Pulmonary Artery Remodelling With Bosentan

NCT00595049 | Completed Phase 4

• 1 other identifier: AC-052-416
• Study Type: interventional
• Target: 11
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hypertension, Pulmonary

Keywords

pulmonary; arterial; artery; hypertension; systemic; sclerosis; scleroderma; remodelling; bosentan; tracleer; intravascular

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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

Study Arms (1)

bosentan

EXPERIMENTAL

Drug: bosentan

Interventions

bosentan DRUG

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

Also known as: Tracleer

bosentan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Actelion: lead

MeSH Terms

Conditions

Hypertension, Pulmonary; Hypertension; Sclerosis; Scleroderma, Diffuse

Interventions

Bosentan

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Scleroderma, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• David Celermajer, Professor

  Royal Prince Alfred Hospital, Camperdown

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2008
• First Posted: January 16, 2008
• Study Start: May 1, 2006
• Primary Completion: December 1, 2008
• Study Completion: June 1, 2010
• Last Updated: February 3, 2025

Record last verified: 2025-01