NCT00071461已完成2 期
A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Assess the Efficacy, Safety, and Tolerability of Bosentan in Patients With Idiopathic Pulmonary Fibrosis, Open Label Extension
Actelion29 个研究点 分布在 8 个国家目标入组 158 人开始时间: 2003年8月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 158
- 试验地点
- 29
- 主要终点
- Change in 6-minute walk distance
研究概览
简要总结
Endothelin-1 (ET-1) is expressed in a variety of pulmonary pathological conditions including pulmonary vascular disease and pulmonary fibrosis.
Bosentan (an oral dual ET-1 receptor antagonist) could delay the progression of idiopathic pulmonary fibrosis (IPF), a condition for which no established treatment is available.
The present trial investigates a possible use of bosentan, which is currently approved for the treatment of symptoms of pulmonary arterial hypertension (PAH) WHO class III and IV, to a new category of patients suffering from IPF.
It was decided to offer Open Label treatment (bosentan) for patients willing to continue in the BUILD 1 study.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients over 18 years of age.
- •Women must be either postmenopausal (i.e., amenorrhea for at least 1 year), or surgically or naturally sterile.
- •Women of childbearing potential must have a negative pre-treatment pregnancy test and use a reliable method of contraception during study treatment and for at least 3 months after study treatment termination.
- •IPF proven diagnosis < 3 years documented according to ATS/ERS international multidisciplinary consensus, with or without surgical (thoracoscopic or open) chest lung biopsy
- •Duration of illness ≥ 3 months.
- •Six-minute walk test distance (limited by dyspnea) ≥ 150 meters and < 500 meters
- •Patients who have signed the informed consent form prior to initiation of any study procedure.
排除标准
- •Interstitial lung disease due to conditions other than IPF, including but not limited to radiation, sarcoidosis, hypersensitivity pneumonitis, bronchiolitis obliterans with organizing pneumonia, and cancer.
- •History of clinically significant environmental exposure known to cause pulmonary fibrosis (drugs, asbestos, beryllium, radiation, domestic birds, etc.).
- •Severe concomitant illness limiting life expectancy (< 1 year).
- •FVC ≥ 90% predicted.
- •Severe restrictive lung disease: FVC < 50% predicted or FVC < 1.2 l, or DLco < 30% predicted or residual volume ≥ 120% predicted.
- •Severe obstructive lung disease: FEV1/FVC< 0.
- •Documented improvement of patient's condition within 12 months prior to randomization with or without IPF-specific therapy (e.g., corticosteroids, immunosuppressive, cytotoxic or antifibrotic drugs, TNFa blocker, interferon g).
- •Recent pulmonary or upper respiratory track infection (within 4 weeks of randomization).
- •PaO2 < 55 mm Hg (sea level) or 50 mm Hg (altitude) at rest on room air.
- •Echocardiographic evidence of severe pulmonary hypertension (PH): systolic pulmonary pressure ≥ 50 mm Hg or tricuspid regurgitation velocity ≥ 3.2 m/sec (unless severe PH is invalidated by a right heart catheterization). If the pulmonary pressure is not quantifiable, presence of significant right ventricular enlargement or hypertrophy or right ventricular dysfunction.
- •Severe chronic heart failure, e.g., NYHA class III or IV and/or left ventricular ejection fraction < 25%.
- •Acute or chronic impairment (other than dyspnea) limiting the ability to comply with study requirements, e.g., the 6MWT or the PFTs.
- •(e.g., angina pectoris, intermittent claudicating, chronic arthritis).
- •Baseline values of liver transaminases, i.e., aspartate aminotransferases (AST) and/or alanine aminotransferases (ALT) > 3 times the upper limit of normal ranges.
- •Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
- •Serum creatinine ≥ 2.5 mg/dl (221 mmol/l) or dialysis.
- •Hemoglobin concentration < 75% the lower limit of normal ranges.
- •Systolic blood pressure < 85 mm Hg.
- •Pregnancy or breast-feeding.
- •Current drug or alcohol dependence.
- •Smoker (≥ 5 cigarettes per day) or former smoker (≥ 5 cigarettes per day) having stopped less than 6 months prior to randomization.
- •Recently started (< 8 weeks from Screening visit) or planned cardio-pulmonary rehabilitation program based on exercise.
- •Treatment with oral corticosteroids (> 15 mg/day prednisone or equivalent), immunosuppressive, cytotoxic or antifibrotic drugs such as TNF alpha blocker, or interferon gamma within 4 weeks of randomization.within 4 weeks of randomization.
- •Treatment with glibenclamide (glyburide), cyclosporine A or tacrolimus within 1 weeks of randomization.
- •Treatment with an endothelin receptor antagonist within 3 months of randomization.
- •Treatment within 3 months of randomization or planned treatment with another investigational drug.
- •Known hypersensitivity to bosentan or any of the excipients.
研究组 & 干预措施
1
Experimental
Initial dose: 62.5 mg b.i.d. for 4 weeks.
- Target dose: - body weight > 40 kg (90 lb): 125 mg b.i.d., (if the initial dose is well tolerated).
- body weight < 40 kg (90 lb): 62.5 mg b.i.d.
干预措施: bosentan (Drug)
2
Placebo Comparator
Initial dose: 62.5 mg b.i.d. for 4 weeks.
- Target dose: - body weight > 40 kg (90 lb): 125 mg b.i.d., (if the initial dose is well tolerated).
- body weight < 40 kg (90 lb): 62.5 mg b.i.d.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in 6-minute walk distance
时间窗: Baseline to End-of-Period 1
次要结局
- Death or treatment failure(Up to End-of-Period 1)
研究者
研究点 (29)
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