Efficacy of remdesivir in COVID-19 patients with a simulated two-arm controlled study

ABSTRACT

While the recent study on the compassionate use of remdesivir for COVID-19 patients has shown a 68% clinical improvement7 it is a one-arm study that renders the evaluation of the efficacy in reducing death and the length of stay of hospitalization intractable due to a lacking of the control group. We came up with a two-arm controlled study design to simulate the treated and the untreated (control group) group by applying two respective transition models to the empirical data on dynamics of the disease severity (Figure 2 of the original article7) that are classified into low- (no and low oxygen supplement), medium- (non-invasive ventilator and high oxygen supplement), and high-(ECMO and invasive ventilator) from enrolment until discharge, death or the end of follow-up. By using a simulated two-arm controlled study, the remdesivir treatment group as opposed to the control group led to a statistically significantly 29% (95% CI 22-35%) reduction of death from COVID-19. The treated group also revealed a 33% (95% CI 28-38%) significantly higher odds of discharge than the control group. The median time to discharge for the treated group (5.5 days, 16.5 days, and 29.5 days for low-, medium-, and high-risk state, respectively) was around half of those of the control arm. Our results with a simulated two-arm controlled study have not only corroborated the efficacy of remdesivir but also made great contribution to designing a further large-scale randomized controlled trial. They have significant implications for reducing transmission probability and infectious time of COVID-19 patients when contacting with susceptible health care workers during hospitalization. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/20088559v1_fig2.gif" ALT="Figure 2"> View larger version (18K) org.highwire.dtl.DTLVardef@1c9a456org.highwire.dtl.DTLVardef@1442cdeorg.highwire.dtl.DTLVardef@ddd9d6org.highwire.dtl.DTLVardef@10895f9_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 2.C_FLOATNO Cumulative rate of discharge and death by treatments C_FIG Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the efficacy of remdesivir in reducing advanced disease state or death from COVID-19 and the length of stay of hospitalization? FindingsRemdesivir treatment results in a 33% significantly higher odds of discharge, a 29% significantly lower risk of death, and a 39% significantly lower risk for the combined endpoint of severe status and death. The median time to discharge for the remdesivir treated group was around half of the median time-to-discharge compared with the control arm. MeaningRemdesivir is effective in treating COVID-19 patients in terms of enhancing recovery and accelerating discharge.