COVID-19恢复协作组研究了洛匹那韦-利托那韦治疗COVID-19住院患者的疗效。2020年10月5日，该研究发表在《柳叶刀》杂志上。
基于体外活性、临床前研究和观察性研究，洛匹那韦-利托那韦被建议用于治疗COVID-19。研究组评估了洛匹那韦-利托那韦是否可改善住院COVID-19的患者的预后。
研究组在英国的176家医院进行了一项随机、对照、开放标签的平台试验，2020年3月19日至6月29日，招募COVID-19住院患者，并将其随机分组，其中1616例接受洛匹那韦-利托那韦治疗，3424例接受常规治疗。主要结局为28天的全因死亡率。
总体而言，洛匹那韦-利托那韦组中有374例（23%）患者在28天内死亡，常规治疗组有767例（22%），比值比为1.03。所有预先指定的患者亚组结果均一致。
研究组观察到两组患者入院至存活出院的时间（中位11天）或28天内存活出院的患者比例（比率0.98）均无显著差异。基线时未进行有创机械通气的患者中，达到有创机械通气或死亡的复合终点的比例无显著差异，风险比1.09。
结果表明，对于COVID-19住院患者，采用洛匹那韦-利托那韦治疗并不能降低28天病死率，缩短住院时间，或降低有创性机械通气或死亡风险，不建议临床使用。
附：英文原文
Title: Lopinavir–ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Author: Peter W Horby, Marion Mafham, Jennifer L Bell, Louise Linsell, Natalie Staplin, Jonathan Emberson, Adrian Palfreeman, Jason Raw, Einas Elmahi, Benjamin Prudon, Christopher Green, Simon Carley, David Chadwick, Matthew Davies, Matthew P Wise, J Kenneth Baillie, Lucy C Chappell, Saul N Faust, Thomas Jaki, Katie Jefferey, Wei Shen Lim, Alan Montgomery, Kathryn Rowan, Edmund Juszczak, Richard Haynes, Martin J Landray
Issue&Volume: 2020-10-05
Abstract:
Background
Lopinavir–ritonavir has been proposed as a treatment for COVID-19 on the basis of in vitro activity, preclinical studies, and observational studies. Here, we report the results of a randomised trial to assess whether lopinavir–ritonavir improves outcomes in patients admitted to hospital with COVID-19.
Methods
In this randomised, controlled, open-label, platform trial, a range of possible treatments was compared with usual care in patients admitted to hospital with COVID-19. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus lopinavir–ritonavir (400 mg and 100 mg, respectively) by mouth for 10 days or until discharge (or one of the other RECOVERY treatment groups: hydroxychloroquine, dexamethasone, or azithromycin) using web-based simple (unstratified) randomisation with allocation concealment. Randomisation to usual care was twice that of any of the active treatment groups (eg, 2:1 in favour of usual care if the patient was eligible for only one active group, 2:1:1 if the patient was eligible for two active groups). The primary outcome was 28-day all-cause mortality. Analyses were done on an intention-to-treat basis in all randomly assigned participants. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.
Findings
Between March 19, 2020, and June 29, 2020, 1616 patients were randomly allocated to receive lopinavir–ritonavir and 3424 patients to receive usual care. Overall, 374 (23%) patients allocated to lopinavir–ritonavir and 767 (22%) patients allocated to usual care died within 28 days (rate ratio 1·03, 95% CI 0·91–1·17; p=0·60). Results were consistent across all prespecified subgroups of patients. We observed no significant difference in time until discharge alive from hospital (median 11 days [IQR 5 to >28] in both groups) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 0·98, 95% CI 0·91–1·05; p=0·53). Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion who met the composite endpoint of invasive mechanical ventilation or death (risk ratio 1·09, 95% CI 0·99–1·20; p=0·092).
Interpretation
In patients admitted to hospital with COVID-19, lopinavir–ritonavir was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death. These findings do not support the use of lopinavir–ritonavir for treatment of patients admitted to hospital with COVID-19.
DOI: 10.1016/S0140-6736(20)32013-4
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32013-4/fulltext
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