Internal medicine

Pathology

Randomized controlled trial

Clinical endpoint

Alternative medicine

Placebo

Systemic inflammation

Inflammation

Mechanical ventilation

Pneumonia

Disease

Canakinumab

Anakinra

Coronavirus disease 2019 (COVID-19)

Infectious disease (medical specialty)

Medicine

JAMA

<h3>Importance</h3> Effective treatments for patients with severe COVID-19 are needed. <h3>Objective</h3> To evaluate the efficacy of canakinumab, an anti–interleukin-1β antibody, in patients hospitalized with severe COVID-19. <h3>Design, Setting, and Participants</h3> 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. <h3>Intervention</h3> Patients were randomly assigned 1:1 to receive a single intravenous infusion of canakinumab (450 mg for body weight of 40-&lt;60 kg, 600 mg for 60-80 kg, and 750 mg for &gt;80 kg; n = 227) or placebo (n = 227). <h3>Main Outcomes and Measures</h3> The primary outcome was survival without IMV from day 3 to day 29. Secondary outcomes were COVID-19–related mortality, measurements of biomarkers of systemic hyperinflammation, and safety evaluations. <h3>Results</h3> 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, −3.1% to 9.3%) and an odds ratio of 1.39 (95% CI, 0.76 to 2.54;<i>P</i> = .29). COVID-19–related 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 −2.3% (95% CI, −6.7% 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. <h3>Conclusions and Relevance</h3> 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. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT04362813

Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19