Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19: A Randomized Clinical Trial<\/h1>\n\n\n\n
Importance<\/strong>\u00a0\u00a0Effective treatments for patients with severe COVID-19 are needed.<\/p>\n\n\n\n
Objective<\/strong>\u00a0\u00a0To evaluate the efficacy of canakinumab, an anti\u2013interleukin-1\u03b2 antibody, in patients hospitalized with severe COVID-19.<\/p>\n\n\n\n
Design, Setting, and Participants<\/strong> This randomized, double-blind, placebo-controlled phase 3 trial was conducted at 39 hospitals in Europe and the United States. A total of 454 hospitalized patients with COVID-19 pneumonia, hypoxia (not requiring invasive mechanical ventilation [IMV]), and systemic hyperinflammation defined by increased blood concentrations of C-reactive protein or ferritin were enrolled between April 30 and August 17, 2020, with the last assessment of the primary end point on September 22, 2020.<\/p>\n\n\n\n
Intervention<\/strong> Patients were randomly assigned 1:1 to receive a single intravenous infusion of canakinumab (450 mg for body weight of 40-<60 kg, 600 mg for 60-80 kg, and 750 mg for >80 kg; n\u2009=\u2009227) or placebo (n\u2009=\u2009227).<\/p>\n\n\n\n
Main Outcomes and Measures<\/strong> The primary outcome was survival without IMV from day 3 to day 29. Secondary outcomes were COVID-19\u2013related mortality, measurements of biomarkers of systemic hyperinflammation, and safety evaluations.<\/p>\n\n\n\n
Results<\/strong> Among 454 patients who were randomized (median age, 59 years; 187 women [41.2%]), 417 (91.9%) completed day 29 of the trial. Between days 3 and 29, 198 of 223 patients (88.8%) survived without requiring IMV in the canakinumab group and 191 of 223 (85.7%) in the placebo group, with a rate difference of 3.1% (95% CI, \u22123.1% to 9.3%) and an odds ratio of 1.39 (95% CI, 0.76 to 2.54; P<\/em>\u2009=\u2009.29). COVID-19\u2013related mortality occurred in 11 of 223 patients (4.9%) in the canakinumab group vs 16 of 222 (7.2%) in the placebo group, with a rate difference of \u22122.3% (95% CI, \u22126.7% to 2.2%) and an odds ratio of 0.67 (95% CI, 0.30 to 1.50). Serious adverse events were observed in 36 of 225 patients (16%) treated with canakinumab vs 46 of 223 (20.6%) who received placebo.<\/p>\n\n\n\n<\/figure>\n\n\n\n
Conclusions and Relevance<\/strong> Among patients hospitalized with severe COVID-19, treatment with canakinumab, compared with placebo, did not significantly increase the likelihood of survival without IMV at day 29.<\/p>\n\n\n\n
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