A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19

Type Journal Article Author Bin Cao Author Yeming Wang Author Danning Wen Author Wen Liu Author Jingli Wang Author Guohui Fan Author Lianguo Ruan Author Bin Song Author Yanping Cai Author Ming Wei Author Xingwang Li Author Jiaan Xia Author Nanshan Chen Author Jie Xiang Author Ting Yu Author Tao Bai Author Xuelei Xie Author Li Zhang Author Caihong Li Author Ye Yuan Author Hua Chen Author Huadong Li Author Hanping Huang Author Shengjing Tu Author Fengyun Gong Author Ying Liu Author Yuan Wei Author Chongya Dong Author Fei Zhou Author Xiaoying Gu Author Jiuyang Xu Author Zhibo Liu Author Yi Zhang Author Hui Li Author Lianhan Shang Author Ke Wang Author Kunxia Li Author Xia Zhou Author Xuan Dong Author Zhaohui Qu Author Sixia Lu Author Xujuan Hu Author Shunan Ruan Author Shanshan Luo Author Jing Wu Author Lu Peng Author Fang Cheng Author Lihong Pan Author Jun Zou Author Chunmin Jia Author Juan Wang Author Xia Liu Author Shuzhen Wang Author Xudong Wu Author Qin Ge Author Jing He Author Haiyan Zhan Author Fang Qiu Author Li Guo Author Chaolin Huang Author Thomas Jaki Author Frederick G. Hayden Author Peter W. Horby Author Dingyu Zhang Author Chen Wang URL https://www.nejm.org/doi/10.1056/NEJMoa2001282 Rights Copyright © 2020 Massachusetts Medical Society. All rights reserved. Volume 382 Pages 1787-1799 Publication New England Journal of Medicine Date 18/03/2020 Loc. in Archive world Extra Publisher: Massachusetts Medical Society DOI 10.1056/NEJMoa2001282 Library Catalog www.nejm.org Language en Abstract Background No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2. Methods We 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 (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) 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. Results A 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.