Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-Blind, Placebo Controlled, Dose Ranging, Parallel Group Study of Oral Sildenafil in the Treatment of Children, Aged 1-17 Years, With Pulmonary Arterial Hypertension.
Brief Summary: This is a clinical research study designed to evaluate sildenafil for the treatment of Pulmonary Arterial Hypertension in children, aged 1 to 17 years. The purpose of the study is to assess the efficacy, safety, and pharmacokinetics of 16 weeks of chronic treatment with oral sildenafil given in three different doses, compared to placebo (inactive treatment). Efficacy will be measured by exercise and hemodynamics. Patients who complete this trial may be eligible to take part in an extension study, in which all patients will receive active treatment of sildenafil.


Options:
A: 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
B: Inclusion Criteria:

* Participant in Apex 2 high altitude expedition

Exclusion Criteria:

* Previous history of high altitude pulmonary edema
C: Inclusion Criteria:

* Male or female subjects aged from 1 to 17 years old and weighing \>= 8 kg with a mean pulmonary artery pressure \>= 25 mmHg at rest, PCWP \<= 15 mmHg, and PVRI \>= 3 Wood units x m2 (if PCWP is not available, then mean LA pressure \<= 15 mmHg or LVEDP \<= 15 mmHg in the absence of left atrial obstruction).
* Females of child bearing potential who were sexually active must have been practicing a suitable method of birth control so that in the opinion of the investigator, they would not become pregnant during the study.
* Subjects who have symptomatic pulmonary arterial hypertension due to: primary pulmonary hypertension; pulmonary arterial hypertension in the presence of a small or hemodynamically insignificant congenital systemic to pulmonary shunt lesion that in the opinion of the investigator is not the cause of pulmonary hypertension; collagen vascular disease; congenital systemic-to-pulmonary shunts with a baseline resting room air oxygen saturation \>= 88% unrepaired or repaired at least 6 months prior to screening; d-transposition of the great arteries repaired within the first 30 days of life; or surgical repair of other congenital heart lesions at least 6 months prior to screening and do not have clinically significant residual left-sided heart disease consistent with the exclusion criteria.
* Subjects, developmentally able to exercise, whose CPX exercise test functional capacity is within the following parameters: Peak VO2 \>= 10 mL/kg/min and \<= 28 mL/kg/min during screening CPX test;
* Written informed consent and assent where applicable before the subject is screened for the study.
* Subjects who undergo a large shift in altitude (defined as approximately 5000 feet or 1524 meters) in order to participate in the study must reside at the "in study" altitude for at least 90 days prior to baseline and during the study period.

Exclusion Criteria:

* Subjects with pulmonary hypertension secondary to sickle cell disease, any other disease known to be associated with PAH, or any etiology other than those specified in the inclusion criteria.
* Left-sided heart disease, including aortic or mitral valve disease (greater than mild), restrictive or congestive cardiomyopathy; PCWP or LVEDP \> 15 mmHg; LVEF \< 40% determined by MUGA, angiography or echocardiography; LV shortening fraction \< 22% determined by echocardiography, symptomatic coronary disease (demonstrable ischemia).
* Pericardial constriction; significant (2+ for regurgitation) valvular disease other than tricuspid or pulmonary regurgitation; acutely decompensated heart failure within previous 30 days from screening; atrial septostomy within previous 6 months of screening;
* Hemodynamic instability or hypo- or hypertension at screening, i.e., SBP outside of 70-140 mmHg.
* A history of stroke, myocardial infarction or life threatening arrhythmia within 6 months of screening.
* Moderate to severe restrictive pulmonary disease (Total Lung Capacity or Forced Vital Capacity \<= 60% of normal) or history of severe lung disease.
* Subjects with bronchopulmonary dysplasia (BPD) and other chronic lung diseases.
* History of pulmonary embolism.
* Subjects whose CPX test is limited by conditions other than pulmonary hypertension-associated dyspnea or fatigue.
* Subjects who are known to be HIV positive
* Subjects with impairment of renal function (serum creatinine \> 2.5x ULN ) or hepatic function (ALT and/or AST \> 3x ULN; and/or bilirubin \>= 2 mg/dL). Hematological abnormalities (e.g., severe anemia, Hgb \< 10 g/dL, leukopenia, WBC \< 2500/mL).
* Subjects who previously received bosentan and whose liver function tests taken at screening are \> 2x ULN.
* Subjects with any medical condition which in the opinion of the investigator may interfere with treatment, evaluation of safety, and/or efficacy.
* Change in class of medication for CHF or PAH within the 10 days prior to qualifying right heart catheterization.
* Subjects who are currently prescribed and/or taking nitrates or nitric oxide donors in any form. Acute vasodilator testing with nitric oxide is permitted during hemodynamic evaluation; taking chronic arginine supplementation including Heart Bar; therapy involving parenteral inotropic medication or parenteral vasodilators within 3 months of screening; current therapy with alpha-blockers, potent cytochrome P450 3A4 inhibitors (e.g., erythromycin, ketoconazole, itraconazole and protease inhibitors), Ritonavir or Nicorandil; chronic treatment with off-label sildenafil, an endothelin antagonist or prostacyclin/prostacyclin analogue within 30 days of randomization.
* Pregnant or lactating female.
* Any medical or psychological condition or social circumstances that would impair their ability to participate reliably in the study or who were not likely to complete the study for any reason; current or past illicit drug use or alcoholism excepting if abstinence can be documented for \>= 1 year.
* Participation in another clinical trial of an investigational drug or device (including placebo) within 30 days of screening for entry into the present study.
* Subjects with known hereditary degenerative retinal disorders (such as retinitis pigmentosa) or history of non-arteritic anterior ischemic optic neuropathy (NAION).
D: 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.

Answer: C