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Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial

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Harvard

Kyriazopoulou, E, Poulakou, G, Milionis, H, Metallidis, S, Adamis, G, Tsiakos, K, Fragkou, A, Rapti, A, Damoulari, C, Fantoni, M, Kalomenidis, I, Chrysos, G, Angheben, A, Kainis, I, Alexiou, Z, Castelli, F, Serino, FS, Tsilika, M, Bakakos, P, Nicastri, E, Tzavara, V, Kostis, E, Dagna, L, Koufargyris, P, Dimakou, K, Savvanis, S, Tzatzagou, G, Chini, M, Cavalli, G, Bassetti, M, Katrini, K, Kotsis, V, Tsoukalas, G, Selmi, C, Bliziotis, I, Samarkos, M, Doumas, M, Ktena, S, Masgala, A, Papanikolaou, I, Kosmidou, M, Myrodia, D-M, Argyraki, A, Cardellino, CS, Koliakou, K, Katsigianni, E-I, Rapti, V, Giannitsioti, E, Cingolani, A, Micha, S, Akinosoglou, K, Liatsis-Douvitsas, O, Symbardi, S, Gatselis, N, Mouktaroudi, M, Ippolito, G, Florou, E, Kotsaki, A, Netea, MG, Eugen-Olsen, J, Kyprianou, M, Panagopoulos, P, Dalekos, GN & Giamarellos-Bourboulis, EJ 2021, 'Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial', Nature Medicine, bind 27, nr. 10, s. 1752-1760. https://doi.org/10.1038/s41591-021-01499-z

APA

Kyriazopoulou, E., Poulakou, G., Milionis, H., Metallidis, S., Adamis, G., Tsiakos, K., Fragkou, A., Rapti, A., Damoulari, C., Fantoni, M., Kalomenidis, I., Chrysos, G., Angheben, A., Kainis, I., Alexiou, Z., Castelli, F., Serino, F. S., Tsilika, M., Bakakos, P., ... Giamarellos-Bourboulis, E. J. (2021). Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial. Nature Medicine, 27(10), 1752-1760. https://doi.org/10.1038/s41591-021-01499-z

CBE

Kyriazopoulou E, Poulakou G, Milionis H, Metallidis S, Adamis G, Tsiakos K, Fragkou A, Rapti A, Damoulari C, Fantoni M, Kalomenidis I, Chrysos G, Angheben A, Kainis I, Alexiou Z, Castelli F, Serino FS, Tsilika M, Bakakos P, Nicastri E, Tzavara V, Kostis E, Dagna L, Koufargyris P, Dimakou K, Savvanis S, Tzatzagou G, Chini M, Cavalli G, Bassetti M, Katrini K, Kotsis V, Tsoukalas G, Selmi C, Bliziotis I, Samarkos M, Doumas M, Ktena S, Masgala A, Papanikolaou I, Kosmidou M, Myrodia D-M, Argyraki A, Cardellino CS, Koliakou K, Katsigianni E-I, Rapti V, Giannitsioti E, Cingolani A, Micha S, Akinosoglou K, Liatsis-Douvitsas O, Symbardi S, Gatselis N, Mouktaroudi M, Ippolito G, Florou E, Kotsaki A, Netea MG, Eugen-Olsen J, Kyprianou M, Panagopoulos P, Dalekos GN, Giamarellos-Bourboulis EJ. 2021. Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial. Nature Medicine. 27(10):1752-1760. https://doi.org/10.1038/s41591-021-01499-z

MLA

Vancouver

Author

Kyriazopoulou, Evdoxia ; Poulakou, Garyfallia ; Milionis, Haralampos ; Metallidis, Simeon ; Adamis, Georgios ; Tsiakos, Konstantinos ; Fragkou, Archontoula ; Rapti, Aggeliki ; Damoulari, Christina ; Fantoni, Massimo ; Kalomenidis, Ioannis ; Chrysos, Georgios ; Angheben, Andrea ; Kainis, Ilias ; Alexiou, Zoi ; Castelli, Francesco ; Serino, Francesco Saverio ; Tsilika, Maria ; Bakakos, Petros ; Nicastri, Emanuele ; Tzavara, Vassiliki ; Kostis, Evangelos ; Dagna, Lorenzo ; Koufargyris, Panagiotis ; Dimakou, Katerina ; Savvanis, Spyridon ; Tzatzagou, Glykeria ; Chini, Maria ; Cavalli, Giulio ; Bassetti, Matteo ; Katrini, Konstantina ; Kotsis, Vasileios ; Tsoukalas, George ; Selmi, Carlo ; Bliziotis, Ioannis ; Samarkos, Michael ; Doumas, Michael ; Ktena, Sofia ; Masgala, Aikaterini ; Papanikolaou, Ilias ; Kosmidou, Maria ; Myrodia, Dimitra-Melia ; Argyraki, Aikaterini ; Cardellino, Chiara Simona ; Koliakou, Katerina ; Katsigianni, Eleni-Ioanna ; Rapti, Vassiliki ; Giannitsioti, Efthymia ; Cingolani, Antonella ; Micha, Styliani ; Akinosoglou, Karolina ; Liatsis-Douvitsas, Orestis ; Symbardi, Styliani ; Gatselis, Nikolaos ; Mouktaroudi, Maria ; Ippolito, Giuseppe ; Florou, Eleni ; Kotsaki, Antigone ; Netea, Mihai G ; Eugen-Olsen, Jesper ; Kyprianou, Miltiades ; Panagopoulos, Periklis ; Dalekos, George N ; Giamarellos-Bourboulis, Evangelos J. / Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels : a double-blind, randomized controlled phase 3 trial. I: Nature Medicine. 2021 ; Bind 27, Nr. 10. s. 1752-1760.

Bibtex

@article{36da67e221ef4aceb2e11f9d7e0570a0,
title = "Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial",
abstract = "Early increase of soluble urokinase plasminogen activator receptor (suPAR) serum levels is indicative of increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure. The SAVE-MORE double-blind, randomized controlled trial evaluated the efficacy and safety of anakinra, an IL-1α/β inhibitor, in 594 patients with COVID-19 at risk of progressing to respiratory failure as identified by plasma suPAR ≥6 ng ml-1, 85.9% (n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26-0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P < 0.0001); the respective median decrease of Sequential Organ Failure Assessment (SOFA) score on day 7 from baseline was 0 and 1 points (OR = 0.63, P = 0.004). Twenty-eight-day mortality decreased (hazard ratio = 0.45, P = 0.045), and hospital stay was shorter.",
keywords = "Aged, COVID-19/drug therapy, Double-Blind Method, Female, Humans, Interleukin 1 Receptor Antagonist Protein/adverse effects, Male, Middle Aged, Placebos, Receptors, Urokinase Plasminogen Activator/blood, SARS-CoV-2/isolation & purification",
author = "Evdoxia Kyriazopoulou and Garyfallia Poulakou and Haralampos Milionis and Simeon Metallidis and Georgios Adamis and Konstantinos Tsiakos and Archontoula Fragkou and Aggeliki Rapti and Christina Damoulari and Massimo Fantoni and Ioannis Kalomenidis and Georgios Chrysos and Andrea Angheben and Ilias Kainis and Zoi Alexiou and Francesco Castelli and Serino, {Francesco Saverio} and Maria Tsilika and Petros Bakakos and Emanuele Nicastri and Vassiliki Tzavara and Evangelos Kostis and Lorenzo Dagna and Panagiotis Koufargyris and Katerina Dimakou and Spyridon Savvanis and Glykeria Tzatzagou and Maria Chini and Giulio Cavalli and Matteo Bassetti and Konstantina Katrini and Vasileios Kotsis and George Tsoukalas and Carlo Selmi and Ioannis Bliziotis and Michael Samarkos and Michael Doumas and Sofia Ktena and Aikaterini Masgala and Ilias Papanikolaou and Maria Kosmidou and Dimitra-Melia Myrodia and Aikaterini Argyraki and Cardellino, {Chiara Simona} and Katerina Koliakou and Eleni-Ioanna Katsigianni and Vassiliki Rapti and Efthymia Giannitsioti and Antonella Cingolani and Styliani Micha and Karolina Akinosoglou and Orestis Liatsis-Douvitsas and Styliani Symbardi and Nikolaos Gatselis and Maria Mouktaroudi and Giuseppe Ippolito and Eleni Florou and Antigone Kotsaki and Netea, {Mihai G} and Jesper Eugen-Olsen and Miltiades Kyprianou and Periklis Panagopoulos and Dalekos, {George N} and Giamarellos-Bourboulis, {Evangelos J}",
note = "{\textcopyright} 2021. The Author(s).",
year = "2021",
month = oct,
doi = "10.1038/s41591-021-01499-z",
language = "English",
volume = "27",
pages = "1752--1760",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "10",

}

RIS

TY - JOUR

T1 - Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels

T2 - a double-blind, randomized controlled phase 3 trial

AU - Kyriazopoulou, Evdoxia

AU - Poulakou, Garyfallia

AU - Milionis, Haralampos

AU - Metallidis, Simeon

AU - Adamis, Georgios

AU - Tsiakos, Konstantinos

AU - Fragkou, Archontoula

AU - Rapti, Aggeliki

AU - Damoulari, Christina

AU - Fantoni, Massimo

AU - Kalomenidis, Ioannis

AU - Chrysos, Georgios

AU - Angheben, Andrea

AU - Kainis, Ilias

AU - Alexiou, Zoi

AU - Castelli, Francesco

AU - Serino, Francesco Saverio

AU - Tsilika, Maria

AU - Bakakos, Petros

AU - Nicastri, Emanuele

AU - Tzavara, Vassiliki

AU - Kostis, Evangelos

AU - Dagna, Lorenzo

AU - Koufargyris, Panagiotis

AU - Dimakou, Katerina

AU - Savvanis, Spyridon

AU - Tzatzagou, Glykeria

AU - Chini, Maria

AU - Cavalli, Giulio

AU - Bassetti, Matteo

AU - Katrini, Konstantina

AU - Kotsis, Vasileios

AU - Tsoukalas, George

AU - Selmi, Carlo

AU - Bliziotis, Ioannis

AU - Samarkos, Michael

AU - Doumas, Michael

AU - Ktena, Sofia

AU - Masgala, Aikaterini

AU - Papanikolaou, Ilias

AU - Kosmidou, Maria

AU - Myrodia, Dimitra-Melia

AU - Argyraki, Aikaterini

AU - Cardellino, Chiara Simona

AU - Koliakou, Katerina

AU - Katsigianni, Eleni-Ioanna

AU - Rapti, Vassiliki

AU - Giannitsioti, Efthymia

AU - Cingolani, Antonella

AU - Micha, Styliani

AU - Akinosoglou, Karolina

AU - Liatsis-Douvitsas, Orestis

AU - Symbardi, Styliani

AU - Gatselis, Nikolaos

AU - Mouktaroudi, Maria

AU - Ippolito, Giuseppe

AU - Florou, Eleni

AU - Kotsaki, Antigone

AU - Netea, Mihai G

AU - Eugen-Olsen, Jesper

AU - Kyprianou, Miltiades

AU - Panagopoulos, Periklis

AU - Dalekos, George N

AU - Giamarellos-Bourboulis, Evangelos J

N1 - © 2021. The Author(s).

PY - 2021/10

Y1 - 2021/10

N2 - Early increase of soluble urokinase plasminogen activator receptor (suPAR) serum levels is indicative of increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure. The SAVE-MORE double-blind, randomized controlled trial evaluated the efficacy and safety of anakinra, an IL-1α/β inhibitor, in 594 patients with COVID-19 at risk of progressing to respiratory failure as identified by plasma suPAR ≥6 ng ml-1, 85.9% (n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26-0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P < 0.0001); the respective median decrease of Sequential Organ Failure Assessment (SOFA) score on day 7 from baseline was 0 and 1 points (OR = 0.63, P = 0.004). Twenty-eight-day mortality decreased (hazard ratio = 0.45, P = 0.045), and hospital stay was shorter.

AB - Early increase of soluble urokinase plasminogen activator receptor (suPAR) serum levels is indicative of increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure. The SAVE-MORE double-blind, randomized controlled trial evaluated the efficacy and safety of anakinra, an IL-1α/β inhibitor, in 594 patients with COVID-19 at risk of progressing to respiratory failure as identified by plasma suPAR ≥6 ng ml-1, 85.9% (n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26-0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P < 0.0001); the respective median decrease of Sequential Organ Failure Assessment (SOFA) score on day 7 from baseline was 0 and 1 points (OR = 0.63, P = 0.004). Twenty-eight-day mortality decreased (hazard ratio = 0.45, P = 0.045), and hospital stay was shorter.

KW - Aged

KW - COVID-19/drug therapy

KW - Double-Blind Method

KW - Female

KW - Humans

KW - Interleukin 1 Receptor Antagonist Protein/adverse effects

KW - Male

KW - Middle Aged

KW - Placebos

KW - Receptors, Urokinase Plasminogen Activator/blood

KW - SARS-CoV-2/isolation & purification

UR - http://www.scopus.com/inward/record.url?scp=85114635853&partnerID=8YFLogxK

U2 - 10.1038/s41591-021-01499-z

DO - 10.1038/s41591-021-01499-z

M3 - Journal article

C2 - 34480127

VL - 27

SP - 1752

EP - 1760

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 10

ER -

ID: 67609433