Safety and Efficacy Study of Bosentan in Progressive Pulmonary Sarcoidosis

NCT ID: NCT00926627

Last Updated: 2016-09-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2010-03-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

placebo b.i.d.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

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

Bosentan

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

Group Type: EXPERIMENTAL

bosentan

Intervention Type: 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)

Interventions

bosentan

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)

Intervention Type: DRUG

placebo

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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
• Uncontrolled other disease like

• Chronic heart failure (NYHA III, IV)
• Diabetes mellitus (blood glucose 2x per day > 250 mg/dl , HbA1c > 10 %)
• Arterial hypertension (SBP > 180 mmHg)
• Concomitant treatment with cyclosporine A
• Concomitant treatment with tacrolimus or sirolimus
• Concomitant treatment with glibenclamide
• Are pregnant, nursing, or planning pregnancy during the trial or within six month period thereafter.
• Have a known substance dependency (drug or alcohol within 3 years of screening).
• Presumed non-compliance.
• Legal incapacity or limited legal capacity at screening.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daniel Doberer

OTHER

Sponsor Role: lead

Responsible Party

Daniel Doberer

Research Associate

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Daniel Doberer, MD, MSc

Role: STUDY_DIRECTOR

Medical University of Vienna

Locations

General Hospital Vienna

Vienna, Vienna, Austria

Wilhelminenspital Wien

Vienna, Vienna, Austria

Countries

Austria

Related Links

http://www.meduniwien.ac.at/klpharm/

Department of Clinical Pharmacology of the Medical University of Vienna

Other Identifiers

EudraCT - 2007-005117-18

Identifier Type: -

Identifier Source: org_study_id