A blinded, randomized controlled trial of the interleukin-1b antagonist, canakinumab, for the treatment of patients with coronavirus disease 2019 (COVID-19) and elevated levels of troponin and C reactive protein has begun recruitment, and the preliminary patient characteristics were published in Clinical Cardiology.
This study (ClinicalTrials.gov Identifier: NCT04365153) was designed as a proof of concept to determine whether antagonizing IL-1b may decrease the autoinflammatory response of a cytokine storm observed during serious COVID-19 infections among high-risk patients.
At publication time, patients with COVID-19 were being recruited across the Cleveland Clinic Health System. Inclusion criteria are the following: enrollment in the study within 5 days of testing positive for COVID-19; presence of acute myocardial injury (ie, troponin >99% of the upper reference range in the absence of acute myocardial ischemia symptoms); elevated levels of (pro) B-type natriuretic peptide, and C-reactive protein >50 mg/L. Patients who had a myocardial infarction, received >48 hours of mechanical ventilation, or those with an uncontrolled bacterial infection are ineligible.
The investigators plan to recruit 45 patients who will be randomized at a 1:1:1 ratio to receive intravenously canakinumab at 600 mg, canakinumab at 300 mg, or placebo. All patients will be allowed to receive any clinically necessary treatment for their COIVD-19 symptoms, regardless of treatment group.
Recruitment began on April 28, 2020 and is expected to continue for 7 months. Patients will be monitored for signs of clinical improvement up to day 14 and for all-cause mortality through day 28. The first 20 patients have been recruited and randomly assigned a treatment group.
At enrollment, most patients had shortness of breath (75.0%) and few required intubation (20.0%). The recruited patients were older (median, 67.0 years; interquartile range [IQR], 60.9-74.0 years), 75.0% were men, 50.0% were White, 45.0% were Black, and comorbidities were common (80.0% had hypertension, 75.0% had hyperlipidemia, 45.0% had diabetes mellitus, and 30.0% had coronary artery disease).
The median high sensitivity troponin T level was 21.0 ng/L (IQR, 14.5-53.0) ng/L, N-terminal pro B-type natriuretic peptide was 313.0 pg/mL (IQR, 208.0-819.0 pg/mL), C reactive protein was 16.2 mg/dL (IQR, 10.2-20.8 mg/dL), ferritin was 1012.2 ng/mL (IQR, 589.4-1962.5 ng/mL), D-dimer was 1400 ng/mL (IQR, 730-1940 ng/mL), and left ventricular ejection fraction was 55% (IQR, 55%-60%).
“[This] study will help inform whether targeting inappropriate activation of the innate immune system should be investigated in larger clinical trials to improve survival in patients with Covid-19 and myocardial injury,” noted the investigators.
Sheng C, Sahoo D, Dugar S, et al. 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). [published online August 24, 2020] Clin Cardiol. doi:10.1002/clc.23451