Nature Medicine publication:

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

An early increase of suPAR serum levels indicates an increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure.

Key highlights from the study

• Results showed a 70% decrease in the relative risk of progression to severe respiratory failure and a significant reduction in 28-d mortality with anakinra treatment compared to standard of care.
• Relative decrease of mortality was 55%, reaching 80% for patients with cytokine storm.
• Average time until hospital and intensive care unit (ICU) discharge was reduced by one to four days.

Method

From 23 December 2020 to 31 March 2021, 1,060 patients positively diagnosed with Covid-19 were screened, and 594 (excluding those at low risk based on low suPAR results) were randomized at 37 study sites. The SAVE-MORE study, conducted by the Hellenic Institute for the Study of Sepsis, is the first large, pivotal randomized controlled trial to specifically evaluate a patient population triaged, when at risk of progressing to a critical state using suPARnostic®. The study demonstrates the considerable benefit of earlier intervention for the prevention of disease progression and death.
189 patients were allocated to the placebo arm, and 405 patients were allocated to the anakinra arm. Baseline characteristics and co-administered treatments were similar between the two treatment arms. Overall, 91.6% of patients had severe pneumonia as defined by the WHO classification for COVID-19. On day 28, the adjusted proportional odds of having a worse clinical status with anakinra, as compared to placebo, was 0.36. Twenty-eight-day mortality decreased, and hospital stay was shorter.