Early Anakinra Treatment for COVID-19 Guided by Urokinase Plasminogen Receptor

  1. Evdoxia Kyriazopoulou
  2. Garyfallia Poulakou
  3. Haralampos Milionis
  4. Simeon Metallidis
  5. Georgios Adamis
  6. Konstantinos Tsiakos
  7. Archontoula Fragkou
  8. Aggeliki Rapti
  9. Christina Damoulari
  10. Massimo Fantoni
  11. Ioannis Kalomenidis
  12. Georgios Chrysos
  13. Andrea Angheben
  14. Ilias Kainis
  15. Zoi Alexiou
  16. Francesco Castelli
  17. Francesco Saverio Serino
  18. Petros Bakakos
  19. Emanuele Nicastri
  20. Vassiliki Tzavara
  21. Evangelos Kostis
  22. Lorenzo Dagna
  23. Panagiotis Koufargyris
  24. Katerina Dimakou
  25. Glykeria Tzatzagou
  26. Maria Chini
  27. Matteo Bassetti
  28. Konstantina Katrini
  29. Vasileios Kotsis
  30. George Tsoukalas
  31. Carlo Selmi
  32. Ioannis Bliziotis
  33. Michael Samarkos
  34. Michael Doumas
  35. Sofia Ktena
  36. Aikaterini Masgala
  37. Ilias Papanikolaou
  38. Aikaterini Argyraki
  39. Chiara Simona Cardellino
  40. Eleni-Ioanna Katsigianni
  41. Efthymia Giannitsioti
  42. Antonella Cingolani
  43. Karolina Akinosoglou
  44. Orestis Liatsis-Douvitsas
  45. Styliani Symbardi
  46. Maria Mouktaroudi
  47. Giuseppe Ippolito
  48. Eleni Florou
  49. Antigone Kotsaki
  50. Mihai G. Netea
  51. Jesper Eugen-Olsen
  52. Miltiades Kyprianou
  53. Periklis Panagopoulos
  54. George N. Dalekos
  55. Evangelos J. Giamarellos-Bourboulis
1 evaluations Published on
Read the full article Related papers
This article on Sciety

Abstract

Background

In a previous open-label trial, early anakinra treatment guided by elevated soluble urokinase plasminogen activator receptor (suPAR) prevented progression of COVID-19 pneumonia into respiratory failure.

Methods

In the SAVE-MORE multicenter trial, 594 hospitalized patients with moderate and severe COVID-19 pneumonia and plasma suPAR 6 ng/ml or more and receiving standard-of-care were 1:2 randomized to subcutaneous treatment with placebo or 100 mg anakinra once daily for 10 days. The primary endpoint was the overall clinical status of the 11-point World Health Organization ordinal Clinical Progression Scale (WHO-CPS) at day 28. The changes of the WHO-CPS and of the sequential organ failure assessment (SOFA) score were the main secondary endpoints.

Results

Anakinra-treated patients were distributed to lower strata of WHO-CPS by day 28 (adjusted odds ratio-OR 0.36; 95%CI 0.26-0.50; P<0.001); anakinra protected from severe disease or death (6 or more points of WHO-CPS) (OR: 0.46; P: 0.010). The median absolute decrease of WHO-CPS in the placebo and anakinra groups from baseline was 3 and 4 points respectively at day 28 (OR 0.40; P<0.0001); and 2 and 3 points at day 14 (OR 0.63; P: 0.003); the absolute decrease of SOFA score was 0 and 1 points (OR 0.63; P: 0.004). 28-day mortality decreased (hazard ratio: 0.45; P: 0.045). Hospital stay was shorter.

Conclusions

Early start of anakinra treatment guided by suPAR provides 2.78 times better improvement of overall clinical status in moderate and severe COVID-19 pneumonia.

(Sponsored by the Hellenic Institute for the Study of Sepsis <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://ClinicalTrials.gov">ClinicalTrials.gov</ext-link> identifier, <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04680949">NCT04680949</ext-link> )

Related articles

Related articles are currently not available for this article.