Cargando…

Deconstructing the Treatment Effect of Remdesivir in the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1: Implications for Critical Care Resource Utilization

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 alon...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499739/
https://www.ncbi.nlm.nih.gov/pubmed/34409989
http://dx.doi.org/10.1093/cid/ciab712
_version_ 1784580361692381184
author 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
author_facet 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
author_sort Fintzi, Jonathan
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8499739
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-84997392021-10-08 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 Clin Infect Dis Major Articles and Commentaries 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. Oxford University Press 2021-08-19 /pmc/articles/PMC8499739/ /pubmed/34409989 http://dx.doi.org/10.1093/cid/ciab712 Text en Published by Oxford University Press for the Infectious Diseases Society of America 2021. This work is written by (a) US Government employee(s) and is in the public domain in the US.
spellingShingle Major Articles and Commentaries
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
Deconstructing the Treatment Effect of Remdesivir in the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1: Implications for Critical Care Resource Utilization
title Deconstructing the Treatment Effect of Remdesivir in the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1: Implications for Critical Care Resource Utilization
title_full Deconstructing the Treatment Effect of Remdesivir in the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1: Implications for Critical Care Resource Utilization
title_fullStr Deconstructing the Treatment Effect of Remdesivir in the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1: Implications for Critical Care Resource Utilization
title_full_unstemmed Deconstructing the Treatment Effect of Remdesivir in the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1: Implications for Critical Care Resource Utilization
title_short Deconstructing the Treatment Effect of Remdesivir in the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1: Implications for Critical Care Resource Utilization
title_sort deconstructing the treatment effect of remdesivir in the adaptive coronavirus disease 2019 (covid-19) treatment trial-1: implications for critical care resource utilization
topic Major Articles and Commentaries
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499739/
https://www.ncbi.nlm.nih.gov/pubmed/34409989
http://dx.doi.org/10.1093/cid/ciab712
work_keys_str_mv AT fintzijonathan deconstructingthetreatmenteffectofremdesivirintheadaptivecoronavirusdisease2019covid19treatmenttrial1implicationsforcriticalcareresourceutilization
AT bonnetttyler deconstructingthetreatmenteffectofremdesivirintheadaptivecoronavirusdisease2019covid19treatmenttrial1implicationsforcriticalcareresourceutilization
AT sweeneydaniela deconstructingthetreatmenteffectofremdesivirintheadaptivecoronavirusdisease2019covid19treatmenttrial1implicationsforcriticalcareresourceutilization
AT huprikarnikhila deconstructingthetreatmenteffectofremdesivirintheadaptivecoronavirusdisease2019covid19treatmenttrial1implicationsforcriticalcareresourceutilization
AT ganesananuradha deconstructingthetreatmenteffectofremdesivirintheadaptivecoronavirusdisease2019covid19treatmenttrial1implicationsforcriticalcareresourceutilization
AT frankmariag deconstructingthetreatmenteffectofremdesivirintheadaptivecoronavirusdisease2019covid19treatmenttrial1implicationsforcriticalcareresourceutilization
AT mclellansusanlf deconstructingthetreatmenteffectofremdesivirintheadaptivecoronavirusdisease2019covid19treatmenttrial1implicationsforcriticalcareresourceutilization
AT doddlorie deconstructingthetreatmenteffectofremdesivirintheadaptivecoronavirusdisease2019covid19treatmenttrial1implicationsforcriticalcareresourceutilization
AT tebaspablo deconstructingthetreatmenteffectofremdesivirintheadaptivecoronavirusdisease2019covid19treatmenttrial1implicationsforcriticalcareresourceutilization
AT mehtaaneeshk deconstructingthetreatmenteffectofremdesivirintheadaptivecoronavirusdisease2019covid19treatmenttrial1implicationsforcriticalcareresourceutilization