Trial Design and Oversight
death
COVID-19 PNEUMONIA, CYTOKINE STORM SYNDROME
This study was performed in accordance with the Declaration of Helsinki,The Clinical Trial of the Use of Anakinra in Cytokine Storm Syndrome Secondary to COVID-19 (ANA-COVID-GEAS) study was a multicenter, randomized, open-label, 2-group, phase 2/3 clinical trial designed to assess the clinical outcomes and safety of anakinra plus SoC (anakinra group) vs SoC alone (SoC group) in patients with severe COVID-19 pneumonia. The trial was decentralized and conducted at 12 hospitals in Spain (see the list of participating centers in eAppendix 1 in Participants were randomly assigned to receive either SoC plus anakinra (anakinra group) or SoC alone (SoC group) in 1:1 proportion. A computer-generated randomization list with permuted blocks of sizes of 10 and 12 was generated by statisticians of the Methodology Unit of Navarrabiomed using the randomizeR library of the R statistical package version 3.4.0 (R Project for Statistical Computing). Allocation sequencing was stratified and concealed by center to guarantee balance between groups within center. A web-based electronic case report form was used for the assignment. The trial participants and investigators and the statisticians who conducted the analysis were not masked to treatment assignment.Anakinra was given intravenously (100 mg 4 times a day) for a maximum of 15 days according to clinical response based on the following criteria: the need for hospital beds given the hospital pressure during the first waves of the pandemic, the persistence of elevated inflammatory markers, the persistence of pneumonic condensation on radiologic images, or the fact that some patients continued to require oxygen therapy and were transferred home under hospitalization at home protocols. The SoC included hydroxychloroquine, lopinavir-ritonavir, and/or azithromycin. Intravenous methylprednisolone pulse therapy was permitted at any time during the study.Patients were monitored during the hospital stay and then were followed up for 28 days after randomization or until premature withdrawal from the study, loss to follow-up, or death, whichever occurred first. Assessments at randomization (day 1) included vital signs, lung function, and laboratory test parameters. After treatment allocation, clinical and laboratory test parameters were assessed in the hospital on days 4, 7, and 15 and by telephone at day 28 if discharged. Details of the trial conduct and procedures can be found in eAppendix 2 of 