Bosentan in Pulmonary Hypertension in Interstitial Lung Disease Treatment Study (B-PHIT)
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|ClinicalTrials.gov Identifier: NCT00637065|
Recruitment Status : Unknown
Verified March 2008 by Royal Brompton & Harefield NHS Foundation Trust.
Recruitment status was: Not yet recruiting
First Posted : March 17, 2008
Last Update Posted : March 17, 2008
Over time, patients with fibrosing or interstitial lung disease (ILD) can develop high lung blood pressures (pulmonary hypertension), and this is associated with poorer prognosis and survival. It is thought that development of PH contributes to the deterioration and death of patients with ILD. Endothelin-1 (ET1) is a substance contributing to the development of both PH and ILD. Bosentan is a drug blocking the action of ET-1 by binding to its receptors. Bosentan clearly benefits patients with PH of unknown cause, or related to other diseases (such as heart conditions, or HIV) both alone and in combination with other treatments. In patients with fibrosing lung disease and PH, there have been no controlled treatment studies. Clearly it is important to evaluate the effectiveness of bosentan in these patients.
This study aims to determine the ability of bosentan to reduce high blood pressure in the lungs (pulmonary hypertension) in patients with scarring (fibrosing) lung disease. It is a placebo-controlled double blinded study for 16 weeks (and it is proposed to follow patients in a 16 week open-label phase with bosentan therapy).
|Condition or disease||Intervention/treatment||Phase|
|Pulmonary Hypertension Interstitial Lung Disease Idiopathic Pulmonary Fibrosis Nonspecific Interstitial Pneumonia||Drug: Bosentan Drug: Placebo||Phase 4|
• Purpose: High blood pressure in the lungs or pulmonary hypertension (PH) is a common complication of fibrosing (or interstitial, ILD) lung disease. When present, it is associated with markedly reduced prognosis and survival. Endothelin-1 (ET-1)is over-expressed in patients with PH and ILD, and is thought to play a role in the development of both conditions. Bosentan blocks the action of ET-1, and has been shown to be beneficial in patients with PH from an unknown cause, or related to other conditions (such as heart conditions, connective-tissue disease, and HIV). It is important to establish whether bosentan treatment also benefits patients with PH and ILD.
This study addresses the effectiveness of bosentan in the context of PH and ILD.
• Objective: To examine the ability of bosentan to reduce high blood pressure in the lungs in patients with fibrosing lung diseases and pulmonary hypertension.
• Design: This is a multi-centre, randomised, double-blinded, placebo-controlled study looking at the effect of bosentan in patients with fibrotic lung disease and PH.
• Methodology: Patients will be recruited from outpatient ILD and PH clinical services and will be consented prior to entering the study. We propose to study 48 patients over a 16 week period. Patients will be included in the study if they have fibrosing lung disease (specifically: idiopathic pulmonary fibrosis or idiopathic fibrosing non-specific pneumonitis) and have PH as determined by measurement on right heart catheter (mean pulmonary artery pressure >=25mmHg, pulmonary capillary wedge pressure =<15mmHg).
Patients will enter a 2 week screening period during which they will have a full medical history and examination. If they have not already had clinically important investigations ( echocardiogram, cardiac MRI, overnight oximetry) within the previous 6 weeks and CT scan within the last 3 months, these will be performed.
The patient will have a baseline 6 minute walk test, ECG (heart tracing), blood tests and pulmonary blood flow study (breath test) and lung function tests (breathing tests) and complete a quality of life questionnaire. The patient will then be randomised to bosentan or placebo (2:1)at the baseline visit. Patients will be followed every 4 weeks with physical examination, and blood tests.
At week 16, the initial investigations (including right heart catheter, lung function, pulmonary blood flow, 6-minute walk, blood tests, echocardiogram and cardiac MRI and complete a quality of life questionnaire) will be repeated.
Patients will be offered treatment with open-labelled bosentan therapy until the results of the trial become available up to a maximum of 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||48 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Use of the Endothelin-1 Antagonist Bosentan in Patients With Established Pulmonary Hypertension and Fibrotic Lung Disease. - A Randomised, Placebo-Controlled, Double-Blinded Study.|
|Study Start Date :||April 2008|
|Estimated Primary Completion Date :||April 2010|
|Estimated Study Completion Date :||August 2010|
Active Comparator: 1
Bosentan tablets (62.5mg bd for first 4 weeks, then 125mg bd as tolerated)
Bosentan tablets - 62.5mg bd for first 4 weeks, then 125mg bd if tolerated until trial completion.
Other Name: Tracleer
Placebo Comparator: 2
Placebo tables - identical to active drug but without the active ingredient -
Other Name: Placebo tablets
- The primary endpoint is a fall in pulmonary vascular resistance (PVR) of 20% over 16 weeks. [ Time Frame: 16 weeks ]
- mean Pulmonary arterial Pressure [ Time Frame: 16 weeks ]
- Six minute walk distance [ Time Frame: 16 weeks ]
- Quality of life scores (Camphor questionnaire) [ Time Frame: 16 weeks ]
- Pulmonary function (DLco, FVC and PaO2) [ Time Frame: 16 weeks ]
- Pulmonary blood flow [ Time Frame: 16 weeks ]
- Right ventricular mass (Cardiac MRI) [ Time Frame: 16 weeks ]
- BNP [ Time Frame: 16 weeks ]
- Progression free survival [ Time Frame: 16 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00637065
|Contact: Stephen J Wort, MRCP PhD||0207 352 8121 ext firstname.lastname@example.org|
|Contact: Athol U Wells, MD FRCP FRCR||0207 352 8121 ext email@example.com|
|St George's Hospital|
|London, United Kingdom, SW1 O7QT|
|Contact: Brendan Madden, MD MSc FRCP 0208 725 5877 Brendan.Madden@stgeorges.nhs.uk|
|Principal Investigator: Brendan Madden, MD MSc FRCP|
|Royal Brompton Hospital|
|London, United Kingdom, SW3 6NP|
|Contact: Stephen J Wort, FRCP PhD 0207 352 8121 ext 8362 firstname.lastname@example.org|
|Contact: Athol U Wells, MD FRCP FRCR 0207 352 8121 ext 3354 A.Wells@rbht.nhs.uk|
|Principal Investigator: Stephen J Wort, FRCP PhD|
|Sub-Investigator: Athol U Wells, MD FRCP FRCR|
|London, United Kingdom, W12 OHS|
|Contact: Luke Howard, DPhil MRCP 0208 383 2330 email@example.com|
|Principal Investigator: Luke Howard, DPhil MRCP|
|Principal Investigator:||Stephen J Wort, FRCP PhD||Royal Brompton Hospital, London|
|Principal Investigator:||Athol U Wells, MD FRCP FRCR||Royal Brompton Hospital, London|
|Principal Investigator:||Luke Howard, DPhil MRCP||Hammersmith Hospitals NHS Trust|
|Principal Investigator:||Brendan Madden, MD MSc FRCP||Royal Brompton & Harefield NHS Foundation Trust|