TY - JOUR
T1 - Timely administration of tocilizumab improves outcome of hospitalized COVID-19 patients
AU - Rutgers, Abraham
AU - Westerweel, Peter E
AU - van der Holt, Bronno
AU - Postma, Simone
AU - van Vonderen, Marit G A
AU - Piersma, Djura P
AU - Postma, Douwe
AU - van den Berge, Maarten
AU - Jong, Eefje
AU - de Vries, Marten
AU - van der Burg, Leonie
AU - Huugen, Dennis
AU - van der Poel, Marjolein
AU - Kampschreur, Linda M
AU - Nijland, Marcel
AU - Strijbos, Jaap H
AU - Tamminga, Menno
AU - Mutsaers, Pim G N J
AU - Schol-Gelok, Suzanne
AU - Dijkstra-Tiekstra, Margriet
AU - Sidorenkov, Grigory
AU - Vincenten, Julien
AU - van Geffen, Wouter H
AU - Knoester, Marjolein
AU - Kosterink, Jos
AU - Gans, Reinold
AU - Stegeman, Coen
AU - Huls, Gerwin
AU - van Meerten, Tom
PY - 2022/8/12
Y1 - 2022/8/12
N2 - INTRODUCTION: The aim of this study was to determine the efficacy of early tocilizumab treatment for hospitalized patients with COVID-19 disease.METHODS: Open-label randomized phase II clinical trial investigating tocilizumab in patients with proven COVID-19 admitted to the general ward and in need of supplemental oxygen. The primary endpoint of the study was 30-day mortality with a prespecified 2-sided significance level of α = 0.10. A post-hoc analysis was performed for a combined endpoint of mechanical ventilation or death at 30 days. Secondary objectives included comparing the duration of hospital stay, ICU admittance and duration of ICU stay and the duration of mechanical ventilation.RESULTS: A total of 354 patients (67% men; median age 66 years) were enrolled of whom 88% received dexamethasone. Thirty-day mortality was 19% (95% CI 14%-26%) in the standard arm versus 12% (95% CI: 8%-18%) in the tocilizumab arm, hazard ratio (HR) = 0.62 (90% CI 0.39-0.98; p = 0.086). 17% of patients were admitted to the ICU in each arm (p = 0.89). The median stay in the ICU was 14 days (IQR 9-28) in the standard arm versus 9 days (IQR 5-14) in the tocilizumab arm (p = 0.014). Mechanical ventilation or death at thirty days was 31% (95% CI 24%-38%) in the standard arm versus 21% (95% CI 16%-28%) in the tocilizumab arm, HR = 0.65 (95% CI 0.42-0.98; p = 0.042).CONCLUSIONS: This randomized phase II study supports efficacy for tocilizumab when given early in the disease course in hospitalized patients who need oxygen support, especially when concomitantly treated with dexamethasone.TRIAL REGISTRATION: https://www.trialregister.nl/trial/8504.
AB - INTRODUCTION: The aim of this study was to determine the efficacy of early tocilizumab treatment for hospitalized patients with COVID-19 disease.METHODS: Open-label randomized phase II clinical trial investigating tocilizumab in patients with proven COVID-19 admitted to the general ward and in need of supplemental oxygen. The primary endpoint of the study was 30-day mortality with a prespecified 2-sided significance level of α = 0.10. A post-hoc analysis was performed for a combined endpoint of mechanical ventilation or death at 30 days. Secondary objectives included comparing the duration of hospital stay, ICU admittance and duration of ICU stay and the duration of mechanical ventilation.RESULTS: A total of 354 patients (67% men; median age 66 years) were enrolled of whom 88% received dexamethasone. Thirty-day mortality was 19% (95% CI 14%-26%) in the standard arm versus 12% (95% CI: 8%-18%) in the tocilizumab arm, hazard ratio (HR) = 0.62 (90% CI 0.39-0.98; p = 0.086). 17% of patients were admitted to the ICU in each arm (p = 0.89). The median stay in the ICU was 14 days (IQR 9-28) in the standard arm versus 9 days (IQR 5-14) in the tocilizumab arm (p = 0.014). Mechanical ventilation or death at thirty days was 31% (95% CI 24%-38%) in the standard arm versus 21% (95% CI 16%-28%) in the tocilizumab arm, HR = 0.65 (95% CI 0.42-0.98; p = 0.042).CONCLUSIONS: This randomized phase II study supports efficacy for tocilizumab when given early in the disease course in hospitalized patients who need oxygen support, especially when concomitantly treated with dexamethasone.TRIAL REGISTRATION: https://www.trialregister.nl/trial/8504.
KW - Aged
KW - Antibodies, Monoclonal, Humanized
KW - COVID-19/drug therapy
KW - Dexamethasone/therapeutic use
KW - Female
KW - Humans
KW - Male
KW - Oxygen
KW - Respiration, Artificial
KW - SARS-CoV-2
KW - Treatment Outcome
U2 - 10.1371/journal.pone.0271807
DO - 10.1371/journal.pone.0271807
M3 - Article
C2 - 35960720
SN - 1932-6203
VL - 17
JO - PLOS ONE
JF - PLOS ONE
IS - 8
M1 - e0271807
ER -