An open-label, randomized trial of the combination of IFN-κ plus TFF2 with standard care in the treatment of patients with moderate COVID-19.
An open-label, randomized trial of the combination of IFN-κ plus TFF2 with standard care in the treatment of patients with moderate COVID-19.
复制标题
一项开放标签、随机试验，将 IFN-γ 加 TFF2 与标准护理相结合，治疗中度 COVID-19 患者。
DOI：
10.1016/j.eclinm.2020.100547
复制
发表时间：
2020-10
影响因子：
15.1
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Fu W;Liu Y;Liu L;Hu H;Cheng X;Liu P;Song Z;Zha L;Bai S;Xu T;Yuan S;Lu F;Shang Z;Zhao Y;Wang J;Zhao J;Ding L;Chen J;Zhang L;Zhu T;Zhang X;Lu H;Xu J
由SARS-CoV-2引起的流行性疫情正在全球范围内恶化，目前还没有治疗COVID-19的靶向药物。IFN-κ抑制SARS-CoV-2的复制; TFF2是一种小的分泌多肽，促进粘膜损伤的修复并减少炎症反应。我们利用这两种蛋白质的协同效应来治疗COVID-19。我们对中度COVID-19患者进行了一项开放标签、随机、临床试验。患者以1：1的比例被分配接受IFN-κ和TFF2的雾化吸入治疗，每24小时一次，连续6次给药（实验组）或仅接受标准治疗（对照组）。主要终点是所有临床样本中SARS-CoV-2病毒RNA转阴的时间。次要临床终点是CT成像改善的时间。根据方案进行数据分析。本研究注册于www.example.com，ChiCTR 2000030262。2020年3月23日至5月23日期间，招募了86名具有中度疾病症状的COVID-19患者，6名患者因不符合入选标准（通过胸部X线检查患有肺炎的患者）而被排除。其余80名患者中，40名患者被分配到实验组，其余患者被分配到对照组，仅接受标准护理。评价两组的疗效和安全性。实验组病毒RNA阴转时间（平均3.80 d，95%CI 2.07~5.53）明显短于对照组（7.40 d，95%CI 4.57~10.23）（p = 0.031），两组平均差异为3.60 d。在所有采样日（12天观察期内的每一天），实验组中病毒RNA转阴的患者百分比与对照组相比显著增加（p = 0.037）。对于次要终点，实验组至CT观察到改善的时间（平均6.21天，N = 38/40，95% CI 5.11 - 7.31）显著短于对照组（8.76天，N = 34/40，95% CI 7.57 - 9.96）（p = 0.002），平均值之间的差异为2.55天。任何实验患者均未向护士报告雾化吸入期间的不适或并发症。总之，我们发现，雾化吸入IFN-κ + TFF 2联合标准治疗是安全的，并且在缩短所有临床样本中病毒RNA阴性转换的时间方面优于单独的标准治疗上级。此外，实验组患者CT影像学改善时间较对照组明显缩短。该研究表明，这种联合治疗能够促进临床改善（病毒阴性，CT改善，住院时间缩短），从而导致提前出院。这些数据支持需要探索IFN-κ加TFF2治疗COVID-19的大规模试验。本项目由国家自然科学基金委员会、国家传染病防治重大专项、上海市科学技术委员会、上海市卫生健康委员会资助。
Epidemic outbreaks caused by SARS-CoV-2 are worsening around the world, and there are no target drugs to treat COVID-19. IFN-κ inhibits the replication of SARS-CoV-2; and TFF2 is a small secreted polypeptide that promotes the repair of mucosal injury and reduces the inflammatory responses. We used the synergistic effect of both proteins to treat COVID-19. We conducted an open-label, randomized, clinical trial involving patients with moderate COVID-19. Patients were assigned in a 1:1 ratio to receive either aerosol inhalation treatment with IFN-κ and TFF2 every 24 h for six consecutive dosages in addition to standard care (experimental group) or standard care alone (control group). The primary endpoint was the time until a viral RNA negative conversion for SARS-CoV-2 in all clinical samples. The secondary clinical endpoint was the time of CT imaging improvement. Data analysis was performed per protocol. This study was registered with chictr.org.cn, ChiCTR2000030262. Between March 23 and May 23 of 2020, 86 COVID-19 patients with symptoms of moderate illness were recruited, and 6 patients were excluded due to not matching the inclusion criteria (patients with pneumonia through chest radiography). Among the remaining 80 patients, 40 patients were assigned to experimental group, and the others were assigned to control group to only receive standard care. Efficacy and safety were evaluated for both groups. The time of viral RNA negative conversion in experimental group (Mean, 3·80 days, 95% CI 2·07–5·53), was significantly shorter than that in control group (7·40 days, 95% CI 4·57 to 10·23) (p = 0.031), and difference between means was 3·60 days. The percentage of patients in experimental group with reversion to negative viral RNA was significantly increased compared with control group on all sampling days (every day during the 12-day observation period) (p = 0·037). For the secondary endpoint, the experimental group had a significantly shorter time until improvement was seen by CT (Mean 6·21 days, N = 38/40, 95% CI 5·11–7·31) than that in control group (8·76 days, N = 34/40, 95% CI 7·57–9·96) (p = 0.002), and difference between means was 2·55 days. No discomfort or complications during aerosol inhalation were reported to the nurses by any experimental patients. In conclusion, we found that aerosol inhalation of IFN-κ plus TFF2 in combination with standard care is safe and superior to standard care alone in shortening the time up to viral RNA negative conversion in all clinical samples. In addition, the patients in experimental group had a significantly shortened CT imaging improvement time than those in control group. This study suggested that this combination treatment is able to facilitate clinical improvement (negative for virus, improvement by CT, reduced hospitalization stay) and thereby result in an early release from the hospital. These data support the need for exploration with a large-scale trial of IFN-κ plus TFF2 to treat COVID-19. Funding was provided by the National Natural Science Foundation of China, National Major Project for Control and Prevention of Infectious Disease in China, Shanghai Science and Technology Commission, Shanghai Municipal Health Commission.
登录
查看更多内容
影响因子：
4.8
作者：
LaFleur, DW;Nardelli, B;Moore, PA
通讯作者：
Moore, PA
影响因子：
6
作者：
Pociask, Derek A.;Scheller, Erich V.;Alcorn, John F.
通讯作者：
Alcorn, John F.
DOI：
10.1165/rcmb.2011-0320oc
发表时间：
2013-01-01
影响因子：
6.4
作者：
Royce, Simon G.;Lim, Clarice;Tang, Mimi L. K.
通讯作者：
Tang, Mimi L. K.
影响因子：
158.5
作者：
Grein, J.;Ohmagari, N.;Flanigan, T.
通讯作者：
Flanigan, T.
影响因子：
3.1
作者：
Dong, Liying;Hu, Shasha;Gao, Jianjun
通讯作者：
Gao, Jianjun