Please select the eligibility criteria that correspond to the clinical trial below.
Title: Prospective, Randomized, Placebo-controlled, Double-blind, Multicenter, Parallel-group, 24-week Study to Assess the Efficacy, Safety and Tolerability of Macitentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension
Brief Summary: Study to evaluate if macitentan is efficient, safe and tolerable enough to be used for treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH).


Options:
A: Inclusion Criteria:

* Male or females from 40 to 80 years of age
* Diagnosis of IPF
* Honeycombing (fibrosis in the lung) on high-resolution computerised tomography (HRCT) scan of less than or equal to 5%
* Willing and able to have 2 right heart catheterizations performed
* Willing to have monthly lab tests to monitor liver function
* Able to perform the 6 minute walk test (indicated adequate physical function)
* Must have meet lung function requirements
* Normal liver function tests
* Negative serum pregnancy test
* Willing to use at least 2 reliable methods of contraception
* Able to understand and willing to sign informed consent form

Exclusion Criteria:

* No restrictive lung disease (other than usual interstitial pneumonia or IPF)
* No obstructive lung disease
* No recent or active respiratory exacerbations
* No recent hospitalization for an IPF exacerbation
* No recent history of alcohol abuse
* Chronic sildenafil (or same drug class) use for pulmonary hypertension
* Chronic treatment with certain medications for IPF within 30 days of randomization
* No other serious medical conditions
B: Inclusion Criteria:

* aged 10 to 80
* treatment naive symptomatic PAH
* 6-MWD of 100-425 m
* resting mean pulmonary artery pressure greater than 25 mm Hg, pulmonary capillary wedge pressure less than 15 mm Hg, and pulmonary vascular resistance of 240 dyn.s.cm-5 or greater.

Exclusion Criteria:

* Patients with thromboembolic disease,
* untreated obstructive sleep apnea,
* portal hypertension,
* chronic liver disease or renal insufficiency,
* left-sided or unrepaired congenital heart disease,
* substantial obstructive (FEV1/FVC\<50% predicted) or restrictive (total lung capacity\<60% predicted) lung disease
* Patients receiving phosphodiesterase inhibitors or other prostanoids and endothelin receptor antagonists
C: Inclusion Criteria:

* Subjects:

  * not participating in the hemodynamic sub-study: males or females ≥ 12 years of age.
  * participating in the hemodynamic sub-study: males or females ≥ 18 years of age.
* Subjects (including those with Down Syndrome \[DS\]) with confirmed Eisenmenger Syndrome \[ES\] (European Society of Cardiology \[ESC\] and the European Respiratory Society \[ERS\] guidelines):

  1. Established by echocardiography as:

     * Large congenital shunting defect at atrial, ventricular or arterial level\*
     * and right to left shunt or bi-directional shunt with prevalent right to left direction.
  2. Resting peripheral oxygen saturation (SpO2) ≤ 90% and \> 70% (pulse oximetry, room air).

The lower limit is 65% if a subject is living at an altitude greater than 2500 m above sea level.

\*Subjects with any of the following open defects are eligible for the study either as an isolated defect or in combination:

* atrial septal defect (ASD)
* ventricular septal defect (VSD)
* partial or complete atrioventricular septal defect (AVSD)
* patent ductus arteriosus (PDA)
* aortopulmonary window (AP window)
* total or partial anomalous pulmonary venous return (TAPVR, PAPVR) The defects may be either unoperated or previously palliated surgically (provided significant residual defect remains).

The Steering Committee will review the echocardiography data of all subjects (main study and sub study) to confirm eligibility prior to Randomization.

* Subjects with the following findings at cardiac catheterization:

  * Mean resting pulmonary arterial pressure (mPAP) \> 25 mmHg
  * Pulmonary capillary wedge pressure (PCWP) or mean left atrial pressure (LAP) or left ventricular end diastolic pressure (LVED) ≤ 15 mmHg
  * Pulmonary vascular resistance (PVR) ≥ 800 dyn∙s/cm5 or ≥ 10 Wood units
* Subjects with WHO functional class ≥ II.
* Subjects able to reliably perform the the 6-minute walk test (6MWT) with a minimum distance of 50 m and a maximum distance of 450 m.

Exclusion Criteria:

- Main study and hemodynamic sub-study: Any of the following conditions previously known or identified via cardiac catheterization or echocardiography:

* Pulmonary arterial or venous stenosis \> 25% size of native pulmonary artery (PA) or pulmonary vein
* Severe tricuspid regurgitation in the setting of left to right shunt at the ventricular or atrial level
* Greater than mild tricuspid stenosis
* Intracavitary RV outflow obstruction
* Greater than mild mitral stenosis
* Intracavitary LV outflow obstruction
* Subvalvular or supravalvular aortic stenosis
* Aortic coarctation
* Greater than moderate mitral regurgitation
* Recognized extracardiac systemic venous collaterals to the pulmonary venous circulation
* Recognized hepatic wedge pressure-inferior vena cava pressure gradient \>12 mm Hg
* PCWP "v" waves \>20 mmHg
* Tetralogy of Fallot
* Truncus arteriosus
* Interrupted aortic arch
* Transposition of great arteries
* Single ventricle defects: absent AV connection (mitral or tricuspid atresia), double inlet AV connections left or right ventricle, functional univentricular heart (unbalanced AVSD, hypoplastic RV, double outlet RV), hypoplastic left heart syndrome
* Ebstein's anomaly
* Severe aortic regurgitation
* Pulmonary atresia
* PAPVR or TAPVR, ONLY if there is lung hypoplasia or if documentation confirming the absence of lung hypoplasia does not exist.

For subjects participating in the hemodynamic sub-study the following will also be considered exclusion criteria:

* SVC stenosis \>25% size of native vessel
* PDA, AP window, TAPVR, PAPVR, or ASD sinus venosus with anomalous pulmonary veins
* Down Syndrome

  * Subjects with deterioration of their clinical status within 3 months prior to Screening or during the Screening period.
  * Known moderate-to-severe restrictive (i.e., total lung capacity \[TLC\] \< 60% of predicted value) or obstructive lung disease (i.e., forced expiratory volume in one second \[FEV1\] \< 80 % of predicted value, and with FEV1 / forced vital capacity \[FVC\] \< 70%)
  * Treatment with prostanoids within 1 month prior to Randomization
  * Subjects who initiated a PDE-5 inhibitor within 1 month prior to Randomization or those on a PDE-5 inhibitor for whom the dose has not been stable within 1 month prior to Randomization
  * Treatment with endothelin receptor antagonists (ERAs) within 1 month prior to Randomization
  * Subjects who initiated diuretics within 1 week prior to Randomization or subjects whose diuretic treatment has not been stable for at least 1 week prior to Randomization
  * Subjects being considered for an organ transplant
D: Inclusion Criteria:

* Written informed consent
* Subject with CTEPH (WHO Group 4) judged as inoperable due to the localization of the obstruction being surgically inaccessible (i.e., distal disease).
* Female of childbearing potential must have a negative pre-treatment serum pregnancy test, be advised on appropriate methods of contraception, and agree to use 2 reliable methods of contraception.

Exclusion Criteria:

* Previous pulmonary endarterectomy.
* Recurrent thromboembolism despite sufficient oral anticoagulants.
* Symptomatic acute pulmonary embolism in the 6-month period prior to randomization.
* Known moderate-to-severe restrictive lung disease (i.e., TLC \< 60% of predicted value) or obstructive lung disease (i.e., FEV1 \< 70% of predicted, with FEV1/FVC \< 65%) or known significant chronic lung disease diagnosed by chest imaging (e.g., interstitial lung disease, emphysema).
* Acute or chronic conditions (other than dyspnea) that limit the ability to comply with study requirements in the 3-month period prior to Screening visit or during the Screening period.

Answer: D