Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial

Wang, Yeming; Zhou, Fei; Zhang, Dingyu; Zhao, Jianping; Du, Ronghui; Hu, Yi; Cheng, Zhenshun; Gao, Ling; Jin, Yang; Luo, Guangwei; Fu, Shouzhi; Lu, Qiaofa; Du, Guanhua; Wang, Ke; Lü, Yang; Fan, Guohui; Zhang, Yi; Liu, Ying; Ruan, Shunan; Wen, Li; Jaki, Thomas; Hayden, Frederick G.; Horby, Peter; Cao, Bin; Wang, Chen

doi:10.1186/s13063-020-04352-9

Cited by 65 publications

(52 citation statements)

References 20 publications

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“…Introduction of antiviral drugs is a common cause of drug-induced AKI 46,47 . In the clinical experiment of Remdesivir, AKI as the most frequent adverse event lead to drug discontinuation 11,12 . Antiviral drugs cause AKI by many mechanisms including direct renal tubular toxicity, allergic interstitial nephritis, and crystal nephropathy 48,49 .…”

Section: Discussionmentioning

confidence: 99%

Whether Remdesivir Increases the Risk of Acute Kidney Injury (AKI) in Patients with COVID-19: A Systematic Review and Meta-Analysis

Xu¹,

Tang²,

Huang³

et al. 2020

Preprint

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Background: Acute kidney injury (AKI) occurs among patients with COVID-19, it is also proved to be associated with in-hospital mortality. Remdesivir, an RNA polymerase inhibitor, has shown its antiviral activity in vitro and animal models. The adverse effect of Remdesivir especially AKI is the most common cause which lead to drug discontinuation. Whether Remdesivir increases the risk of AKI in patients with COVID-19 is not clear. We conducted a systematic review and meta-analysis to evaluate the incidence rate of AKI in hospitalized COVID-19 patients and whether Remdesivir increases the risk of AKI. Methods: A thorough search was carried out to find relevant studies in PubMed, medRxiv, and Web of Science from 1 Jan 2020 till 1 June 2020. 15135 COVID-19 patients and 981 COVID-19 patients using Remdesivir were included in our meta-analysis. Results: The pooled estimated incidence of AKI in all hospitalized COVID-19 patients was 12.0% (95% CI:9.0%-15.0%). According to our subgroup study, the incidence of AKI was associated with the age, disease severity and race of patients. The incidence of AKI in hospitalized COVID-19 patients using Remdesivir was 6% (95% CI: 3%-13%) with a total of 5 studies. Comparing with COVID-19 patients without Remdesivir treatment, Remdesivir treatment do not increase the risk of AKI in COVID-19 patients showing OR 0.80(95%CI: 0.44-1.46, P>0.05). Conclusions: We found out that AKI was not rare in hospitalized COVID-19 patients. The incidence of AKI was associated with age, disease severity and race. Remdesivir treatment did not increase the risk of AKI in hospitalized COVID-19 patients. Our meta-analysis may provide an evidence for future study that AKI is associated with the natural cause of COVID-19, not the adverse event after the usage of Remdesivir.

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Section: Discussionmentioning

confidence: 99%

Whether Remdesivir Increases the Risk of Acute Kidney Injury (AKI) in Patients with COVID-19: A Systematic Review and Meta-Analysis

Xu¹,

Tang²,

Huang³

et al. 2020

Preprint

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“…Moreover, two clinical trials in China have been registered on ClinicalTrials.gov : NCT04257656 for severe disease and NCT04252664 for mild-to-moderate disease ( 72 ). Recently, Yeming et al published the results of the NCT04257656 clinical trial, which showed no clear outcome because of the death or discharge of patients ( 73 ). Moreover, in another clinical trial, the benefit in terms of the time to clinical improvement was not statistically significant (21 vs. 23 days), even though the study was underpowered ( 74 ).…”

Section: Potential Therapeutic Approachesmentioning

confidence: 99%

Mechanisms Underlying Potential Therapeutic Approaches for COVID-19

Benani

Mkaddem

2020

Front. Immunol.

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Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is a betacoronavirus, and is associated with cytokine storm inflammation and lung injury, leading to respiratory distress. The transmission of the virus is mediated by human contact. To control and prevent the spread of this virus, the majority of people worldwide are facing quarantine; patients are being subjected to non-specific treatments under isolation. To prevent and stop the COVID-19 pandemic, several clinical trials are in the pipeline. The current clinical trials either target the intracellular replication and spread of the virus or the cytokine storm inflammation seen in COVID-19 cases during the later stages of the disease. Since both targeting strategies are different, the window drug administration plays a crucial role in the efficacy of the treatment. Here, we review the mechanism underlying SARS-CoV-2 cell infection and potential future therapeutic approaches.

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“…Multiple studies reported that Remdesivir is one of the top computational drug repurposing, and repositioning agents possess promising pharmacodynamics to combat COVID-19 [88][89][90]. On the contrary, some studies indicated that remdesivir was not correlated with statistically significant clinical benefits among severe COVID-19 patients [91,92]. One systematic review comprising of twenty original studies regarding lopinavir-ritonavir antiviral efficacy against COVID-19.…”

Section: Role Of Clinical Available Antiviral Medication In Covid-19mentioning

confidence: 99%

The COVID-19 Pandemic - A Global Public Health Crisis: A Brief Overview Regarding Pharmacological Interventions

Haque

2020

Pesqui. Bras. Odontopediatria Clín. Integr.

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Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial

Cited by 65 publications

References 20 publications

Whether Remdesivir Increases the Risk of Acute Kidney Injury (AKI) in Patients with COVID-19: A Systematic Review and Meta-Analysis

Whether Remdesivir Increases the Risk of Acute Kidney Injury (AKI) in Patients with COVID-19: A Systematic Review and Meta-Analysis

Mechanisms Underlying Potential Therapeutic Approaches for COVID-19

The COVID-19 Pandemic - A Global Public Health Crisis: A Brief Overview Regarding Pharmacological Interventions

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