Pulmonary Artery Remodelling With Bosentan
Primary Purpose
Hypertension, Pulmonary
Status
Completed
Phase
Phase 4
Locations
Australia
Study Type
Interventional
Intervention
bosentan
Sponsored by
About this trial
This is an interventional treatment trial for Hypertension, Pulmonary focused on measuring pulmonary, arterial, artery, hypertension, systemic, sclerosis, scleroderma, remodelling, bosentan, tracleer, intravascular
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.
Sites / Locations
- Royal Prince Alfred Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
bosentan
Arm Description
Outcomes
Primary Outcome Measures
Change from baseline (BL) to 6 mths in the IVUS-derived measurement of pulmonary artery wall thickness.
Change from BL to 6 mths in pulmonary microvascular circulation dilator responses to actylcholine (Ach).
Secondary Outcome Measures
Change from BL to 6 mths in each of the IVUS derived pulmonary artery parameters.
Change from BL to 6 mths in pulmonary microvascular circulation dilator responses to sodium nitroprusside.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00595049
Brief Title
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
2. Study Status
Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
May 2006 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
June 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actelion
4. Oversight
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension, Pulmonary
Keywords
pulmonary, arterial, artery, hypertension, systemic, sclerosis, scleroderma, remodelling, bosentan, tracleer, intravascular
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
bosentan
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
bosentan
Other Intervention Name(s)
Tracleer
Intervention Description
Bosentan 62.5 mg bid for 4 weeks, then 125 mg bid
Primary Outcome Measure Information:
Title
Change from baseline (BL) to 6 mths in the IVUS-derived measurement of pulmonary artery wall thickness.
Time Frame
Baseline to 6 months
Title
Change from BL to 6 mths in pulmonary microvascular circulation dilator responses to actylcholine (Ach).
Time Frame
Baseline to 6 months
Secondary Outcome Measure Information:
Title
Change from BL to 6 mths in each of the IVUS derived pulmonary artery parameters.
Time Frame
Baseline to 6 months
Title
Change from BL to 6 mths in pulmonary microvascular circulation dilator responses to sodium nitroprusside.
Time Frame
Baseline to 6 months
Title
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.
Time Frame
Baseline to 6 months
Title
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.
Time Frame
Baseline to 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Celermajer, Professor
Organizational Affiliation
Royal Prince Alfred Hospital, Camperdown
Official's Role
Principal Investigator
Facility Information:
Facility Name
Royal Prince Alfred Hospital
City
Camperdown
Country
Australia
12. IPD Sharing Statement
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Pulmonary Artery Remodelling With Bosentan
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