A Prospective Randomized, Double Blind, Placebo-controlled, Safety and Efficacy Study of Bosentan as add-on Therapy in Progressive Pulmonary Sarcoidosis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- 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)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Placebo
placebo b.i.d.
干预措施: placebo (Drug)
Bosentan
62.5 mg/125 mg bosentan b.i.d.
干预措施: bosentan (Drug)
结局指标
主要结局
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)
时间窗: 6 months
次要结局
- 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)
研究者
Daniel Doberer
Research Associate
Medical University of Vienna