Please select the eligibility criteria that correspond to the clinical trial below.
Title: Vasodilator Therapy and Exercise Tolerance in IPF Patients
Brief Summary: Medicines that decrease blood pressure in the lungs may help idiopathic pulmonary fibrosis (IPF) patients function better. This study will test whether sildenafil improves the ability to exercise in patients with pulmonary fibrosis of unknown cause.


Options:
A: Inclusion Criteria:

* Clinical diagnosis of IPF
* 40-85 years of age
* 6-minute walk distance 150-500 m
* FVC 40-90% predicted
* DLCO 30-90% predicted

Exclusion Criteria:

* Severe pulmonary hypertension
* Severe heart failure
* FEV1/FVC \< 0.7
B: 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.
C: Inclusion Criteria:

* Subjects must have a diagnosis of Pulmonary Arterial Hypertension (PAH) due to the following:

  a. idiopathic or heritable PAH b. PAH associated with: i. connective tissue disease (e.g., limited scleroderma, diffuse scleroderma, mixed connective tissue disease, systemic lupus erythematosus, or overlap syndrome) ii. drugs or toxins iii. Human Immunodeficiency Virus (HIV) infection iv. congenital heart defects repaired greater than 1 year prior to screening (i.e., atrial septal defects, ventricular septal defects, and patent ductus arteriosus) NB: subjects with portopulmonary hypertension and pulmonary veno-occlusive disease are NOT eligible for the study
* Subject must have a current diagnosis of being in World Health Organisation (WHO) Functional Class II or III.
* Subject must meet all of the following haemodynamic criteria by means of a right heart catheterization prior to screening:

  i. mPAP of ≥25 mmHg ii. PVR ≥ 300 dynes/sec/cm5 iii. PCWP or LVEDP of ≤12 mmHg if PVR ≥300 to \<500 dyne/sec/cm5 , or PCWP/LVEDP ≤ 15 mmHg if PVR ≥500 dynes/sec/cm5
* Subject must walk a distance of ≥125m and ≤500m at the screening visit

Exclusion Criteria:

* Subject received previous PAH therapy (phosphodiesterase type 5 inhibitor (PDE5i), endothelin receptor antagonist (ERA), chronic prostanoid\*) within 4 weeks prior to the screening visit (\*Chronic prostanoid use is considered \>7 days of treatment)
* Subject received ERA treatment (e.g., bosentan or sitaxentan) or PDE5i treatment (e.g. Sildenafil) at any time AND discontinued due to tolerance issues other than those associated with liver function abnormalities
* Subjects who have previously discontinued ambrisentan or tadalafil in either another clinical study or commercial product (Volibris/Letairis or Adcirca) for safety or tolerability reasons.
D: Inclusion Criteria:

* \>18 years
* Written inform consent
* PH secondary to diastolic left heart failure defined as
* PAP mean \>25 mmHg
* Wedge mean \>15 mmHg
* Normal systolic left ventricular (LV) function on echo/nuclear imaging (left ventricular ejection fraction (LVEF) \> or =45%)
* New York Heart Association class (NYHA) II-IV despite heart failure therapy

Exclusion Criteria:

* Severe noncardiac limitation to exercise (as severe chronic obstructive pulmonary disease)
* Other cause of PH besides diastolic heart failure
* Coronary ischemia or recent myocardial infarction (\<6 months)
* Hypotension ( \<90/50 mmHg)
* Ongoing nitrate therapy
* Ongoing therapy with citochrome P450 3A4 ( CYP3A4) inhibitors (ketoconazole, erythromycin, cimetidine, clarithromycin, itraconazole, voriconazole and protease inhibitors) or CYP3A4 inductors(carbamacepine, phenytoin, phenobarbital, rifampicin, Sint Janskruid ). Furthermore patients will be informed not to drink grapefruit juice while on study medication because of the known impact of grape fruit on pharmacokinetics of Sildenafil.
* Ongoing therapy with alpha -inhibitors
* Significant mitral or aortic valve dysfunction
* Severe liver dysfunction
* Pregnancy
* Unable to read and comprehend Dutch language

Answer: A