Remdesivir for Severe Coronavirus Disease 2019 (COVID-19) Versus a Cohort Receiving Standard of Care
Susan A Olender, Katherine K Perez, Alan S Go, Bindu Balani, Eboni G Price-Haywood, Nirav S Shah, Su Wang, Theresa L Walunas, Shobha Swaminathan, Jihad Slim, Bumsik Chin, Stéphane De Wit, Shamim M Ali, Alex Soriano Viladomiu, Philip Robinson, Robert L Gottlieb, Tak Yin Owen Tsang, I-Heng Lee, Hao Hu, Richard H Haubrich, Anand P Chokkalingam, Lanjia Lin, Lijie Zhong, B Nebiyou Bekele, Robertino Mera-Giler, Chloé Phulpin, Holly Edgar, Joel Gallant, Helena Diaz-Cuervo, Lindsey E Smith, Anu O Osinusi, Diana M Brainard, Jose I Bernardino
Clinical Infectious Diseases, doi:10.1093/cid/ciaa1041
Background. We compared the efficacy of the antiviral agent, remdesivir, versus standard-of-care treatment in adults with severe coronavirus disease 2019 (COVID-19) using data from a phase 3 remdesivir trial and a retrospective cohort of patients with severe COVID-19 treated with standard of care. Methods. GS-US-540-5773 is an ongoing phase 3, randomized, open-label trial comparing two courses of remdesivir (remdesivircohort). GS-US-540-5807 is an ongoing real-world, retrospective cohort study of clinical outcomes in patients receiving standardof-care treatment (non-remdesivir-cohort). Inclusion criteria were similar between studies: patients had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, were hospitalized, had oxygen saturation ≤94% on room air or required supplemental oxygen, and had pulmonary infiltrates. Stabilized inverse probability of treatment weighted multivariable logistic regression was used to estimate the treatment effect of remdesivir versus standard of care. The primary endpoint was the proportion of patients with recovery on day 14, dichotomized from a 7-point clinical status ordinal scale. A key secondary endpoint was mortality. Results. After the inverse probability of treatment weighting procedure, 312 and 818 patients were counted in the remdesivirand non-remdesivir-cohorts, respectively. At day 14, 74.4% of patients in the remdesivir-cohort had recovered versus 59.0% in the non-remdesivir-cohort (adjusted odds ratio [aOR] 2.03: 95% confidence interval [CI]: 1.34-3.08, P < .001). At day 14, 7.6% of patients in the remdesivir-cohort had died versus 12.5% in the non-remdesivir-cohort (aOR 0.38, 95% CI: .22-.68, P = .001). Conclusions. In this comparative analysis, by day 14, remdesivir was associated with significantly greater recovery and 62% reduced odds of death versus standard-of-care treatment in patients with severe COVID-19. clinical Trials Registration. NCT04292899 and EUPAS34303.
Supplementary Data Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author. Acknowledgments. The authors extend their gratitude to the participants and their families, participating sites, site investigators, and study staff. The incredible work of the site investigators and their healthcare teams in times of enormous challenges and personal risk cannot be overstated. The full list of site investigators is provided in Supplemental Digital Content 1). The authors dedicate this work to those that are or have been ill with COVID-19 and to the memory of healthcare workers who have given their lives in the care of these patients. Medical writing support was provided by Ryan Woodrow and Emma McConnell from Aspire Scientific Ltd (Bollington, UK), and was funded by Gilead Sciences, Inc., Foster City, CA, USA. Gilead Sciences makes available anonymized individual patient data upon request or as required by law or regulation with external researchers. Approval of such requests is at Gilead Sciences's discretion and is dependent on the nature of the request, the merit of the research proposed, the availability of the data, and the intended use of the data. Data requests should be sent to datarequest@gilead.com. Data from GS-US-540-5807 can..
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{ 'DOI': '10.1093/cid/ciaa1041',
'ISSN': ['1058-4838', '1537-6591'],
'URL': 'http://dx.doi.org/10.1093/cid/ciaa1041',
'abstract': '<jats:title>Abstract</jats:title>\n'
' <jats:sec>\n'
' <jats:title>Background</jats:title>\n'
' <jats:p>We compared the efficacy of the antiviral agent, remdesivir, versus '
'standard-of-care treatment in adults with severe coronavirus disease 2019 (COVID-19) using '
'data from a phase 3 remdesivir trial and a retrospective cohort of patients with severe '
'COVID-19 treated with standard of care.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Methods</jats:title>\n'
' <jats:p>GS-US-540–5773 is an ongoing phase 3, randomized, open-label trial '
'comparing two courses of remdesivir (remdesivir-cohort). GS-US-540–5807 is an ongoing '
'real-world, retrospective cohort study of clinical outcomes in patients receiving '
'standard-of-care treatment (non-remdesivir-cohort). Inclusion criteria were similar between '
'studies: patients had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) '
'infection, were hospitalized, had oxygen saturation ≤94% on room air or required supplemental '
'oxygen, and had pulmonary infiltrates. Stabilized inverse probability of treatment weighted '
'multivariable logistic regression was used to estimate the treatment effect of remdesivir '
'versus standard of care. The primary endpoint was the proportion of patients with recovery on '
'day 14, dichotomized from a 7-point clinical status ordinal scale. A key secondary endpoint '
'was mortality.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Results</jats:title>\n'
' <jats:p>After the inverse probability of treatment weighting procedure, 312 '
'and 818 patients were counted in the remdesivir- and non-remdesivir-cohorts, respectively. At '
'day 14, 74.4% of patients in the remdesivir-cohort had recovered versus 59.0% in the '
'non-remdesivir-cohort (adjusted odds ratio [aOR] 2.03: 95% confidence interval [CI]: '
'1.34–3.08, P &lt; .001). At day 14, 7.6% of patients in the remdesivir-cohort had died '
'versus 12.5% in the non-remdesivir-cohort (aOR 0.38, 95% CI: .22–.68, P = .001).</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Conclusions</jats:title>\n'
' <jats:p>In this comparative analysis, by day 14, remdesivir was associated '
'with significantly greater recovery and 62% reduced odds of death versus standard-of-care '
'treatment in patients with severe COVID-19.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Clinical Trials Registration</jats:title>\n'
' <jats:p>NCT04292899 and EUPAS34303.</jats:p>\n'
' </jats:sec>',
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{ 'article-title': 'Hydroxychloroquine or chloroquine with or without a macrolide for '
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'title': 'Remdesivir for Severe Coronavirus Disease 2019 (COVID-19) Versus a Cohort Receiving Standard of '
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