Remdesivir for the treatment of COVID-19 - Kölner UniversitätsPublikationsServer

Ansems, Kelly, Grundeis, Felicitas, Dahms, Karolina, Mikolajewska, Agata, Thieme, Volker, Piechotta, Vanessa, Metzendorf, Maria-Inti, Stegemann, Miriam, Benstoem, Carina and Fichtner, Falk (2021). Remdesivir for the treatment of COVID-19. Cochrane Database Syst Rev. (8). HOBOKEN: WILEY. ISSN 1361-6137

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DOI:10.1002/14651858.CD014962

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 eMects of remdesivir as a treatment for SARS-CoV-2 infection based on randomised controlled trials (RCTs) is required. Objectives To assess the eMects of remdesivir compared to placebo or standard care alone-on clinical outcomes in hospitalised patients with SARSCoV-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 noninvasive 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 diMerence to all-cause mortality at up to day 28 (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.81 to 1.06; risk diMerence (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 eMect 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 eMect 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 eMect on all-cause mortality at up to 28 days in hospitalised adults with SARS-CoV-2 infection. We are uncertain about the eMects of remdesivir on clinical improvement and worsening. There were insuMicient data available to examine the eMect of remdesivir on mortality across subgroups defined by respiratory support at baseline. Future studies should provide additional data on eMicacy and safety of remdesivir for defined core outcomes in COVID-19 research, especially for diMerent 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.

Item Type:

Journal Article

Creators:

Creators	Email	ORCID	ORCID Put Code
Ansems, Kelly	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Grundeis, Felicitas	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Dahms, Karolina	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Mikolajewska, Agata	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Thieme, Volker	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Piechotta, Vanessa	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Metzendorf, Maria-Inti	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Stegemann, Miriam	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Benstoem, Carina	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Fichtner, Falk	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED