A single center, double blind, randomized, placebo controlled trial of anakinra in adult patients with features of Cytokine Storm Syndrome in COVID-19

(, NCT04362111) Adult inpatients were recruited with PCR confirmed SARS-CoV-2 infection, radiographic confirmation of COVID-19 pneumonia, new or increasing oxygen requirement, ferritin ≥700 ng/mL, and any 3 of the following: D-dimer ≥500 ng/mL, platelet count lt;130,000/mm3, white blood cell count lt;3500/mm3 or lymphocyte count lt;1000/mm3, AST or ALT gt;2X the upper limit of normal (ULN), LDH gt;2X the ULN, C-reactive protein gt;100 mg/L. Eligible patients were randomly assigned (1:1) to standard of care (SoC) plus anakinra (100 mg subcutaneous every 6 hours for 10 days) or SoC plus placebo. Primary outcome was survival and discharge from the hospital without need for intubation/mechanical ventilation at day 10. Analyses were done on a modified intention-to-treat basis.

Between August 2020 and January 2021, 32 patients (235 screened) were recruited: 15 assigned to anakinra group and 17 to placebo group. 2 patients in the placebo group withdrew in the initial 48 hours and were excluded from analysis. Median age was 63 years (IQR 56 – 70.3), 20 (66.7%) were men, and 20 (66.7%) Caucasian. At day 10, 1 (6.7%) patient in the anakinra group had died and 2 (13.3%) in the placebo group had died (p=0.54). At hospital discharge, 4 (26.7%) patients in the anakinra group and 4 (26.7%) in the SoC group had died. Confirmed infections occurred in 4 (anakinra) and 2 (placebo), respectively (p=0.36).

Anakinra added to SoC with dexamethasone did not significantly impact outcomes in study patients with clinical lab features of early cytokine storm syndrome and mild-to-moderate COVID-19 pneumonia. Additional studies are needed to assess efficacy and optimal dosing duration of anakinra in patients with more severe COVID-19.
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