AUTHOR=Mohiuddin Chowdhury Abu Taiub Mohammed , Kamal Aktar , Abbas Kafil Uddin , Talukder Shubhashis , Karim Md Rezaul , Ali Md. Ahsan , Nuruzzaman Md. , Li Yarui , He Shuixiang 

TITLE=Efficacy and Outcome of Remdesivir and Tocilizumab Combination Against Dexamethasone for the Treatment of Severe COVID-19: A Randomized Controlled Trial

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.690726

DOI=10.3389/fphar.2022.690726

ISSN=1663-9812

ABSTRACT=<p><bold>Objective:</bold> In this study, we investigated the efficacy and safety of remdesivir and tocilizumab combination therapy against dexamethasone for the management of severe COVID-19 patients.</p><p><bold>Methods:</bold> This was a multicenter study. Cases were randomly chosen and divided into two groups using an odd–even ratio of 1:1 applied to the hospital registration number. Group A received remdesivir [5 mg/kg (&lt;40 kg) or 200 mg (&gt;40 kg) on day 1 and then 2.5 mg/kg (&lt;40 kg) or 100 mg (&gt;40 kg) daily] + tocilizumab [8 mg/kg up to 800 mg highest 12 h apart], and group B was the control and received dexamethasone 6 mg/day. In addition, a broad-spectrum antibiotic and other essential treatments were received by all patients. To evaluate the mortality risk, the sequential organ failure assessment (SOFA) score was calculated on day-1. Treatment outcomes were measured as time to clinical improvement; mortality rate; duration of ICU stay; total period of hospitalization; the rate of (<xref ref-type="sec" rid="s15">Supplementary Material</xref>) oxygen use; time to clinical failure; National Early Warning Score-2 (NEWS), and the percentage of lung recovery on CT of chest on discharge. Clinical trial registration ID: <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT04678739" xmlns:xlink="http://www.w3.org/1999/xlink">NCT04678739</ext-link>.</p><p><bold>Results:</bold> Remdesivir-Tocilizumab group had a lower mortality rate (25.49%) than the control (30.77%). The time to clinical improvement (Group A-9.41; B-14.21 days), NEWS-2 on discharge (Group A-0.89; B-1.2), duration of ICU stay (Group A-7.68; B-10.58), and duration of hospitalization (Group A-9.91; B-14.68) were less in the treatment group. Group A had a better percentage of lung recovery on chest CT than the control (Group A-22.13; B-11.74). All these differences were statistically significant (<italic>p</italic>= &lt;0.05) in a <italic>t</italic>-test. However, no significant survival benefit was found among the study groups in Kaplan–Meier survival analysis, <italic>p</italic> = 0.739.</p><p><bold>Conclusion:</bold> The remdesivir–tocilizumab combination had preferable outcomes compared to the dexamethasone therapy for the treatment of severe COVID-19 concerning mortality rate and clinical and pulmonary improvement, although it did not demonstrate a significant survival benefit.</p><p><bold>Clinical Trial Registration:</bold><ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">https://clinicaltrials.gov</ext-link>, NCT04678739.</p>