Pulmonary Artery Remodelling With Bosentan

Open Label, Non Comparative Study to Investigate the Effect of Bosentan on Pulmonary Artery Remodelling in Pulmonary Arterial Hypertension (PAH).

The main purpose of this study is to investigate whether bosentan (Tracleer®) affects the wall thickness of the pulmonary arteries in patients with idiopathic pulmonary arterial hypertension (iPAH) and PAH related to systemic sclerosis (PAH-SSc).

The second purpose is to investigate if bosentan affects the enlargement of small vessels in the lungs in response to natural chemicals in patients with iPAH and PAH-SSc.

Inclusion Criteria : · Men or women >18 years of age.·

• Symptomatic (modified NYHA class III) iPAH or PAH-SSc·
• PAH confirmed by right heart catheterization performed within 3 months before enrolment mPAP > 25 mmHg, PCWP < 15 mmHg and PVR > 3 mmHg/l/min.
• Women of childbearing potential must have a negative pre-treatment pregnancy test and use a reliable method of contraception during study treatment and for 3 months after study treatment termination.
• Bosentan naïve patients

Exclusion Criteria : · PAH other than iPAH or PAH-SSc

• Significant vasoreactivity during right heart catheterization defined as a fall in mPAP to < 40 mmHg with a decrease >= 10 mmHg and with a normal cardiac index (>= 2.5 l/min.m2)· Severe obstructive lung disease: FEV1/FVC < 0.5
• Severe restrictive lung disease: TLC < 0.7 of normal predicted value
• Hemoglobin <75% of the lower limit of the normal range· Systolic blood pressure < 85 mmHg
• Body weight < 40 kg
• Pregnancy or breast-feeding
• Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
• Baseline aminotransferases, i.e., aspartate aminotransferases (AST) and/or alanine aminotransferases (ALT) > 3 times the upper limit of the normal (ULN) range.
• Treatment for iPAH or PAH-SSc within 1 month before start of study treatment, excluding warfarin and acute administration of vasodilators for vascular reactivity testing during heart catheterization.
• Treatment with epoprostenol or other prostacyclin analogs for iPAH or PAH-SSc within 1 month before start of study treatment
• Treatment with glibenclamide (glyburide), fluconazole ketoconazole or ritonavir within 1 week before start of study treatment.
• Current treatment with cyclosporine A or tacrolimus
• Hypersensitivity to bosentan or any of the excipients of its formulation.
• Patient who received an investigational drug (such as sildenafil) within 3 months before start of study treatment
• Conditions that prevent compliance with the protocol or adherence to therapy.