Favipiravir for COVID-19 in adults in the community in PRINCIPLE, an open-label, randomised, controlled, adaptive platform trial of short- and longer-term outcomes

IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES
FD Richard Hobbs , Oghenekome A. Gbinigie-Thompson , Milensu Shanyinde , Ly-Mee Yu , Victoria Harris , Jienchi Dorward , Gail Hayward , Benjamin R. Saville , Nicholas S. Berry , Philip H. Evans , Nicholas PB Thomas , Mahendra G. Patel , Duncan Richards , Oliver Van Hecke , Michelle A. Detry , Christina T. Saunders , Mark Fitzgerald , Jared Robinson , Charlotte Latimer-Bell , Julie Allen , Christopher C. Butler
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引用次数: 0

Abstract

Background

Evidence for the effect of favipiravir treatment of acute COVID-19 on recovery, hospital admissions and longer-term outcomes in community settings is limited.

Methods

In this multicentre. open-label, multi-arm, adaptive platform randomised controlled trial participants aged ≥18 years in the community with a positive test for SARS-CoV-2 and symptoms lasting ≤14 days were randomised to: usual care; usual care plus favipiravir tablets (loading dose of 3600 mg in divided doses on day one, then 800 mg twice a day for four days); or, usual care plus other interventions. Co-primary endpoints were time to first self-reported recovery and hospitalisation/death related to COVID-19, within 28 days, analysed using Bayesian models. Recovery at six months was the primary longer-term outcome. Trial registration: ISRCTN86534580.

Findings

The primary analysis model included 8811 SARS-CoV-2 positive mostly COVID vaccinated participants, randomised to favipiravir (n = 1829), usual care (n = 3256), and other treatments (n = 3726). Time to self-reported recovery was shorter in the favipiravir group than usual care (estimated hazard ratio 1·23 [95% credible interval 1·14 to 1·33]), a reduction of 2·98 days [1·99 to 3·94] from 16 days in median time to self-reported recovery for favipiravir versus usual care alone. COVID-19 related hospitalisations/deaths were similar (estimated odds ratio 0·99 [0·61 to 1·61]; estimated difference 0% [−0·9% to 0·6%]). 14 serious adverse events occurred in the favipiravir group and 4 in usual care. By six months, the proportion feeling fully recovered was 74·9% for favipiravir versus 71·3% for usual care (RR = 1·05, [1·02 to 1·08]).

Interpretation

In this open-label trial in a largely vaccinated population with COVID-19 in the community, favipiravir did not reduce hospital admissions, but shortened time to recovery and had a marginal positive impact on long term outcomes.

PRINCIPLE 是一项开放标签、随机对照、适应性平台试验,对短期和长期疗效进行研究。
背景:在社区环境中,法非拉韦治疗急性COVID-19对康复、入院和长期疗效的影响证据有限:在这项多中心、开放标签、多臂、适应性平台随机对照试验中,年龄≥18岁、SARS-CoV-2检测呈阳性且症状持续时间≤14天的社区参与者被随机分配到:常规治疗;常规治疗加法非拉韦片(第一天分次服用3600毫克的负荷剂量,然后在四天内每天两次,每次800毫克);或常规治疗加其他干预措施。共同主要终点是28天内首次自我报告痊愈和因COVID-19住院/死亡的时间,采用贝叶斯模型进行分析。6个月后的康复是主要的长期结果:ISRCTN86534580.Findings:主要分析模型包括8811名SARS-CoV-2阳性、大部分接种过COVID疫苗的参与者,他们随机接受了法非拉韦(1829人)、常规治疗(3256人)和其他治疗(3726人)。与常规治疗相比,法匹拉韦组的自我报告康复时间更短(估计危险比为1-23[95%可信区间为1-14至1-33]),与常规治疗相比,法匹拉韦组的自我报告康复时间中位数从16天缩短了2-98天[1-99至3-94]。与COVID-19相关的住院/死亡情况相似(估计几率比0-99 [0-61至1-61];估计差异0% [-0-9%至0-6%])。法非拉韦组发生了14起严重不良事件,常规治疗组发生了4起。6个月后,感觉完全康复的比例为:法非拉韦组74-9%,常规治疗组71-3%(RR=1-05,[1-02至1-08]):这项开放标签试验主要针对社区中接种过COVID-19疫苗的人群,在这项试验中,法匹拉韦未减少入院人数,但缩短了康复时间,并对长期疗效产生了微弱的积极影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Infection
Journal of Infection 医学-传染病学
CiteScore
45.90
自引率
3.20%
发文量
475
审稿时长
16 days
期刊介绍: The Journal of Infection publishes original papers on all aspects of infection - clinical, microbiological and epidemiological. The Journal seeks to bring together knowledge from all specialties involved in infection research and clinical practice, and present the best work in the ever-changing field of infection. Each issue brings you Editorials that describe current or controversial topics of interest, high quality Reviews to keep you in touch with the latest developments in specific fields of interest, an Epidemiology section reporting studies in the hospital and the general community, and a lively correspondence section.
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