Safety and Efficacy Study of Bosentan in Progressive Pulmonary Sarcoidosis

NCT00926627 | Terminated Phase 2

• 1 other identifier: EudraCT - 2007-005117-18
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

Progressive pulmonary sarcoidosis occurs in up to twenty percent of patients who require persistent treatment, but available treatment options have shown considerable long-term toxicity and uncertain or unproven efficacy. In these patients, pulmonary fibrosis and pulmonary hypertension are common complications which have major prognostic impact. Endothelin-1 (ET-1) has been demonstrated to play a key role in pulmonary fibrosis and pulmonary hypertension, and a potential role in pulmonary sarcoidosis. ET-1 is a potent vasoconstrictor and can promote fibrosis, cell proliferation, and remodeling, and is pro-inflammatory. Preliminary data have shown the therapeutic potential of the endothelin receptor antagonist (ERA) bosentan in sarcoidosis associated pulmonary hypertension. In this light, the therapeutic potential of bosentan as an add-on treatment in progressive pulmonary sarcoidosis needs to be evaluated.

Conditions

Sarcoidosis; Pulmonary Hypertension

Keywords

endothelin receptor antagonist; bosentan

Outcome Measures

Primary Outcomes (1)

• Treatment efficacy is assessed by a composite clinical score, including six parameters: Pulmonary function test (FVC and DLCO), Blood gas analysis (AaDO2), HRCT (Oberstein score), 6 minute walk test (6-MWD), Dyspnoea (ATS dyspnea scale)

  6 months

Secondary Outcomes (2)

• Assess safety and tolerability of bosentan in progressive pulmonary sarcoidosis

  6 months

• To evaluate the efficacy of bosentan treatment in the subgroups of patents with and without sarcoidosis-associated pulmonary hypertension.

  6 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

placebo b.i.d.

Drug: placebo

Bosentan

EXPERIMENTAL

62.5 mg/125 mg bosentan b.i.d.

Drug: bosentan

Interventions

bosentan DRUG

62.5 mg tablets b.i.d. administered orally for 4 weeks followed by the maintenance dose of 125 mg b.i.d. (62.5 mg b.i.d. if body weight \< 40 kg/90 lb)

Bosentan

placebo DRUG

identical preparation as the study drug, but without the active substance, administered b.i.d.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent prior to any study-mandated procedure.
• Male and female patients aged \> 18 and \< 70 years.
• Histologically proven sarcoidosis diagnosed at least one year before screening.
• Diagnosis of sarcoidosis and with evidence of pulmonary parenchymal disease on chest X-ray or CT (radiological stage II, III) with or without pulmonary hypertension. Subjects with concurrent extrapulmonary sarcoidosis are encouraged to be enrolled.
• Progressive disease, defined as follows:
• Deterioration in the 3-12 month period prior to screening in at least two of the following criteria:
• increase in clinical symptoms (cough, shortness of breath, chest pain, fatigue or hemoptysis).
• lung function: decrease of 10% in TLC, FVC or DLCO.
• worsening of radiographic opacities.
• Have been receiving pre-study treatment with prednisolone (or equivalent dose of corticosteroid) as a single agent (≥ 10 mg/day) or other immunosuppressants (methotrexate, azathioprine, cyclophosphamide, TNF inhibitors, etc.) within the 3-month period immediately prior to screening. Patients must be on a stable dose of these medications for \> 4 weeks before starting the study medication.
• AST and ALT values within three times upper limit of normal.
• Ability to communicate well with the investigator, in the local language, and to understand and comply with the requirements of the study.
• Negative pregnancy test in female patients.
• Adequate contraception in female patients of childbearing age.

You may not qualify if:

• Known hypersensitivity to any excipients of the drug formulation or to bosentan.
• Treatment with another investigational drug within 3 months prior to screening.
• Pulmonary sarcoidosis:
• without disease progression as defined above
• with radiological stage I
• with radiological stage IV (pulmonary fibrosis with evidence of honey-combing, hilar retraction, bullae and cysts)
• Other cause of pulmonary disease:
• Active tuberculosis (or positive Quantiferon test), fungi infection, lymphoma.
• Chronic obstructive pulmonary disease, asthma, interstitial lung disease other than sarcoid-related
• Anamnesis of beryllium or asbestos exposition
• Previous smoking (\> 10 PY), or active smoker
• Previous administration of bosentan
• Positive results from the hepatitis serology, except for vaccinated subjects, at screening.
• Positive results from the HIV serology at screening.
• Malignancy requiring chemotherapy or radiation

Sponsors & Collaborators

• Daniel Doberer: lead

Study Sites (2)

General Hospital Vienna

Vienna, Vienna, 1090, Austria

Location

Wilhelminenspital Wien

Vienna, Vienna, 1180, Austria

Location

Related Links

• Department of Clinical Pharmacology of the Medical University of Vienna

MeSH Terms

Conditions

Sarcoidosis; Hypertension, Pulmonary

Interventions

Bosentan

Condition Hierarchy (Ancestors)

Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Daniel Doberer, MD, MSc

  Medical University of Vienna

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Research Associate

Study Record Dates

• First Submitted: June 22, 2009
• First Posted: June 23, 2009
• Study Start: April 1, 2009
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: September 15, 2016

Record last verified: 2016-09

Locations

AU (2)