Randomized trial of acetylcysteine in idiopathic pulmonary fibrosis.
Randomized trial of acetylcysteine in idiopathic pulmonary fibrosis.
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DOI：
10.1056/nejmoa1401739
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发表时间：
2014-05-29
期刊：
影响因子：
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通讯作者：
Raghu G
中科院分区：
文献类型：
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作者：
Idiopathic Pulmonary Fibrosis Clinical Research Network;Martinez FJ;de Andrade JA;Anstrom KJ;King TE Jr;Raghu G
N-乙酰半胱氨酸(NAC)已被认为是治疗特发性肺纤维化(IPF)的有益药物。在IPF人群中单独口服该药的安慰剂对照研究尚未进行。一项最初设计的三组随机、双盲、安慰剂对照试验，即强的松+硫唑嘌呤+NAC(三种药物方案)与NAC与安慰剂在IPF患者中的轻中度肺功能损害，由于与三种药物方案相关的安全问题而中断。这项试验继续采用双臂设计(NAC与安慰剂对照)，没有其他改变，分别纳入了NAC组和安慰剂组的133名和131名患者。主要的结果衡量标准是用力肺活量(FVC)在60周内的变化。在60周的治疗期间，NAC组和安慰剂组之间在用力肺活量下降方面没有差异(60周后，NAC组的−下降0.18升，而安慰剂组的−下降0.19升，p=0.77)。此外，NAC和安慰剂在死亡率(6[4.9%]对3[2.5%]事件，p=0.50)或急性加重(3[2.3%]对3[2.3%]事件，p>；0.99)方面没有显著差异。与安慰剂相比，NAC对有轻度到中度生理异常的IPF患者的FVC保存没有好处。
N-acetylcysteine (NAC) has been suggested as a beneficial treatment for idiopathic pulmonary fibrosis (IPF). A placebo-controlled study of this agent administrated orally alone in an IPF population has not been conducted. An initially designed three-arm randomized, double-blind, placebo-controlled trial of prednisone plus azathioprine plus NAC (three-drug regimen) versus NAC versus placebo in IPF patients with mild-moderate impairment in pulmonary function was interrupted due to safety concerns associated with the three-drug regimen. The trial continued as a two-arm design (NAC vs. placebo) without other changes and enrolled 133 and 131 patients in the NAC and placebo arms, respectively. The primary outcome measure was the change in forced vital capacity (FVC) over a 60-week period. Over the 60-week treatment period, there was no difference between the NAC and placebo groups in the decline of FVC (60-week change of −0.18 liters for NAC vs. −0.19 liters for placebo, p=0.77). In addition, there were no significant differences between NAC and placebo for mortality (6 [4.9%] vs. 3 [2.5%] events, p=0.50) or acute exacerbation (3 [2.3%] vs. 3 [2.3%] events, p>0.99). Compared to placebo NAC offered no benefit for the preservation of FVC in IPF patients with mild-to-moderate physiological abnormalities.