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 (median 16.2 mg/dL) with modest elevations in high-sensitivity troponin T (median 21 ng/L), in keeping with the concept of enrolling patients with early myocardial injury.

CONCLUSIONS:

The three C study will provide insights regarding whether IL-1β inhibition may improve outcomes in patients with SARS-CoV2 associated myocardial injury and increased inflammation.

• Authors: Calvin C Sheng, Debasis Sahoo, Siddharth Dugar, Robier Aguillon Prada, Tom Kai Ming Wang, Ossama K Abou Hassan, Danielle Brennan, Daniel A Culver, Prabalini Rajendram, Abhijit Duggal, A Michael Lincoff, Steven E Nissen, Venu Menon, Paul C Cremer
• Journal: Clinical cardiology (Clin Cardiol) Vol. 43 Issue 10 Pg. 1055-1063 (Oct 2020) ISSN: 1932-8737 [Electronic] United States
• PMID: 32830894 (Publication Type: Clinical Trial Protocol, Journal Article)
• Copyright: © 2020 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.

Chemical References

• Antibodies, Monoclonal, Humanized
• Biomarkers
• canakinumab

Topics

• Antibodies, Monoclonal, Humanized (therapeutic use)
• Biomarkers (blood)
• COVID-19 (complications)
• Clinical Trials, Phase II as Topic
• Comorbidity
• Double-Blind Method
• Heart Failure (drug therapy, virology)
• Humans
• Inflammation
• Proof of Concept Study
• Prospective Studies
• Randomized Controlled Trials as Topic
• Respiratory Insufficiency (drug therapy, virology)
• SARS-CoV-2