Remdesivir for the treatment of COVID‐19
Background Remdesivir is an antiviral medicine with properties to inhibit viral replication of SARS‐CoV‐2. Positive results from early studies attracted media attention and led to emergency use authorisation of remdesivir in COVID‐19. A thorough understanding of the current evidence regarding the e...
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| Veröffentlicht in: | Cochrane database of systematic reviews 2021-08, Vol.2021 (8), p.CD014962 |
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| creator | Grundeis, Felicitas Ansems, Kelly Grundeis, Felicitas Dahms, Karolina Mikolajewska, Agata Thieme, Volker Piechotta, Vanessa Metzendorf, Maria-Inti Stegemann, Miriam Benstoem, Carina Fichtner, Falk |
| description | Background
Remdesivir is an antiviral medicine with properties to inhibit viral replication of SARS‐CoV‐2. Positive results from early studies attracted media attention and led to emergency use authorisation of remdesivir in COVID‐19. A thorough understanding of the current evidence regarding the effects of remdesivir as a treatment for SARS‐CoV‐2 infection based on randomised controlled trials (RCTs) is required.
Objectives
To assess the effects of remdesivir compared to placebo or standard care alone on clinical outcomes in hospitalised patients with SARS‐CoV‐2 infection, and to maintain the currency of the evidence using a living systematic review approach.
Search methods
We searched the Cochrane COVID‐19 Study Register (which comprises the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and medRxiv) as well as Web of Science (Science Citation Index Expanded and Emerging Sources Citation Index) and WHO COVID‐19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions. We conducted the searches on 16 April 2021.
Selection criteria
We followed standard Cochrane methodology.
We included RCTs evaluating remdesivir for the treatment of SARS‐CoV‐2 infection in hospitalised adults compared to placebo or standard care alone irrespective of disease severity, gender, ethnicity, or setting.
We excluded studies that evaluated remdesivir for the treatment of other coronavirus diseases.
Data collection and analysis
We followed standard Cochrane methodology.
To assess risk of bias in included studies, we used the Cochrane RoB 2 tool for RCTs. We rated the certainty of evidence using the GRADE approach for outcomes that were reported according to our prioritised categories: all‐cause mortality at up to day 28, duration to liberation from invasive mechanical ventilation, duration to liberation from supplemental oxygen, new need for mechanical ventilation (high‐flow oxygen, non‐invasive, or invasive mechanical ventilation), new need for invasive mechanical ventilation, new need for non‐invasive mechanical ventilation or high‐flow oxygen, new need for oxygen by mask or nasal prongs, quality of life, serious adverse events, and adverse events (any grade).
Main results
We included five RCTs with 7452 participants diagnosed with SARS‐CoV‐2 infection and a mean age of 59 years, of whom 3886 participants were randomised to |
| doi_str_mv | 10.1002/14651858.CD014962 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8406992</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2558453946</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5442-40f43c67981c0b24c8a0a8418f44a6ecc1f59048cb7f80966ba11fbeee79fd793</originalsourceid><addsrcrecordid>eNp1kM9KAzEQxoMotlYfwIvsUYTWJJtkk4sgW_8UCoKo15BNJ3Zlt1uTbaU3H8Fn9Enc0j_Wg6cZZr75fcOH0CnBPYIxvSRMcCK57KV9TJgSdA-1l7Pucri_07fQUQhvGMdC0eQQtWIWc8wlbaOLRyhHEPJ57iNX-ageQ1R7MHUJkzqqXJQ-vAz6359fRB2jA2eKACfr2kHPtzdP6X13-HA3SK-HXcsZo12GHYutSJQkFmeUWWmwkYxIx5gRYC1xXGEmbZY4iZUQmSHEZQCQKDdKVNxBVyvudJaVMLLNI94Ueurz0viFrkyu_24m-Vi_VnMtGRZK0QZwvgb46n0GodZlHiwUhZlANQuaci4ZjxUTjZSspNZXIXhwWxuC9TJjvclYbzJubs52_9tebEJtBHIl-MgLWGhb2bFvrP9H_rJ_AAqVhro</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2558453946</pqid></control><display><type>article</type><title>Remdesivir for the treatment of COVID‐19</title><source>MEDLINE</source><source>Cochrane Library</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Grundeis, Felicitas ; Ansems, Kelly ; Grundeis, Felicitas ; Dahms, Karolina ; Mikolajewska, Agata ; Thieme, Volker ; Piechotta, Vanessa ; Metzendorf, Maria-Inti ; Stegemann, Miriam ; Benstoem, Carina ; Fichtner, Falk</creator><creatorcontrib>Grundeis, Felicitas ; Ansems, Kelly ; Grundeis, Felicitas ; Dahms, Karolina ; Mikolajewska, Agata ; Thieme, Volker ; Piechotta, Vanessa ; Metzendorf, Maria-Inti ; Stegemann, Miriam ; Benstoem, Carina ; Fichtner, Falk</creatorcontrib><description>Background
Remdesivir is an antiviral medicine with properties to inhibit viral replication of SARS‐CoV‐2. Positive results from early studies attracted media attention and led to emergency use authorisation of remdesivir in COVID‐19. A thorough understanding of the current evidence regarding the effects of remdesivir as a treatment for SARS‐CoV‐2 infection based on randomised controlled trials (RCTs) is required.
Objectives
To assess the effects of remdesivir compared to placebo or standard care alone on clinical outcomes in hospitalised patients with SARS‐CoV‐2 infection, and to maintain the currency of the evidence using a living systematic review approach.
Search methods
We searched the Cochrane COVID‐19 Study Register (which comprises the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and medRxiv) as well as Web of Science (Science Citation Index Expanded and Emerging Sources Citation Index) and WHO COVID‐19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions. We conducted the searches on 16 April 2021.
Selection criteria
We followed standard Cochrane methodology.
We included RCTs evaluating remdesivir for the treatment of SARS‐CoV‐2 infection in hospitalised adults compared to placebo or standard care alone irrespective of disease severity, gender, ethnicity, or setting.
We excluded studies that evaluated remdesivir for the treatment of other coronavirus diseases.
Data collection and analysis
We followed standard Cochrane methodology.
To assess risk of bias in included studies, we used the Cochrane RoB 2 tool for RCTs. We rated the certainty of evidence using the GRADE approach for outcomes that were reported according to our prioritised categories: all‐cause mortality at up to day 28, duration to liberation from invasive mechanical ventilation, duration to liberation from supplemental oxygen, new need for mechanical ventilation (high‐flow oxygen, non‐invasive, or invasive mechanical ventilation), new need for invasive mechanical ventilation, new need for non‐invasive mechanical ventilation or high‐flow oxygen, new need for oxygen by mask or nasal prongs, quality of life, serious adverse events, and adverse events (any grade).
Main results
We included five RCTs with 7452 participants diagnosed with SARS‐CoV‐2 infection and a mean age of 59 years, of whom 3886 participants were randomised to receive remdesivir. Most participants required low‐flow oxygen (n=4409) or mechanical ventilation (n=1025) at baseline. Studies were mainly conducted in high‐ and upper‐middle‐income countries. We identified two ongoing studies, one was suspended due to a lack of COVID‐19 patients to recruit.
Risk of bias assessments were considered to be some concerns or high risk for clinical status and safety outcomes because participants who had died did not contribute information to these outcomes. Without adjustment, this leads to an uncertain amount of missing values and the potential for bias due to missing data.
Effects of remdesivir in hospitalised individuals
Remdesivir probably makes little or no difference to all‐cause mortality at up to day 28 (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.81 to 1.06; risk difference (RD) 8 fewer per 1000, 95% CI 21 fewer to 7 more; 4 studies, 7142 participants; moderate‐certainty evidence). There was limited evidence for a beneficial effect of remdesivir on mortality in a subset of 435 participants who received low flow oxygen at baseline in one study (RR 0.32, 95% CI 0.15 to 0.66). We could not confirm this finding due to restricted availability of relevant subgroup data from other studies.
Remdesivir may have little or no effect on the duration to liberation from invasive mechanical ventilation (2 studies, 1298 participants, data not pooled, low‐certainty evidence). We are uncertain whether remdesivir increases or decreases the chance of clinical improvement in terms of duration to liberation from supplemental oxygen at up to day 28 (3 studies, 1691 participants, data not pooled, very low‐certainty evidence).
We are very uncertain whether remdesivir decreases or increases the risk of clinical worsening in terms of new need for mechanical ventilation at up to day 28 (high‐flow oxygen or non‐invasive ventilation or invasive mechanical ventilation) (RR 0.78, 95% CI 0.48 to 1.24; RD 29 fewer per 1000, 95% CI 68 fewer to 32 more; 3 studies, 6696 participants; very low‐certainty evidence); new need for non‐invasive mechanical ventilation or high‐flow oxygen (RR 0.70, 95% CI 0.51 to 0.98; RD 72 fewer per 1000, 95% CI 118 fewer to 5 fewer; 1 study, 573 participants; very low‐certainty evidence); and new need for oxygen by mask or nasal prongs (RR 0.81, 95% CI 0.54 to 1.22; RD 84 fewer per 1000, 95% CI 204 fewer to 98 more; 1 study, 138 participants; very low‐certainty evidence). Remdesivir may decrease the risk of clinical worsening in terms of new need for invasive mechanical ventilation (67 fewer participants amongst 1000 participants; RR 0.56, 95% CI 0.41 to 0.77; 2 studies, 1159 participants; low‐certainty evidence).
None of the included studies reported quality of life.
Remdesivir probably decreases the serious adverse events rate at up to 28 days (RR 0.75, 95% CI 0.63 to 0.90; RD 63 fewer per 1000, 95% CI 94 fewer to 25 fewer; 3 studies, 1674 participants; moderate‐certainty evidence). We are very uncertain whether remdesivir increases or decreases adverse events rate (any grade) (RR 1.05, 95% CI 0.86 to 1.27; RD 29 more per 1000, 95% CI 82 fewer to 158 more; 3 studies, 1674 participants; very low‐certainty evidence).
Authors' conclusions
Based on the currently available evidence remdesivir probably has little or no effect on all‐cause mortality at up to 28 days in hospitalised adults with SARS‐CoV‐2 infection. We are uncertain about the effects of remdesivir on clinical improvement and worsening. There were insufficient data available to examine the effect of remdesivir on mortality across subgroups defined by respiratory support at baseline.
Future studies should provide additional data on efficacy and safety of remdesivir for defined core outcomes in COVID‐19 research, especially for different population subgroups. This could allow us to draw more reliable conclusions on the potential benefits and harms of remdesivir in future updates of this review. Due to the living approach of this work, we will update the review periodically.</description><identifier>ISSN: 1465-1858</identifier><identifier>ISSN: 1469-493X</identifier><identifier>EISSN: 1465-1858</identifier><identifier>EISSN: 1469-493X</identifier><identifier>DOI: 10.1002/14651858.CD014962</identifier><identifier>PMID: 34350582</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Adenosine Monophosphate ; Adenosine Monophosphate - analogs & derivatives ; Adenosine Monophosphate - therapeutic use ; Alanine ; Alanine - analogs & derivatives ; Alanine - therapeutic use ; Antiviral Agents ; Antiviral Agents - therapeutic use ; Bias ; Cause of Death ; Confidence Intervals ; COVID-19 ; COVID-19 - mortality ; COVID-19 Drug Treatment ; Disease Progression ; Humans ; Infectious disease ; Medicine General & Introductory Medical Sciences ; Middle Aged ; Oxygen ; Oxygen - administration & dosage ; Randomized Controlled Trials as Topic ; Respiration, Artificial ; SARS-CoV-2 ; Ventilator Weaning</subject><ispartof>Cochrane database of systematic reviews, 2021-08, Vol.2021 (8), p.CD014962</ispartof><rights>Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5442-40f43c67981c0b24c8a0a8418f44a6ecc1f59048cb7f80966ba11fbeee79fd793</citedby><cites>FETCH-LOGICAL-c5442-40f43c67981c0b24c8a0a8418f44a6ecc1f59048cb7f80966ba11fbeee79fd793</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34350582$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Grundeis, Felicitas</creatorcontrib><creatorcontrib>Ansems, Kelly</creatorcontrib><creatorcontrib>Grundeis, Felicitas</creatorcontrib><creatorcontrib>Dahms, Karolina</creatorcontrib><creatorcontrib>Mikolajewska, Agata</creatorcontrib><creatorcontrib>Thieme, Volker</creatorcontrib><creatorcontrib>Piechotta, Vanessa</creatorcontrib><creatorcontrib>Metzendorf, Maria-Inti</creatorcontrib><creatorcontrib>Stegemann, Miriam</creatorcontrib><creatorcontrib>Benstoem, Carina</creatorcontrib><creatorcontrib>Fichtner, Falk</creatorcontrib><title>Remdesivir for the treatment of COVID‐19</title><title>Cochrane database of systematic reviews</title><addtitle>Cochrane Database Syst Rev</addtitle><description>Background
Remdesivir is an antiviral medicine with properties to inhibit viral replication of SARS‐CoV‐2. Positive results from early studies attracted media attention and led to emergency use authorisation of remdesivir in COVID‐19. A thorough understanding of the current evidence regarding the effects of remdesivir as a treatment for SARS‐CoV‐2 infection based on randomised controlled trials (RCTs) is required.
Objectives
To assess the effects of remdesivir compared to placebo or standard care alone on clinical outcomes in hospitalised patients with SARS‐CoV‐2 infection, and to maintain the currency of the evidence using a living systematic review approach.
Search methods
We searched the Cochrane COVID‐19 Study Register (which comprises the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and medRxiv) as well as Web of Science (Science Citation Index Expanded and Emerging Sources Citation Index) and WHO COVID‐19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions. We conducted the searches on 16 April 2021.
Selection criteria
We followed standard Cochrane methodology.
We included RCTs evaluating remdesivir for the treatment of SARS‐CoV‐2 infection in hospitalised adults compared to placebo or standard care alone irrespective of disease severity, gender, ethnicity, or setting.
We excluded studies that evaluated remdesivir for the treatment of other coronavirus diseases.
Data collection and analysis
We followed standard Cochrane methodology.
To assess risk of bias in included studies, we used the Cochrane RoB 2 tool for RCTs. We rated the certainty of evidence using the GRADE approach for outcomes that were reported according to our prioritised categories: all‐cause mortality at up to day 28, duration to liberation from invasive mechanical ventilation, duration to liberation from supplemental oxygen, new need for mechanical ventilation (high‐flow oxygen, non‐invasive, or invasive mechanical ventilation), new need for invasive mechanical ventilation, new need for non‐invasive mechanical ventilation or high‐flow oxygen, new need for oxygen by mask or nasal prongs, quality of life, serious adverse events, and adverse events (any grade).
Main results
We included five RCTs with 7452 participants diagnosed with SARS‐CoV‐2 infection and a mean age of 59 years, of whom 3886 participants were randomised to receive remdesivir. Most participants required low‐flow oxygen (n=4409) or mechanical ventilation (n=1025) at baseline. Studies were mainly conducted in high‐ and upper‐middle‐income countries. We identified two ongoing studies, one was suspended due to a lack of COVID‐19 patients to recruit.
Risk of bias assessments were considered to be some concerns or high risk for clinical status and safety outcomes because participants who had died did not contribute information to these outcomes. Without adjustment, this leads to an uncertain amount of missing values and the potential for bias due to missing data.
Effects of remdesivir in hospitalised individuals
Remdesivir probably makes little or no difference to all‐cause mortality at up to day 28 (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.81 to 1.06; risk difference (RD) 8 fewer per 1000, 95% CI 21 fewer to 7 more; 4 studies, 7142 participants; moderate‐certainty evidence). There was limited evidence for a beneficial effect of remdesivir on mortality in a subset of 435 participants who received low flow oxygen at baseline in one study (RR 0.32, 95% CI 0.15 to 0.66). We could not confirm this finding due to restricted availability of relevant subgroup data from other studies.
Remdesivir may have little or no effect on the duration to liberation from invasive mechanical ventilation (2 studies, 1298 participants, data not pooled, low‐certainty evidence). We are uncertain whether remdesivir increases or decreases the chance of clinical improvement in terms of duration to liberation from supplemental oxygen at up to day 28 (3 studies, 1691 participants, data not pooled, very low‐certainty evidence).
We are very uncertain whether remdesivir decreases or increases the risk of clinical worsening in terms of new need for mechanical ventilation at up to day 28 (high‐flow oxygen or non‐invasive ventilation or invasive mechanical ventilation) (RR 0.78, 95% CI 0.48 to 1.24; RD 29 fewer per 1000, 95% CI 68 fewer to 32 more; 3 studies, 6696 participants; very low‐certainty evidence); new need for non‐invasive mechanical ventilation or high‐flow oxygen (RR 0.70, 95% CI 0.51 to 0.98; RD 72 fewer per 1000, 95% CI 118 fewer to 5 fewer; 1 study, 573 participants; very low‐certainty evidence); and new need for oxygen by mask or nasal prongs (RR 0.81, 95% CI 0.54 to 1.22; RD 84 fewer per 1000, 95% CI 204 fewer to 98 more; 1 study, 138 participants; very low‐certainty evidence). Remdesivir may decrease the risk of clinical worsening in terms of new need for invasive mechanical ventilation (67 fewer participants amongst 1000 participants; RR 0.56, 95% CI 0.41 to 0.77; 2 studies, 1159 participants; low‐certainty evidence).
None of the included studies reported quality of life.
Remdesivir probably decreases the serious adverse events rate at up to 28 days (RR 0.75, 95% CI 0.63 to 0.90; RD 63 fewer per 1000, 95% CI 94 fewer to 25 fewer; 3 studies, 1674 participants; moderate‐certainty evidence). We are very uncertain whether remdesivir increases or decreases adverse events rate (any grade) (RR 1.05, 95% CI 0.86 to 1.27; RD 29 more per 1000, 95% CI 82 fewer to 158 more; 3 studies, 1674 participants; very low‐certainty evidence).
Authors' conclusions
Based on the currently available evidence remdesivir probably has little or no effect on all‐cause mortality at up to 28 days in hospitalised adults with SARS‐CoV‐2 infection. We are uncertain about the effects of remdesivir on clinical improvement and worsening. There were insufficient data available to examine the effect of remdesivir on mortality across subgroups defined by respiratory support at baseline.
Future studies should provide additional data on efficacy and safety of remdesivir for defined core outcomes in COVID‐19 research, especially for different population subgroups. This could allow us to draw more reliable conclusions on the potential benefits and harms of remdesivir in future updates of this review. Due to the living approach of this work, we will update the review periodically.</description><subject>Adenosine Monophosphate</subject><subject>Adenosine Monophosphate - analogs & derivatives</subject><subject>Adenosine Monophosphate - therapeutic use</subject><subject>Alanine</subject><subject>Alanine - analogs & derivatives</subject><subject>Alanine - therapeutic use</subject><subject>Antiviral Agents</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Bias</subject><subject>Cause of Death</subject><subject>Confidence Intervals</subject><subject>COVID-19</subject><subject>COVID-19 - mortality</subject><subject>COVID-19 Drug Treatment</subject><subject>Disease Progression</subject><subject>Humans</subject><subject>Infectious disease</subject><subject>Medicine General & Introductory Medical Sciences</subject><subject>Middle Aged</subject><subject>Oxygen</subject><subject>Oxygen - administration & dosage</subject><subject>Randomized Controlled Trials as Topic</subject><subject>Respiration, Artificial</subject><subject>SARS-CoV-2</subject><subject>Ventilator Weaning</subject><issn>1465-1858</issn><issn>1469-493X</issn><issn>1465-1858</issn><issn>1469-493X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>RWY</sourceid><sourceid>EIF</sourceid><recordid>eNp1kM9KAzEQxoMotlYfwIvsUYTWJJtkk4sgW_8UCoKo15BNJ3Zlt1uTbaU3H8Fn9Enc0j_Wg6cZZr75fcOH0CnBPYIxvSRMcCK57KV9TJgSdA-1l7Pucri_07fQUQhvGMdC0eQQtWIWc8wlbaOLRyhHEPJ57iNX-ageQ1R7MHUJkzqqXJQ-vAz6359fRB2jA2eKACfr2kHPtzdP6X13-HA3SK-HXcsZo12GHYutSJQkFmeUWWmwkYxIx5gRYC1xXGEmbZY4iZUQmSHEZQCQKDdKVNxBVyvudJaVMLLNI94Ueurz0viFrkyu_24m-Vi_VnMtGRZK0QZwvgb46n0GodZlHiwUhZlANQuaci4ZjxUTjZSspNZXIXhwWxuC9TJjvclYbzJubs52_9tebEJtBHIl-MgLWGhb2bFvrP9H_rJ_AAqVhro</recordid><startdate>20210805</startdate><enddate>20210805</enddate><creator>Grundeis, Felicitas</creator><creator>Ansems, Kelly</creator><creator>Grundeis, Felicitas</creator><creator>Dahms, Karolina</creator><creator>Mikolajewska, Agata</creator><creator>Thieme, Volker</creator><creator>Piechotta, Vanessa</creator><creator>Metzendorf, Maria-Inti</creator><creator>Stegemann, Miriam</creator><creator>Benstoem, Carina</creator><creator>Fichtner, Falk</creator><general>John Wiley & Sons, Ltd</general><scope>7PX</scope><scope>RWY</scope><scope>ZYTZH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20210805</creationdate><title>Remdesivir for the treatment of COVID‐19</title><author>Grundeis, Felicitas ; Ansems, Kelly ; Grundeis, Felicitas ; Dahms, Karolina ; Mikolajewska, Agata ; Thieme, Volker ; Piechotta, Vanessa ; Metzendorf, Maria-Inti ; Stegemann, Miriam ; Benstoem, Carina ; Fichtner, Falk</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5442-40f43c67981c0b24c8a0a8418f44a6ecc1f59048cb7f80966ba11fbeee79fd793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adenosine Monophosphate</topic><topic>Adenosine Monophosphate - analogs & derivatives</topic><topic>Adenosine Monophosphate - therapeutic use</topic><topic>Alanine</topic><topic>Alanine - analogs & derivatives</topic><topic>Alanine - therapeutic use</topic><topic>Antiviral Agents</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Bias</topic><topic>Cause of Death</topic><topic>Confidence Intervals</topic><topic>COVID-19</topic><topic>COVID-19 - mortality</topic><topic>COVID-19 Drug Treatment</topic><topic>Disease Progression</topic><topic>Humans</topic><topic>Infectious disease</topic><topic>Medicine General & Introductory Medical Sciences</topic><topic>Middle Aged</topic><topic>Oxygen</topic><topic>Oxygen - administration & dosage</topic><topic>Randomized Controlled Trials as Topic</topic><topic>Respiration, Artificial</topic><topic>SARS-CoV-2</topic><topic>Ventilator Weaning</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Grundeis, Felicitas</creatorcontrib><creatorcontrib>Ansems, Kelly</creatorcontrib><creatorcontrib>Grundeis, Felicitas</creatorcontrib><creatorcontrib>Dahms, Karolina</creatorcontrib><creatorcontrib>Mikolajewska, Agata</creatorcontrib><creatorcontrib>Thieme, Volker</creatorcontrib><creatorcontrib>Piechotta, Vanessa</creatorcontrib><creatorcontrib>Metzendorf, Maria-Inti</creatorcontrib><creatorcontrib>Stegemann, Miriam</creatorcontrib><creatorcontrib>Benstoem, Carina</creatorcontrib><creatorcontrib>Fichtner, Falk</creatorcontrib><collection>Wiley-Blackwell Cochrane Library</collection><collection>Cochrane Library</collection><collection>Cochrane Library (Open Aceess)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cochrane database of systematic reviews</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Grundeis, Felicitas</au><au>Ansems, Kelly</au><au>Grundeis, Felicitas</au><au>Dahms, Karolina</au><au>Mikolajewska, Agata</au><au>Thieme, Volker</au><au>Piechotta, Vanessa</au><au>Metzendorf, Maria-Inti</au><au>Stegemann, Miriam</au><au>Benstoem, Carina</au><au>Fichtner, Falk</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Remdesivir for the treatment of COVID‐19</atitle><jtitle>Cochrane database of systematic reviews</jtitle><addtitle>Cochrane Database Syst Rev</addtitle><date>2021-08-05</date><risdate>2021</risdate><volume>2021</volume><issue>8</issue><spage>CD014962</spage><pages>CD014962-</pages><issn>1465-1858</issn><issn>1469-493X</issn><eissn>1465-1858</eissn><eissn>1469-493X</eissn><abstract>Background
Remdesivir is an antiviral medicine with properties to inhibit viral replication of SARS‐CoV‐2. Positive results from early studies attracted media attention and led to emergency use authorisation of remdesivir in COVID‐19. A thorough understanding of the current evidence regarding the effects of remdesivir as a treatment for SARS‐CoV‐2 infection based on randomised controlled trials (RCTs) is required.
Objectives
To assess the effects of remdesivir compared to placebo or standard care alone on clinical outcomes in hospitalised patients with SARS‐CoV‐2 infection, and to maintain the currency of the evidence using a living systematic review approach.
Search methods
We searched the Cochrane COVID‐19 Study Register (which comprises the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and medRxiv) as well as Web of Science (Science Citation Index Expanded and Emerging Sources Citation Index) and WHO COVID‐19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions. We conducted the searches on 16 April 2021.
Selection criteria
We followed standard Cochrane methodology.
We included RCTs evaluating remdesivir for the treatment of SARS‐CoV‐2 infection in hospitalised adults compared to placebo or standard care alone irrespective of disease severity, gender, ethnicity, or setting.
We excluded studies that evaluated remdesivir for the treatment of other coronavirus diseases.
Data collection and analysis
We followed standard Cochrane methodology.
To assess risk of bias in included studies, we used the Cochrane RoB 2 tool for RCTs. We rated the certainty of evidence using the GRADE approach for outcomes that were reported according to our prioritised categories: all‐cause mortality at up to day 28, duration to liberation from invasive mechanical ventilation, duration to liberation from supplemental oxygen, new need for mechanical ventilation (high‐flow oxygen, non‐invasive, or invasive mechanical ventilation), new need for invasive mechanical ventilation, new need for non‐invasive mechanical ventilation or high‐flow oxygen, new need for oxygen by mask or nasal prongs, quality of life, serious adverse events, and adverse events (any grade).
Main results
We included five RCTs with 7452 participants diagnosed with SARS‐CoV‐2 infection and a mean age of 59 years, of whom 3886 participants were randomised to receive remdesivir. Most participants required low‐flow oxygen (n=4409) or mechanical ventilation (n=1025) at baseline. Studies were mainly conducted in high‐ and upper‐middle‐income countries. We identified two ongoing studies, one was suspended due to a lack of COVID‐19 patients to recruit.
Risk of bias assessments were considered to be some concerns or high risk for clinical status and safety outcomes because participants who had died did not contribute information to these outcomes. Without adjustment, this leads to an uncertain amount of missing values and the potential for bias due to missing data.
Effects of remdesivir in hospitalised individuals
Remdesivir probably makes little or no difference to all‐cause mortality at up to day 28 (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.81 to 1.06; risk difference (RD) 8 fewer per 1000, 95% CI 21 fewer to 7 more; 4 studies, 7142 participants; moderate‐certainty evidence). There was limited evidence for a beneficial effect of remdesivir on mortality in a subset of 435 participants who received low flow oxygen at baseline in one study (RR 0.32, 95% CI 0.15 to 0.66). We could not confirm this finding due to restricted availability of relevant subgroup data from other studies.
Remdesivir may have little or no effect on the duration to liberation from invasive mechanical ventilation (2 studies, 1298 participants, data not pooled, low‐certainty evidence). We are uncertain whether remdesivir increases or decreases the chance of clinical improvement in terms of duration to liberation from supplemental oxygen at up to day 28 (3 studies, 1691 participants, data not pooled, very low‐certainty evidence).
We are very uncertain whether remdesivir decreases or increases the risk of clinical worsening in terms of new need for mechanical ventilation at up to day 28 (high‐flow oxygen or non‐invasive ventilation or invasive mechanical ventilation) (RR 0.78, 95% CI 0.48 to 1.24; RD 29 fewer per 1000, 95% CI 68 fewer to 32 more; 3 studies, 6696 participants; very low‐certainty evidence); new need for non‐invasive mechanical ventilation or high‐flow oxygen (RR 0.70, 95% CI 0.51 to 0.98; RD 72 fewer per 1000, 95% CI 118 fewer to 5 fewer; 1 study, 573 participants; very low‐certainty evidence); and new need for oxygen by mask or nasal prongs (RR 0.81, 95% CI 0.54 to 1.22; RD 84 fewer per 1000, 95% CI 204 fewer to 98 more; 1 study, 138 participants; very low‐certainty evidence). Remdesivir may decrease the risk of clinical worsening in terms of new need for invasive mechanical ventilation (67 fewer participants amongst 1000 participants; RR 0.56, 95% CI 0.41 to 0.77; 2 studies, 1159 participants; low‐certainty evidence).
None of the included studies reported quality of life.
Remdesivir probably decreases the serious adverse events rate at up to 28 days (RR 0.75, 95% CI 0.63 to 0.90; RD 63 fewer per 1000, 95% CI 94 fewer to 25 fewer; 3 studies, 1674 participants; moderate‐certainty evidence). We are very uncertain whether remdesivir increases or decreases adverse events rate (any grade) (RR 1.05, 95% CI 0.86 to 1.27; RD 29 more per 1000, 95% CI 82 fewer to 158 more; 3 studies, 1674 participants; very low‐certainty evidence).
Authors' conclusions
Based on the currently available evidence remdesivir probably has little or no effect on all‐cause mortality at up to 28 days in hospitalised adults with SARS‐CoV‐2 infection. We are uncertain about the effects of remdesivir on clinical improvement and worsening. There were insufficient data available to examine the effect of remdesivir on mortality across subgroups defined by respiratory support at baseline.
Future studies should provide additional data on efficacy and safety of remdesivir for defined core outcomes in COVID‐19 research, especially for different population subgroups. This could allow us to draw more reliable conclusions on the potential benefits and harms of remdesivir in future updates of this review. Due to the living approach of this work, we will update the review periodically.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>34350582</pmid><doi>10.1002/14651858.CD014962</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1465-1858 |
| ispartof | Cochrane database of systematic reviews, 2021-08, Vol.2021 (8), p.CD014962 |
| issn | 1465-1858 1469-493X 1465-1858 1469-493X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8406992 |
| source | MEDLINE; Cochrane Library; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adenosine Monophosphate Adenosine Monophosphate - analogs & derivatives Adenosine Monophosphate - therapeutic use Alanine Alanine - analogs & derivatives Alanine - therapeutic use Antiviral Agents Antiviral Agents - therapeutic use Bias Cause of Death Confidence Intervals COVID-19 COVID-19 - mortality COVID-19 Drug Treatment Disease Progression Humans Infectious disease Medicine General & Introductory Medical Sciences Middle Aged Oxygen Oxygen - administration & dosage Randomized Controlled Trials as Topic Respiration, Artificial SARS-CoV-2 Ventilator Weaning |
| title | Remdesivir for the treatment of COVID‐19 |
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