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Safety and Efficacy Study of Bosentan in Progressive Pulmonary Sarcoidosis (BOPSAC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00926627
Recruitment Status : Terminated (Not enough patients with the specified criteria could not)
First Posted : June 23, 2009
Last Update Posted : September 15, 2016
Information provided by (Responsible Party):
Daniel Doberer, Medical University of Vienna

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.

Condition or disease Intervention/treatment Phase
Sarcoidosis Pulmonary Hypertension Drug: bosentan Drug: placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Prospective Randomized, Double Blind, Placebo-controlled, Safety and Efficacy Study of Bosentan as add-on Therapy in Progressive Pulmonary Sarcoidosis
Study Start Date : April 2009
Actual Primary Completion Date : March 2010
Actual Study Completion Date : March 2010

Resource links provided by the National Library of Medicine

Drug Information available for: Bosentan

Arm Intervention/treatment
Placebo Comparator: Placebo
placebo b.i.d.
Drug: placebo
identical preparation as the study drug, but without the active substance, administered b.i.d.

Experimental: Bosentan
62.5 mg/125 mg bosentan b.i.d.
Drug: 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)

Primary Outcome Measures :
  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) [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Assess safety and tolerability of bosentan in progressive pulmonary sarcoidosis [ Time Frame: 6 months ]
  2. To evaluate the efficacy of bosentan treatment in the subgroups of patents with and without sarcoidosis-associated pulmonary hypertension. [ Time Frame: 6 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00926627

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General Hospital Vienna
Vienna, Austria, 1090
Wilhelminenspital Wien
Vienna, Austria, 1180
Sponsors and Collaborators
Daniel Doberer
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Study Director: Daniel Doberer, MD, MSc Medical University of Vienna
Additional Information:
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Responsible Party: Daniel Doberer, Research Associate, Medical University of Vienna Identifier: NCT00926627    
Other Study ID Numbers: EudraCT - 2007-005117-18
First Posted: June 23, 2009    Key Record Dates
Last Update Posted: September 15, 2016
Last Verified: September 2016
Keywords provided by Daniel Doberer, Medical University of Vienna:
endothelin receptor antagonist
Additional relevant MeSH terms:
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Hypertension, Pulmonary
Sarcoidosis, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Lung Diseases, Interstitial
Antihypertensive Agents
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action