학술논문
Efficacy and safety of early soluble urokinase plasminogen receptor plasma-guided anakinra treatment of COVID-19 pneumonia: a subgroup analysis of the SAVE-MORE randomised trialResearch in context
Document Type
article
Author
Karolina Akinosoglou; Antigone Kotsaki; Ioanna-Maria Gounaridi; Eirini Christaki; Simeon Metallidis; Georgios Adamis; Archontoula Fragkou; Massimo Fantoni; Aggeliki Rapti; Ioannis Kalomenidis; Georgios Chrysos; Gloria Boni; Ilias Kainis; Zoi Alexiou; Francesco Castelli; Francesco Saverio Serino; Petros Bakakos; Emanuele Nicastri; Vassiliki Tzavara; Asimina Safarika; Sofia Ioannou; Lorenzo Dagna; Katerina Dimakou; Glykeria Tzatzagou; Maria Chini; Matteo Bassetti; Vasileios Kotsis; Andrea Angheben; George Tsoukalas; Carlo Selmi; Olga-Maria Spiropoulou; Michael Samarkos; Michael Doumas; Georgia Damoraki; Aikaterini Masgala; Ilias Papanikolaou; Aikaterini Argyraki; Marcantonio Negri; Konstantinos Leventogiannis; Styliani Sympardi; Nikolaos K. Gatselis; Vasileios Petrakis; Mihai G. Netea; Periklis Panagopoulos; Vissaria Sakka; Haralampos Milionis; George N. Dalekos; Evangelos J. Giamarellos-Bourboulis
Source
EClinicalMedicine, Vol 56, Iss , Pp 101785- (2023)
Subject
Language
English
ISSN
2589-5370
Abstract
Summary: Background: The SAVE-MORE trial demonstrated that anakinra treatment in COVID-19 pneumonia with plasma soluble urokinase plasminogen activator (suPAR) levels of 6 ng/mL or more was associated with 0.36 odds for a worse outcome compared to placebo when expressed by the WHO-Clinical Progression Scale (CPS) at day 28. Herein, we report the results of subgroup analyses and long-term outcomes. Methods: This prospective, double-blind, randomised clinical trial, recruited patients with a confirmed SARS-CoV-2 infection, in need of hospitalisation, lower respiratory tract infection and plasma suPAR ≥6 ng/mL from 37 academic and community hospitals in Greece and Italy. Patients were 1:2 randomised to subcutaneous treatment with placebo or anakinra (100 mg) once daily for 10 days. Pre-defined subgroups of Charlson's comorbidity index (CCI), sex, age, level of suPAR, and time from symptom onset were analysed for the primary endpoint (overall comparison of distribution of frequencies of the scores from the WHO-CPS between treatments on day 28), by multivariable ordinal regression analysis in the intention to treat (ITT) population. This trial is registered with the EU Clinical Trials Register (2020-005828-11) and ClinicalTrials.gov (NCT04680949). Findings: Patients were enrolled between 23 December 2020 and 31 March 2021; 189 patients in the placebo arm and 405 patients in the anakinra arm were the ITT population. Multivariable analysis showed that anakinra treatment was accompanied by significantly lower odds for worse outcome compared to placebo at day 28 for all studied subgroups (CCI ≥ 2, OR: 0.34, 95% confidence intervals [CI] 0.22–0.50; CCI < 2, OR: 0.38, 95% CI 0.21–0.68; suPAR > 9 ng/mL, OR: 0.35, 95% CI 0.19–0.66; suPAR 6–9 ng/mL, OR: 0.35, 95% CI 0.24–0.52; patients ≥65 years, OR: 0.41, 95% CI 0.25–0.66; and patients