Early Anakinra Treatment for COVID-19 Guided by Urokinase Plasminogen Receptor
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<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://ClinicalTrials.gov">ClinicalTrials.gov</jats:ext-link>identifier,<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04680949">NCT04680949</jats:ext-link>).
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
bioRxiv.org - (2022) vom: 27. Dez. Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2021.05.16.21257283 |
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| PPN (Katalog-ID): |
XBI020571143 |
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| 520 | |a 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<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://ClinicalTrials.gov">ClinicalTrials.gov</jats:ext-link>identifier,<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04680949">NCT04680949</jats:ext-link>) | ||
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