Major Update: Remdesivir for Adults With COVID-19 : A Living Systematic Review and Meta-analysis for the American College of Physicians Practice Points

Abstract

Background: Remdesivir is being studied and used for treatment of coronavirus disease 2019 (COVID-19).

Purpose: To update a previous review of remdesivir for adults with COVID-19, including new meta-analyses of patients with COVID-19 of any severity compared with control.

Data sources: Several sources from 1 January 2020 through 7 December 2020.

Study selection: English-language, randomized controlled trials (RCTs) of remdesivir for COVID-19. New evidence is incorporated by using living review methods.

Data extraction: 1 reviewer abstracted data; a second reviewer verified the data. The Cochrane Risk of Bias Tool and GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used.

Data synthesis: The update includes 5 RCTs, incorporating data from a new large RCT and the final results of a previous RCT. Compared with control, a 10-day course of remdesivir probably results in little to no reduction in mortality (risk ratio [RR], 0.93 [95% CI, 0.82 to 1.06]; 4 RCTs) but may result in a small reduction in the proportion of patients receiving mechanical ventilation (RR, 0.71 [CI, 0.56 to 0.90]; 3 RCTs). Remdesivir probably results in a moderate increase in the percentage of patients who recovered and a moderate decrease in serious adverse events and may result in a large reduction in time to recovery. Effect on hospital length of stay or percentage remaining hospitalized is mixed. Compared with a 10-day course for those not requiring ventilation at baseline, a 5-day course may reduce mortality, the need for ventilation, and serious adverse events while increasing the percentage of patients who recovered or clinically improved.

Limitation: Summarizing findings was challenging because of varying disease severity definitions and outcomes.

Conclusion: In hospitalized adults with COVID-19, remdesivir probably results in little to no mortality difference but probably improves the percentage recovered and reduces serious harms and may result in a small reduction in the proportion receiving ventilation. For patients not receiving ventilation, a 5-day course may provide greater benefits and fewer harms with lower drug costs than a 10-day course.

Primary funding source: U.S. Department of Veterans Affairs.

Conflict of interest statement

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-8148.

Figures

Appendix Figure.. Evidence search and selection.

Figure 1.. Mortality for remdesivir 10-d course vs.

control (placebo or standard care). The black diamonds reflect pooled results from randomized controlled trials (listed above) that enrolled patients in the corresponding respiratory support subgroups. ACTT-1 = Adaptive COVID-19 Treatment Trial; ECMO = extracorporeal membrane oxygenation; RR = risk ratio; SIMPLE-2 = Study to Evaluate the Safety and Antiviral Activity of Remdesivir [GS-5734] in Participants With Moderate Coronavirus Disease [COVID-19] Compared to Standard of Care Treatment. Top. Overall. Bottom. Results by initial respiratory status.

Figure 2.. Nonmortality outcomes for remdesivir 10-d course vs.

control (placebo or standard care). ACTT-1 = Adaptive COVID-19 Treatment Trial; ECMO = extracorporeal membrane oxygenation; RR = risk ratio; SIMPLE-2 = Study to Evaluate the Safety and Antiviral Activity of Remdesivir [GS-5734] in Participants With Moderate Coronavirus Disease [COVID-19] Compared to Standard of Care Treatment. Top. Proportion of patients recovered. Middle. Need for invasive ventilation/ECMO. Bottom. Patients with ≥1 serious adverse event. * For the pooled trials, defined as proportion receiving invasive ventilation/ECMO (new vs. continued from baseline) at follow-up (ACTT-1 on day 15, Wang et al on day 14, and SIMPLE-2 on day 11). † Unpooled Solidarity trial, defined as subsequent need for ventilation in those not receiving ventilation at baseline (through day 28).