King Talmadge E, Behr Jürgen, Brown Kevin K, du Bois Roland M, Lancaster Lisa, de Andrade Joao A, Stähler Gerd, Leconte Isabelle, Roux Sébastien, Raghu Ganesh
Department of Medicine, UCSF, 505 Parnassus Avenue, Room M994, San Francisco, CA 94110, USA.
Am J Respir Crit Care Med. 2008 Jan 1;177(1):75-81. doi: 10.1164/rccm.200705-732OC. Epub 2007 Sep 27.
Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease lacking effective treatment.
To determine the effects of bosentan on exercise capacity and time to disease progression in patients with IPF.
In a double-blind, multicenter trial, patients with IPF were randomized to receive oral bosentan 62.5 mg twice daily for 4 weeks, increased to 125 mg twice daily thereafter, or placebo, for 12 months or longer. The primary efficacy endpoint was change from baseline up to Month 12 in exercise capacity, as measured by a modified six-minute-walk test. Secondary endpoints were time to death or disease progression (worsening pulmonary function tests [PFTs] or acute decompensation), change in PFT scores, and quality of life (QOL) assessed using Short-Form 36 and St. George's Respiratory Questionnaire.
A total of 158 patients randomly received bosentan (n = 74) or placebo (n = 84). Bosentan showed no superiority over placebo in six-minute-walk distance (6MWD) up to Month 12, the primary efficacy endpoint. A trend in favor of bosentan was observed in the secondary endpoint of time to death or disease progression (hazard ratio [HR], 0.613; 95% confidence interval [CI], 0.328-1.144; P = 0.119), which was more pronounced in a patient subgroup diagnosed using surgical lung biopsy (post hoc analysis; HR, 0.315; 95% CI, 0.126-0.789; P = 0.009). Changes from baseline up to Month 12 in assessments of dyspnea and QOL favored treatment with bosentan. No unexpected adverse events were reported.
Bosentan treatment in patients with IPF did not show superiority over placebo on 6MWD. A trend in delayed time to death or disease progression, and improvement in QOL, was observed with bosentan. The more pronounced treatment effect in patients with biopsy-proven IPF warrants further investigation. Clinical trial registered with www.clinicaltrials.gov (NCT 00071461).
特发性肺纤维化（IPF）是一种进行性、致命的肺部疾病，缺乏有效的治疗方法。
确定波生坦对IPF患者运动能力和疾病进展时间的影响。
在一项双盲、多中心试验中，IPF患者被随机分为两组，一组每日两次口服波生坦62.5毫克，持续4周，之后增至每日两次125毫克，另一组服用安慰剂，为期12个月或更长时间。主要疗效终点是通过改良的六分钟步行试验测量的至第12个月时运动能力相对于基线的变化。次要终点包括死亡或疾病进展时间（肺功能测试[PFT]恶化或急性失代偿）、PFT评分变化以及使用简短健康调查问卷36和圣乔治呼吸问卷评估的生活质量（QOL）。
共有158例患者随机接受波生坦（n = 74）或安慰剂（n = 84）治疗。在至第12个月时的主要疗效终点六分钟步行距离（6MWD）方面，波生坦未显示出优于安慰剂。在死亡或疾病进展时间的次要终点方面观察到有利于波生坦的趋势（风险比[HR]，0.613；95%置信区间[CI]，0.328 - 1.144；P = 0.119），在使用外科肺活检诊断的患者亚组中更为明显（事后分析；HR，0.315；95% CI，0.126 - 0.789；P = 0.009）。在至第12个月时，呼吸困难和QOL评估相对于基线的变化有利于波生坦治疗。未报告意外不良事件。
IPF患者使用波生坦治疗在6MWD方面未显示出优于安慰剂。观察到波生坦有延迟死亡或疾病进展时间以及改善QOL的趋势。在经活检证实的IPF患者中更显著的治疗效果值得进一步研究。临床试验已在www.clinicaltrials.gov注册（NCT 00071461）。
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