A Randomized, Double-Blind, Placebo-Controlled Study of Pulsed, Inhaled Nitric Oxide in Subjects at Risk of Pulmonary Hypertension Associated With Pulmonary Fibrosis
A Randomized, Double-Blind, Placebo-Controlled Study of Pulsed, Inhaled Nitric Oxide in Subjects at Risk of Pulmonary Hypertension Associated With Pulmonary Fibrosis
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DOI：
10.1016/j.chest.2020.02.016
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发表时间：
2020-08-01
期刊：
影响因子：
9.6
通讯作者：
Lancaster, Lisa
中科院分区：
文献类型：
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作者：
Nathan, Steven D.;Flaherty, Kevin. R.;Lancaster, Lisa
背景：间质性肺疾病包括多种疾病，其中许多以纤维化改变（fILD）为特征。其中以特发性肺纤维化最为常见。肺动脉高压（PH）经常使fILD并发，并与功能能力受损、体力活动减少和预期寿命显著缩短相关。我们报告了在fILD-PH患者中进行的脉冲吸入一氧化氮（iNO）的2b/3期试验的第一个队列的结果。方法：队列1中的受试者随机接受iNO 30 μ g/kg理想体重/h（iNO 30）或安慰剂，进行8周的盲法治疗;然后受试者过渡到iNO 30的开放标签扩展（OLE），然后剂量递增到iNO 45，然后是iNO 75。活动监测用于评估日常活动的变化。结果：23例患者被随机分配到iNO 30组，18例患者被随机分配到安慰剂组。在盲法治疗期间，iNO 30受试者显示出中度/剧烈体力活动（MVPA）的平均改善，并且总体活动保持稳定。安慰剂组的MVPA平均下降了26%，总体活动下降了12%。iNO组的氧饱和度有所改善。在OLE期间，受试者维持其活动水平，包括所有活动参数从下降转变为维持的安慰剂受试者。吸入一氧化氮在所有剂量（30，45，和75）是安全和良好的tolerated.CONCLUSIONS：治疗与iNO 30表现出临床和统计学显着的好处MVPA和临床显着的整体活动的好处。在OLE中，较高剂量的iNO也是安全的且耐受性良好，同时显示活性参数的维持。
BACKGROUND: The interstitial lung diseases include a variety of disorders, many of which are characterized by fibrotic changes (fILD). Of the fILDs, Idiopathic pulmonary fibrosis is the most common. Pulmonary hypertension (PH) frequently complicates fILD and is associated with impaired functional capability, lower physical activity, and significantly reduced life expectancy. There is no proven treatment for patients with fILD-PH. We report results from the first cohort of a phase 2b/3 trial with pulsed inhaled nitric oxide (iNO) in patients with fILD-PH.METHODS: Subjects in cohort 1 were randomized to iNO 30 mu g/kg ideal body weight/h (iNO30) or placebo for 8 weeks of blinded treatment; subjects then transitioned to open-label extension (OLE) on iNO30 followed by dose escalation to iNO45 then iNO75. Activity monitoring was used to assess changes in daily activity. Safety and efficacy were evaluated.RESULTS: Twenty-three patients were randomized to iNO30 and 18 to placebo. During blinded treatment, iNO30 subjects showed an average improvement in moderate/vigorous physical activity (MVPA) and remained stable in overall activity. Placebo subjects showed an average drop of 26% in MVPA and a 12% drop in overall activity. The iNO group had an improvement in oxygen saturation. During OLE, subjects maintained their activity levels including placebo subjects who transitioned from a decline to a maintenance in all activity parameters. Inhaled nitric oxide at all doses (30, 45, and 75) was safe and well tolerated.CONCLUSIONS: Treatment with iNO30 demonstrated clinically and statistically significant benefit in MVPA and clinically significant benefit in overall activity. In the OLE, higher doses of iNO were also safe and well tolerated while showing maintenance in activity parameters.