Please select the eligibility criteria that correspond to the clinical trial below.
Title: TRIUMPH I: Double Blind Placebo Controlled Clinical Investigation Into the Efficacy and Tolerability of Inhaled Treprostinil Sodium in Patients With Severe Pulmonary Arterial Hypertension
Brief Summary: This is a double-blind placebo-controlled clinical investigation into the efficacy and tolerability of inhaled treprostinil in patients with severe pulmonary arterial hypertension. The primary outcome is the change in 6-minute walk distance from baseline to week 12.


Options:
A: Inclusion Criteria:

* Male and female patients 18-75 years old, with symptomatic PAH
* PAH belonging to the following subgroups of the updated Dana Point Clinical Classification Group 1 (Idiopathic, or Heritable, or Drug or toxin induced, or Associated (APAH) with Connective tissue disease, Congenital heart disease with simple systemic-to-pulmonary shunt at least 1 year after surgical repair, or HIV infection)
* Documented hemodynamic diagnosis of PAH by right heart catheterization, performed at any time prior to Screening
* Six minute walk distance (6MWD) between 50 and 450 m at Screening within 2 weeks prior to the Baseline Visit
* Signed informed consent

Exclusion Criteria:

* Patients with pulmonary hypertension (PH) in the Updated Dana Point Classification Groups 2-5, and PAH Group 1 subgroups that are not covered by the inclusion criteria
* Patients who have received prostacyclin or its analogs within 1 month before Baseline Visit, or are scheduled to receive any of these compounds during the trial
* Patients with moderate or severe obstructive lung disease
* Patients with moderate or severe restrictive lung disease
* Patients with moderate or severe hepatic impairment (Child-Pugh B and C)
* Patients with documented left ventricular dysfunction
* Patients with severe renal insufficiency
* Patients with BMI \<18.5 Kg/m2
* Patients who are receiving or have been receiving any investigational drugs within 1 month before the Baseline Visit
* Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements, in particular with 6MWT
* Recently conducted or planned cardio-pulmonary rehabilitation program based on exercise training
* Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements
* Life expectancy less than 12 months
* Females who are lactating or pregnant or plan to become pregnant during the study
* Known hypersensitivity to any of the excipients of the drug formulations
B: 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.
C: Inclusion Criteria:

* Clinically stable, pulmonary arterial hypertension diagnosed as either idiopathic or familial PAH, collagen vascular disease associated PAH, HIV PAH, or PAH induced by anorexigens, New York Heart Association (NYHA) Class III or Class IV.
* Been on a stable dose of 125 mg twice daily (bid) of bosentan OR any stable dose of sildenafil for at least three months prior to study start
* An unencouraged six minute walk test (6MWT) of between 200 and 450 meters at screening
* Cardiac catheterization within the past 13 months consistent with PAH, specifically mean pulmonary artery pressure (PAPm) ≥25 mmHg (at rest), pulmonary capillary wedge pressure (PCWP) (or left ventricular end diastolic pressure) ≤15 mmHg, and pulmonary vascular resistance (PVR) \>3 mmHg/L/min
* Within the past 12 months, patients must have had a chest radiograph consistent with the diagnosis of PAH
* Willing and able to follow all study procedures

Exclusion Criteria:

* Considering pregnancy, are pregnant and/or lactating
* PAH due to conditions other than noted in the above inclusion criteria.
* Have had any change in or discontinued any PAH medication within the last three months, including but not limited to endothelin receptor antagonist (ERA), or calcium channel blockers (CCB) (with the exception of anticoagulants)
* Have received any prostanoid within the 30 days before screening or are scheduled to receive any during the course of the study
* Have received any investigational medication within 30 days prior to the start of this study or are scheduled to receive another investigational drug during the course of this study
* Have a known intolerance to any drug, especially to treprostinil sodium or prostanoids
* Have an increased risk of hemorrhage
* Have a new type of chronic therapy (e.g., a different category of vasodilator, diuretic) for PAH added within the last month, except anticoagulants
* Have any musculoskeletal disease or any other disease that would limit ambulation.
D: Inclusion Criteria:

* LVEF \>50%
* sinus rhythm and stable clinical condition defined as no changes in therapeutic regimen, or hospitalization in the 6 months preceding recruitment.
* pulmonary artery systolic pressure \> 40 mm Hg,

Exclusion Criteria:

* Patients receiving nitrates
* A history of pulmonary disease
* Alternative causes of PH other than cardiac-related
* Renal failure (creatinine \> 2mg/dL)
* Anemia
* Pericardial disease
* Cardiac amyloidosis

Answer: C