Pulmonary Artery Remodelling With Bosentan

Sponsor

Actelion (Industry)

Overall Status

Completed

CT.gov ID

NCT00595049

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypertension, Pulmonary	Drug: bosentan	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

11 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2006

Actual Primary Completion Date :

Dec 1, 2008

Actual Study Completion Date :

Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: bosentan	Drug: bosentan Bosentan 62.5 mg bid for 4 weeks, then 125 mg bid Other Names: Tracleer

Arm

Intervention/Treatment

Experimental: bosentan

Drug: bosentan

Bosentan 62.5 mg bid for 4 weeks, then 125 mg bid

Other Names:

Tracleer

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.