Clinical trial NCT00595049: Pulmonary Artery Remodelling With Bosentan
Official title: Open Label, Non Comparative Study to Investigate the Effect of Bosentan on Pulmonary Artery Remodelling in Pulmonary Arterial Hypertension (PAH).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension, Pulmonary
Keywords: pulmonary
arterial
artery
hypertension
systemic
sclerosis
scleroderma
remodelling
bosentan
tracleer
intravascular
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2008-01-16
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline (BL) to 6 mths in the IVUS-derived measurement of pulmonary artery wall thickness.
timeFrame: Baseline to 6 months
measure: Change from BL to 6 mths in pulmonary microvascular circulation dilator responses to actylcholine (Ach).
timeFrame: Baseline to 6 months
Secondary outcomes:
measure: Change from BL to 6 mths in each of the IVUS derived pulmonary artery parameters.
timeFrame: Baseline to 6 months
measure: Change from BL to 6 mths in pulmonary microvascular circulation dilator responses to sodium nitroprusside.
timeFrame: Baseline to 6 months
measure: 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.
timeFrame: Baseline to 6 months
measure: 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.
timeFrame: Baseline to 6 months
Other outcomes:
Locations:
Study officials:
affiliation: Royal Prince Alfred Hospital, Camperdown
name: David Celermajer, Professor
role: PRINCIPAL_INVESTIGATOR
References: