NCT00637065

Brief 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. 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).

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
48

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Apr 2008

Typical duration for phase_4

Geographic Reach
1 country

3 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 10, 2008

Completed
7 days until next milestone

First Posted

Study publicly available on registry

March 17, 2008

Completed
15 days until next milestone

Study Start

First participant enrolled

April 1, 2008

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2010

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2010

Completed
Last Updated

March 17, 2008

Status Verified

March 1, 2008

Enrollment Period

2 years

First QC Date

March 10, 2008

Last Update Submit

March 10, 2008

Conditions

Pulmonary HypertensionInterstitial Lung DiseaseIdiopathic Pulmonary FibrosisNonspecific Interstitial Pneumonia

Keywords

Pulmonary hypertensionInterstitial lung diseaseIdiopathic pulmonary fibrosisNonspecific interstitial pneumoniaBosentanEndothelin receptor antagonistsPulmonary vascular resistance

Outcome Measures

Primary Outcomes (1)

  • The primary endpoint is a fall in pulmonary vascular resistance (PVR) of 20% over 16 weeks.

    16 weeks

Secondary Outcomes (8)

  • mean Pulmonary arterial Pressure

    16 weeks

  • Six minute walk distance

    16 weeks

  • Quality of life scores (Camphor questionnaire)

    16 weeks

  • Pulmonary function (DLco, FVC and PaO2)

    16 weeks

  • Pulmonary blood flow

    16 weeks

  • +3 more secondary outcomes

Study Arms (2)

1

ACTIVE COMPARATOR

Bosentan tablets (62.5mg bd for first 4 weeks, then 125mg bd as tolerated)

Drug: Bosentan

2

PLACEBO COMPARATOR

Placebo tablets

Drug: Placebo

Interventions

BosentanDRUG

Bosentan tablets - 62.5mg bd for first 4 weeks, then 125mg bd if tolerated until trial completion.

Also known as: Tracleer
1
PlaceboDRUG

Placebo tables - identical to active drug but without the active ingredient -

Also known as: Placebo tablets
2

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

St George's Hospital

London, London, SW1 O7QT, United Kingdom

Location

Royal Brompton Hospital

London, London, SW3 6NP, United Kingdom

Location

Hammersmith Hospital

London, London, W12 OHS, United Kingdom

Location

Related Publications (1)

  • 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.

    PMID: 24937643DERIVED

MeSH Terms

Conditions

Hypertension, PulmonaryLung Diseases, InterstitialIdiopathic Pulmonary Fibrosis

Interventions

Bosentan

Condition Hierarchy (Ancestors)

Lung DiseasesRespiratory Tract DiseasesHypertensionVascular DiseasesCardiovascular DiseasesPulmonary Fibrosis

Intervention Hierarchy (Ancestors)

BenzenesulfonamidesSulfonamidesAmidesOrganic ChemicalsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSulfonesSulfur CompoundsPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • 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

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephen J Wort, MRCP PhD

CONTACT

0207 352 8121s.wort@imperial.ac.uk

Athol U Wells, MD FRCP FRCR

CONTACT

0207 352 8121a.wells@rbht.nhs.uk

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

March 10, 2008

First Posted

March 17, 2008

Study Start

April 1, 2008

Primary Completion

April 1, 2010

Study Completion

August 1, 2010

Last Updated

March 17, 2008

Record last verified: 2008-03

Locations

GB(3)