Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19: A Randomized Clinical Trial

IMPORTANCE: Effective treatments for patients with severe COVID-19 are needed. OBJECTIVE: To evaluate the efficacy of canakinumab, an anti–interleukin-1β antibody, in patients hospitalized with severe COVID-19. DESIGN, SETTING, AND PARTICIPANTS: This randomized, double-blind, placebo-controlled phas...

Full description

Saved in:

Bibliographic Details
Published in:	JAMA : the journal of the American Medical Association Vol. 326; no. 3; pp. 230 - 239
Main Authors:	Caricchio, Roberto, Abbate, Antonio, Gordeev, Ivan, Meng, Jamie, Hsue, Priscilla Y, Neogi, Tuhina, Arduino, Roberto, Fomina, Daria, Bogdanov, Roman, Stepanenko, Tatiana, Ruiz-Seco, Pilar, Gónzalez-García, Andrés, Chen, Yu, Li, Yuhan, Whelan, Sarah, Noviello, Stephanie
Format:	Journal Article
Language:	English
Published:	United States American Medical Association 20-07-2021
Subjects:	Adverse events Aged Antibodies Antibodies, Monoclonal, Humanized - adverse effects Antibodies, Monoclonal, Humanized - therapeutic use Biomarkers Body weight C-reactive protein C-Reactive Protein - analysis Clinical trials Combined Modality Therapy Coronaviruses COVID-19 COVID-19 - drug therapy COVID-19 - mortality COVID-19 - therapy Double-Blind Method Double-blind studies Evaluation Female Ferritin Ferritins - blood Fibrin Fibrinogen Degradation Products - analysis Hospitalization Humans Hypoxia IL-1β Interleukin-1beta - antagonists & inhibitors Interleukins Intravenous administration Intravenous infusion Kaplan-Meier Estimate Male Mechanical ventilation Middle Aged Monoclonal antibodies Mortality Original Investigation Patients Placebos Respiration, Artificial - statistics & numerical data Survival Survival Rate Treatment Outcome Ventilation
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	IMPORTANCE: Effective treatments for patients with severe COVID-19 are needed. OBJECTIVE: To evaluate the efficacy of canakinumab, an anti–interleukin-1β antibody, in patients hospitalized with severe COVID-19. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTION: 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 = 227) or placebo (n = 227). MAIN OUTCOMES AND MEASURES: 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. RESULTS: 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; P = .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. CONCLUSIONS AND RELEVANCE: 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04362813
ISSN:	0098-7484 1538-3598
DOI:	10.1001/jama.2021.9508