Pulmonary Artery Remodelling With Bosentan

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT00595049
First received: January 7, 2008
Last updated: March 9, 2012
Last verified: March 2012
  Purpose

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 Intervention Phase
Hypertension, Pulmonary
Drug: bosentan
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: 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).

Resource links provided by NLM:


Further study details as provided by Actelion:

Primary Outcome Measures:
  • Change from baseline (BL) to 6 mths in the IVUS-derived measurement of pulmonary artery wall thickness. [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
  • Change from BL to 6 mths in pulmonary microvascular circulation dilator responses to actylcholine (Ach). [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from BL to 6 mths in each of the IVUS derived pulmonary artery parameters. [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
  • Change from BL to 6 mths in pulmonary microvascular circulation dilator responses to sodium nitroprusside. [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 11
Study Start Date: May 2006
Study Completion Date: June 2010
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: bosentan Drug: bosentan
Bosentan 62.5 mg bid for 4 weeks, then 125 mg bid
Other Name: Tracleer

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00595049

Locations
United States, New York
New York, New York, United States
Australia
Royal Prince Alfred Hospital
Camperdown, Australia
Sponsors and Collaborators
Actelion
Investigators
Principal Investigator: David Celermajer, Professor Royal Prince Alfred Hospital, Camperdown
  More Information

No publications provided

Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT00595049     History of Changes
Other Study ID Numbers: AC-052-416
Study First Received: January 7, 2008
Last Updated: March 9, 2012
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Actelion:
pulmonary
arterial
artery
hypertension
systemic
sclerosis
scleroderma
remodelling
bosentan
tracleer
intravascular

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Bosentan
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014