Pulmonary Artery Remodelling With Bosentan

Hypertension, Pulmonary Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00595049
• Other study ID #: AC-052-416
• Status: Completed
• Phase: Phase 4
• First received: January 7, 2008
• Last updated: April 28, 2015
• Start date: May 2006
• Est. completion date: June 2010

Study information

• Verified date: April 2015
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: June 2010
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary

Intervention

Drug:
• bosentan
Bosentan 62.5 mg bid for 4 weeks, then 125 mg bid

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital	Camperdown

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline (BL) to 6 mths in the IVUS-derived measurement of pulmonary artery wall thickness.		Baseline to 6 months	No
Primary	Change from BL to 6 mths in pulmonary microvascular circulation dilator responses to actylcholine (Ach).		Baseline to 6 months	No
Secondary	Change from BL to 6 mths in each of the IVUS derived pulmonary artery parameters.		Baseline to 6 months	No
Secondary	Change from BL to 6 mths in pulmonary microvascular circulation dilator responses to sodium nitroprusside.		Baseline to 6 months	No
Secondary	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	No
Secondary	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	No