Please select the eligibility criteria that correspond to the clinical trial below.
Title: COMPASS 3: An Open-label, Multi-Center Study Employing a Targeted 6-Minute Walk Test (6-MWT) Distance Threshold Approach to Guide Bosentan-Based Therapy and to Assess the Utility of Magnetic Resonance Imaging (MRI) on Cardiac Remodeling
Brief Summary: An open label, non-comparative study design is appropriate for this Phase 4 study designed to assess whether a core therapy of bosentan, either as monotherapy or with the addition of sildenafil, enables patients with pulmonary arterial hypertension (PAH) to achieve a 6-minute walk distance (6 MWD) of ≥380 meters after 28 weeks of therapy This design is also appropriate to pioneer the utility of cardiac MRI in assessing improved functional capacity in PAH and exploring its correlation with other parameters.


Options:
A: Inclusion Criteria:

1. Signed informed consent prior to initiation of any study-mandated procedures.
2. Males or females ≥ 12 years of age (females of child-bearing potential must have been surgically sterilized or use a reliable method of contraception).
3. Symptomatic patients with the following types of PAH belonging to World Health Organization (WHO) Pulmonary Hypertension Classification Group I:

   * Idiopathic (IPAH)
   * Familial (FPAH)
   * Associated with PAH (APAH):

     * Collagen vascular disease
     * Drugs and toxins
4. Patients naïve to treatment with advanced PAH therapies (i.e., endothelin receptor antagonists (ERAs), phosphodiesterase-5 (PDE-5) inhibitors or prostacyclins) with a right heart catheterization (RHC) showing all of the following:

   * Mean pulmonary arterial pressure (mPAP) ≥ 25 mm Hg
   * Pulmonary capillary wedge pressure (PCWP) ≤ 15 mm Hg or left ventricular end diastolic pressure (LVEDP) ≤ 15 mm Hg when PCWP is not accurately obtained
   * Pulmonary vascular resistance ≥ 3 Wood units
5. 6-MWT distance ≥ 150 meters and \< 360 meters.

Exclusion Criteria:

1. Patients with Pulmonary Hypertension (PH) belonging to WHO Classification Group II-V.
2. Patients with PAH (WHO PH Classification Group I) other than that listed in the Inclusion Criteria.
3. Pregnant and/or nursing.
4. Women of childbearing potential not using a reliable method of contraception.
5. Patients with known human immunodeficiency virus (HIV) infection.
6. Patients with significant vasoreactivity during right heart catheterization (i.e., a fall in mPAP to \< 40 mm Hg with a decrease of ≥ 10 mm Hg and with a normal cardiac index ≥ 2.5 l/min.m\^2).
7. Patients with restrictive lung disease (i.e., total lung capacity (TLC) \< 60% of normal predicted value).
8. Patients with obstructive lung disease (i.e., forced expiratory volume/ forced vital capacity (FEV1/FVC) \< 0.5).
9. Patients with impaired left ventricular function (LVEF \<50%) or diastolic dysfunction.
10. Patients with portal hypertension, cirrhosis, moderate to severe liver impairment (Child-Pugh Class B or C), or liver enzymes (Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)) \> 3.0 times the upper limit of normal range.
11. Treatment with glibenclamide (glyburide) and calcineurin inhibitors (cyclosporine A, tacrolimus) sirolimus, everolimus up to 1 week prior to Baseline (Day 1).
12. Patients currently receiving or predicted to require treatment, during the course of the study, with nitrates, protease inhibitors, or alpha-blockers.
13. Patients with a hemoglobin concentration \< 75 % of the lower limit of the normal range or \< 8.5 g/dL.
14. Patients currently receiving or predicted to require treatment with a prostanoid during the course of the study.
15. Patients with systolic blood pressure \< 85 mm Hg.
16. Patients with body weight \< 40 kg.
17. Patients who have received any investigational product within 90 days prior to Baseline.
18. Patients who previously received any advanced therapy for PAH (e.g., ERAs, PDE-5 inhibitors or prostacyclins).
19. Patients with hypersensitivity to sildenafil or any excipients of its formulation.
20. Patients with any contraindication to sildenafil treatment (i.e., nitrates).
21. Patients with any recent medical condition limiting the ability to comply with the study requirements (i.e., stroke, myocardial infarction).
22. Patients with unstable PAH whose disease state would prohibit the completion of study procedures, in the opinion of the investigator.
23. Patients unable to complete a MRI scan (e.g., claustrophobia).
24. Patients with permanent cardiac pacemakers, automatic internal cardioverter defibrillators (AICD's), neurostimulators, hearing aides, and other implanted metallic devices that are contraindicated during a MRI study.
25. Patients with conditions that would interfere with proper cardiac gating during MRI, such as atrial fibrillation or multiple premature ventricular contractions (PVCs)/premature atrial contractions (PACs).
26. Patients with conditions that prevent compliance with the protocol or the ability to adhere to therapy.
B: Inclusion Criteria:

* COPD, FEV1 \< 80% ref. and FEV1/FVC \< 0.7 post bronchodilator
* Age 40-80 years
* Pulmonary hypertension
* Consent to participate in the study

Exclusion Criteria:

* Pulmonary or extrapulmonary disease that modifies gas exchange or pulmonary hemodynamics
* Recent exacerbation (\<4 weeks) (temporally)
* Patients treated with nitrates or CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir)
* Ischemic optic neuropathy
* Patients treated with phosphodiesterase-5 inhibitors
* Patients with ischemic cardiopathy
* Systemic disease that could modified the results
* Patients unable to practise exercise
C: Inclusion Criteria:

* Age at the date of selection ≥ 18 years
* Mean pulmonary pressure ≥ 30 mmHg, measured by a Swan-Ganz catheter placed in the pulmonary artery
* Heart valve intervention: surgical or percutaneous replacement, repair or dilatation performed at least one year before inclusion
* Stable clinical condition for at least one month, without hospital admissions for heart failure, and on appropriate and stable doses of conventional cardiovascular medications

Exclusion Criteria:

* Requiring or likely to require the following medications: organic nitrates, alpha-blocker therapy, potent cytochrome P450 3A4 inhibitors (erythromycin, ketoconazole, cimetidine, HIV protease inhibitors such ritonavir and saquinavir) Patients who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months.
* Patients with resting hypotension, with systolic blood pressure \< 90 mmHg
* Patients with retinitis pigmentosa
* Anatomical deformation of the penis (such as angulation, cavernosal fibrosis or Peyronie's disease) or patients who have conditions which may predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia)
* Severe renal impairment with creatinine clearance \< 30 ml/min
* Significant hepatic dysfunction
* Prosthesis or valvular dysfunction with hemodynamic repercussion.
* Pregnant or breast-feeding women
* Patients unlikely to cooperate in the study or with inability or unwillingness to give informed consent
* Life expectancy less than 2 years due to non-cardiac disease
D: Inclusion Criteria:

* COPD (FEV1/FVC\<0.7)
* Age 40-75
* Pulmonary hypertension (Vmax TI\>=2.8m/sec)

Exclusion Criteria:

* Treatment with CYP3A4 inhibitors, nitrates, PDE-5 inhibitors
* Coronary disease
* Ischemic optical neuritis

Answer: A