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Showing content from https://pubmed.ncbi.nlm.nih.gov/32187464/ below:

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

Randomized Controlled Trial

. 2020 May 7;382(19):1787-1799. doi: 10.1056/NEJMoa2001282. Epub 2020 Mar 18. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19 Yeming Wang¹, Danning Wen¹, Wen Liu¹, Jingli Wang¹, Guohui Fan¹, Lianguo Ruan¹, Bin Song¹, Yanping Cai¹, Ming Wei¹, Xingwang Li¹, Jiaan Xia¹, Nanshan Chen¹, Jie Xiang¹, Ting Yu¹, Tao Bai¹, Xuelei Xie¹, Li Zhang¹, Caihong Li¹, Ye Yuan¹, Hua Chen¹, Huadong Li¹, Hanping Huang¹, Shengjing Tu¹, Fengyun Gong¹, Ying Liu¹, Yuan Wei¹, Chongya Dong¹, Fei Zhou¹, Xiaoying Gu¹, Jiuyang Xu¹, Zhibo Liu¹, Yi Zhang¹, Hui Li¹, Lianhan Shang¹, Ke Wang¹, Kunxia Li¹, Xia Zhou¹, Xuan Dong¹, Zhaohui Qu¹, Sixia Lu¹, Xujuan Hu¹, Shunan Ruan¹, Shanshan Luo¹, Jing Wu¹, Lu Peng¹, Fang Cheng¹, Lihong Pan¹, Jun Zou¹, Chunmin Jia¹, Juan Wang¹, Xia Liu¹, Shuzhen Wang¹, Xudong Wu¹, Qin Ge¹, Jing He¹, Haiyan Zhan¹, Fang Qiu¹, Li Guo¹, Chaolin Huang¹, Thomas Jaki¹, Frederick G Hayden¹, Peter W Horby¹, Dingyu Zhang¹, Chen Wang¹

Affiliations

Affiliation

¹ From the Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases (B.C., Yeming Wang, G.F., F.Z., X.G., Z.L., Y.Z., Hui Li, L.S., C.W.), and the Institute of Clinical Medical Sciences (G.F., X.G.), China-Japan Friendship Hospital, the Institute of Respiratory Medicine, Chinese Academy of Medical Sciences (B.C., Yeming Wang, F.Z., Z.L., Y.Z., Hui Li, C.W.), the Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University (Xingwang Li), Peking University Clinical Research Institute, Peking University First Hospital (C.D.), Tsinghua University School of Medicine (Jiuyang Xu), Beijing University of Chinese Medicine (L.S.), NHC Key Laboratory of Systems Biology of Pathogens and Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences (L.G.), and Peking Union Medical College (L.G., C.W.), Beijing, and Jin Yin-tan Hospital, Wuhan (D.W., W.L., Jingli Wang, L.R., B.S., Y.C., M.W., Jiaan Xia, N.C., Jie Xiang, T.Y., T.B., X.X., L.Z., C.L., Y.Y., H.C., Huadong Li, H.H., S.T., F.G., Y.L., Yuan Wei, K.W., K.L., X.Z., X.D., Z.Q., Sixia Lu, X.H., S.R., Shanshan Luo, Jing Wu, Lu Peng, F.C., Lihong Pan, J.Z., C.J., Juan Wang, Xia Liu, S.W., X.W., Q.G., J.H., H.Z., F.Q., C.H., D.Z.) - all in China; Lancaster University, Lancaster (T.J.), and the University of Oxford, Oxford (P.W.H.) - both in the United Kingdom; and the University of Virginia School of Medicine, Charlottesville (F.G.H.).

PMID: 32187464
PMCID: PMC7121492
DOI: 10.1056/NEJMoa2001282

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Randomized Controlled Trial

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

Bin Cao et al. N Engl J Med. 2020.

. 2020 May 7;382(19):1787-1799. doi: 10.1056/NEJMoa2001282. Epub 2020 Mar 18. Authors Bin Cao¹, Yeming Wang¹, Danning Wen¹, Wen Liu¹, Jingli Wang¹, Guohui Fan¹, Lianguo Ruan¹, Bin Song¹, Yanping Cai¹, Ming Wei¹, Xingwang Li¹, Jiaan Xia¹, Nanshan Chen¹, Jie Xiang¹, Ting Yu¹, Tao Bai¹, Xuelei Xie¹, Li Zhang¹, Caihong Li¹, Ye Yuan¹, Hua Chen¹, Huadong Li¹, Hanping Huang¹, Shengjing Tu¹, Fengyun Gong¹, Ying Liu¹, Yuan Wei¹, Chongya Dong¹, Fei Zhou¹, Xiaoying Gu¹, Jiuyang Xu¹, Zhibo Liu¹, Yi Zhang¹, Hui Li¹, Lianhan Shang¹, Ke Wang¹, Kunxia Li¹, Xia Zhou¹, Xuan Dong¹, Zhaohui Qu¹, Sixia Lu¹, Xujuan Hu¹, Shunan Ruan¹, Shanshan Luo¹, Jing Wu¹, Lu Peng¹, Fang Cheng¹, Lihong Pan¹, Jun Zou¹, Chunmin Jia¹, Juan Wang¹, Xia Liu¹, Shuzhen Wang¹, Xudong Wu¹, Qin Ge¹, Jing He¹, Haiyan Zhan¹, Fang Qiu¹, Li Guo¹, Chaolin Huang¹, Thomas Jaki¹, Frederick G Hayden¹, Peter W Horby¹, Dingyu Zhang¹, Chen Wang¹ Affiliation

¹ From the Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases (B.C., Yeming Wang, G.F., F.Z., X.G., Z.L., Y.Z., Hui Li, L.S., C.W.), and the Institute of Clinical Medical Sciences (G.F., X.G.), China-Japan Friendship Hospital, the Institute of Respiratory Medicine, Chinese Academy of Medical Sciences (B.C., Yeming Wang, F.Z., Z.L., Y.Z., Hui Li, C.W.), the Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University (Xingwang Li), Peking University Clinical Research Institute, Peking University First Hospital (C.D.), Tsinghua University School of Medicine (Jiuyang Xu), Beijing University of Chinese Medicine (L.S.), NHC Key Laboratory of Systems Biology of Pathogens and Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences (L.G.), and Peking Union Medical College (L.G., C.W.), Beijing, and Jin Yin-tan Hospital, Wuhan (D.W., W.L., Jingli Wang, L.R., B.S., Y.C., M.W., Jiaan Xia, N.C., Jie Xiang, T.Y., T.B., X.X., L.Z., C.L., Y.Y., H.C., Huadong Li, H.H., S.T., F.G., Y.L., Yuan Wei, K.W., K.L., X.Z., X.D., Z.Q., Sixia Lu, X.H., S.R., Shanshan Luo, Jing Wu, Lu Peng, F.C., Lihong Pan, J.Z., C.J., Juan Wang, Xia Liu, S.W., X.W., Q.G., J.H., H.Z., F.Q., C.H., D.Z.) - all in China; Lancaster University, Lancaster (T.J.), and the University of Oxford, Oxford (P.W.H.) - both in the United Kingdom; and the University of Virginia School of Medicine, Charlottesville (F.G.H.).

PMID: 32187464
PMCID: PMC7121492
DOI: 10.1056/NEJMoa2001282

Item in Clipboard

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.

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.).

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Conflict of interest statement

No potential conflict of interest relevant to this article was reported.

Figures
Figure 1. Randomization and Treatment Assignment.

Figure 1. Randomization and Treatment Assignment.
Figure 1. Randomization and Treatment Assignment.
Figure 2. Time to Clinical Improvement in…

Figure 2. Time to Clinical Improvement in the Intention-to-Treat Population.
Figure 2. Time to Clinical Improvement in the Intention-to-Treat Population.
Figure 3. Mean Change from Baseline in…

Figure 3. Mean Change from Baseline in SARS-CoV-2 Viral RNA Load by qPCR on Throat…
Figure 3. Mean Change from Baseline in SARS-CoV-2 Viral RNA Load by qPCR on Throat Swabs.

bars indicate 95% confidence intervals. Results less than the lower limit of quantification of polymerase-chain-reaction (PCR) assay and greater than the limit of qualitative detection are imputed with 1 log₁₀ copies per milliliter; results for patients with viral-negative RNA are imputed with 0 log₁₀ copies per milliliter. Among the 199 patients, 130 (59 patients in the lopinavir–ritonavir group and 71 in the standard-care group) had virologic data that were used for viral load calculation, whereas the rest of the patients had undetectable viral RNA on throat swabs over the time.

Comment in

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