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

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

Abstract

Objective: 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. Methods: 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 (<40 kg) or 200 mg (>40 kg) on day 1 and then 2.5 mg/kg (<40 kg) or 100 mg (>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 (Supplementary Material) 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: NCT04678739. Results: 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 (p= <0.05) in a t-test. However, no significant survival benefit was found among the study groups in Kaplan-Meier survival analysis, p = 0.739. Conclusion: 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. Clinical Trial Registration: https://ichgcp.net/clinical-trials-registry/NCT04678739" title="See in ClinicalTrials.gov">NCT04678739.

Keywords: Bangladesh; COVID-19; COVID-19 ARDS; SARS-Cov-2; dexamethasone; remdecivir; tocilizumab.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Mohiuddin Chowdhury, Kamal, Abbas, Talukder, Karim, Ali, Nuruzzaman, Li and He.

Figures

FIGURE 1
FIGURE 1
Flow diagram.
FIGURE 2
FIGURE 2
Kaplan–Meier survival analysis among the study groups.

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