一项评估法匹拉韦/伊维菌素/氯硝柳胺联合用药对轻至中度新冠肺炎成年患者病毒清除加速作用的随机试验（FINCOV）。

A randomized trial to assess the acceleration of viral clearance by the combination Favipiravir/Ivermectin/Niclosamide in mild-to-moderate COVID-19 adult patients (FINCOV).

作者信息

Siripongboonsitti Taweegrit, Tawinprai Kriangkrai, Avirutnan Panisadee, Jitobaom Kunlakanya, Auewarakul Prasert

机构信息

Division of Infectious Diseases, Department of Medicine, Chulabhorn Hospital, Chulabhorn Royal Academy, Bangkok, Thailand; Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand.

出版信息

J Infect Public Health. 2024 May;17(5):897-905. doi: 10.1016/j.jiph.2024.03.030. Epub 2024 Mar 29.

DOI:10.1016/j.jiph.2024.03.030

PMID:38569269

Abstract

BACKGROUND

The efficacy of the viral clearance and clinical outcomes of favipiravir (FPV) in outpatients being treated for coronavirus disease 2019 (COVID-19) is unclear. Ivermectin (IVM), niclosamide (NCL), and FPV demonstrated synergistic effects in vitro for exceed 78% inhibiting severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) replication.

METHODS

A phase 2, open-label, 1:1, randomized, controlled trial was conducted on Thai patients with mild-to-moderate COVID-19 who received either combination FPV/IVM/NCL therapy or FPV alone to assess the rate of viral clearance among individuals with mild-to-moderate COVID-19.

RESULTS

Sixty non-high-risk comorbid patients with mild-to-moderate COVID-19 were randomized; 30 received FPV/IVM/NCL, and 30 received FPV alone. Mixed-effects multiple linear regression analysis of the cycle threshold value from SARS-CoV-2 PCR demonstrated no statistically significant differences in viral clearance rates between the combined FPV/IVM/NCL therapy group and the FPV-alone group. World Health Organization Clinical Progression scores and symptomatic improvement did not differ between arms on days 3, 6, and 10, and no adverse events were reported. No patients required hospitalization, intensive care unit admission, or supplemental oxygen or died within 28 days. C-reactive protein on day 3 was lower in the FPV/IVM/NCL group.

CONCLUSION

Viral clearance rates did not differ significantly between the FPV/IVM/NCL combination therapy and FPV-alone groups of individuals with mild-to-moderate COVID-19, although the combined regimen demonstrated a synergistic effect in vitro. No discernible clinical benefit was observed. Further research is required to explore the potential benefits of FVP beyond its antiviral effects.

TRIAL REGISTRATION

TCTR20230403007, Registered 3 April 2023 - Retrospectively registered,https://trialsearch.who.int/Trial2.aspx?TrialID=TCTR20230403007.

摘要

背景

法匹拉韦（FPV）用于治疗2019冠状病毒病（COVID-19）门诊患者的病毒清除疗效和临床结局尚不清楚。伊维菌素（IVM）、氯硝柳胺（NCL）和FPV在体外对抑制严重急性呼吸综合征冠状病毒2（SARS-CoV-2）复制表现出协同效应，抑制率超过78%。

方法

对泰国轻至中度COVID-19患者进行了一项2期、开放标签、1:1随机对照试验，这些患者接受FPV/IVM/NCL联合治疗或单独使用FPV，以评估轻至中度COVID-19患者的病毒清除率。

结果

60例轻至中度COVID-19非高危合并症患者被随机分组；30例接受FPV/IVM/NCL治疗，30例单独接受FPV治疗。对SARS-CoV-2 PCR循环阈值进行的混合效应多元线性回归分析表明，FPV/IVM/NCL联合治疗组和单独使用FPV组之间的病毒清除率无统计学显著差异。在第3天、第6天和第10天，两组的世界卫生组织临床进展评分和症状改善情况无差异，且未报告不良事件。28天内无患者需要住院、入住重症监护病房、使用补充氧气或死亡。第3天，FPV/IVM/NCL组的C反应蛋白较低。