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Comment
. 2021 Jul 29;1(1):oeab002.
doi: 10.1093/ehjopen/oeab002. eCollection 2021 Aug.

Double-blind randomized proof-of-concept trial of canakinumab in patients with COVID-19 associated cardiac injury and heightened inflammation

Paul C Cremer  1 , Calvin C Sheng  1 , Debasis Sahoo  2 , Siddharth Dugar  2 , Robier Aguillon Prada  2 , Tom Kai Ming Wang  1 , Ossama K Abou Hassan  1 , Jamie Hernandez-Montfort  1 , David A Wolinsky  1 , Daniel A Culver  2 , Prabalini Rajendram  2 , Abhijit Duggal  2 , Danielle M Brennan  1   3 , Katherine E Wolski  1   3 , A Michael Lincoff  1 , Steven E Nissen  1 , Venu Menon  1
Affiliations
Comment

Double-blind randomized proof-of-concept trial of canakinumab in patients with COVID-19 associated cardiac injury and heightened inflammation

Paul C Cremer et al. Eur Heart J Open. .

Erratum in

Abstract

Aims: In coronavirus disease 2019 (COVID-19), myocardial injury is associated with systemic inflammation and higher mortality. Our aim was to perform a proof of concept trial with canakinumab, a monoclonal antibody to interleukin-1β, in patients with COVID-19, myocardial injury, and heightened inflammation.

Methods and results: This trial required hospitalization due to COVID-19, elevated troponin, and a C-reactive protein concentration more than 50 mg/L. The primary endpoint was time to clinical improvement at Day 14, defined as either an improvement of two points on a seven-category ordinal scale or discharge from the hospital. The secondary endpoint was mortality at Day 28. Forty-five patients were randomly assigned to canakinumab 600 mg (n = 15), canakinumab 300 mg (n = 14), or placebo (n = 16). There was no difference in time to clinical improvement compared to placebo [recovery rate ratio (RRR) for canakinumab 600 mg 1.15, 95% confidence interval (CI) 0.46-2.91; RRR for canakinumab 300 mg 0.61, 95% CI 0.23-1.64]. At Day 28, 3 (18.8%) of 15 patients had died in the placebo group, compared with 3 (21.4%) of 14 patients with 300 mg canakinumab, and 1 (6.7%) of 15 patients with 600 mg canakinumab. There were no treatment-related deaths, and adverse events were similar between groups.

Conclusion: There was no difference in time to clinical improvement at Day 14 in patients treated with canakinumab, and no safety concerns were identified. Future studies could focus on high dose canakinumab in the treatment arm and assess efficacy outcomes at Day 28.

Keywords: COVID-19; Canakinumab; Interleukin-1; Myocardial injury.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1
Figure 1
CONSORT flow diagram.
Figure 2
Figure 2
Exploratory endpoints of survival at study completion (150 days) (A) and time to clinical improvement at Day 28 (B).
Figure 3
Figure 3
Exploratory endpoint of proportion of patients in categories during follow-up at 28 days.
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