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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2022
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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. |
format | Online Article Text |
id | pubmed-9668361 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
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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