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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

Title: Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial
Authors: 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.; Nicastri E.; Tzavara V.; Kostis E.; Dagna L.; Koufargyris P.; Dimakou K.; Savvanis S.; Tzatzagou G.; Chini M.; Cavalli Giulio.; 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 C. S.; 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 M. G.; Eugen-Olsen J.; Kyprianou M.; Panagopoulos P.; Dalekos G. N.; Giamarellos-Bourboulis E. J.
Contributors: 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.; Nicastri, E.; Tzavara, V.; Kostis, E.; Dagna, L.; Koufargyris, P.; Dimakou, K.; Savvanis, S.; Tzatzagou, G.; Chini, M.; Cavalli, Giulio.; 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, C. S.; 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, M. G.; Eugen-Olsen, J.; Kyprianou, M.; Panagopoulos, P.; Dalekos, G. N.; Giamarellos-Bourboulis, E. J.
Publisher Information: Nature Research
Publication Year: 2021
Subject Terms: Aged; COVID-19; Double-Blind Method; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Male; Middle Aged; Placebos; Receptors; Urokinase Plasminogen Activator; SARS-CoV-2
Description: 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.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/wos/WOS:000692308000001; volume:27; issue:10; firstpage:1752; lastpage:1760; numberofpages:9; journal:NATURE MEDICINE; https://hdl.handle.net/20.500.11768/126281
DOI: 10.1038/s41591-021-01499-z
Availability: https://hdl.handle.net/20.500.11768/126281; https://doi.org/10.1038/s41591-021-01499-z
Rights: info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.D85B7E7D
Database: BASE