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 μg/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.

中文翻译：

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一项随机、双盲、安慰剂对照研究，旨在评估 30 mcg/kg-IBW/hr (iNO 30) 剂量的脉冲吸入式一氧化氮 (iNO) 在有肺动脉高压相关风险的受试者中的安全性和有效性肺纤维化 (PH-PF) 接受氧气治疗

背景间质性肺疾病包括多种疾病，其中许多疾病的特征在于纤维化改变 (fILD)。在 fILD 中，特发性肺纤维化是最常见的。肺动脉高压 (PH) 经常使 fILD 复杂化，并与功能受损、体力活动减少和预期寿命显着缩短有关。对 fILD-PH 患者没有经过验证的治疗方法。我们报告了在 fILD-PH 患者中使用脉冲吸入一氧化氮 (iNO) 进行的第一组 2b/3 期试验的结果。方法 队列 1 中的受试者随机接受 iNO 30 μg/kg 理想体重/h (iNO30) 或安慰剂进行 8 周的盲法治疗；然后，受试者在 iNO30 上过渡到开放标签扩展 (OLE)，随后剂量增加到 iNO45，然后是 iNO75。活动监测用于评估日常活动的变化。评估了安全性和有效性。结果 23 名患者被随机分配到 iNO30 组，18 名患者被随机分配到安慰剂组。在盲法治疗期间，iNO30 受试者在中等/剧烈运动 (MVPA) 方面表现出平均改善，并在整体活动中保持稳定。安慰剂受试者的 MVPA 平均下降 26%，整体活动下降 12%。iNO 组的氧饱和度有所改善。在 OLE 期间，受试者保持其活动水平，包括在所有活动参数中从下降过渡到维持的安慰剂受试者。所有剂量（30、45 和 75）的吸入一氧化氮均安全且耐受性良好。结论 用 iNO30 治疗在 MVPA 中表现出临床和统计学上显着的益处，在总体活动中表现出临床上显着的益处。在 OLE 中，更高剂量的 iNO 也是安全且耐受性良好的，同时显示出活动参数的维持。