Canakinumab to reduce deterioration of cardiac and respiratory function in SARS‐CoV‐2 associated myocardial injury with heightened inflammation (canakinumab in Covid‐19 cardiac injury: The three C study)

Abstract

Background: In patients with Covid-19, myocardial injury and increased inflammation are associated with morbidity and mortality. We designed a proof-of-concept randomized controlled trial to evaluate whether treatment with canakinumab prevents progressive respiratory failure and worsening cardiac dysfunction in patients with SARS-CoV2 infection, myocardial injury, and high levels of inflammation. Hypothesis: The primary hypothesis is that canakiumab will shorten time to recovery. Methods: The three C study (canakinumab in Covid-19 Cardiac Injury, NCT04365153) is a double-blind, randomized controlled trial comparing canakinumab 300 mg IV, 600 mg IV, or placebo in a 1:1:1 ratio in hospitalized Covid-19 patients with elevations in troponin and C-reactive protein (CRP). The primary endpoint is defined as the time in days from randomization to either an improvement of two points on a seven category ordinal scale or discharge from the hospital, whichever occurs first up to 14 days postrandomization. The secondary endpoint is mortality at day 28. A total of 45 patients will be enrolled with an anticipated 5 month follow up period. Results: Baseline characteristics for the first 20 randomized patients reveal a predominantly male (75%), elderly population (median 67 years) with a high prevalence of hypertension (80%) and hyperlipidemia (75%). CRPs have been markedly elevated

Incidence of Myocardial Injury in COVID-19-Infected Patients: A Systematic Review and Meta-Analysis

“…For novel therapies such as Remdesevir and IL-6 inhibitors, the data are still limited. Recently, Sheng et al began a clinical trial using Canakinumab to minimize the risk of myocardial injury, which is currently in the enrolling state [ 44 ]. At the moment, we do not have any effective treatments which reduce COVID-19 complications.…”

COVID-19 and diabetes mellitus: from pathophysiology to clinical management

“…By contrast, canakinumab, another IL-1β inhibitor that is under investigation in a clinical trial for the treatment of COVID-19 (ref. 197 ), was not effective in the treatment of recent-onset T1DM 198 . In animal studies, Janus kinase 1/2 inhibitors and Bruton’s tyrosine kinase inhibitors, other investigational agents for COVID-19 treatment 199 , improved glycaemia 200 , 201 and insulitis 200 and impaired the levels of anti-insulin B lymphocytes 202 and insulin antibodies 203 , which might have protective roles in T1DM.…”

Risk factors for severe and critically ill COVID‐19 patients: A review

“…Anakinra, a recombinant human IL‐1 receptor antagonist, was reported to reduce the need for invasive mechanical ventilation and mortality in patients with severe forms of COVID‐19 223 . Similarly, canakinumab, an anti‐IL‐1β mAb, may inhibit the dysregulated immune response in COVID‐19 patients and dampen myocardial injury or other immunopathological diseases 222,224 …”