Pulmonary HypertensionPhase 4B-PHITNCT00637065
Bosentan in Pulmonary Hypertension in Interstitial Lung Disease Treatment Study
A Phase 4 study testing Bosentan in people with Pulmonary Hypertension and Interstitial Lung Disease, run by Royal Brompton & Harefield NHS Foundation Trust at 3 sites in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Pulmonary Hypertension, Interstitial Lung Disease, Idiopathic Pulmonary Fibrosis
- What is being tested?
- Bosentan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Apr 2008to Aug 2010
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients >=18yrs, <80yrs
- Patients with idiopathic pulmonary fibrosis (IPF) or idiopathic fibrotic non-specific interstitial pneumonitis (NSIP) confirmed by their respiratory physician according to ATS/ERS criteria.
- Patients with pulmonary hypertension on right heart catheter (mean pulmonary arterial pressure >=25mmHg with pulmonary artery occlusion pressure, left atrial pressure or left ventricular end-diastolic pressure <15mmHg).
- Patients providing written informed consent.
Who cannot join
- Patients <18, >80yrs.
- Patients with unstable disease, or an acute exacerbation of their underlying fibrotic lung disease.
- Patients with significant other organ co-morbidity including hepatic or renal impairment.
- Patients with systolic BP < 85mmHg
- Patients with other conditions that may affect the ability to perform a 6-minute walk test.
- Patients unable to provide informed consent and comply with the patient protocol.
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- Patients receiving excluded medications (including: epoprostenol, or prostacyclin analogues, phosphodiesterase inhibitors, other endothelin receptor antagonists, drugs with potential interaction with bosentan such as glibenclamide, fluconazole, cyclosporin A, or tacrolimus, and other investigational agents).
- Patients with planned surgical intervention during the study period.
- Pregnant patients or women of child-bearing age, who are not using a reliable contraceptive method.
- Patients with clinically overt ischaemic heart disease.
- Patients with predominant emphysema on high resolution CT scan (emphysema greater in extent than interstitial changes).
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
St George's Hospital
London, London, SW1 O7QT
Brendan Madden, MD MSc FRCP, 0208 725 5877, Brendan.Madden@stgeorges.nhs.uk
Brendan Madden, MD MSc FRCP
Royal Brompton Hospital
London, London, SW3 6NP
Stephen J Wort, FRCP PhD, 0207 352 8121 ext. 8362, s.wort@imperial.ac.uk
Athol U Wells, MD FRCP FRCR, 0207 352 8121 ext. 3354, A.Wells@rbht.nhs.uk
Hammersmith Hospital
London, London, W12 OHS
Luke Howard, DPhil MRCP, 0208 383 2330, luke.howard@hhnt.nhs.uk
Luke Howard, DPhil MRCP
About this study
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.
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).
Read the detailed description
- 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.
- Conditions
- Pulmonary Hypertension, Interstitial Lung Disease, Idiopathic Pulmonary Fibrosis, Nonspecific Interstitial Pneumonia
- Being tested
- Bosentan, Placebo
- Keywords
- Pulmonary hypertension, Interstitial lung disease, Idiopathic pulmonary fibrosis, Nonspecific interstitial pneumonia, Bosentan, Endothelin receptor antagonists, Pulmonary vascular resistance
- Medical subject headings
- Hypertension, Pulmonary, Lung Diseases, Interstitial, Idiopathic Pulmonary Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BosentanDrug
Also called Tracleer
Bosentan tablets - 62.5mg bd for first 4 weeks, then 125mg bd if tolerated until trial completion.
PlaceboDrug
Also called Placebo tablets
Placebo tables - identical to active drug but without the active ingredient -
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Bosentan tablets (62.5mg bd for first 4 weeks, then 125mg bd as tolerated) Receives: Drug: Bosentan |
| 2 | Placebo comparator | Placebo tablets Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint is a fall in pulmonary vascular resistance (PVR) of 20% over 16 weeks.
Measured: 16 weeks
Secondary outcomes (8)
mean Pulmonary arterial Pressure
Measured: 16 weeks
Six minute walk distance
Measured: 16 weeks
Quality of life scores (Camphor questionnaire)
Measured: 16 weeks
Pulmonary function (DLco, FVC and PaO2)
Measured: 16 weeks
Pulmonary blood flow
Measured: 16 weeks
Right ventricular mass (Cardiac MRI)
Measured: 16 weeks
BNP
Measured: 16 weeks
Progression free survival
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2008 (estimated)
- Study startApr 2008
- Primary completionApr 2010 (estimated)
- Study completionAug 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royal Brompton & Harefield NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Actelion
- Investigators
- Stephen J Wort, FRCP PhD, Principal investigator, Royal Brompton Hospital, LondonAthol U Wells, MD FRCP FRCR, Principal investigator, Royal Brompton Hospital, LondonLuke Howard, DPhil MRCP, Principal investigator, Hammersmith Hospitals NHS TrustBrendan Madden, MD MSc FRCP, Principal investigator, Royal Brompton & Harefield NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00637065
- Sponsor's protocol ID
- 2007OE002B
- Other IDs
- REC number: 07/H0714/125, EudraCT no: 2007-001643-21
- Acronym
- B-PHIT
- Status last verified
- Mar 2008
- First submitted
- 10 Mar 2008
- Last updated
- 17 Mar 2008
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Corte TJ, Keir GJ, Dimopoulos K, Howard L, Corris PA, Parfitt L, Foley C, Yanez-Lopez M, Babalis D, Marino P, Maher TM, Renzoni EA, Spencer L, Elliot CA, Birring SS, O'Reilly K, Gatzoulis MA, Wells AU, Wort SJ; BPHIT Study Group. Bosentan in pulmonary hypertension associated with fibrotic idiopathic interstitial pneumonia. Am J Respir Crit Care Med. 2014 Jul 15;190(2):208-17. doi: 10.1164/rccm.201403-0446OC.
PubMed 24937643
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00637065
- Acronym / sponsor ID
- B-PHIT / 2007OE002B
- Conditions
- Pulmonary Hypertension, Interstitial Lung Disease, Idiopathic Pulmonary Fibrosis, Nonspecific Interstitial Pneumonia
- Keywords
- Pulmonary hypertension, Interstitial lung disease, Idiopathic pulmonary fibrosis, Nonspecific interstitial pneumonia, Bosentan, Endothelin receptor antagonists, Pulmonary vascular resistance
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Royal Brompton & Harefield NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Actelion
- Study start
- Apr 2008
- Primary completion
- Apr 2010 (estimated)
- Study completion
- Aug 2010 (estimated)
- First posted
- 17 Mar 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: BosentanBosentan tablets (62.5mg bd for first 4 weeks, then 125mg bd as tolerated) |
| 2 | Placebo comparator | Drug: PlaceboPlacebo tablets |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients >=18yrs, <80yrs
- Patients with idiopathic pulmonary fibrosis (IPF) or idiopathic fibrotic non-specific interstitial pneumonitis (NSIP) confirmed by their respiratory physician according to ATS/ERS criteria.
- Patients with pulmonary hypertension on right heart catheter (mean pulmonary arterial pressure >=25mmHg with pulmonary artery occlusion pressure, left atrial pressure or left ventricular end-diastolic pressure <15mmHg).
- Patients providing written informed consent.
Key exclusion criteria (11 listed)
- Patients <18, >80yrs.
- Patients with unstable disease, or an acute exacerbation of their underlying fibrotic lung disease.
- Patients with significant other organ co-morbidity including hepatic or renal impairment.
- Patients with systolic BP < 85mmHg
- Patients with other conditions that may affect the ability to perform a 6-minute walk test.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BosentanAlso: TracleerBosentan tablets - 62.5mg bd for first 4 weeks, then 125mg bd if tolerated until trial completion. | Drug | 1 |
| PlaceboAlso: Placebo tabletsPlacebo tables - identical to active drug but without the active ingredient - | Drug | 2 |
Primary outcome
The primary endpoint is a fall in pulmonary vascular resistance (PVR) of 20% over 16 weeks.
Time frame: 16 weeks
8 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2008.
- Derived from this study: PubMed 24937643Corte TJ, Keir GJ, Dimopoulos K, Howard L, Corris PA, Parfitt L, Foley C, Yanez-Lopez M, Babalis D, Marino P, Maher TM, Renzoni EA, Spencer L, Elliot CA, Birring SS, O'Reilly K, Gatzoulis MA, Wells AU, Wort SJ; BPHIT Study Group. Bosentan in pulmonary hypertension associated with fibrotic idiopathic interstitial pneumonia. Am J Respir Crit Care Med. 2014 Jul 15;190(2):208-17. doi: 10.1164/rccm.201403-0446OC.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen J Wort, FRCP PhD principal investigator
Royal Brompton Hospital, London
Athol U Wells, MD FRCP FRCR principal investigator
Royal Brompton Hospital, London
Luke Howard, DPhil MRCP principal investigator
Hammersmith Hospitals NHS Trust
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bosentan in people with Pulmonary Hypertension and Interstitial Lung Disease, run by Royal Brompton & Harefield NHS Foundation Trust at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Stephen J Wort, MRCP PhD (0207 352 8121 ext. 8362, s.wort@imperial.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary endpoint is a fall in pulmonary vascular resistance (PVR) of 20% over 16 weeks. (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00637065, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2008.