A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19
A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19
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DOI：
10.1056/nejmc2008043
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发表时间：
2020-05-07
影响因子：
158.5
通讯作者：
Wang, C.
中科院分区：
文献类型：
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作者：
Cao, B.;Wang, Y.;Wang, C.
背景：目前还没有任何疗法被证明对治疗SARS-CoV-2引起的严重疾病有效。方法我们进行了一项随机、对照、开放标签试验，患者包括确诊为SARS-CoV-2感染的住院成人患者。SARS-CoV-2感染会导致呼吸道疾病新冠肺炎，当他们呼吸环境空气或氧分压(PaO(2))与吸入氧分数(FiO(2))低于300 mm Hg时，血氧饱和度(SaO(2))不超过94%。患者按1：1的比例随机分配，在标准护理的基础上，每天两次接受洛匹那韦-利托那韦(分别为400毫克和100毫克)，连续14天，或者只接受标准护理。主要终点是临床改善的时间，定义为从随机到七类序贯量表中改善两分或出院的时间，以先到者为准。结果总共199名实验室确认的SARS-CoV-2感染患者接受了随机分组；99人被分配到洛匹那韦-利托那韦组，100人被分配到标准护理组。使用洛比那韦-利托那韦的治疗与标准治疗到临床改善的时间差异没有相关性(临床改善的风险比为1.31；95%可信区间[CI]为0.95至1.80)。洛匹那韦-利托那韦组和标准护理组28天的死亡率相似(19.2%比25.0%；差异-5.8个百分点；95%可信区间-17.3比5.7)。在不同时间点可检测到病毒RNA的患者的百分比相似。在一项改良的意向治疗分析中，洛匹那韦-利托那韦导致临床改善的中位时间比标准治疗观察到的时间缩短了1天(风险比1.39；95%可信区间1.00至1.91)。胃肠道不良事件在洛匹那韦-利托那韦组中更常见，但严重不良事件在标准护理组中更常见。13例(13.8%)患者因不良反应提前停止治疗。结论在住院的重度新冠肺炎患者中，除标准护理外，洛匹那韦-利托那韦治疗没有任何益处。未来对重症患者的试验可能有助于确认或排除治疗受益的可能性。(由国家新药研发重大科技专项等资助；中国临床试验注册号：ChiCTR2000029308。)
BACKGROUNDNo therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2.METHODSWe conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao(2)) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao(2)) to the fraction of inspired oxygen (Fio(2)) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first.RESULTSA total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir-ritonavir group, and 100 to the standard-care group. Treatment with lopinavir-ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.31; 95% confidence interval [CI], 0.95 to 1.80). Mortality at 28 days was similar in the lopinavir-ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, -5.8 percentage points; 95% CI, -17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir-ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir-ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir-ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events.CONCLUSIONSIn hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir-ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308.)