Remdesivir Treatment in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19): A Comparative Analysis of In-hospital All-cause Mortality in a Large Multicenter Observational Cohort

Essy Mozaffari, Aastha Chandak, Zhiji Zhang, Shuting Liang, Mark Thrun, Robert L Gottlieb, Daniel R Kuritzkes, Paul E Sax, David A Wohl, Roman Casciano, Paul Hodgkins, Richard Haubrich, Essy Mozaffari, Aastha Chandak, Zhiji Zhang, Shuting Liang, Mark Thrun, Robert L Gottlieb, Daniel R Kuritzkes, Paul E Sax, David A Wohl, Roman Casciano, Paul Hodgkins, Richard Haubrich

Abstract

Background: Remdesivir (RDV) improved clinical outcomes among hospitalized patients with coronavirus disease 2019 (COVID-19) in randomized trials, but data from clinical practice are limited.

Methods: We examined survival outcomes for US patients hospitalized with COVID-19 between August and November 2020 and treated with RDV within 2 days of hospitalization vs those not receiving RDV during their hospitalization using the Premier Healthcare Database. Preferential within-hospital propensity score matching with replacement was used. Additionally, patients were also matched on baseline oxygenation level (no supplemental oxygen charges [NSO], low-flow oxygen [LFO], high-flow oxygen/noninvasive ventilation [HFO/NIV], and invasive mechanical ventilation/extracorporeal membrane oxygenation [IMV/ECMO]) and 2-month admission window and excluded if discharged within 3 days of admission (to exclude anticipated discharges/transfers within 72 hours, consistent with the Adaptive COVID-19 Treatment Trial [ACTT-1] study). Cox proportional hazards models were used to assess time to 14-/28-day mortality overall and for patients on NSO, LFO, HFO/NIV, and IMV/ECMO.

Results: A total of 28855 RDV patients were matched to 16687 unique non-RDV patients. Overall, 10.6% and 15.4% RDV patients died within 14 and 28 days, respectively, compared with 15.4% and 19.1% non-RDV patients. Overall, RDV was associated with a reduction in mortality at 14 days (hazard ratio [95% confidence interval]: 0.76 [0.70-0.83]) and 28 days (0.89 [0.82-0.96]). This mortality benefit was also seen for NSO, LFO, and IMV/ECMO at 14 days (NSO: 0.69 [0.57-0.83], LFO: 0.68 [0.80-0.77], IMV/ECMO: 0.70 [0.58-0.84]) and 28 days (NSO: 0.80 [0.68-0.94], LFO: 0.77 [0.68-0.86], IMV/ECMO: 0.81 [0.69-0.94]). Additionally, HFO/NIV RDV group had a lower risk of mortality at 14 days (0.81 [0.70-0.93]) but no statistical significance at 28 days.

Conclusions: RDV initiated upon hospital admission was associated with improved survival among patients with COVID-19. Our findings complement ACTT-1 and support RDV as a foundational treatment for hospitalized COVID-19 patients.

Trial registration: ClinicalTrials.gov NCT03383419.

Keywords: COVID-19; comparative effectiveness research; hospitalization; mortality; remdesivir.

© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Study population.
Figure 2.
Figure 2.
Kaplan-Meier curves among matched patients (preferential within-hospital matching) hospitalized for COVID-19, August–November 2020. P value from log-rank tests and mortality rates in the 2 treatments groups are presented for A, overall; B, no supplemental oxygen charges (NSO); C, low-flow oxygen (LFO); D, high-flow oxygen/non-invasive ventilation (HFO/NIV); and E, invasive mechanical ventilation/extracorporeal membrane oxygenation (IMV/ECMO). COVID-19, coronavirus disease 2019.
Figure 3.
Figure 3.
Cox proportional hazard model for time to 14- and 28-day mortality among matched patients (preferential within-hospital matching) hospitalized for COVID-19, August–November 2020. Adjusted for hospital-level random effects and age, admission month, anticoagulants use at baseline, convalescent plasma at baseline, corticosteroids use at baseline, tocilizumab use at baseline, intensive care unit stay/stepdown/general ward at baseline and other covariates with absolute standardized mean difference>0.15. COVID-19, coronavirus disease 2019.

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Source: PubMed

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