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Practice
Open Access

Remdesivir for patients with COVID-19

Peter E. Wu and Andrew M. Morris
CMAJ January 25, 2021 193 (4) E125; DOI: https://doi.org/10.1503/cmaj.202505
Peter E. Wu
Department of Medicine (Wu, Morris) Division of Clinical Pharmacology & Toxicology (Wu) and Division of Infectious Diseases (Morris), University of Toronto; Division of General Internal Medicine and Geriatrics (Wu), University Health Network; Division of Infectious Diseases (Morris), Sinai Health and University Health Network, Toronto, Ont.
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Andrew M. Morris
Department of Medicine (Wu, Morris) Division of Clinical Pharmacology & Toxicology (Wu) and Division of Infectious Diseases (Morris), University of Toronto; Division of General Internal Medicine and Geriatrics (Wu), University Health Network; Division of Infectious Diseases (Morris), Sinai Health and University Health Network, Toronto, Ont.
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Remdesivir is an antiviral drug with activity against an array of RNA viruses

Remdesivir is an intravenous inhibitor of the viral RNA-dependent RNA polymerase with in vitro and in vivo activity against Middle East respiratory syndrome coronavirus, severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and SARS-CoV-2.1–3 In Canada, it is authorized and available through Health Canada for patients (≥ 12 yr of age and weighing ≥ 40 kg) with coronavirus disease 2019 (COVID-19) who require oxygen.3

Remdesivir has been tested as a treatment for COVID-19 in 2 large clinical trials

There are 4 published randomized controlled trials (RCTs) that evaluated remdesivir for treatment of COVID-19.1,2,4,5 The 2 largest were the Adaptive Covid-19 Treatment Trial (ACTT-1), a placebo-controlled RCT involving 1062 patients,1 and Solidarity, an open-label RCT that compared treatment with remdesivir to standard of care in 6838 patients.5

Remdesivir may reduce recovery time but does not reduce mortality

The ACTT-1 found that median time to clinical improvement was shortened from 15 to 10 days, with the greatest improvement seen in patients requiring low-flow oxygen. The trial did not find a difference in mortality (hazard ratio 0.73, 95% confidence interval [CI] 0.52–1.03), although it was not powered to do so.1 Solidarity failed to show a mortality benefit (rate ratio 0.95, 95% CI 0.81–1.11) and also did not show a benefit in the prespecified secondary outcomes of ventilation or time to discharge.5

Remdesvir does not help critically ill patients

Subgroup analyses from ACTT-1 and Solidarity showed that remdesivir conferred no benefit in patients who were intubated or on extracorporeal membrane oxygenation.1,5 Although less certain, there did not appear to be significant benefit for patients on high-flow oxygen.1,5

Data for adverse events are limited but include hepatotoxicity and hypersensitivity reactions

Patients with elevated levels of liver enzymes or a glomerular filtration rate less than 30 mL/min were excluded from the published trials. 1,2,4,5 Drug-induced liver injuries have been reported,6 and anaphylaxis and infusion-related reactions can occur.1

Footnotes

  • Competing interests: Peter Wu is a member of and Andrew Morris chairs the Ontario COVID-19 Clinical Practice Guideline working group, a volunteer provincial working group aimed at providing consensus-based, evidence-informed treatment guidelines for COVID-19. No other competing interests were declared.

  • This article has been peer reviewed.

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) license, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e. research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/

References

  1. ↵
    1. Beigel JH,
    2. Tomashek KM,
    3. Dodd LE,
    4. et al.
    ACTT-1 Study Group Members. Remdesivir for the treatment of COVID-19: final report. N Engl J Med 2020;383:1813–26.
    OpenUrlCrossRefPubMed
  2. ↵
    1. Wang Y,
    2. Zhang D,
    3. Du G,
    4. et al
    . Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2020;395:1569–78.
    OpenUrlCrossRefPubMed
  3. ↵
    Update on remdesivir: continued monitoring. Ottawa: Health Canada; modified 2020 Nov. 26. Available: www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/remdesivir-update.html (accessed 2020 Dec. 8).
  4. ↵
    1. Spinner CD,
    2. Gottlieb RL,
    3. Criner GJ,
    4. et al.
    GS-US-540-5774 Investigators. Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: a randomized clinical trial. JAMA 2020;324:1048–57.
    OpenUrlPubMed
  5. ↵
    WHO Solidarity Trial Consortium; Pan H, Peto R, Henao-Restrepo A-M, et al. Repurposed antiviral drugs for COVID-19: interim WHO Solidarity Trial results. N Engl J Med 2020 Dec. 2 [Epub ahead of print]. doi: 10.1056/NEJMoa2023184.
    OpenUrlCrossRef
  6. ↵
    1. Carothers C,
    2. Birrer K,
    3. Vo M
    . Acetylcysteine for the treatment of suspected remdesivir-associated acute liver failure in COVID-19: a case series. Pharmacotherapy 2020;40:1166–71.
    OpenUrl
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Canadian Medical Association Journal: 193 (4)
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Vol. 193, Issue 4
25 Jan 2021
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Remdesivir for patients with COVID-19
Peter E. Wu, Andrew M. Morris
CMAJ Jan 2021, 193 (4) E125; DOI: 10.1503/cmaj.202505

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Peter E. Wu, Andrew M. Morris
CMAJ Jan 2021, 193 (4) E125; DOI: 10.1503/cmaj.202505
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    • Remdesivir is an antiviral drug with activity against an array of RNA viruses
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    • Remdesivir may reduce recovery time but does not reduce mortality
    • Remdesvir does not help critically ill patients
    • Data for adverse events are limited but include hepatotoxicity and hypersensitivity reactions
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