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Randomized Phase 3 Trial of Ruxolitinib for COVID-19–Associated Acute Respiratory Distress Syndrome*

Evaluate the safety and efficacy of the Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib in COVID-19–associated acute respiratory distress syndrome requiring mechanical ventilation. DESIGN: Phase 3 randomized, double-blind, placebo-controlled trial Ruxolitinib in Participants With COVID-19–Associated...

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Autores principales: Rein, Lindsay, Calero, Karel, Shah, Ronak, Ojielo, Charles, Hudock, Kristin M., Lodhi, Saba, Sadaka, Farid, Bellam, Shashi, Palma, Christopher, Hager, David N., Daniel, Jeannie, Schaub, Richard, O’Hayer, Kevin, Theodoropoulos, Nicole M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668361/
https://www.ncbi.nlm.nih.gov/pubmed/36226977
http://dx.doi.org/10.1097/CCM.0000000000005682
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author Rein, Lindsay
Calero, Karel
Shah, Ronak
Ojielo, Charles
Hudock, Kristin M.
Lodhi, Saba
Sadaka, Farid
Bellam, Shashi
Palma, Christopher
Hager, David N.
Daniel, Jeannie
Schaub, Richard
O’Hayer, Kevin
Theodoropoulos, Nicole M.
author_facet Rein, Lindsay
Calero, Karel
Shah, Ronak
Ojielo, Charles
Hudock, Kristin M.
Lodhi, Saba
Sadaka, Farid
Bellam, Shashi
Palma, Christopher
Hager, David N.
Daniel, Jeannie
Schaub, Richard
O’Hayer, Kevin
Theodoropoulos, Nicole M.
author_sort Rein, Lindsay
collection PubMed
description Evaluate the safety and efficacy of the Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib in COVID-19–associated acute respiratory distress syndrome requiring mechanical ventilation. DESIGN: Phase 3 randomized, double-blind, placebo-controlled trial Ruxolitinib in Participants With COVID-19–Associated Acute Respiratory Distress Syndrome Who Require Mechanical Ventilation (RUXCOVID-DEVENT; NCT04377620). SETTING: Hospitals and community-based private or group practices in the United States (29 sites) and Russia (4 sites). PATIENTS: Eligible patients were greater than or equal to 12 years old, hospitalized with severe acute respiratory syndrome coronavirus 2 infection, and mechanically ventilated with a Pao(2)/Fio(2) of less than or equal to 300 mm Hg within 6 hours of randomization. INTERVENTIONS: Patients were randomized 2:2:1 to receive twice-daily ruxolitinib 15 mg, ruxolitinib 5 mg, or placebo, each plus standard therapy. MEASUREMENTS AND MAIN RESULTS: The primary endpoint, 28-day mortality, was tested for each ruxolitinib group versus placebo using a mixed-effects logistic regression model and one-tailed significance test (significance threshold: p < 0.025); no type 1 error was allocated to secondary endpoints. Between May 24, 2020 and December 15, 2020, 211 patients (age range, 24–87 yr) were randomized (ruxolitinib 15/5 mg, n = 77/87; placebo, n = 47). Acute respiratory distress syndrome was categorized as severe in 27% of patients (58/211) at randomization; 90% (190/211) received concomitant steroids. Day-28 mortality was 51% (39/77; 95% CI, 39–62%) for ruxolitinib 15 mg, 53% (45/85; 95% CI, 42–64%) for ruxolitinib 5 mg, and 70% (33/47; 95% CI, 55–83%) for placebo. Neither ruxolitinib 15 mg (odds ratio, 0.46 [95% CI, 0.201–1.028]; one-sided p = 0.029) nor 5 mg (odds ratio, 0.42 [95% CI, 0.171–1.023]; one-sided p = 0.028) significantly reduced 28-day mortality versus placebo. Numerical improvements with ruxolitinib 15 mg versus placebo were observed in secondary outcomes including ventilator-, ICU-, and vasopressor-free days. Rates of overall and serious treatment-emergent adverse events were similar across treatments. CONCLUSIONS: The observed reduction in 28-day mortality rate between ruxolitinib and placebo in mechanically ventilated patients with COVID-19–associated acute respiratory distress syndrome was not statistically significant; however, the trial was underpowered owing to early termination.
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spelling pubmed-96683612022-11-17 Randomized Phase 3 Trial of Ruxolitinib for COVID-19–Associated Acute Respiratory Distress Syndrome* Rein, Lindsay Calero, Karel Shah, Ronak Ojielo, Charles Hudock, Kristin M. Lodhi, Saba Sadaka, Farid Bellam, Shashi Palma, Christopher Hager, David N. Daniel, Jeannie Schaub, Richard O’Hayer, Kevin Theodoropoulos, Nicole M. Crit Care Med Feature Articles Evaluate the safety and efficacy of the Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib in COVID-19–associated acute respiratory distress syndrome requiring mechanical ventilation. DESIGN: Phase 3 randomized, double-blind, placebo-controlled trial Ruxolitinib in Participants With COVID-19–Associated Acute Respiratory Distress Syndrome Who Require Mechanical Ventilation (RUXCOVID-DEVENT; NCT04377620). SETTING: Hospitals and community-based private or group practices in the United States (29 sites) and Russia (4 sites). PATIENTS: Eligible patients were greater than or equal to 12 years old, hospitalized with severe acute respiratory syndrome coronavirus 2 infection, and mechanically ventilated with a Pao(2)/Fio(2) of less than or equal to 300 mm Hg within 6 hours of randomization. INTERVENTIONS: Patients were randomized 2:2:1 to receive twice-daily ruxolitinib 15 mg, ruxolitinib 5 mg, or placebo, each plus standard therapy. MEASUREMENTS AND MAIN RESULTS: The primary endpoint, 28-day mortality, was tested for each ruxolitinib group versus placebo using a mixed-effects logistic regression model and one-tailed significance test (significance threshold: p < 0.025); no type 1 error was allocated to secondary endpoints. Between May 24, 2020 and December 15, 2020, 211 patients (age range, 24–87 yr) were randomized (ruxolitinib 15/5 mg, n = 77/87; placebo, n = 47). Acute respiratory distress syndrome was categorized as severe in 27% of patients (58/211) at randomization; 90% (190/211) received concomitant steroids. Day-28 mortality was 51% (39/77; 95% CI, 39–62%) for ruxolitinib 15 mg, 53% (45/85; 95% CI, 42–64%) for ruxolitinib 5 mg, and 70% (33/47; 95% CI, 55–83%) for placebo. Neither ruxolitinib 15 mg (odds ratio, 0.46 [95% CI, 0.201–1.028]; one-sided p = 0.029) nor 5 mg (odds ratio, 0.42 [95% CI, 0.171–1.023]; one-sided p = 0.028) significantly reduced 28-day mortality versus placebo. Numerical improvements with ruxolitinib 15 mg versus placebo were observed in secondary outcomes including ventilator-, ICU-, and vasopressor-free days. Rates of overall and serious treatment-emergent adverse events were similar across treatments. CONCLUSIONS: The observed reduction in 28-day mortality rate between ruxolitinib and placebo in mechanically ventilated patients with COVID-19–associated acute respiratory distress syndrome was not statistically significant; however, the trial was underpowered owing to early termination. Lippincott Williams & Wilkins 2022-10-13 2022-12 /pmc/articles/PMC9668361/ /pubmed/36226977 http://dx.doi.org/10.1097/CCM.0000000000005682 Text en Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY) (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Feature Articles
Rein, Lindsay
Calero, Karel
Shah, Ronak
Ojielo, Charles
Hudock, Kristin M.
Lodhi, Saba
Sadaka, Farid
Bellam, Shashi
Palma, Christopher
Hager, David N.
Daniel, Jeannie
Schaub, Richard
O’Hayer, Kevin
Theodoropoulos, Nicole M.
Randomized Phase 3 Trial of Ruxolitinib for COVID-19–Associated Acute Respiratory Distress Syndrome*
title Randomized Phase 3 Trial of Ruxolitinib for COVID-19–Associated Acute Respiratory Distress Syndrome*
title_full Randomized Phase 3 Trial of Ruxolitinib for COVID-19–Associated Acute Respiratory Distress Syndrome*
title_fullStr Randomized Phase 3 Trial of Ruxolitinib for COVID-19–Associated Acute Respiratory Distress Syndrome*
title_full_unstemmed Randomized Phase 3 Trial of Ruxolitinib for COVID-19–Associated Acute Respiratory Distress Syndrome*
title_short Randomized Phase 3 Trial of Ruxolitinib for COVID-19–Associated Acute Respiratory Distress Syndrome*
title_sort randomized phase 3 trial of ruxolitinib for covid-19–associated acute respiratory distress syndrome*
topic Feature Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668361/
https://www.ncbi.nlm.nih.gov/pubmed/36226977
http://dx.doi.org/10.1097/CCM.0000000000005682
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