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

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 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.