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

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  • Source:
    New England journal of medicine 2020 382 19, 1787 (1787-1799) Published by: NLM (Medline) United States
  • Additional Information
    • Author(s):
      Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C
    • Language:
      English
    • Publication Type:
      Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
    • Record Status:
      This record is this issue.
    • 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.).
    • EMBASE keywords:
      adult; adverse drug reaction; ambient air; arterial oxygen saturation; article; clinical trial; controlled study; drug therapy; female; health care quality; human; major clinical study; male; mortality; nonhuman; open study; partial pressure; randomization; randomized controlled trial; respiratory tract disease; SARS coronavirus; side effect
      Adult
      Aged
      Female
      Humans
      Male
      Middle Aged
      Antiviral Agents/adverse effects
      Betacoronavirus/genetics
      Clinical Laboratory Techniques
      Coronavirus Infections/diagnosis
      Coronavirus Infections/mortality
      Coronavirus Infections/virology
      Cytochrome P-450 CYP3A Inhibitors/adverse effects
      Drug Therapy, Combination
      Hospital Mortality
      Intention to Treat Analysis
      Lopinavir/adverse effects
      Pandemics
      Patient Acuity
      Pneumonia, Viral/mortality
      Pneumonia, Viral/virology
      Proportional Hazards Models
      Reverse Transcriptase Polymerase Chain Reaction
      Ritonavir/adverse effects
      Time-to-Treatment
      Treatment Failure
      Viral Load
      Antiviral Agents/*therapeutic use
      Betacoronavirus/*isolation & purification
      Coronavirus Infections/*drug therapy
      Cytochrome P-450 CYP3A Inhibitors/*therapeutic use
      Lopinavir/*therapeutic use
      Pneumonia, Viral/*drug therapy
      Ritonavir/*therapeutic use
    • Accession Number:
      631281906
    • Source:
      This document should be cited as: Cao B Wang Y Wen D Liu W Wang J Fan G Ruan L Song B Cai Y Wei M Li X Xia J Chen N Xiang J Yu T Bai T Xie X Zhang L Li C Yuan Y Chen H Li H Huang H Tu S Gong F Liu Y Wei Y Dong C Zhou F Gu X Xu J Liu Z Zhang Y Shang L Wang K Li K Zhou X Dong X Qu Z Lu S Hu X Ruan S Luo S Wu J Peng L Cheng F Pan L Zou J Jia C Liu X Wang S Wu X Ge Q He J Zhan H Qiu F Guo L Huang C Jaki T Hayden FG Horby PW Zhang D Wang C. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19 2020 (The Cochrane Controlled Trials Register (CCTR/CENTRAL). DOI: 10.1056/NEJMoa2001282. Oxford: Update Software. Updated quarterly.
    • Accession Number:
      CN-02096979
  • Citations
    • ABNT:
      CAO B et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. New England journal of medicine, [s. l.], v. 382, n. 19, p. 1787–1799, 2020. DOI 10.1056/NEJMoa2001282. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cgh&AN=CN-02096979. Acesso em: 24 set. 2020.
    • AMA:
      Cao B, Wang Y, Wen D, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. New England journal of medicine. 2020;382(19):1787-1799. doi:10.1056/NEJMoa2001282
    • APA:
      Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, … Wang C. (2020). A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. New England Journal of Medicine, 382(19), 1787–1799. https://doi.org/10.1056/NEJMoa2001282
    • Chicago/Turabian: Author-Date:
      Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, et al. 2020. “A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19.” New England Journal of Medicine 382 (19): 1787–99. doi:10.1056/NEJMoa2001282.
    • Harvard:
      Cao B et al. (2020) ‘A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19’, New England journal of medicine, 382(19), pp. 1787–1799. doi: 10.1056/NEJMoa2001282.
    • Harvard: Australian:
      Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D & Wang C 2020, ‘A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19’, New England journal of medicine, vol. 382, no. 19, pp. 1787–1799, viewed 24 September 2020, .
    • MLA:
      Cao B, et al. “A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19.” New England Journal of Medicine, vol. 382, no. 19, Jan. 2020, pp. 1787–1799. EBSCOhost, doi:10.1056/NEJMoa2001282.
    • Chicago/Turabian: Humanities:
      Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, et al. “A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19.” New England Journal of Medicine 382, no. 19 (January 1, 2020): 1787–99. doi:10.1056/NEJMoa2001282.
    • Vancouver/ICMJE:
      Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. New England journal of medicine [Internet]. 2020 Jan 1 [cited 2020 Sep 24];382(19):1787–99. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cgh&AN=CN-02096979