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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

Tracking Information
First Submitted Date  ICMJE June 22, 2009
First Posted Date  ICMJE June 23, 2009
Last Update Posted Date September 15, 2016
Study Start Date  ICMJE April 2009
Actual Primary Completion Date March 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 22, 2009)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 22, 2009)
  • Assess safety and tolerability of bosentan in progressive pulmonary sarcoidosis [ Time Frame: 6 months ]
  • To evaluate the efficacy of bosentan treatment in the subgroups of patents with and without sarcoidosis-associated pulmonary hypertension. [ Time Frame: 6 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of Bosentan in Progressive Pulmonary Sarcoidosis
Official Title  ICMJE A Prospective Randomized, Double Blind, Placebo-controlled, Safety and Efficacy Study of Bosentan as add-on Therapy in Progressive Pulmonary Sarcoidosis
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Sarcoidosis
  • Pulmonary Hypertension
Intervention  ICMJE
  • 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)
  • Drug: placebo
    identical preparation as the study drug, but without the active substance, administered b.i.d.
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    placebo b.i.d.
    Intervention: Drug: placebo
  • Experimental: Bosentan
    62.5 mg/125 mg bosentan b.i.d.
    Intervention: Drug: bosentan
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 22, 2009)
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2010
Actual Primary Completion Date March 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00926627
Other Study ID Numbers  ICMJE EudraCT - 2007-005117-18
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Daniel Doberer, Medical University of Vienna
Study Sponsor  ICMJE Daniel Doberer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Daniel Doberer, MD, MSc Medical University of Vienna
PRS Account Medical University of Vienna
Verification Date September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP