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

Evdoxia Kyriazopoulou, Garyfallia Poulakou, Haralampos Milionis, Simeon Metallidis, Georgios Adamis, Konstantinos Tsiakos, Archontoula Fragkou, Aggeliki Rapti, Christina Damoulari, Massimo Fantoni, Ioannis Kalomenidis, Georgios Chrysos, Andrea Angheben, Ilias Kainis, Zoi Alexiou, Francesco Castelli, Francesco Saverio Serino, Maria Tsilika, Petros Bakakos, Emanuele NicastriVassiliki Tzavara, Evangelos Kostis, Lorenzo Dagna, Panagiotis Koufargyris, Katerina Dimakou, Spyridon Savvanis, Glykeria Tzatzagou, Maria Chini, Giulio Cavalli, Matteo Bassetti, Konstantina Katrini, Vasileios Kotsis, George Tsoukalas, Carlo Selmi, Ioannis Bliziotis, Michael Samarkos, Michael Doumas, Sofia Ktena, Aikaterini Masgala, Ilias Papanikolaou, Maria Kosmidou, Dimitra Melia Myrodia, Aikaterini Argyraki, Chiara Simona Cardellino, Katerina Koliakou, Eleni Ioanna Katsigianni, Vassiliki Rapti, Efthymia Giannitsioti, Antonella Cingolani, Styliani Micha, Karolina Akinosoglou, Orestis Liatsis-Douvitsas, Styliani Symbardi, Nikolaos Gatselis, Maria Mouktaroudi, Giuseppe Ippolito, Eleni Florou, Antigone Kotsaki, Mihai G. Netea, Jesper Eugen-Olsen, Miltiades Kyprianou, Periklis Panagopoulos, George N. Dalekos, Evangelos J. Giamarellos-Bourboulis

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalNature Medicine
DOIs
Publication statusAccepted/In press - 2021

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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