Major Update 2: 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 approved for the treatment of adults hospitalized with COVID-19.

Purpose: To update a living review of remdesivir for adults with COVID-19.

Data sources: Several electronic U.S. Food and Drug Administration, company, and journal websites from 1 January 2020 through 19 October 2021.

Study selection: English-language, randomized controlled trials (RCTs) of remdesivir for COVID-19.

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

Data synthesis: Since the last update (search date 9 August 2021), 1 new RCT and 1 new subtrial comparing a 10-day course of remdesivir with control (placebo or standard care) were identified. This review summarizes and updates the evidence on the cumulative 5 RCTs and 2 subtrials for this comparison. Our updated results confirm a 10-day course of remdesivir, compared with control, probably results in little to no mortality reduction (5 RCTs). Updated results also confirm that remdesivir probably results in a moderate increase in the proportion of patients recovered by day 29 (4 RCTs) and may reduce time to clinical improvement (2 RCTs) and hospital length of stay (4 RCTs). New RCTs, by increasing the strength of evidence, lead to an updated conclusion that remdesivir probably results in a small reduction in the proportion of patients receiving ventilation or extracorporeal membrane oxygenation at specific follow-up times (4 RCTs). New RCTs also alter the conclusions for harms-remdesivir, compared with control, may lead to a small reduction in serious adverse events but may lead to a small increase in any adverse event.

Limitation: The RCTs differed in definitions of COVID-19 severity and outcomes reported.

Conclusion: In hospitalized adults with COVID-19, the findings confirm that remdesivir probably results in little to no difference in mortality and increases the proportion of patients recovered. Remdesivir may reduce time to clinical improvement and may lead to small reductions in serious adverse events but may result in a small increase in any adverse event.

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

Appendix Figure.. Evidence search and selection.

RCT = randomized controlled trial.

Figure 1.. Mortality for remdesivir 10-day course versus control (placebo or standard care).

ACTT-1 = Adaptive COVID-19 Treatment Trial; 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.

Figure 2.. Nonmortality outcomes for remdesivir 10-day course versus control (placebo or standard care).

ACTT-1 = Adaptive COVID-19 Treatment Trial; DisCoVeRy = Trial of Treatments for COVID-19 in Hospitalized Adults; 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 recovered. Middle. Need for invasive ventilation or ECMO. Bottom. Patients with ≥1 serious adverse events.