism within 6 months prior to randomization.
* Pulmonary endarterectomy within 6 months prior to randomization.
* Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements.
* Illness with a life expectancy of less than 6 months.
* Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
* AST and/or ALT \> 3 times the upper limit of normal ranges.· Hemoglobin concentration \< 75% the lower limit of normal ranges.
* Pregnancy or breast-feeding.
* Systolic blood pressure (BP) \< 85 mmHg.
* Treatment or planned treatment with another investigational drug and/or pulmonary angioplasty within 3 months prior to randomization.
* Treatment with an endothelin receptor antagonist, a phosphodiesterase inhibitor, L-arginine or with prostanoids (excluding acute administration during a catheterization procedure to test vascular reactivity) within 3 months prior to randomization.
* Treatment for pulmonary hypertension within 1 month prior to randomization, excluding calcium channel blockers if present for at least 1 month before randomization.
* Treatment with calcineurin-inhibitors (e.g., cyclosporine A and tacrolimus), sirolimus, fluconazole, glibenclamide (glyburide) within 1 week prior to randomization.
* Known hypersensitivity to bosentan or any of the excipients.
B: Inclusion Criteria:

* PAH NYHA Class II
* Significant elevation of mean pulmonary arterial pressure
* Significant elevation of pulmonary vascular resistance at rest
* Limited 6-minute walk distance

Exclusion Criteria:

* PAH secondary to portal hypertension, complex congenital heart disease or reverse shunt
* Restrictive or obstructive lung disease
* Significant vasoreactivity
* Treatments for PAH (within 4 weeks of randomization)
C: Inclusion Criteria:

* At least 12 years of age.
* Body weight at least 40 kg (approximately 88 pounds).
* Pulmonary hypertension (PAH) that is either idiopathic; related to collagen vascular disease; related to anorexigen use; associated with an atrial septal defect (resting SaO2 greater than or equal to 88%); with surgical repair, of at least 1 year duration, of a congenital systemic-to-pulmonary shunt.
* If on bosentan, must be at the maximal dose of 125 mg twice daily for a minimum of 12 weeks prior to screening and have an AST/ALT less than 3 times normal.
* History of PAH established by a resting mean pulmonary artery pressure greater than or equal to 25 mm Hg, pulmonary artery wedge pressure less than or equal to 15 mm Hg, and pulmonary vascular resistance greater than or equal to 3 Wood units via right heart catheterization
* Have World Health Organization functional class I, II, III or IV status.
* Have a qualifying 6-minute walk test distance at screening
* Have no evidence of significant parenchymal lung disease

Exclusion Criteria:

* Are nursing or pregnant.
* PAH due to conditions other than noted in the above inclusion criteria.
* History of left-sided heart disease.
* History of atrial septostomy within 3 months before study entry
* History of angina pectoris or other condition that was treated with long-or short-acting nitrates within 12 weeks before administration of study drug.
* History of symptomatic coronary disease.
* Have any therapy with a prostacyclin or analogue, L-arginine, phosphodiesterase (PDE) inhibitor, or investigational drug within 4 weeks before administration of study drug.
D: 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

Answer: A