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

[tetano]

Nat Med


. 2021 Sep 3.
doi: 10.1038/s41591-021-01499-z. Online ahead of print.
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 ¹ , Garyfallia Poulakou ² , Haralampos Milionis ³ , Simeon Metallidis ⁴ , Georgios Adamis ⁵ , Konstantinos Tsiakos ⁶ , Archontoula Fragkou ⁷ , Aggeliki Rapti ⁶ , Christina Damoulari ¹ , Massimo Fantoni ⁸ , Ioannis Kalomenidis ⁹ , Georgios Chrysos ¹⁰ , Andrea Angheben ¹¹ , Ilias Kainis ¹² , Zoi Alexiou ¹³ , Francesco Castelli ¹⁴ , Francesco Saverio Serino ¹⁵ , Maria Tsilika ¹ , Petros Bakakos ¹⁶ , Emanuele Nicastri ¹⁷ , Vassiliki Tzavara ¹⁸ , Evangelos Kostis ¹⁹ , Lorenzo Dagna ²⁰ , Panagiotis Koufargyris ¹ , Katerina Dimakou ²¹ , Spyridon Savvanis ⁷ , Glykeria Tzatzagou ²² , Maria Chini ²³ , Giulio Cavalli ²⁰ , Matteo Bassetti ²⁴ , Konstantina Katrini ¹ , Vasileios Kotsis ²⁵ , George Tsoukalas ²⁶ , Carlo Selmi ²⁷ , Ioannis Bliziotis ²⁸ , Michael Samarkos ²⁹ , Michael Doumas ³⁰ , Sofia Ktena ¹ , Aikaterini Masgala ³¹ , Ilias Papanikolaou ³² , Maria Kosmidou ³ , Dimitra-Melia Myrodia ² , Aikaterini Argyraki ³³ , Chiara Simona Cardellino ¹¹ , Katerina Koliakou ³⁴ , Eleni-Ioanna Katsigianni ³⁴ , Vassiliki Rapti ² , Efthymia Giannitsioti ¹⁰ , Antonella Cingolani ⁸ , Styliani Micha ³⁴ , Karolina Akinosoglou ³⁵ , Orestis Liatsis-Douvitsas ³⁴ , Styliani Symbardi ³⁶ , Nikolaos Gatselis ³⁷ , Maria Mouktaroudi ^{1 34} , Giuseppe Ippolito ¹⁷ , Eleni Florou ³⁴ , Antigone Kotsaki ¹ , Mihai G Netea ^{38 39} , Jesper Eugen-Olsen ⁴⁰ , Miltiades Kyprianou ³⁴ , Periklis Panagopoulos ⁴¹ , George N Dalekos ³⁷ , Evangelos J Giamarellos-Bourboulis ^{42 43}



Affiliations

• PMID: 34480127
• DOI: 10.1038/s41591-021-01499-z

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.