Efficacy and Safety of Remdesivir for COVID-19 Treatment: An Analysis of Randomized, Double-Blind, Placebo-Controlled Trials

Zhu et al., medRxiv, doi:10.1101/2020.06.22.20136531 , Jun 2020

https://c19early.org/zhu.html

Meta analysis of Beigel and Wang RCTs showing remdesivir significantly decreased mortality (8.18% vs. 12.70%, RR 0.64 [0.44-0.92], p = 0.175).

Remdesivir efficacy disappears with longer followup. Mixed-effects meta-regression of efficacy as a function of followup duration across all remdesivir studies shows decreasing efficacy with longer followup1. This may reflect antiviral efficacy being offset by serious adverse effects of treatment.

Currently there are 81 remdesivir studies and meta analysis shows:

Outcome	Improvement
Mortality	1% lower [-9‑10%]
Ventilation	11% higher [-11‑38%]
ICU admission	119% higher [33‑259%]
Hospitalization	10% higher [-10‑35%]

Important missing comments or errors? Let us know.

risk of death, 36.0% lower, RR 0.64, p = 0.02.

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

1. c19early.org, c19early.org/smeta.html.c19early.org/smeta.html.

Zhu et al., 29 Jun 2020, preprint, 11 authors.

This Paper Remdesivir All

Efficacy and Safety of Remdesivir for COVID-19 Treatment: An Analysis of Randomized, Double-Blind, Placebo-Controlled Trials

Yun Zhu, M.D Zhaowei Teng, Ph.D Lirong Yang, Ph.D Shuanglan Xu, M.D Jie Liu, M.D Yirong Teng, M.D Qinggang Hao, M.D Dake Zhao, Xiaolan Xiaolan Li, M.D Sheng Lu, M.D Yong Zeng

doi:10.1101/2020.06.22.20136531

BACKGROUND Remdesivir, an inhibitor of viral RNA-dependent RNA polymerases, has been identified as a candidate for COVID-19 treatment. However, the therapeutic effect of remdesivir is controversial. METHODS We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, from inception to June 11, 2020 for randomized controlled trials on the clinical efficacy of remdesivir. The main outcomes were discharge rate, mortality, and adverse events. This study is registered at INPLASY (INPLASY202060046). RESULTS Data of 1075 subjects showed that remdesivir significantly increased the discharge rate of patients with COVID-19 compared with the placebo (50.4% vs. 45.29%; relative risk [RR] 1.19 [95% confidence interval [CI], 1.05-1.34], I 2 = 0.0%, P = 0.754). It also significantly decreased mortality (8.18% vs. 12.70%; RR 0.64 [95% CI, 0.44-0.92], I 2 = 45.7%, P = 0.175) compared to the placebo. Data of 1296 subjects showed that remdesivir significantly decreased the occurrence of serious adverse events (RR 0.77 [95% CI, 0.63-0.94], I 2 = 0.0%, P = 0.716). CONCLUSION Remdesivir is efficacious and safe for the treatment of COVID-19. TRIAL REGISTRATION NUMBER 2 .

Efficacy and Safety of

References

Beigel, Tomashek, Dodd, Remdesivir for the treatment of Covid-19 -preliminary report, N Engl J Med, doi:10.1056/NEJMoa2007764

Bhatraju, Ghassemieh, Nichols, Covid-19 in critically ill patients in the Seattle region -case series, N Engl J Med

Dersimonian, Laird, Meta-analysis in clinical trials, Control Clin Trials

Eastman, Roth, Brimacombe, Remdesivir: A review of its discovery and development leading to emergency use authorization for treatment of COVID-19, ACS Cent Sci

Goldman, Lye, Hui, Remdesivir for 5 or 10 days in patients with severe Covid-19, N Engl J Med, doi:10.1056/NEJMoa2015301

Grein, Ohmagari, Shin, Compassionate use of remdesivir for patients with severe Covid-19, N Engl J Med

Higgins, Thompson, Deeks, Measuring inconsistency in meta-analyses, BMJ

Holshue, Debolt, Lindquist, First case of 2019 novel coronavirus in the United States, N Engl J Med

Jadad, Moore, Carroll, Assessing the quality of reports of randomised clinical trials: is blinding necessary?, Control Clin Trials

Mahase, Covid-19: Remdesivir is helpful but not a wonder drug, say researchers, BMJ

Or, )) OR (Novel coronavirus pneumonia)

Patel, Jernigan, Ncdcr, Initial public health response and interim clinical guidance for the 2019 novel coronavirus outbreak -United States, December 31, 2019-February 4, 2020, Am J Transplant

Sheahan, Sims, Graham, Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses, Sci Transl Med

Sheahan, Sims, Leist, Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV, Nat Commun

Wang, Cao, Zhang, Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res

Wang, Zhang, Du, Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial, Lancet

Williamson, Feldmann, Schwarz, Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2, Nature, doi:10.1038/s41586-020-2423-5

Woolf, On estimating the relation between blood group and disease, Ann Hum Genet

Zhou, Yu, Du, Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study, Lancet

Zhu, Zhang, Wang, A novel coronavirus from patients with pneumonia in China, 2019, N Engl J Med

DOI record: { "DOI": "10.1101/2020.06.22.20136531", "URL": "http://dx.doi.org/10.1101/2020.06.22.20136531", "abstract": "AbstractBACKGROUNDRemdesivir, an inhibitor of viral RNA-dependent RNA polymerases, has been identified as a candidate for COVID-19 treatment. However, the therapeutic effect of remdesivir is controversial.METHODSWe searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, from inception to June 11, 2020 for randomized controlled trials on the clinical efficacy of remdesivir. The main outcomes were discharge rate, mortality, and adverse events. This study is registered at INPLASY (INPLASY202060046).RESULTSData of 1075 subjects showed that remdesivir significantly increased the discharge rate of patients with COVID-19 compared with the placebo (50.4% vs. 45.29%; relative risk [RR] 1.19 [95% confidence interval [CI], 1.05–1.34], I2 = 0.0%, P = 0.754). It also significantly decreased mortality (8.18% vs. 12.70%; RR 0.64 [95% CI, 0.44–0.92], I2 = 45.7%, P = 0.175) compared to the placebo. Data of 1296 subjects showed that remdesivir significantly decreased the occurrence of serious adverse events (RR 0.77 [95% CI, 0.63–0.94], I2 = 0.0%, P = 0.716).CONCLUSIONRemdesivir is efficacious and safe for the treatment of COVID-19.TRIAL REGISTRATION NUMBERThis study is registered at the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY202060046).", "accepted": { "date-parts": [ [ 2020, 6, 29 ] ] }, "author": [ { "affiliation": [], "family": "Zhu", "given": "Yun", "sequence": "first" }, { "affiliation": [], "family": "Teng", "given": "Zhaowei", "sequence": "additional" }, { "affiliation": [], "family": "Yang", "given": "Lirong", "sequence": "additional" }, { "affiliation": [], "family": "Xu", "given": "Shuanglan", "sequence": "additional" }, { "affiliation": [], "family": "Liu", "given": "Jie", "sequence": "additional" }, { "affiliation": [], "family": "Teng", "given": "Yirong", "sequence": "additional" }, { "affiliation": [], "family": "Hao", "given": "Qinggang", "sequence": "additional" }, { "affiliation": [], "family": "Zhao", "given": "Dake", "sequence": "additional" }, { "affiliation": [], "family": "Li", "given": "Xiaolan", "sequence": "additional" }, { "affiliation": [], "family": "Lu", "given": "Sheng", "sequence": "additional" }, { "affiliation": [], "family": "Zeng", "given": "Yong", "sequence": "additional" } ], "container-title": [], "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2020, 6, 29 ] ], "date-time": "2020-06-29T20:15:13Z", "timestamp": 1593461713000 }, "deposited": { "date-parts": [ [ 2021, 1, 5 ] ], "date-time": "2021-01-05T22:27:20Z", "timestamp": 1609885640000 }, "group-title": "Epidemiology", "indexed": { "date-parts": [ [ 2024, 3, 12 ] ], "date-time": "2024-03-12T12:21:28Z", "timestamp": 1710246088757 }, "institution": [ { "name": "medRxiv" } ], "is-referenced-by-count": 2, "issued": { "date-parts": [ [ 2020, 6, 29 ] ] }, "link": [ { "URL": "https://syndication.highwire.org/content/doi/10.1101/2020.06.22.20136531", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "246", "original-title": [], "posted": { "date-parts": [ [ 2020, 6, 29 ] ] }, "prefix": "10.1101", "published": { "date-parts": [ [ 2020, 6, 29 ] ] }, "publisher": "Cold Spring Harbor Laboratory", "reference": [ { "DOI": "10.1016/S0140-6736(20)30566-3", "doi-asserted-by": "publisher", "key": "2021010507151271000_2020.06.22.20136531v1.1" }, { "DOI": "10.1056/NEJMoa2001017", "doi-asserted-by": "publisher", "key": "2021010507151271000_2020.06.22.20136531v1.2" }, { "DOI": "10.1111/ajt.15805", "article-title": "Team nCDCR. Initial public health response and interim clinical guidance for the 2019 novel coronavirus outbreak - United States, December 31, 2019-February 4, 2020", "doi-asserted-by": "crossref", "first-page": "889", "journal-title": "Am J Transplant", "key": "2021010507151271000_2020.06.22.20136531v1.3", "volume": "20", "year": "2020" }, { "DOI": "10.1038/s41467-019-13940-6", "doi-asserted-by": "publisher", "key": "2021010507151271000_2020.06.22.20136531v1.4" }, { "DOI": "10.1038/s41422-020-0282-0", "doi-asserted-by": "publisher", "key": "2021010507151271000_2020.06.22.20136531v1.5" }, { "DOI": "10.1126/scitranslmed.aal3653", "doi-asserted-by": "publisher", "key": "2021010507151271000_2020.06.22.20136531v1.6" }, { "DOI": "10.1016/S0140-6736(20)31022-9", "doi-asserted-by": "publisher", "key": "2021010507151271000_2020.06.22.20136531v1.7" }, { "DOI": "10.1056/NEJMoa2007764", "doi-asserted-by": "publisher", "key": "2021010507151271000_2020.06.22.20136531v1.8" }, { "DOI": "10.1056/NEJMoa2015301", "doi-asserted-by": "publisher", "key": "2021010507151271000_2020.06.22.20136531v1.9" }, { "DOI": "10.1056/NE-JMoa2007016", "doi-asserted-by": "publisher", "key": "2021010507151271000_2020.06.22.20136531v1.10" }, { "DOI": "10.1016/0197-2456(95)00134-4", "doi-asserted-by": "publisher", "key": "2021010507151271000_2020.06.22.20136531v1.11" }, { "DOI": "10.1136/bmj.327.7414.557", "doi-asserted-by": "publisher", "key": "2021010507151271000_2020.06.22.20136531v1.12" }, { "DOI": "10.1111/j.1469-1809.1955.tb01348.x", "doi-asserted-by": "publisher", "key": "2021010507151271000_2020.06.22.20136531v1.13" }, { "DOI": "10.1016/0197-2456(86)90046-2", "doi-asserted-by": "publisher", "key": "2021010507151271000_2020.06.22.20136531v1.14" }, { "DOI": "10.1038/s41586-020-2423-5", "doi-asserted-by": "publisher", "key": "2021010507151271000_2020.06.22.20136531v1.15" }, { "DOI": "10.1056/NEJMoa2004500", "doi-asserted-by": "publisher", "key": "2021010507151271000_2020.06.22.20136531v1.16" }, { "DOI": "10.1056/NEJMoa2001191", "doi-asserted-by": "publisher", "key": "2021010507151271000_2020.06.22.20136531v1.17" }, { "DOI": "10.1021/acscentsci.0c00489", "article-title": "Remdesivir: A review of its discovery and development leading to emergency use authorization for treatment of COVID-19", "doi-asserted-by": "crossref", "first-page": "672", "journal-title": "ACS Cent Sci", "key": "2021010507151271000_2020.06.22.20136531v1.18", "volume": "6", "year": "2020" }, { "DOI": "10.1136/bmj.m1798", "doi-asserted-by": "publisher", "key": "2021010507151271000_2020.06.22.20136531v1.19" } ], "reference-count": 19, "references-count": 19, "relation": {}, "resource": { "primary": { "URL": "http://medrxiv.org/lookup/doi/10.1101/2020.06.22.20136531" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "subtype": "preprint", "title": "Efficacy and Safety of Remdesivir for COVID-19 Treatment: An Analysis of Randomized, Double-Blind, Placebo-Controlled Trials", "type": "posted-content" }

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.

Submit

Post

@CovidAnalysis

FAQ

Public domain CC0 1.0