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).
Antibodies, Monoclonal, Humanized
/ therapeutic use
Biomarkers
/ blood
COVID-19
/ complications
Clinical Trials, Phase II as Topic
Comorbidity
Double-Blind Method
Heart Failure
/ drug therapy
Humans
Inflammation
Proof of Concept Study
Prospective Studies
Randomized Controlled Trials as Topic
Respiratory Insufficiency
/ drug therapy
SARS-CoV-2
Covid-19
SARS-CoV-2
canakinumab
myocardial injury
Journal
Clinical cardiology
ISSN: 1932-8737
Titre abrégé: Clin Cardiol
Pays: United States
ID NLM: 7903272
Informations de publication
Date de publication:
Oct 2020
Oct 2020
Historique:
received:
09
07
2020
revised:
04
08
2020
accepted:
11
08
2020
pubmed:
25
8
2020
medline:
15
12
2020
entrez:
25
8
2020
Statut:
ppublish
Résumé
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. The primary hypothesis is that canakiumab will shorten time to recovery. 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. 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. 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.
Sections du résumé
BACKGROUND
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
OBJECTIVE
The primary hypothesis is that canakiumab will shorten time to recovery.
METHODS
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
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
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.
Identifiants
pubmed: 32830894
doi: 10.1002/clc.23451
pmc: PMC7461303
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Biomarkers
0
canakinumab
37CQ2C7X93
Types de publication
Clinical Trial Protocol
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1055-1063Informations de copyright
© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.
Références
JAMA. 2020 Apr 7;323(13):1239-1242
pubmed: 32091533
Ann Emerg Med. 2016 Jul;68(1):76-87.e4
pubmed: 26794254
Crit Care Med. 2020 Apr;48(4):451-458
pubmed: 32205590
Respir Res. 2020 Apr 15;21(1):83
pubmed: 32293449
N Engl J Med. 2009 Jun 4;360(23):2416-25
pubmed: 19494217
JAMA Cardiol. 2020 Nov 1;5(11):1281-1285
pubmed: 32730555
Circulation. 2020 Sep 15;142(11):1120-1122
pubmed: 32673505
Int J Infect Dis. 2020 Apr;93:339-344
pubmed: 32198088
Cell Death Discov. 2019 Jun 5;5:101
pubmed: 31231549
MMWR Morb Mortal Wkly Rep. 2020 Mar 27;69(12):343-346
pubmed: 32214079
Lancet Rheumatol. 2020 Jun;2(6):e325-e331
pubmed: 32501454
N Engl J Med. 2021 Feb 25;384(8):693-704
pubmed: 32678530
N Engl J Med. 2020 May 7;382(19):1787-1799
pubmed: 32187464
Clin Pharmacokinet. 2012 Jun 1;51(6):e1-18
pubmed: 22550964
JAMA Cardiol. 2020 Nov 01;5(11):1265-1273
pubmed: 32730619
JAMA. 2020 Mar 24;323(12):1129-1130
pubmed: 32207807
JAMA. 2020 Mar 17;323(11):1061-1069
pubmed: 32031570
JAMA Cardiol. 2020 Jul 1;5(7):811-818
pubmed: 32219356
Clin Cardiol. 2020 Oct;43(10):1055-1063
pubmed: 32830894
Lancet Rheumatol. 2020 Aug;2(8):e457-ee458
pubmed: 32835251
N Engl J Med. 2020 Sep 3;383(10):994
pubmed: 32649078
Clin Infect Dis. 2020 Jul 28;71(15):762-768
pubmed: 32161940
Circ Res. 2016 Jan 8;118(1):145-56
pubmed: 26837745
Travel Med Infect Dis. 2020 Mar - Apr;34:101623
pubmed: 32179124
J Am Coll Cardiol. 2018 Oct 30;72(18):2231-2264
pubmed: 30153967
N Engl J Med. 2020 Jun 11;382(24):2372-2374
pubmed: 32302078
Intensive Care Med. 2020 May;46(5):846-848
pubmed: 32125452
JAMA. 1994 Jun 15;271(23):1836-43
pubmed: 8196140
JAMA Cardiol. 2020 Jul 1;5(7):802-810
pubmed: 32211816
Lancet Infect Dis. 2020 May;20(5):553-558
pubmed: 32171059
BMJ. 2020 Mar 26;368:m1091
pubmed: 32217556
JAMA Netw Open. 2020 Jun 1;3(6):e2013136
pubmed: 32579195
N Engl J Med. 2017 Sep 21;377(12):1119-1131
pubmed: 28845751
JAMA. 2020 May 12;323(18):1775-1776
pubmed: 32203977
Ann Rheum Dis. 2011 Dec;70(12):2095-102
pubmed: 21859692
Blood. 2011 Apr 7;117(14):3720-32
pubmed: 21304099
Lancet. 2020 Feb 15;395(10223):497-506
pubmed: 31986264
Crit Care Med. 2016 Feb;44(2):275-81
pubmed: 26584195
JAMA. 2020 Aug 4;324(5):460-470
pubmed: 32492084
Cytokine. 1992 Sep;4(5):353-60
pubmed: 1420996
Circulation. 2002 Mar 5;105(9):1135-43
pubmed: 11877368
Lancet. 2020 Mar 28;395(10229):1033-1034
pubmed: 32192578
N Engl J Med. 2020 Jun 11;382(24):2327-2336
pubmed: 32275812
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
Trends Pharmacol Sci. 2004 Jun;25(6):291-4
pubmed: 15165741
Nat Rev Cardiol. 2020 May;17(5):259-260
pubmed: 32139904