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Deconstructing the Treatment Effect of Remdesivir in the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1: Implications for Critical Care Resource Utilization.
Fintzi, Jonathan; Bonnett, Tyler; Sweeney, Daniel A; Huprikar, Nikhil A; Ganesan, Anuradha; Frank, Maria G; McLellan, Susan L F; Dodd, Lori E; Tebas, Pablo; Mehta, Aneesh K.
  • Fintzi J; Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, USA.
  • Bonnett T; Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
  • Sweeney DA; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
  • Huprikar NA; Pulmonary and Critical Care Service, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, Maryland, USA.
  • Ganesan A; Walter Reed National Military Medical Center, Infectious Disease Clinical Research Program, Department of Preventative Medicine and Biostatistics, Uniformed Services University of Health Sciences, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
  • Frank MG; Department of Medicine, Denver Health Hospital Authority, Associate Professor of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
  • McLellan SLF; Division of Infectious Disease, University of Texas Medical Branch, Galveston, Texas, USA.
  • Dodd LE; Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, USA.
  • Tebas P; Division of Infectious Diseases/Clinical Trials Unit, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Mehta AK; Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Clin Infect Dis ; 74(12): 2209-2217, 2022 07 06.
Article in English | MEDLINE | ID: covidwho-1706701
ABSTRACT

BACKGROUND:

The Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1 (ACTT-1) found that remdesivir therapy hastened recovery in patients hospitalized with COVID-19, but the pathway for this improvement was not explored. We investigated how the dynamics of clinical progression changed along 4 pathways recovery, improvement in respiratory therapy requirement, deterioration in respiratory therapy requirement, and death.

METHODS:

We analyzed trajectories of daily ordinal severity scores reflecting oxygen requirements of 1051 patients hospitalized with COVID-19 who participated in ACTT-1. We developed competing risks models that estimate the effect of remdesivir therapy on cumulative incidence of clinical improvement and deterioration, and multistate models that utilize the entirety of each patient's clinical course to characterize the effect of remdesivir on progression along the 4 pathways above.

RESULTS:

Based on a competing risks analysis, remdesivir reduced clinical deterioration (hazard ratio [HR], 0.73; 95% confidence interval [CI] .59-.91) and increased clinical improvement (HR, 1.22; 95% CI 1.08, 1.39) relative to baseline. Our multistate models indicate that remdesivir inhibits worsening to ordinal scores of greater clinical severity among patients on room air or low-flow oxygen (HR, 0.74; 95% CI .57-.94) and among patients receiving mechanical ventilation or high-flow oxygen/noninvasive positive-pressure ventilation (HR, 0.73; 95% CI .53-1.00) at baseline. We also find that remdesivir reduces expected intensive care respiratory therapy utilization among patients not mechanically ventilated at baseline.

CONCLUSIONS:

Remdesivir speeds time to recovery by preventing worsening to clinical states that would extend the course of hospitalization and increase intensive respiratory support, thereby reducing the overall demand for hospital care.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Limits: Humans Language: English Journal: Clin Infect Dis Journal subject: Communicable Diseases Year: 2022 Document Type: Article Affiliation country: Cid

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Limits: Humans Language: English Journal: Clin Infect Dis Journal subject: Communicable Diseases Year: 2022 Document Type: Article Affiliation country: Cid