Effect of Arbidol (Umifenovir) on COVID-19: a randomized controlled trial

Nojomi, Marzieh; Yassin, Zeynab; Keyvani, Hossein; Makiani, Mahin Jamshidi; Roham, Maryam; Laali, Azadeh; Dehghan, Nasir; Navaei, Mehrnaz; Ranjbar, Mahdy

doi:10.1186/s12879-020-05698-w

Cited by 143 publications

(140 citation statements)

References 24 publications

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“…One single trial randomizing 78 participants compared bromhexine hydrochloride versus standard care and showed evidence of a beneficial effect of bromhexine hydrochloride on admittance to intensive care ( p = 0.013) and receipt of mechanical ventilation ( p = 0.014) [ 103 ]. One single trial randomizing 100 participants compared hydroxychloroquine combined with arbidol versus hydroxychloroquine combined with lopinavir-ritonavir and showed evidence of a beneficial effect of hydroxychloroquine combined with arbidol on admission to intensive care ( p = 0.0001) [ 108 ].…”

Section: Resultsmentioning

confidence: 99%

Interventions for treatment of COVID-19: Second edition of a living systematic review with meta-analyses and trial sequential analyses (The LIVING Project)

et al. 2021

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Background COVID-19 is a rapidly spreading disease that has caused extensive burden to individuals, families, countries, and the world. Effective treatments of COVID-19 are urgently needed. This is the second edition of a living systematic review of randomized clinical trials assessing the effects of all treatment interventions for participants in all age groups with COVID-19. Methods and findings We planned to conduct aggregate data meta-analyses, trial sequential analyses, network meta-analysis, and individual patient data meta-analyses. Our systematic review was based on PRISMA and Cochrane guidelines, and our eight-step procedure for better validation of clinical significance of meta-analysis results. We performed both fixed-effect and random-effects meta-analyses. Primary outcomes were all-cause mortality and serious adverse events. Secondary outcomes were admission to intensive care, mechanical ventilation, renal replacement therapy, quality of life, and non-serious adverse events. According to the number of outcome comparisons, we adjusted our threshold for significance to p = 0.033. We used GRADE to assess the certainty of evidence. We searched relevant databases and websites for published and unpublished trials until November 2, 2020. Two reviewers independently extracted data and assessed trial methodology. We included 82 randomized clinical trials enrolling a total of 40,249 participants. 81 out of 82 trials were at overall high risk of bias. Meta-analyses showed no evidence of a difference between corticosteroids versus control on all-cause mortality (risk ratio [RR] 0.89; 95% confidence interval [CI] 0.79 to 1.00; p = 0.05; I2 = 23.1%; eight trials; very low certainty), on serious adverse events (RR 0.89; 95% CI 0.80 to 0.99; p = 0.04; I2 = 39.1%; eight trials; very low certainty), and on mechanical ventilation (RR 0.86; 95% CI 0.55 to 1.33; p = 0.49; I2 = 55.3%; two trials; very low certainty). The fixed-effect meta-analyses showed indications of beneficial effects. Trial sequential analyses showed that the required information size for all three analyses was not reached. Meta-analysis (RR 0.93; 95% CI 0.82 to 1.07; p = 0.31; I2 = 0%; four trials; moderate certainty) and trial sequential analysis (boundary for futility crossed) showed that we could reject that remdesivir versus control reduced the risk of death by 20%. Meta-analysis (RR 0.82; 95% CI 0.68 to 1.00; p = 0.05; I2 = 38.9%; four trials; very low certainty) and trial sequential analysis (required information size not reached) showed no evidence of difference between remdesivir versus control on serious adverse events. Fixed-effect meta-analysis showed indications of a beneficial effect of remdesivir on serious adverse events. Meta-analysis (RR 0.40; 95% CI 0.19 to 0.87; p = 0.02; I2 = 0%; two trials; very low certainty) showed evidence of a beneficial effect of intravenous immunoglobulin versus control on all-cause mortality, but trial sequential analysis (required information size not reached) showed that the result was severely underpowered to confirm or reject realistic intervention effects. Meta-analysis (RR 0.63; 95% CI 0.35 to 1.14; p = 0.12; I2 = 77.4%; five trials; very low certainty) and trial sequential analysis (required information size not reached) showed no evidence of a difference between tocilizumab versus control on serious adverse events. Fixed-effect meta-analysis showed indications of a beneficial effect of tocilizumab on serious adverse events. Meta-analysis (RR 0.70; 95% CI 0.51 to 0.96; p = 0.02; I2 = 0%; three trials; very low certainty) showed evidence of a beneficial effect of tocilizumab versus control on mechanical ventilation, but trial sequential analysis (required information size not reached) showed that the result was severely underpowered to confirm of reject realistic intervention effects. Meta-analysis (RR 0.32; 95% CI 0.15 to 0.69; p < 0.00; I2 = 0%; two trials; very low certainty) showed evidence of a beneficial effect of bromhexine versus standard care on non-serious adverse events, but trial sequential analysis (required information size not reached) showed that the result was severely underpowered to confirm or reject realistic intervention effects. Meta-analyses and trial sequential analyses (boundary for futility crossed) showed that we could reject that hydroxychloroquine versus control reduced the risk of death and serious adverse events by 20%. Meta-analyses and trial sequential analyses (boundary for futility crossed) showed that we could reject that lopinavir-ritonavir versus control reduced the risk of death, serious adverse events, and mechanical ventilation by 20%. All remaining outcome comparisons showed that we did not have enough information to confirm or reject realistic intervention effects. Nine single trials showed statistically significant results on our outcomes, but were underpowered to confirm or reject realistic intervention effects. Due to lack of data, it was not relevant to perform network meta-analysis or possible to perform individual patient data meta-analyses. Conclusions No evidence-based treatment for COVID-19 currently exists. Very low certainty evidence indicates that corticosteroids might reduce the risk of death, serious adverse events, and mechanical ventilation; that remdesivir might reduce the risk of serious adverse events; that intravenous immunoglobin might reduce the risk of death and serious adverse events; that tocilizumab might reduce the risk of serious adverse events and mechanical ventilation; and that bromhexine might reduce the risk of non-serious adverse events. More trials with low risks of bias and random errors are urgently needed. This review will continuously inform best practice in treatment and clinical research of COVID-19. Systematic review registration PROSPERO CRD42020178787.

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Section: Resultsmentioning

confidence: 99%

Interventions for treatment of COVID-19: Second edition of a living systematic review with meta-analyses and trial sequential analyses (The LIVING Project)

et al. 2021

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“…However in another study, umifenovir was shown to shorten the viral shedding interval as well as decreased the duration and cost of hospitalization for non-severe, COVID-19 patients ( Wang et al, 2020d ). A randomized controlled trial from Iran also highlighted that umifenovir monotherapy significantly contributes to clinical and laboratory improvements in COVID-19 patients including peripheral oxygen saturation, ICU admissions, hospitalization duration, ESR, WBC, and chest CT requirements ( Nojomi et al, 2020 ). A randomized, double-blinded, placebo-controlled, Phase III trial is ongoing in India for the use of umifenovir to analyze the efficacy, safety, and tolerability of umifenovir in Indian COVID-19 patients (CSIR, 2020) ( Kitagawa et al, 2020 ).…”

Section: Covid-19 Therapeuticsmentioning

confidence: 99%

Wuhan to World: The COVID-19 Pandemic

Kumar

Singh

Kaur

et al. 2021

Front. Cell. Infect. Microbiol.

168

111

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COVID-19 is a Severe Acute Respiratory Syndrome (SARS), caused by SARS-CoV-2, a novel virus which belongs to the family Coronaviridae. It was first reported in December 2019 in the Wuhan city of China and soon after, the virus and hence the disease got spread to the entire world. As of February 26, 2021, SARS-CoV-2 has infected ~112.20 million people and caused ~2.49 million deaths across the globe. Although the case fatality rate among SARS-CoV-2 patient is lower (~2.15%) than its earlier relatives, SARS-CoV (~9.5%) and MERS-CoV (~34.4%), the SARS-CoV-2 has been observed to be more infectious and caused higher morbidity and mortality worldwide. As of now, only the knowledge regarding potential transmission routes and the rapidly developed diagnostics has been guiding the world for managing the disease indicating an immediate need for a detailed understanding of the pathogen and the disease-biology. Over a very short period of time, researchers have generated a lot of information in unprecedented ways in the key areas, including viral entry into the host, dominant mutation, potential transmission routes, diagnostic targets and their detection assays, potential therapeutic targets and drug molecules for inhibiting viral entry and/or its replication in the host including cross-neutralizing antibodies and vaccine candidates that could help us to combat the ongoing COVID-19 pandemic. In the current review, we have summarized the available knowledge about the pathogen and the disease, COVID-19. We believe that this readily available knowledge base would serve as a valuable resource to the scientific and clinical community and may help in faster development of the solution to combat the disease.

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“…55, 58, 68, 81, 93, 101, 122, 123 Treatments in four trials were not connected in the network. 73, 77, 86, 98…”

Section: Resultsmentioning

confidence: 99%

A Systematic Review and Network Meta-Analysis for COVID-19 Treatments

Zhang

Jin

Wen

et al. 2020

Preprint

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BackgroundNumerous interventions for coronavirus disease 2019 (COVID-19) have been investigated by randomized controlled trials (RCTs). This systematic review and Bayesian network meta-analysis (NMA) aim to provide a comprehensive evaluation of efficacy of available treatments for COVID-19.MethodsWe searched for candidate COVID-19 studies in WHO COVID-19 Global Research Database, PubMed, PubMed Central, LitCovid, Proquest Central and Ovid up to December 19, 2020. RCTs for suspected or confirmed COVID-19 patients were included, regardless of publication status or demographic characteristics. Bayesian NMA with fixed effects was conducted to estimate the effect sizes using posterior means and 95% equal-tailed credible intervals (CrIs), while that with random effects was carried out as well for sensitivity analysis. Bayesian hierarchical models were used to estimate effect sizes of treatments grouped by their drug classifications.ResultsWe identified 96 eligible RCTs with a total of 51187 patients. Compared with the standard of care (SOC), this NMA showed that dexamethasone led to lower risk of mortality with an odds ratio (OR) of 0.85 (95% CrI [0.76, 0.95]; moderate certainty) and lower risk of mechanical ventilation (MV) with an OR of 0.68 (95% CrI [0.56, 0.83]; low certainty). For hospital discharge, remdesivir (OR 1.37, 95% CrI [1.15, 1.64]; moderate certainty), dexamethasone (OR 1.20, 95% CrI [1.08, 1.34]; low certainty), interferon beta (OR 2.15, 95% CrI [1.26, 3.74]; moderate certainty), tocilizumab (OR 1.40, 95% CrI [1.05, 1.89]; moderate certainty) and baricitinib plus remdesivir (OR 1.75, 95% CrI [1.28, 2.39]; moderate certainty) could all increase the discharge rate respectively. Recombinant human granulocyte colony-stimulating factor indicated lower risk of MV (OR 0.20, 95% CrI [0.10, 0.40]; moderate certainty); and patients receiving convalescent plasma resulted in better viral clearance (OR 2.28, 95% CrI [1.57, 3.34]; low certainty). About two-thirds of the studies included in this NMA were rated as high risk of bias, and the certainty of evidence was either low or very low for most of the comparisons.ConclusionThe Bayesian NMA identified superiority of several COVID-19 treatments over SOC in terms of mortality, requirement of MV, hospital discharge and viral clearance. These results provide a comprehensive comparison of current COVID-19 treatments and shed new light on further research and discovery of potential COVID-19 treatments.

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Effect of Arbidol (Umifenovir) on COVID-19: a randomized controlled trial

Cited by 143 publications

References 24 publications

Interventions for treatment of COVID-19: Second edition of a living systematic review with meta-analyses and trial sequential analyses (The LIVING Project)

Interventions for treatment of COVID-19: Second edition of a living systematic review with meta-analyses and trial sequential analyses (The LIVING Project)

Wuhan to World: The COVID-19 Pandemic

A Systematic Review and Network Meta-Analysis for COVID-19 Treatments

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