Santibanez Valeria, Mathur Aditi, Zatakia Jigna, Ng Nicole, Cohen Michele, Bagiella Emilia, Brown Stacey-Ann, Rosas Ivan O, Patel Nina M, Olson Amy, Li Peide, Padilla Maria
Icahn School of Medicine at Mount Sinai, New York, New York, USA
Pulmonary, Hackensack Meridian Hackensack University Medical Center, Hackensack, New Jersey, USA.
BMJ Open Respir Res. 2025 Apr 10;12(1):e002323. doi: 10.1136/bmjresp-2024-002323.
In December 2019, the novel SARS-CoV-2 triggered a global pneumonia outbreak, leading to millions of deaths worldwide. A subset of survivors faces increased morbidity and mortality, particularly due to subacute lung injury evolving to chronic fibrosing interstitial lung disease. While nintedanib, a tyrosine-kinase inhibitor, shows promise in treating progressive fibrotic lung disease, limited randomised trial data exists for post-COVID-19-induced lung injury. We hypothesise that treatment with nintedanib may attenuate advancement to the fibrotic stages, offering a potential avenue for improving outcomes in this specific patient subset.
We describe the design of a multicentre, randomised, double-blind, placebo-controlled trial involving approximately 170 patients with subacute lung injury secondary to COVID-19, who required respiratory support with oxygen supplementation. Patients are randomised by site and disease phenotype (fibrotic vs non-fibrotic) in a 1:1 ratio to either oral nintedanib or placebo. Patients will be followed for 180 days. The primary endpoint is to assess change from baseline in forced vital capacity (FVC, mL) at 180 days. Secondary objectives include change in FVC (mL) at 90 days; diffusing capacity of carbon monoxide (% of predicted) and 6-min walk test (feet) at 180 days; and mortality at 90 and 180 days. Qualitative and quantitative changes in high-resolution computerised tomography (HRCT), change in patient-reported outcome measures (PROMs) and safety endpoints will also be assessed. Analysis will be performed according to the intention-to-treat principle.
The study is conducted in accordance with the Good Clinical Practices as outlined by the Food and Drug Administration and the Declaration of Helsinki 2008. This study received approval from participating sites' Institutional Review Boards and committees, including The Ethics Committee of the Medical Board at the Mount Sinai Hospital (ID: HS#20-01166). The Independent Oversight Committee oversees study conduct, data and patient safety for the duration of the study investigation. The trial details presented align with the trial protocol V.8. (April 2022). Results will be presented at national and international conferences, published in a peer-reviewed journal and disseminated to patients, funders and researchers on data analysis completion.
NCT04619680. First posted 6 November 2020.
2019年12月，新型严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引发了全球肺炎疫情，导致全球数百万人死亡。一部分幸存者面临着发病率和死亡率的增加，尤其是由于亚急性肺损伤演变为慢性纤维化间质性肺病。虽然酪氨酸激酶抑制剂尼达尼布在治疗进行性纤维化肺病方面显示出前景，但关于新型冠状病毒肺炎（COVID-19）后肺损伤的随机试验数据有限。我们假设，使用尼达尼布治疗可能会减缓向纤维化阶段的进展，为改善这一特定患者亚群的预后提供一条潜在途径。
我们描述了一项多中心、随机、双盲、安慰剂对照试验的设计，该试验涉及约170例因COVID-19导致亚急性肺损伤且需要吸氧进行呼吸支持的患者。患者按地点和疾病表型（纤维化与非纤维化）以1:1的比例随机分为口服尼达尼布组或安慰剂组。患者将被随访180天。主要终点是评估180天时用力肺活量（FVC，mL）相对于基线的变化。次要目标包括90天时FVC（mL）的变化；180天时一氧化碳弥散量（预测值的百分比）和6分钟步行试验（英尺）；以及90天和180天时的死亡率。还将评估高分辨率计算机断层扫描（HRCT）的定性和定量变化、患者报告结局指标（PROMs）的变化以及安全性终点。分析将根据意向性分析原则进行。
本研究按照美国食品药品监督管理局概述的良好临床实践以及2008年《赫尔辛基宣言》进行。本研究获得了参与研究地点的机构审查委员会和委员会的批准，包括西奈山医院医学委员会伦理委员会（编号：HS#20 - 01166）。独立监督委员会在研究调查期间监督研究实施、数据和患者安全。所展示的试验细节与试验方案V.8（2022年4月）一致。结果将在国内和国际会议上公布，发表在同行评审期刊上，并在数据分析完成后向患者、资助者和研究人员传播。
NCT04619680。首次发布于2020年11月6日。
