评估索非布韦和达卡他韦在住院 COVID-19 患者中的疗效：一项随机、双盲临床试验（DISCOVER）。

Evaluation of the effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER).

机构信息

Abadan University of Medical Sciences, Abadan, Iran.

Imam Khomeini Hospital of Abadan Petroleum Health Organization, Abadan, Iran.

出版信息

J Antimicrob Chemother. 2022 Feb 23;77(3):758-766. doi: 10.1093/jac/dkab433.

DOI:10.1093/jac/dkab433

PMID:34849957

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8690191/

Abstract

BACKGROUND

The combination of sofosbuvir and daclatasvir has shown preliminary efficacy for hospitalized patients with COVID-19 in four open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir/daclatasvir to standard care improved clinical outcomes in hospitalized patients with COVID-19.

METHODS

This was a placebo-controlled, double-blind, randomized clinical trial in adults hospitalized with COVID-19 at 19 hospitals in Iran. Patients were randomized to oral sofosbuvir/daclatasvir 400/60 mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O2 saturation <95% and compatible symptoms. The primary outcome was hospital discharge within 10 days of randomization. Secondary outcomes included mortality and time to clinical events. The trial is registered on the Iran Registry of Clinical Trials under IRCT20200624047908N1.

RESULTS

Between July and October 2020, 1083 patients were randomized to either the sofosbuvir/daclatasvir arm (n = 541) or the placebo arm (n = 542). No significant difference was observed in the primary outcome of hospital discharge within 10 days, which was achieved by 415/541 (77%) in the sofosbuvir/daclatasvir arm and 411/542 (76%) in the placebo arm [risk ratio (RR) 1.01, 95% CI 0.95-1.08, P = 0.734]. In-hospital mortality was 60/541 (11%) in the sofosbuvir/daclatasvir arm versus 55/542 (10%) in the placebo arm (RR 1.09, 95% CI 0.77-1.54, P = 0.615). No differences were observed in time to hospital discharge or time to in-hospital mortality.

CONCLUSIONS

We observed no significant effect of sofosbuvir/daclatasvir versus placebo on hospital discharge or survival in hospitalized COVID-19 patients.

摘要

背景

四项小规模开放标签研究表明，索非布韦联合达卡他韦对 COVID-19 住院患者具有初步疗效。本项更大规模的试验旨在评估在 COVID-19 住院患者中，加用索非布韦/达卡他韦是否能改善临床结局。

方法

这是在伊朗 19 家医院开展的一项安慰剂对照、双盲、随机临床试验，纳入了 COVID-19 住院患者。患者随机分为口服索非布韦/达卡他韦 400/60mg 每日一次或安慰剂，加用标准治疗。患者需满足以下标准：PCR 或诊断性胸部 CT 阳性、氧饱和度<95%和符合症状。主要结局为随机分组后 10 天内出院。次要结局包括死亡率和临床事件发生时间。该试验在伊朗临床试验注册中心注册，编号为 IRCT20200624047908N1。

结果

2020 年 7 月至 10 月，1083 例患者被随机分为索非布韦/达卡他韦组（n=541）或安慰剂组（n=542）。两组主要结局即 10 天内出院率无显著差异，索非布韦/达卡他韦组有 415/541（77%）例患者出院，安慰剂组有 411/542（76%）例患者出院[风险比（RR）1.01，95%可信区间（CI）0.95-1.08，P=0.734]。索非布韦/达卡他韦组住院死亡率为 60/541（11%），安慰剂组为 55/542（10%）[RR 1.09，95%CI 0.77-1.54，P=0.615]。两组患者出院时间和住院死亡率无显著差异。