Tags

Type your tag names separated by a space and hit enter

Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19: A Randomized Clinical Trial.
JAMA. 2021 07 20; 326(3):230-239.JAMA

Abstract

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.

Authors+Show Affiliations

Division of Rheumatology, Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond.City Clinical Hospital No. 15 Named After O.M. Filatov, Moscow, Russian Federation.Maimonides Medical Center, Brooklyn, New York.University of California, San Francisco, Zuckerberg San Francisco General Hospital, San Francisco.Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts.McGovern Medical School at The University of Texas Health Science Center at Houston.Center of Allergy and Immunology, Clinical City Hospital No. 52, Moscow, Russian Federation. Department of Allergy and Clinical Immunology, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russian Federation.Therapeutic Department, Aleksandrovskaya Hospital, St Petersburg, Russian Federation.City Multi-specialty Hospital No. 2, St Petersburg, Russian Federation.Unidad Medicina Interna, Hospital Universitario Infanta Sofía, Madrid, Spain.Unidad de Enfermedades Sistémicas Autoinmunes y Minoritarias, Servicio de Medicina Interna, Hospital Ramón y Cajal, Madrid, Spain.Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.Novartis Ireland Ltd, Dublin, Ireland.Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.No affiliation info available

Pub Type(s)

Clinical Trial, Phase III
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34283183

Citation

Caricchio, Roberto, et al. "Effect of Canakinumab Vs Placebo On Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19: a Randomized Clinical Trial." JAMA, vol. 326, no. 3, 2021, pp. 230-239.
Caricchio R, Abbate A, Gordeev I, et al. Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19: A Randomized Clinical Trial. JAMA. 2021;326(3):230-239.
Caricchio, R., Abbate, A., Gordeev, I., Meng, J., Hsue, P. Y., Neogi, T., Arduino, R., Fomina, D., Bogdanov, R., Stepanenko, T., Ruiz-Seco, P., Gónzalez-García, A., Chen, Y., Li, Y., Whelan, S., & Noviello, S. (2021). Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19: A Randomized Clinical Trial. JAMA, 326(3), 230-239. https://doi.org/10.1001/jama.2021.9508
Caricchio R, et al. Effect of Canakinumab Vs Placebo On Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19: a Randomized Clinical Trial. JAMA. 2021 07 20;326(3):230-239. PubMed PMID: 34283183.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19: A Randomized Clinical Trial. AU - Caricchio,Roberto, AU - Abbate,Antonio, AU - Gordeev,Ivan, AU - Meng,Jamie, AU - Hsue,Priscilla Y, AU - Neogi,Tuhina, AU - Arduino,Roberto, AU - Fomina,Daria, AU - Bogdanov,Roman, AU - Stepanenko,Tatiana, AU - Ruiz-Seco,Pilar, AU - Gónzalez-García,Andrés, AU - Chen,Yu, AU - Li,Yuhan, AU - Whelan,Sarah, AU - Noviello,Stephanie, AU - ,, PY - 2022/01/20/pmc-release PY - 2021/7/20/entrez PY - 2021/7/21/pubmed PY - 2021/7/27/medline SP - 230 EP - 239 JF - JAMA JO - JAMA VL - 326 IS - 3 N2 - 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. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/34283183/Effect_of_Canakinumab_vs_Placebo_on_Survival_Without_Invasive_Mechanical_Ventilation_in_Patients_Hospitalized_With_Severe_COVID-19:_A_Randomized_Clinical_Trial. L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2021.9508 DB - PRIME DP - Unbound Medicine ER -