TY - JOUR
T1 - Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: 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.
PY - 2021
Y1 - 2021
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 - COVID-19 / virology
KW - COVID-19 / virology
UR - http://hdl.handle.net/10807/302540
U2 - 10.1038/s41591-021-01499-z
DO - 10.1038/s41591-021-01499-z
M3 - Article
SN - 1546-170X
VL - 27
SP - 1752
EP - 1760
JO - Nature Medicine
JF - Nature Medicine
ER -