ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients

  1. Eleni Karakike
  2. George N. Dalekos
  3. Ioannis Koutsodimitropoulos
  4. Maria Saridaki
  5. Chryssa Pourzitaki
  6. Georgios Papathanakos
  7. Antigone Kotsaki
  8. Stamatios Chalvatzis
  9. Vasiliki Dimakopoulou
  10. Nikolaos Vechlidis
  11. Elisabeth Paramythiotou
  12. Christina Avgoustou
  13. Aikaterini Ioakeimidou
  14. Elli Kouriannidi
  15. Apostolos Komnos
  16. Evangelia Neou
  17. Nikoletta Rovina
  18. Eleni Stefanatou
  19. Haralampos Milionis
  20. George Nikolaidis
  21. Antonia Koutsoukou
  22. Georgia Damoraki
  23. George Dimopoulos
  24. Vassileios Zoumpos
  25. Jesper Eugen-Olsen
  26. Karolina Akinosoglou
  27. Nikolaos K. Gatselis
  28. Vasilios Koulouras
  29. Eleni Gkeka
  30. Nikolaos Markou
  31. Mihai G. Netea
  32. Evangelos J. Giamarellos-Bourboulis

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Abstract

<b><i>Background:</i></b> Macrophage activation-like syndrome (MALS) and complex immune dysregulation (CID) often underlie acute respiratory distress (ARDS) in COVID-19. We aimed to investigate the effect of personalized immunotherapy on clinical improvement of critical COVID-19. <b><i>Methods:</i></b> In this open-label prospective trial, 102 patients with ARDS by SARS-CoV-2 were screened for MALS (ferritin &#x3e;4,420 ng/mL) and CID (ferritin ≤4,420 ng/mL and low human leukocyte antigen (HLA)-DR expression on CD14-monocytes). Patients with MALS or CID with increased aminotransferases received intravenous anakinra; those with CID and normal aminotransferases received tocilizumab. The primary outcome was ≥25% decrease in the Sequential Organ Failure Assessment (SOFA) score and/or 50% increase in the respiratory ratio by day 8; 28-day mortality, change of SOFA score by day 28, serum biomarkers, and cytokine production by mononuclear cells were secondary endpoints. <b><i>Results:</i></b> The primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (<i>p</i>: 0.01). Most patients in both groups received dexamethasone as standard of care. No differences were found in secondary outcomes, mortality, and SOFA score changes. Ferritin decreased among anakinra-treated patients; interleukin-6, soluble urokinase plasminogen activator receptor, and HLA-DR expression increased among tocilizumab-treated patients. Survivors by day 28 who received anakinra were distributed to lower severity levels of the WHO clinical progression scale. Greater incidence of secondary infections was found with tocilizumab treatment. <b><i>Conclusion:</i></b> Immune assessment resulted in favorable anakinra responses among critically ill patients with COVID-19 and features of MALS<i>.</i>

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  1. Version published to 10.1159/000519090
  2. ScreenIT

    SciScore for 10.1101/2021.01.20.21250182: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: ESCAPE was an open-label phase II prospective clinical trial conducted in four departments of Internal Medicine and seven Intensive Care Units (ICUs) of tertiary hospitals in Greece between April and November 2020 (EudraCT number 2020-001039-29; Clinicaltrials.gov NCT04339712; approval 30/20 by the National Ethics Committee of Greece; approval IS 021-20 by the National Organization for Medicines of Greece).
    Consent: Enrolled patients were adults of both genders with written informed consent provided by legal representatives; organ dysfunction; and laboratory findings of MAS or CID.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisThe study was exploratory and no power calculation was done.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    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
    NCT04339712CompletedPersonalised Immunotherapy for SARS-CoV-2 (COVID-19) Associa…

    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

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  3. Version published to 10.1101/2021.01.20.21250182v1 on medRxiv