An open label trial of anakinra to prevent respiratory failure in COVID-19

  1. Evdoxia Kyriazopoulou
  2. Periklis Panagopoulos
  3. Symeon Metallidis
  4. George N Dalekos
  5. Garyphallia Poulakou
  6. Nikolaos Gatselis
  7. Eleni Karakike
  8. Maria Saridaki
  9. Georgia Loli
  10. Aggelos Stefos
  11. Danai Prasianaki
  12. Sarah Georgiadou
  13. Olga Tsachouridou
  14. Vasileios Petrakis
  15. Konstantinos Tsiakos
  16. Maria Kosmidou
  17. Vassiliki Lygoura
  18. Maria Dareioti
  19. Haralampos Milionis
  20. Ilias C Papanikolaou
  21. Karolina Akinosoglou
  22. Dimitra-Melia Myrodia
  23. Areti Gravvani
  24. Aliki Stamou
  25. Theologia Gkavogianni
  26. Konstantina Katrini
  27. Theodoros Marantos
  28. Ioannis P Trontzas
  29. Konstantinos Syrigos
  30. Loukas Chatzis
  31. Stamatios Chatzis
  32. Nikolaos Vechlidis
  33. Christina Avgoustou
  34. Stamatios Chalvatzis
  35. Miltiades Kyprianou
  36. Jos WM van der Meer
  37. Jesper Eugen-Olsen
  38. Mihai G Netea
  39. Evangelos J Giamarellos-Bourboulis

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Abstract

It was studied if early suPAR-guided anakinra treatment can prevent severe respiratory failure (SRF) of COVID-19.

Methods:

A total of 130 patients with suPAR ≥6 ng/ml were assigned to subcutaneous anakinra 100 mg once daily for 10 days. Primary outcome was SRF incidence by day 14 defined as any respiratory ratio below 150 mmHg necessitating mechanical or non-invasive ventilation. Main secondary outcomes were 30-day mortality and inflammatory mediators; 28-day WHO-CPS was explored. Propensity-matched standard-of care comparators were studied.

Results:

22.3% with anakinra treatment and 59.2% comparators (hazard ratio, 0.30; 95% CI, 0.20–0.46) progressed into SRF; 30-day mortality was 11.5% and 22.3% respectively (hazard ratio 0.49; 95% CI 0.25–0.97). Anakinra was associated with decrease in circulating interleukin (IL)−6, sCD163 and sIL2-R; IL-10/IL-6 ratio on day 7 was inversely associated with SOFA score; patients were allocated to less severe WHO-CPS strata.

Conclusions:

Early suPAR-guided anakinra decreased SRF and restored the pro-/anti-inflammatory balance.

Funding:

This study was funded by the Hellenic Institute for the Study of Sepsis, Technomar Shipping Inc, Swedish Orphan Biovitrum, and the Horizon 2020 Framework Programme.

Clinical trial number:

NCT04357366 .

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  1. Version published to 10.7554/elife.66125 on eLife
  2. ScreenIT

    SciScore for 10.1101/2020.10.28.20217455: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: Trial oversight: SAVE is an ongoing open-label non-randomized trial conducted in six study sites in Greece (EudraCT number 2020-001466-11; National Ethics Committee approval 38/20; National Organization for Medicines approval ISO 28/20;
    Consent: Written informed consent was provided by the patient or legal representative before screening.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisTo achieve so with 90% power at the 5% level of significance, 260 patients were needed.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Trial oversight: SAVE is an ongoing open-label non-randomized trial conducted in six study sites in Greece (EudraCT number 2020-001466-11; National Ethics Committee approval 38/20; National Organization for Medicines approval ISO 28/20;
    SAVE
    suggested: (SAVES, RRID:SCR_018219)
    Comparison with anakinra-treated patients was performed by the Fisher’s exact test using confirmatory forward stepwise Cox analysis (IBM SPSS Statistics v. 25.0).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04357366RecruitingsuPAR-guided Anakinra Treatment for Validation of the Risk a…

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.10.28.20217455 on medRxiv