Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for COVID-19 Pneumonia

Background. Few antiviral therapies have been studied in patients with coronavirus disease 2019 (COVID-19) and kidney impairment. Herein, the efficacy, safety, and pharmacokinetics of remdesivir, its metabolites, and sulfobutylether-β-cyclodextrin excipient were evaluated in hospitalized patients wi...

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Autores: Sise, M.E., Santos, Jose Ramon, Goldman, J.D., Tuttle, K.R., Pedro Teixeira, J., Seibert, A.F., Koullias, Y., Llewellyn, J., Regan, S., Zhao, Y., Huang, H., Hyland, R.H., Osinusi, A., Winter, H., Humeniuk, R., Hulter, H.N., Gottlieb, R.L., Fusco, D.N., Birne, R., Stancampiano, F.F., Libertin, C.R., Small, C.B., Plate, M., McPhail, M.J.
Formato: artículo
Fecha de publicación:2024
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:311092
Acesso em linha:https://ddd.uab.cat/record/311092
https://dx.doi.org/urn:doi:10.1093/cid/ciae333
Access Level:acceso abierto
Palavra-chave:COVID-19
SARS-CoV-2
Kidney impairment
Remdesivir
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spelling Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for COVID-19 PneumoniaA Randomized Clinical TrialSise, M.E.Santos, Jose RamonGoldman, J.D.Tuttle, K.R.Pedro Teixeira, J.Seibert, A.F.Koullias, Y.Llewellyn, J.Regan, S.Zhao, Y.Huang, H.Hyland, R.H.Osinusi, A.Winter, H.Humeniuk, R.Hulter, H.N.Gottlieb, R.L.Fusco, D.N.Birne, R.Stancampiano, F.F.Libertin, C.R.Small, C.B.Plate, M.McPhail, M.J.COVID-19SARS-CoV-2Kidney impairmentRemdesivirBackground. Few antiviral therapies have been studied in patients with coronavirus disease 2019 (COVID-19) and kidney impairment. Herein, the efficacy, safety, and pharmacokinetics of remdesivir, its metabolites, and sulfobutylether-β-cyclodextrin excipient were evaluated in hospitalized patients with COVID-19 and severe kidney impairment. Methods. In REDPINE, a phase 3, randomized, double-blind, placebo-controlled study, participants aged ≥12 years hospitalized for COVID-19 pneumonia with acute kidney injury, chronic kidney disease, or kidney failure were randomized 2:1 to receive intravenous remdesivir (200 mg on day 1; 100 mg daily up to day 5) or placebo (enrollment from March 2021 to March 2022). The primary efficacy end point was the composite of the all-cause mortality rate or invasive mechanical ventilation rate through day 29. Safety was evaluated through day 60. Results. Although enrollment concluded early, 243 participants were enrolled and treated (remdesivir, n = 163; placebo, n = 80). At baseline, 90 participants (37.0%) had acute kidney injury (remdesivir, n = 60; placebo, n = 30), 64 (26.3%) had chronic kidney disease (remdesivir, n = 44; placebo, n = 20), and 89 (36.6%) had kidney failure (remdesivir, n = 59; placebo, n = 30); and 31 (12.8%) were vaccinated against COVID-19. Composite all-cause mortality or invasive mechanical ventilation rates through day 29 were 29.4% and 32.5% in the remdesivir and placebo group, respectively (P =.61). Treatment-emergent adverse events were reported in 80.4% for remdesivir versus 77.5% for placebo, and serious adverse events in 50.3% versus 50.0%, respectively. Pharmacokinetic plasma exposure to remdesivir was not affected by kidney function. Conclusions. Although the study was underpowered, no significant difference in efficacy was observed between treatment groups. REDPINE demonstrated that remdesivir is safe in patients with COVID-19 and severe kidney impairment.Universitat Autònoma de Barcelona 22024-01-0120242024-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/311092https://dx.doi.org/urn:doi:10.1093/cid/ciae333reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3110922026-06-06T12:50:31Z
dc.title.none.fl_str_mv Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for COVID-19 Pneumonia
A Randomized Clinical Trial
title Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for COVID-19 Pneumonia
spellingShingle Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for COVID-19 Pneumonia
Sise, M.E.
COVID-19
SARS-CoV-2
Kidney impairment
Remdesivir
title_short Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for COVID-19 Pneumonia
title_full Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for COVID-19 Pneumonia
title_fullStr Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for COVID-19 Pneumonia
title_full_unstemmed Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for COVID-19 Pneumonia
title_sort Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for COVID-19 Pneumonia
dc.creator.none.fl_str_mv Sise, M.E.
Santos, Jose Ramon
Goldman, J.D.
Tuttle, K.R.
Pedro Teixeira, J.
Seibert, A.F.
Koullias, Y.
Llewellyn, J.
Regan, S.
Zhao, Y.
Huang, H.
Hyland, R.H.
Osinusi, A.
Winter, H.
Humeniuk, R.
Hulter, H.N.
Gottlieb, R.L.
Fusco, D.N.
Birne, R.
Stancampiano, F.F.
Libertin, C.R.
Small, C.B.
Plate, M.
McPhail, M.J.
author Sise, M.E.
author_facet Sise, M.E.
Santos, Jose Ramon
Goldman, J.D.
Tuttle, K.R.
Pedro Teixeira, J.
Seibert, A.F.
Koullias, Y.
Llewellyn, J.
Regan, S.
Zhao, Y.
Huang, H.
Hyland, R.H.
Osinusi, A.
Winter, H.
Humeniuk, R.
Hulter, H.N.
Gottlieb, R.L.
Fusco, D.N.
Birne, R.
Stancampiano, F.F.
Libertin, C.R.
Small, C.B.
Plate, M.
McPhail, M.J.
author_role author
author2 Santos, Jose Ramon
Goldman, J.D.
Tuttle, K.R.
Pedro Teixeira, J.
Seibert, A.F.
Koullias, Y.
Llewellyn, J.
Regan, S.
Zhao, Y.
Huang, H.
Hyland, R.H.
Osinusi, A.
Winter, H.
Humeniuk, R.
Hulter, H.N.
Gottlieb, R.L.
Fusco, D.N.
Birne, R.
Stancampiano, F.F.
Libertin, C.R.
Small, C.B.
Plate, M.
McPhail, M.J.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv COVID-19
SARS-CoV-2
Kidney impairment
Remdesivir
topic COVID-19
SARS-CoV-2
Kidney impairment
Remdesivir
description Background. Few antiviral therapies have been studied in patients with coronavirus disease 2019 (COVID-19) and kidney impairment. Herein, the efficacy, safety, and pharmacokinetics of remdesivir, its metabolites, and sulfobutylether-β-cyclodextrin excipient were evaluated in hospitalized patients with COVID-19 and severe kidney impairment. Methods. In REDPINE, a phase 3, randomized, double-blind, placebo-controlled study, participants aged ≥12 years hospitalized for COVID-19 pneumonia with acute kidney injury, chronic kidney disease, or kidney failure were randomized 2:1 to receive intravenous remdesivir (200 mg on day 1; 100 mg daily up to day 5) or placebo (enrollment from March 2021 to March 2022). The primary efficacy end point was the composite of the all-cause mortality rate or invasive mechanical ventilation rate through day 29. Safety was evaluated through day 60. Results. Although enrollment concluded early, 243 participants were enrolled and treated (remdesivir, n = 163; placebo, n = 80). At baseline, 90 participants (37.0%) had acute kidney injury (remdesivir, n = 60; placebo, n = 30), 64 (26.3%) had chronic kidney disease (remdesivir, n = 44; placebo, n = 20), and 89 (36.6%) had kidney failure (remdesivir, n = 59; placebo, n = 30); and 31 (12.8%) were vaccinated against COVID-19. Composite all-cause mortality or invasive mechanical ventilation rates through day 29 were 29.4% and 32.5% in the remdesivir and placebo group, respectively (P =.61). Treatment-emergent adverse events were reported in 80.4% for remdesivir versus 77.5% for placebo, and serious adverse events in 50.3% versus 50.0%, respectively. Pharmacokinetic plasma exposure to remdesivir was not affected by kidney function. Conclusions. Although the study was underpowered, no significant difference in efficacy was observed between treatment groups. REDPINE demonstrated that remdesivir is safe in patients with COVID-19 and severe kidney impairment.
publishDate 2024
dc.date.none.fl_str_mv 2
2024-01-01
2024
2024-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
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dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/311092
https://dx.doi.org/urn:doi:10.1093/cid/ciae333
url https://ddd.uab.cat/record/311092
https://dx.doi.org/urn:doi:10.1093/cid/ciae333
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
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eu_rights_str_mv openAccess
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dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
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