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/nejmoa2001282
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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.
研究背景目前尚无有效的治疗方法可用于治疗由SARS-CoV-2引起的严重疾病。方法我们进行了一项随机、对照、开放标签试验，涉及确诊为SARS-CoV-2感染的住院成人患者，该感染可导致呼吸系统疾病Covid-19，以及当他们呼吸环境空气时氧饱和度（Sao（2））为94%或更低，或者氧分压（Pao（2））与吸入氧分数（Fio（（2）小于300 mm Hg。患者以1：1的比例随机分配接受洛匹那韦-利托那韦（分别为400 mg和100 mg），每天两次，持续14天，除标准治疗外，或仅接受标准治疗。主要终点是临床改善的时间，定义为从随机化到七类有序量表上两个点的改善或出院的时间，以先发生者为准。共有199名实验室确诊的SARS-CoV-2感染患者接受了随机化; 99名被分配到洛匹那韦-利托那韦组，100名被分配到标准治疗组。洛匹那韦-利托那韦治疗与标准治疗在临床改善时间上的差异无关（临床改善的风险比，1.31; 95%置信区间[CI]，0.95 - 1.80）。洛匹那韦-利托那韦组和标准治疗组的28天死亡率相似（19.2% vs. 25.0%;差异，-5.8个百分点; 95%CI，-17.3至5.7）。在不同时间点可检测到病毒RNA的患者百分比相似。在一项修改的意向治疗分析中，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短1天（风险比，1.39; 95%CI，1.00至1.91）。胃肠道不良事件在洛匹那韦-利托那韦组更常见，但严重不良事件在标准治疗组更常见。13名患者（13.8%）因不良事件而提前停止洛匹那韦-利托那韦治疗。结论在严重Covid-19的住院成人患者中，没有观察到洛匹那韦-利托那韦治疗超过标准治疗的益处。未来在重症患者中进行的试验可能有助于确认或排除治疗获益的可能性。（国家科技重大专项新药创制等项目资助;中国临床试验注册号：ChiCTR 2000029308）
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.)