Hypertension, Pulmonary
Conditions
Keywords
pulmonary, arterial, artery, hypertension, systemic, sclerosis, scleroderma, remodelling, bosentan, tracleer, intravascular
Brief summary
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.
Interventions
DRUGbosentan
Bosentan 62.5 mg bid for 4 weeks, then 125 mg bid
Sponsors
Actelion
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline (BL) to 6 mths in the IVUS-derived measurement of pulmonary artery wall thickness. | Baseline to 6 months |
| Change from BL to 6 mths in pulmonary microvascular circulation dilator responses to actylcholine (Ach). | Baseline to 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Change from BL to 6 mths in each of the IVUS derived pulmonary artery parameters. | Baseline to 6 months |
| Change from BL to 6 mths in pulmonary microvascular circulation dilator responses to sodium nitroprusside. | Baseline to 6 months |
| Correlation between the change from BL to 6 mths of each of the IVUS-derived parameters and the pulmonary microvascular circulation (PMVC) dilator responses versus changes in PVR. | Baseline to 6 months |
| Correlation between the change from BL to 6 mths of each of the IVUS-derived parameters and the PMVC dilator responses versus changes in 6MWD. | Baseline to 6 months |
Countries
Australia
Contacts
PRINCIPAL_INVESTIGATORDavid Celermajer, Professor
Royal Prince Alfred Hospital, Camperdown
Outcome results
None listed