Bosentan in Pulmonary Hypertension in Interstitial Lung Disease Treatment Study (B-PHIT)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2008 by Royal Brompton & Harefield NHS Foundation Trust.
Recruitment status was  Not yet recruiting
Sponsor:
Collaborator:
Actelion
Information provided by:
Royal Brompton & Harefield NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT00637065
First received: March 10, 2008
Last updated: NA
Last verified: March 2008
History: No changes posted
  Purpose

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 Intervention Phase
Pulmonary Hypertension
Interstitial Lung Disease
Idiopathic Pulmonary Fibrosis
Nonspecific Interstitial Pneumonia
Drug: Bosentan
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Royal Brompton & Harefield NHS Foundation Trust:

Primary Outcome Measures:
  • The primary endpoint is a fall in pulmonary vascular resistance (PVR) of 20% over 16 weeks. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • mean Pulmonary arterial Pressure [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Six minute walk distance [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Quality of life scores (Camphor questionnaire) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Pulmonary function (DLco, FVC and PaO2) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Pulmonary blood flow [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Right ventricular mass (Cardiac MRI) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • BNP [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Progression free survival [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: April 2008
Estimated Study Completion Date: August 2010
Estimated Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Bosentan tablets (62.5mg bd for first 4 weeks, then 125mg bd as tolerated)
Drug: Bosentan
Bosentan tablets - 62.5mg bd for first 4 weeks, then 125mg bd if tolerated until trial completion.
Other Name: Tracleer
Placebo Comparator: 2
Placebo tablets
Drug: Placebo
Placebo tables - identical to active drug but without the active ingredient -
Other Name: Placebo tablets

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients >=18yrs, <80yrs
  2. Patients with idiopathic pulmonary fibrosis (IPF) or idiopathic fibrotic non-specific interstitial pneumonitis (NSIP) confirmed by their respiratory physician according to ATS/ERS criteria.
  3. 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).
  4. Patients providing written informed consent.

Exclusion Criteria:

  1. Patients <18, >80yrs.
  2. Patients with unstable disease, or an acute exacerbation of their underlying fibrotic lung disease.
  3. Patients with significant other organ co-morbidity including hepatic or renal impairment.
  4. Patients with systolic BP < 85mmHg
  5. Patients with other conditions that may affect the ability to perform a 6-minute walk test.
  6. Patients unable to provide informed consent and comply with the patient protocol.
  7. 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).
  8. Patients with planned surgical intervention during the study period.
  9. Pregnant patients or women of child-bearing age, who are not using a reliable contraceptive method.
  10. Patients with clinically overt ischaemic heart disease.
  11. Patients with predominant emphysema on high resolution CT scan (emphysema greater in extent than interstitial changes).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00637065

Contacts
Contact: Stephen J Wort, MRCP PhD 0207 352 8121 ext 8362 s.wort@imperial.ac.uk
Contact: Athol U Wells, MD FRCP FRCR 0207 352 8121 ext 3354 a.wells@rbht.nhs.uk

Locations
United Kingdom
Hammersmith Hospital Not yet recruiting
London, United Kingdom, W12 OHS
Contact: Luke Howard, DPhil MRCP    0208 383 2330    luke.howard@hhnt.nhs.uk   
Principal Investigator: Luke Howard, DPhil MRCP         
Royal Brompton Hospital Not yet recruiting
London, United Kingdom, SW3 6NP
Contact: Stephen J Wort, FRCP PhD    0207 352 8121 ext 8362    s.wort@imperial.ac.uk   
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         
St George's Hospital Not yet recruiting
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         
Sponsors and Collaborators
Royal Brompton & Harefield NHS Foundation Trust
Actelion
Investigators
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 Hospital
Principal Investigator: Brendan Madden, MD MSc FRCP Royal Brompton Hospital
  More Information

No publications provided by Royal Brompton & Harefield NHS Foundation Trust

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Royal Brompton Hospital NHS Trust
ClinicalTrials.gov Identifier: NCT00637065     History of Changes
Other Study ID Numbers: 2007OE002B, REC number: 07/H0714/125, EudraCT no: 2007-001643-21
Study First Received: March 10, 2008
Last Updated: March 10, 2008
Health Authority: United Kingdom: Department of Health

Keywords provided by Royal Brompton & Harefield NHS Foundation Trust:
Pulmonary hypertension
Interstitial lung disease
Idiopathic pulmonary fibrosis
Nonspecific interstitial pneumonia
Bosentan
Endothelin receptor antagonists
Pulmonary vascular resistance

Additional relevant MeSH terms:
Fibrosis
Hypertension
Hypertension, Pulmonary
Idiopathic Pulmonary Fibrosis
Lung Diseases
Lung Diseases, Interstitial
Pneumonia
Pulmonary Fibrosis
Cardiovascular Diseases
Idiopathic Interstitial Pneumonias
Pathologic Processes
Respiratory Tract Diseases
Respiratory Tract Infections
Vascular Diseases
Bosentan
Antihypertensive Agents
Cardiovascular Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014