Remdesivir for Severe Coronavirus Disease 2019 (COVID-19) Versus a Cohort Receiving Standard of Care

Olender et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa1041, Jul 2020

https://c19early.org/olender.html

Comparative analysis between remdesivir trial GS-US-540–5773 and a retrospective SOC cohort with similar inclusion criteria, showing lower mortality and higher recovery at day 14 with remdesivir.

Gérard, Zhou, Wu, Kamo, Choi, Kim show increased risk of acute kidney injury with remdesivir. Leo, Briciu, Muntean, Petrov show increased risk of liver injury with remdesivir.

Standard of Care (SOC) for COVID-19 in the study country, the USA, is very poor with very low average efficacy for approved treatments11. Only expensive, high-profit treatments were approved. Low-cost treatments were excluded, reducing the probability of treatment—especially early—due to access and cost barriers, and eliminating complementary and synergistic benefits seen with many low-cost treatments.

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risk of death, 58.8% lower, RR 0.41, p = 0.001, treatment 24 of 312 (7.7%), control 102 of 818 (12.5%), odds ratio converted to relative risk, weighted multivariable logistic regression, day 14.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

1. Gérard et al., Remdesivir and Acute Renal Failure: A Potential Safety Signal From Disproportionality Analysis of the WHO Safety Database, Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.2145.wiley.com, doi.org.

2. Zhou et al., Acute Kidney Injury and Drugs Prescribed for COVID-19 in Diabetes Patients: A Real-World Disproportionality Analysis, Frontiers in Pharmacology, doi:10.3389/fphar.2022.833679.frontiersin.org, doi.org.

3. Wu et al., Acute Kidney Injury Associated With Remdesivir: A Comprehensive Pharmacovigilance Analysis of COVID-19 Reports in FAERS, Frontiers in Pharmacology, doi:10.3389/fphar.2022.692828.frontiersin.org, doi.org.

4. Kamo et al., Association of Antiviral Drugs for the Treatment of COVID-19 With Acute Renal Failure, In Vivo, doi:10.21873/invivo.13637.iiarjournals.org, doi.org.

5. Choi et al., Comparative effectiveness of combination therapy with nirmatrelvir–ritonavir and remdesivir versus monotherapy with remdesivir or nirmatrelvir–ritonavir in patients hospitalised with COVID-19: a target trial emulation study, The Lancet Infectious Diseases, doi:10.1016/S1473-3099(24)00353-0.sciencedirect.com, doi.org.

6. Kim et al., Investigating the Safety Profile of Fast‐Track COVID‐19 Drugs Using the FDA Adverse Event Reporting System Database: A Comparative Observational Study, Pharmacoepidemiology and Drug Safety, doi:10.1002/pds.70043.wiley.com, doi.org.

7. Leo et al., Hepatocellular liver injury in hospitalized patients affected by COVID-19: Presence of different risk factors at different time points, Digestive and Liver Disease, doi:10.1016/j.dld.2021.12.014.sciencedirect.com, doi.org.

8. Briciu et al., Evolving Clinical Manifestations and Outcomes in COVID-19 Patients: A Comparative Analysis of SARS-CoV-2 Variant Waves in a Romanian Hospital Setting, Pathogens, doi:10.3390/pathogens12121453.mdpi.com, doi.org.

9. Muntean et al., Effects of COVID-19 on the Liver and Mortality in Patients with SARS-CoV-2 Pneumonia Caused by Delta and Non-Delta Variants: An Analysis in a Single Centre, Pharmaceuticals, doi:10.3390/ph17010003.mdpi.com, doi.org.

10. Petrov et al., The Effect of Potentially Hepatotoxic Medicinal Products on Alanine Transaminase Levels in COVID-19 Patients: A Case–Control Study, Safety and Risk of Pharmacotherapy, doi:10.30895/2312-7821-2025-458.risksafety.ru, doi.org.

11. c19early.org, c19early.org/soc/usa.html.c19early.org/soc/usa.html.

Olender et al., 24 Jul 2020, retrospective, USA, peer-reviewed, 33 authors.

This Paper Remdesivir All

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 record: { "DOI": "10.1093/cid/ciaa1041", "ISSN": [ "1058-4838", "1537-6591" ], "URL": "http://dx.doi.org/10.1093/cid/ciaa1041", "abstract": "Abstract\n \n Background\n 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.\n \n \n Methods\n 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.\n \n \n Results\n 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).\n \n \n Conclusions\n 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.\n \n \n Clinical Trials Registration\n NCT04292899 and EUPAS34303.\n ", "author": [ { "affiliation": [ { "name": "Division of Infectious Diseases, Department of Internal Medicine, Columbia University Irving Medical Center, New York, New York, USA" } ], "family": "Olender", "given": "Susan A", "sequence": "first" }, { "affiliation": [ { "name": "Houston Methodist, Houston, Texas, USA" } ], "family": "Perez", "given": "Katherine K", "sequence": "additional" }, { "affiliation": [ { "name": "Division of Research, Kaiser Permanente Northern California, Oakland, California, USA" } ], "family": "Go", "given": "Alan S", "sequence": 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"volume": "382", "year": "2020" }, { "DOI": "10.1001/jamanetworkopen.2020.8857", "article-title": "Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial", "author": "Borba", "doi-asserted-by": "crossref", "first-page": "e208857", "journal-title": "JAMA Netw Open", "key": "2021121011165717000_CIT0021", "volume": "3", "year": "2020" }, { "DOI": "10.1016/S0140-6736(20)30633-4", "article-title": "Clinical course and mortality risk of severe COVID-19", "author": "Weiss", "doi-asserted-by": "crossref", "first-page": "1014", "journal-title": "Lancet", "key": "2021121011165717000_CIT0022", "volume": "395", "year": "2020" }, { "DOI": "10.1016/j.jaci.2020.04.006", "article-title": "Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan", "author": "Li", "doi-asserted-by": "crossref", "journal-title": "J Allergy Clin 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Late treatment
is less effective

Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. IMA and WCH provide treatment protocols.

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