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

Nat Med. 2021 Oct;27(10):1752-1760. doi: 10.1038/s41591-021-01499-z. Epub 2021 Sep 3.

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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • COVID-19 / virology
  • COVID-19 Drug Treatment*
  • Double-Blind Method
  • Female
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / adverse effects
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use*
  • Male
  • Middle Aged
  • Placebos
  • Receptors, Urokinase Plasminogen Activator / blood*
  • SARS-CoV-2 / isolation & purification

Substances

  • Interleukin 1 Receptor Antagonist Protein
  • Placebos
  • Receptors, Urokinase Plasminogen Activator