N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282.
A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19.
Cao B1, Wang Y1, Wen D1, Liu W1, Wang J1, Fan G1, Ruan L1, Song B1, Cai Y1, Wei M1, Li X1, Xia J1, Chen N1, Xiang J1, Yu T1, Bai T1, Xie X1, Zhang L1, Li C1, Yuan Y1, Chen H1, Li H1, Huang H1, Tu S1, Gong F1, Liu Y1, Wei Y1, Dong C1, Zhou F1, Gu X1, Xu J1, Liu Z1, Zhang Y1, Li H1, Shang L1, Wang K1, Li K1, Zhou X1, Dong X1, Qu Z1, Lu S1, Hu X1, Ruan S1, Luo S1, Wu J1, Peng L1, Cheng F1, Pan L1, Zou J1, Jia C1, Wang J1, Liu X1, Wang S1, Wu X1, Ge Q1, He J1, Zhan H1, Qiu F1, Guo L1, Huang C1, Jaki T1, Hayden FG1, Horby PW1, Zhang D1, Wang C1.
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, 1.24; 95% confidence interval [CI], 0.90 to 1.72). 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.CONCLUSIONS: In 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.).Copyright © 2020 Massachusetts Medical Society.
PMID: 32187464 DOI: 10.1056/NEJMoa2001282