A Phase-2 Exploratory Randomized Controlled Trial of INOpulse in Patients with Fibrotic Interstitial Lung Disease Requiring Oxygen
A Phase-2 Exploratory Randomized Controlled Trial of INOpulse in Patients with Fibrotic Interstitial Lung Disease Requiring Oxygen
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DOI：
10.1513/annalsats.202107-864oc
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发表时间：
2022-04-01
影响因子：
8.3
通讯作者：
Nathan, Steven D.
中科院分区：
文献类型：
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作者：
King, Christopher S.;Flaherty, Kevin R.;Nathan, Steven D.
理论基础：纤维化间质性肺病患者通常进展到需要补充氧气的地步。这总是伴随着生活质量的下降和日常生活活动的限制。目的：本研究旨在评估需要补充氧气的间质性肺病患者经脉冲吸入一氧化氮(贝乐芬疗法)治疗后体力活动的改善。此外，还试图探讨INOPulse对多个患者报告的结果的安全性和临床益处。方法：将补充氧气的纤维肺疾病患者按2：1的比例随机分为两组，分别以45 mg/kg理想体重/小时(INO45)或安慰剂进行4个月(基线后3个月)的盲法治疗。这项研究评估了多个探索性疗效终点，包括通过活动描记测量的中等到剧烈的体力活动，以及使用加州大学圣地亚哥分校气短问卷和圣乔治呼吸问卷(SGRQ)报告的患者结果。结果：共有44名患者入选，其中30名为iNO45，14名为安慰剂。在安慰剂校正的临床受益中，iNO45组的MVPA每天增加12.3分钟。加州大学圣地亚哥分校的呼吸短促问卷(6.05分)和SGRQ总分(3.75分)，以及SGRQ活动(5.84分)和SGRQ影响(6.30分)领域出现了有临床意义的有益趋势。结论：INOPulse对需要补充氧气的间质性肺病患者具有良好的耐受性，并与维持体力活动和改善症状有关。对这一有益效果的进一步验证需要在目前正在进行的第三阶段试验中进一步研究。
Rationale: Patients with fibrotic interstitial lung disease often progress to the point of requiring supplemental oxygen. This is invariably accompanied by an impaired quality of life and limitations on activities of daily living.Objectives: This study aimed to assess the improvement in physical activity in patients with interstitial lung disease requiring supplemental oxygen treated with pulsed inhaled nitric oxide via INOpulse (Bellerophon Therapeutics). In addition, it sought to explore the safety and clinical benefits of INOpulse on multiple patient-reported outcomes.Methods: Ambulatory patients with fibrotic lung disease on supplemental oxygen were randomized in a 2:1 ratio to inhaled nitric oxide at 45 mu g/kg ideal body weight/h (iNO45) or placebo for 4 months (3 months after baseline) of blinded treatment. The study assessed multiple exploratory efficacy endpoints, including moderate to vigorous physical activity as measured by actigraphy and patient-reported outcomes using the University of California San Diego shortness of breath questionnaire and the St. Georges Respiratory Questionnaire (SGRQ).Results: A total of 44 patients (30 iNO45 and 14 placebo) were enrolled. A placebo-corrected clinical benefit of 12.3 min/d increase in MVPA was observed in the iNO45 group. Clinically meaningful beneficial trends were observed for the University of California San Diego shortness of breath questionnaire (6.05 points) and the SGRQ total (3.75) scores, as well as the SGRQ activity (5.84), and SGRQ impact (6.30) domains.Conclusions: INOpulse was well tolerated and associated with maintenance of physical activity and improved symptomatology in patients with interstitial lung disease who require supplemental oxygen. Further validation of this beneficial effect warrants further study in a phase-3 trial that is currently underway.