Remdesivir for the treatment of coronavirus COVID-19: A meta-analysis of randomised controlled trials.
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ABSTRACT:
SUBMITTER: Enoki Y
PROVIDER: S-EPMC7833743 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
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Remdesivir for the treatment of coronavirus COVID-19: A meta-analysis of randomised controlled trials.
Enoki Yuki Y Igarashi Yuki Y Watabe Yuki Y Honma Kyoka K Suzuki Yuto Y Hayashi Yukitaka Y Hiraoka Kana K Taguchi Kazuaki K Matsumoto Kazuaki K
Journal of global antimicrobial resistance 20201208
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Project description:BackgroundThe nucleotide analogue prodrug remdesivir was among the first antiviral therapies to be tested in randomized controlled trials (RCTs) for COVID-19. We performed a meta-analysis to understand efficacy and safety.MethodsWe searched PubMed, EMBASE, Cochrane library, and ClinicalTrials.gov databases (from January 1, 2020 to November 5, 2020). We included RCTs comparing the efficacy and safety of remdesivir to control/placebo in COVID-19. Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence.ResultsA total of 4 RCTs with 7334 patients with COVID-19 were included. At a follow-up of 28-29 days from randomization, very low certainty evidence showed that use of remdesivir compared with control group (placebo and/or standard of care) was not associated with a significant decrease in time to clinical improvement (standardized mean difference -0.80 day; [CI, -2.12, 0.53]). However, moderate certainty of evidence showed that remdesivir was associated with higher rates of recovered patients (risk difference [RD] 0.07 [0.05, 0.08]) and discharged patients (RD 0.07 [0.03, 0.11]) and lower rates of developing serious adverse events (RD -0.05 [-0.10, -0.01]) compared with control. Moderate and very low certainty of evidence showed there was no significant difference in deaths at 28-29 days follow-up (RD -0.01 [-0.03, 0.01]) and developing any adverse events (RD 0.01 [-0.17, 0.19]) between both groups, respectively.ConclusionPatients given remdesivir are more likely to demonstrate recovery and were associated with higher rates of hospital discharge, but not with significant reduction in mean time to clinical improvement or mortality.
| S-EPMC7789823 | biostudies-literature
Project description:BackgroundIn view of many unanswered clinical questions regarding treatment of COVID-19 with remdesivir, we systematically identified, critically appraised and summarized the findings from randomized controlled trials (RCTs) of remdesivir for COVID-19.MethodsWe searched relevant databases/websites (up to September 2020) and selected English-language RCT publications of remdesivir for COVID-19. We conducted meta-analysis using an inverse variance, random-effects model in addition to trial sequential analysis (TSA) for the efficacy outcomes: all-cause mortality, viral burden and clinical progression. Safety outcomes were diarrhoea, nausea, and vomiting. We calculated the relative risk (RR) and 95% confidence interval (CI) for all outcomes. Statistical heterogeneity was calculated using the I2 statistic.ResultsWe included five RCTs (7540 participants) from 7237 citations. Most (80%) were of an unclear to high risk of bias. There was no evidence of a significant improvement with remdesivir (100 mg, 10 days) regarding all-cause mortality (RR 0.94, CI 0.82-1.07; I2 = 0%; 4 RCTs; 7143 patients), clinical progression (RR 1.08, CI 0.99-1.18; I2 = 70.4%; 3 RCTs; 1692 patients), or diarrhoea (RR 0.82, CI 0.40-1.66; I2 = 0%; 2 RCTs; 630 patients). Nausea occurred more often with remdesivir (RR 2.77, CI 1.28-6.03; I2 = 0%; 2 RCTs; 630 patients). TSA showed that the required information size was not reached for firm conclusions to be drawn.Conclusions and relevanceThere is insufficient evidence to support the use of remdesivir for treatment of COVID-19. More high-quality RCTs are needed for a stronger evidence. Until then, remdesivir should remain an experimental drug for COVID-19.
| S-EPMC8127173 | biostudies-literature
Project description:BackgroundDespite global containment measures to fight the coronavirus disease 2019 (COVID-19), the pandemic continued to rise, rapidly spread across the world, and resulting in 2.6 million confirmed cases and 185 061 deaths worldwide as of 23 April 2020. Yet, there are no approved vaccines or drugs to make the disease less deadly, while efforts are underway. Remdesivir, a nucleotide-analogue antiviral drug developed for Ebola, is determined to prevent and stop infections with COVID-19, while results are yet controversial. Here, we aim to conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) to evaluate the efficacy of remdesivir in patients with COVID-19.Method and analysisWe will search MEDLINE-PubMed, Embase, Cochrane Library, ClinicalTrials.gov and Google scholar databases for articles published as of 30 June 2020 and we will complete the study on 30 August 2020. We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 guidelines for the design and reporting of the results. We will include RCTs that assessed the efficacy of remdesivir versus placebo or standard of care. The primary endpoint will be time to clinical recovery. The secondary endpoints will be proportion of participants relieved from clinical symptoms defined at the time (in hours) from initiation of the study treatment, all-cause mortality, discharged date, frequency of respiratory progression and treatment-emergent adverse events. RevMan V.5.3 software will be used for statistical analysis. Random effects model will be carried out to calculate mean differences for continuous outcome data and risk ratio for dichotomous outcome data between remdesivir and placebo or standard of care.Ethics and disseminationThere are no ethical considerations associated with this study as we will use publicly available data from previously published studies. We plan to publish results in open-access peer-reviewed journals and present at international and national conferences.Prospero registration numberCRD42020177953.
| S-EPMC7298683 | biostudies-literature
Project description:Remdesivir is one of the proposed therapies for the corona virus disease 2019 (COVID-19). To assess the effect of remdesivir on mortality, need for invasive mechanical ventilation (IMV) and extracorporeal membrane oxygenation (ECMO), time to clinical improvement, and significant adverse effects. The study protocol was prospectively registered with The International Prospective Register of Systematic Reviews (Registration #CRD42021283221). Randomized controlled trials (RCTs) published in English detailing use of remdesivir in hospitalized patients with COVID-19 were included. Primary outcome was in hospital mortality among patients receiving remdesivir. Secondary outcomes were need for IMV and ECMO, time to clinical recovery, and significant adverse effects associated with remdesivir. Odds ratios (ORs) of worse outcome with 95% confidence interval (CI) in a forest plot were used to show the results of random effects meta-analysis. Remdesivir and placebo had similar in hospital mortality in the pooled analysis of five RCTs (OR: 0.93, 95% CI: 0.82-1.06). The remdesivir group needed less IMV/ECMO (OR: 0.59, 95% CI: 0.46-0.76) and recovered 1.06 days faster than placebo. Remdesivir did not affect transaminitis or renal damage. Trial sequence analysis showed that death has not reached the number of instances needed to predict futility. This meta-analysis shows that remdesivir therapy for COVID-19 is not associated with a mortality benefit. However, there is significant reduction in the need for IMV/ECMO.
| S-EPMC10824204 | biostudies-literature
Project description:BackgroundInterpretation of the evidence from randomised controlled trials (RCTs) of remdesivir in patients treated in hospital for COVID-19 is conflicting. We aimed to assess the benefits and harms of remdesivir compared with placebo or usual care in these patients, and whether treatment effects differed between prespecified patient subgroups.MethodsFor this systematic review and meta-analysis, we searched PubMed, Embase, the Cochrane COVID-19 trial registry, ClinicalTrials.gov, the International Clinical Trials Registry Platform, and preprint servers from Jan 1, 2020, until April 11, 2022, for RCTs of remdesivir in adult patients hospitalised with COVID-19, and contacted the authors of eligible trials to request individual patient data. The primary outcome was all-cause mortality at day 28 after randomisation. We used multivariable hierarchical regression-adjusting for respiratory support, age, and enrollment period-to investigate effect modifiers. This study was registered with PROSPERO, CRD42021257134.FindingsOur search identified 857 records, yielding nine RCTs eligible for inclusion. Of these nine eligible RCTs, individual data were provided for eight, covering 10 480 patients hospitalised with COVID-19 (99% of such patients included in such RCTs worldwide) recruited between Feb 6, 2020, and April 1, 2021. Within 28 days of randomisation, 662 (12·5%) of 5317 patients assigned to remdesivir and 706 (14·1%) of 5005 patients assigned to no remdesivir died (adjusted odds ratio [aOR] 0·88, 95% CI 0·78-1·00, p=0·045). We found evidence for a credible subgroup effect according to respiratory support at baseline (pinteraction=0·019). Of patients who were ventilated-including those who received high-flow oxygen-253 (30·0%) of 844 patients assigned to remdesivir died compared with 241 (28·5%) of 846 patients assigned to no remdesivir (aOR 1·10 [0·88-1·38]; low-certainty evidence). Of patients who received no oxygen or low-flow oxygen, 409 (9·1%) of 4473 patients assigned to remdesivir died compared with 465 (11·2%) of 4159 patients assigned to no remdesivir (0·80 [0·70-0·93]; high-certainty evidence). No credible subgroup effect was found for time to start of remdesivir after symptom onset, age, presence of comorbidities, enrolment period, or corticosteroid use. Remdesivir did not increase the frequency of severe or serious adverse events.InterpretationThis individual patient data meta-analysis showed that remdesivir reduced mortality in patients hospitalised with COVID-19 who required no or conventional oxygen support, but was underpowered to evaluate patients who were ventilated when receiving remdesivir. The effect size of remdesivir in patients with more respiratory support or acquired immunity and the cost-effectiveness of remdesivir remain to be further elucidated.FundingEU-RESPONSE.
| S-EPMC10156140 | biostudies-literature
Project description:PurposeTo perform a systematic review and meta-analysis of randomized controlled trials that examined remdesivir treatment for COVID-19.Materials and methodsA systematic literature search was performed using Pubmed, Embase, and ClinicalTrials.gov to identify studies published up to October 25, 2020 that examined COVID-19 treatment with remdesivir. A total of 3 randomized controlled trials that consisted of 1691 patients were included in the meta-analysis.ResultsThe odds for mechanical ventilation (MV) or extracorporeal membrane oxygenation (ECMO) following treatment was significantly lower in the remdesivir group compared to the control group (OR = 0.48 [95% CI: 0.34; 0.69], p < 0.001). The odds of early (at day 14/15; OR = 1.42 [95% CI: 1.16; 1.74], p < 0.001) and late (at day 28/29; OR = 1.44 [95% CI: 1.16; 1.79], p = 0.001) hospital discharge were significantly higher in the remdesivir group compared to the control group. There was no difference in the odds for mortality in patients treated with remdesivir (OR = 0.77 [95% CI: 0.56; 1.06], p = 0.108).ConclusionsRemdesivir attenuates disease progression, leading to lower odds of MV/ECMO and greater odds of hospital discharge for COVID-19 patients. However, remdesivir does not affect odds of mortality.
| S-EPMC7806502 | biostudies-literature
Project description:BackgroundTo date, only dexamethasone and tocilizumab have been shown to reduce mortality in patients with COVID-19. Baricitinib is a Janus kinase 1/2 inhibitor with known anti-inflammatory and anti-viral properties. We performed a meta-analysis of RCTs assessing the role of baricitinib in hospitalised patients with COVID-19.MethodsElectronic databases such as MEDLINE, EMBASE, and Cochrane Central were searched up until March 31, 2022, for RCTs evaluating the efficacy of baricitinib in hospitalised patients with COVID-19. The outcomes assessed were 28-day mortality, progression to invasive mechanical ventilation (IMV) or ECMO, progression to respiratory failure needing positive pressure ventilation, IMV or death, duration of hospitalisation and time to discharge. The meta-analysis was registered in the PROSPERO database (CRD42022314579).FindingsFour studies (with 10,815 patients) were included in the analysis. Pooled analysis using random-effects model showed a statistically significant reduction in 28-day mortality (OR 0.69, 95% CI 0.50-0.94; p=0.04, I2=65%) and composite outcome of progression to severe disease needing positive pressure ventilation, IMV or death (OR 0.89, 95% CI 0.80-0.99, p= 0.03, I2=0%). There was a favorable trend towards reduced progression to IMV or ECMO (OR 0.76, 95% CI 0.58-1.01; p=0.06, I2=49%) in the baricitinib arm compared to standard therapy, even though it was not statistically significant. Statistical significance was achieved for all outcomes with fixed-effects model analysis.InterpretationIn hospitalised patients with COVID-19, baricitinib was associated with reduced 28-day mortality although there was not a statistically significant reduction in progression to IMV or ECMO. Baricitinib used in conjunction with standard of care treatments is associated with improved mortality in hospitalised patients with COVID-19 disease.FundingNone.
| S-EPMC9163705 | biostudies-literature
Project description:BackgroundTo summarise specific adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir in patients with COVID-19.MethodsWe searched 32 databases through 27 October 2020. We included randomised trials comparing any of the drugs of interest to placebo or standard care, or against each other. We conducted fixed-effects pairwise meta-analysis and assessed the certainty of evidence using the grading of recommendations assessment, development and evaluation approach.ResultsWe included 16 randomised trials which enrolled 8152 patients. For most interventions and outcomes the certainty of the evidence was very low to low except for gastrointestinal adverse effects from hydroxychloroquine, which was moderate certainty. Compared with standard care or placebo, low certainty evidence suggests that remdesivir may not have an important effect on acute kidney injury (risk difference (RD) 8 fewer per 1000, 95% CI 27 fewer to 21 more) or cognitive dysfunction/delirium (RD 3 more per 1000, 95% CI 12 fewer to 19 more). Low certainty evidence suggests that hydroxychloroquine may increase the risk of cardiac toxicity (RD 10 more per 1000, 95% CI 0 more to 30 more) and cognitive dysfunction/delirium (RD 33 more per 1000, 95% CI 18 fewer to 84 more), whereas moderate certainty evidence suggests hydroxychloroquine probably increases the risk of diarrhoea (RD 106 more per 1000, 95% CI 48 more to 175 more) and nausea and/or vomiting (RD 62 more per 1000, 95% CI 23 more to 110 more) compared with standard care or placebo. Low certainty evidence suggests lopinavir/ritonavir may increase the risk of diarrhoea (RD 168 more per 1000, 95% CI 58 more to 330 more) and nausea and/or vomiting (RD 160 more per 1000, 95% CI 100 more to 210 more) compared with standard care or placebo.DiscussionHydroxychloroquine probably increases the risk of diarrhoea and nausea and/or vomiting and may increase the risk of cardiac toxicity and cognitive dysfunction/delirium. Lopinavir/ritonavir may increase the risk of diarrhoea and nausea and/or vomiting. Remdesivir may have no important effect on risk of acute kidney injury or cognitive dysfunction/delirium. These findings provide important information to support the development of evidence-based management strategies for patients with COVID-19.
| S-EPMC8895418 | biostudies-literature
Project description:The coronavirus disease 2019 (COVID-19) pandemic has caused a worldwide outbreak of respiratory illness. This review aims to evaluate the effectiveness and adverse events of herbal medicines for the treatment of COVID-19. Twelve databases were searched through 12 May 2020. Randomized controlled trials (RCTs) and quasi-RCTs assessing the effects of herbal medicines for the treatment of COVID-19 were eligible. The study selection and data extraction were performed by two independent reviewers. The Cochrane risk of bias tool was used for the assessment of the risk of bias in all included RCTs. Mean differences (MDs), risk ratios (RRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, and the effect sizes of the studies were pooled. Seven RCTs with a total of 855 patients were included. All included trials compared the combined therapy of herbal medicine with Western medicine to Western medicine alone. The combined therapy significantly improved the total effective rate (RR 1.23, 95% CI 1.13 to 1.34, p < 0.001), cough symptom disappearance rate (RR 1.45, 95% CI 1.12 to 1.89, p = 0.005), and sputum production symptom disappearance rate (RR 1.73, 95% CI 1.19 to 2.50, p = 0.004). Beneficial effects of the combined therapy were also seen in TCM syndrome score of cough (MD -1.18, 95% CI -1.34 to -1.03, p < 0.001), fever (MD -0.62, 95% CI -0.79 to -0.45, p < 0.001), dry and sore throat (MD -0.83, 95% CI -1.45 to -0.20, p = 0.009), and fatigue (MD -0.60, 95% CI -1.04 to -0.17, p = 0.007). The overall risk of bias of the included studies was unclear. No serious adverse events were reported. Significant effects of the combined therapy of herbal medicine with Western medicine were found, and revealed the potential role of herbal medicine in treating COVID-19. More high-quality RCTs are needed to further validate the effectiveness and adverse events of herbal medicine in the treatment of COVID-19.
| S-EPMC7290825 | biostudies-literature
Project description:BackgroundAlthough the US government approved hydroxychloroquine (HCQ) and chloroquine (CQ) for hospitalized coronavirus disease 19 (COVID-19) patients, some studies denied efficacy of HCQ and CQ. We aimed to evaluate HCQ/CQ treatment for COVID-19.MethodsFive databases were searched on April 15, 2020, without publication date restriction. We followed both Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology statement reporting recommendations. A random-model meta-analysis was conducted to pool odds ratio (OR) and hazard ratio (HR). The quality of evidence for each outcome and the final recommendation was assessed using the GRADE guidelines of the American College of Chest Physicians.ResultsWe identified four randomized controlled trials (RCTs) and four observational studies with 2,063 COVID-19 cases. All-cause mortality was not affected by the administration of HCQ/CQ [OR: 1.05, 95% confidence interval (CI): 0.53-2.09, P=0.89]. No improvement of viral clearance was found neither by time-to-event analysis (HR: 1.19, 95% CI: 0.74-1.94, P=0.47) nor frequency on day 7 (OR: 1.47, 95% CI: 0.33-6.63, P=0.62). HCQ/CQ treatment increased the risk of the any adverse event with OR of 3.56 (95% CI: 1.62-7.83, P=0.002).ConclusionsHCQ/CQ failed to decrease the all-cause mortality (very low quality evidence) and did not improve viral clearance (low or very low quality evidence) but increased the risk of any adverse event (moderate quality evidence). Routine administration of HCQ/CQ for COVID-19 patients is not recommended (weak recommendation, Grade 2C).
| S-EPMC7867802 | biostudies-literature