Effect of anti-interleukin drugs in patients with COVID-19 and signs of cytokine release syndrome (COV-AID): a factorial, randomised, controlled trial.
peer reviewed ; BACKGROUND: Infections with SARS-CoV-2 continue to cause significant morbidity and mortality. Interleukin (IL)-1 and IL-6 blockade have been proposed as therapeutic strategies in COVID-19, but study outcomes have been conflicting. We sought to study whether blockade of the IL-6 or IL-1 pathway shortened the time to clinical improvement in patients with COVID-19, hypoxic respiratory failure, and signs of systemic cytokine release syndrome. METHODS: We did a prospective, multicentre, open-label, randomised, controlled trial, in hospitalised patients with COVID-19, hypoxia, and si... Mehr ...
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Dokumenttyp: | journal article |
Erscheinungsdatum: | 2021 |
Verlag/Hrsg.: |
Elsevier
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Schlagwörter: | Aged / Antibodies / Monoclonal/therapeutic use / Monoclonal / Humanized/therapeutic use / Belgium / COVID-19/drug therapy / Cytokine Release Syndrome/drug therapy/virology / Female / Ferritins / Humans / Hypoxia / Interleukin-1/antagonists & inhibitors / Interleukin-6/antagonists & inhibitors / Male / Middle Aged / Oxygen / Prospective Studies / Respiratory Insufficiency/drug therapy/virology / SARS-CoV-2 / Treatment Outcome / Human health sciences / Anesthesia & intensive care / Sciences de la santé humaine / Anesthésie & soins intensifs |
Sprache: | Englisch |
Permalink: | https://search.fid-benelux.de/Record/base-28534768 |
Datenquelle: | BASE; Originalkatalog |
Powered By: | BASE |
Link(s) : | https://orbi.uliege.be/handle/2268/268482 |
peer reviewed ; BACKGROUND: Infections with SARS-CoV-2 continue to cause significant morbidity and mortality. Interleukin (IL)-1 and IL-6 blockade have been proposed as therapeutic strategies in COVID-19, but study outcomes have been conflicting. We sought to study whether blockade of the IL-6 or IL-1 pathway shortened the time to clinical improvement in patients with COVID-19, hypoxic respiratory failure, and signs of systemic cytokine release syndrome. METHODS: We did a prospective, multicentre, open-label, randomised, controlled trial, in hospitalised patients with COVID-19, hypoxia, and signs of a cytokine release syndrome across 16 hospitals in Belgium. Eligible patients had a proven diagnosis of COVID-19 with symptoms between 6 and 16 days, a ratio of the partial pressure of oxygen to the fraction of inspired oxygen (PaO(2):FiO(2)) of less than 350 mm Hg on room air or less than 280 mm Hg on supplemental oxygen, and signs of a cytokine release syndrome in their serum (either a single ferritin measurement of more than 2000 μg/L and immediately requiring high flow oxygen or mechanical ventilation, or a ferritin concentration of more than 1000 μg/L, which had been increasing over the previous 24 h, or lymphopenia below 800/mL with two of the following criteria: an increasing ferritin concentration of more than 700 μg/L, an increasing lactate dehydrogenase concentration of more than 300 international units per L, an increasing C-reactive protein concentration of more than 70 mg/L, or an increasing D-dimers concentration of more than 1000 ng/mL). The COV-AID trial has a 2 × 2 factorial design to evaluate IL-1 blockade versus no IL-1 blockade and IL-6 blockade versus no IL-6 blockade. Patients were randomly assigned by means of permuted block randomisation with varying block size and stratification by centre. In a first randomisation, patients were assigned to receive subcutaneous anakinra once daily (100 mg) for 28 days or until discharge, or to receive no IL-1 blockade (1:2). In a second randomisation step, ...