Division of Pulmonary and Critical Care Medicine, University of Washington Medical Center, 1959 NE Pacific, Campus Box 356175, Seattle, WA 98195, USA.
Ann Intern Med. 2013 May 7;158(9):641-9. doi: 10.7326/0003-4819-158-9-201305070-00003.
Idiopathic pulmonary fibrosis (IPF) is characterized by formation and proliferation of fibroblast foci. Endothelin-1 induces lung fibroblast proliferation and contractile activity via the endothelin A (ETA) receptor.
To determine whether ambrisentan, an ETA receptor-selective antagonist, reduces the rate of IPF progression.
Randomized, double-blind, placebo-controlled, event-driven trial. (ClinicalTrials.gov: NCT00768300).
Academic and private hospitals.
Patients with IPF aged 40 to 80 years with minimal or no honeycombing on high-resolution computed tomography scans.
Ambrisentan, 10 mg/d, or placebo.
Time to disease progression, defined as death, respiratory hospitalization, or a categorical decrease in lung function.
The study was terminated after enrollment of 492 patients (75% of intended enrollment; mean duration of exposure to study medication, 34.7 weeks) because an interim analysis indicated a low likelihood of showing efficacy for the end point by the scheduled end of the study. Ambrisentan-treated patients were more likely to meet the prespecified criteria for disease progression (90 [27.4%] vs. 28 [17.2%] patients; P = 0.010; hazard ratio, 1.74 [95% CI, 1.14 to 2.66]). Lung function decline was seen in 55 (16.7%) ambrisentan-treated patients and 19 (11.7%) placebo-treated patients (P = 0.109). Respiratory hospitalizations were seen in 44 (13.4%) and 9 (5.5%) patients in the ambrisentan and placebo groups, respectively (P = 0.007). Twenty-six (7.9%) patients who received ambrisentan and 6 (3.7%) who received placebo died (P = 0.100). Thirty-two (10%) ambrisentan-treated patients and 16 (10%) placebo-treated patients had pulmonary hypertension at baseline, and analysis stratified by the presence of pulmonary hypertension revealed similar results for the primary end point.
The study was terminated early.
Ambrisentan was not effective in treating IPF and may be associated with an increased risk for disease progression and respiratory hospitalizations.
Gilead Sciences.
特发性肺纤维化（IPF）的特征是成纤维细胞灶的形成和增殖。内皮素-1 通过内皮素 A（ETA）受体诱导肺成纤维细胞增殖和收缩活性。
确定内皮素 A 受体选择性拮抗剂安贝生坦是否能降低 IPF 的进展速度。
随机、双盲、安慰剂对照、事件驱动试验。（ClinicalTrials.gov：NCT00768300）。
学术和私人医院。
年龄在 40 至 80 岁之间的 IPF 患者，高分辨率计算机断层扫描显示最小或无蜂巢样改变。
安贝生坦，10mg/d，或安慰剂。
疾病进展时间，定义为死亡、呼吸住院或肺功能的分类下降。
在招募了 492 名患者（计划入组人数的 75%；接受研究药物治疗的平均时间为 34.7 周）后，该研究提前终止，因为中期分析表明，按照研究结束时的计划，该终点显示疗效的可能性很低。安贝生坦治疗的患者更有可能符合疾病进展的预设标准（90[27.4%]例 vs. 28[17.2%]例；P=0.010；风险比，1.74[95%CI，1.14 至 2.66]）。在安贝生坦治疗组中有 55 名（16.7%）和 19 名（11.7%）安慰剂治疗组的患者出现肺功能下降（P=0.109）。在安贝生坦组和安慰剂组中，分别有 44 名（13.4%）和 9 名（5.5%）患者需要呼吸住院治疗（P=0.007）。26 名（7.9%）接受安贝生坦治疗的患者和 6 名（3.7%）接受安慰剂治疗的患者死亡（P=0.100）。32 名（10%）接受安贝生坦治疗的患者和 16 名（10%）接受安慰剂治疗的患者在基线时有肺动脉高压，对主要终点进行的肺动脉高压存在情况分层分析显示出相似的结果。
研究提前终止。
安贝生坦治疗特发性肺纤维化无效，并且可能与疾病进展和呼吸住院风险增加相关。
吉利德科学公司。
