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

This study has been terminated.
(Not enough patients with the specified criteria could not)
Sponsor:
Information provided by:
Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT00926627
First received: June 22, 2009
Last updated: August 10, 2010
Last verified: June 2009
  Purpose

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 Intervention Phase
Sarcoidosis
Pulmonary Hypertension
Drug: bosentan
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assess safety and tolerability of bosentan in progressive pulmonary sarcoidosis [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • To evaluate the efficacy of bosentan treatment in the subgroups of patents with and without sarcoidosis-associated pulmonary hypertension. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 32
Study Start Date: April 2009
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00926627

Locations
Austria
Wilhelminenspital Wien
Vienna, Austria, 1180
General Hospital Vienna
Vienna, Austria, 1090
Sponsors and Collaborators
Medical University of Vienna
Investigators
Study Director: Daniel Doberer, MD, MSc Medical University of Vienna
  More Information

Additional Information:
No publications provided

Responsible Party: Michael Wolzt, Department of Clinical Pharmacology
ClinicalTrials.gov Identifier: NCT00926627     History of Changes
Other Study ID Numbers: EudraCT - 2007-005117-18
Study First Received: June 22, 2009
Last Updated: August 10, 2010
Health Authority: Austria: Agency for Health and Food Safety

Keywords provided by Medical University of Vienna:
endothelin receptor antagonist
bosentan

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Sarcoidosis
Sarcoidosis, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Lung Diseases, Interstitial
Bosentan
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 14, 2014