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Interleukin-6 receptor antibodies (tocilizumab) in acute myocardial infarction with intermediate to high risk of cardiogenic shock development (DOBERMANN-T): study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial: study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial

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Title: Interleukin-6 receptor antibodies (tocilizumab) in acute myocardial infarction with intermediate to high risk of cardiogenic shock development (DOBERMANN-T): study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial: study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial
Authors: Kunkel, Joakim Bo, Holle, Sarah Louise Duus, Hassager, Christian, Pecini, Redi, Wiberg, Sebastian, Palm, Pernille, Holmvang, Lene, Bang, Lia Evi, Kjærgaard, Jesper, Thomsen, Jakob Hartvig, Engstrøm, Thomas, Møller, Jacob Eifer, Lønborg, Jacob Thomsen, Frydland, Martin, Søholm, Helle
Source: Trials
Trials, Vol 25, Iss 1, Pp 1-12 (2024)
Kunkel, J B, Holle, S L D, Hassager, C, Pecini, R, Wiberg, S, Palm, P, Holmvang, L, Bang, L E, Kjærgaard, J, Thomsen, J H, Engstrøm, T, Møller, J E, Lønborg, J T, Frydland, M & Søholm, H 2024, ' Interleukin-6 receptor antibodies (tocilizumab) in acute myocardial infarction with intermediate to high risk of cardiogenic shock development (DOBERMANN-T) : study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial ', Trials, vol. 25, no. 1, 739 . https://doi.org/10.1186/s13063-024-08573-0
Publisher Information: Springer Science and Business Media LLC, 2024.
Publication Year: 2024
Subject Terms: Male, Medicine (General), Time Factors, Humanized/therapeutic use, Myocardial Infarction, Anti-Inflammatory Agents, Anti-Inflammatory Agents/therapeutic use, Left/drug effects, Percutaneous coronary intervention, Study Protocol, Risk Factors, Receptors, Monoclonal, Natriuretic Peptide, Brain, Ventricular Function, Percutaneous Coronary Intervention/adverse effects, Randomized Controlled Trials as Topic, Shock, IL-6RA, Tocilizumab, Middle Aged, Neurohormonal activation, ORBI risk score, Treatment Outcome, Female, Adult, Shock, Cardiogenic, Acute myocardial infarction, Antibodies, Monoclonal, Humanized, Risk Assessment, Antibodies, R5-920, Percutaneous Coronary Intervention, Double-Blind Method, Natriuretic Peptide, Cardiogenic/etiology, Humans, Cardiogenic shock, Cardiac magnetic resonance imaging, Aged, Inflammation, Receptors, Interleukin-6, Peptide Fragments, Interleukin-6/antagonists & inhibitors, ProBNP, Brain/blood, Myocardial Infarction/blood, Peptide Fragments/blood, Biomarkers/blood, Biomarkers
Description: Background Inflammation and neurohormonal activation play a significant role in the adverse outcome seen in acute myocardial infarction (AMI) and the development of cardiogenic shock (CS), which is associated with a mortality rate up to 50%. Treatment with anti-inflammatory drugs such as tocilizumab, an interleukin-6 receptor antagonist, has been shown to reduce troponin release and reduce the myocardial infarct size in AMI patients and it may therefore have cardioprotective properties. Methods This is a double-blind, placebo-controlled, single-center randomized clinical trial, including adult AMI patients without CS at hospital arrival, undergoing percutaneous coronary intervention (PCI) within 24 h from symptom onset, and at intermediate to high risk of developing CS (ORBI risk score ≥ 10). A total of 100 participants will be randomized to receive a single intravenous dose of tocilizumab (280 mg) or placebo (normal saline). The primary outcome is peak plasma pro-B-type natriuretic peptide (proBNP) within 48 h, assessed using serial measurements at intervals: before infusion, 12, 24, 36, and 48 h after infusion. Secondary endpoints include the following: (1) cardiac magnetic resonance imaging (CMR) during 24–48 h after admission and at follow-up after 3 months with assessment of left ventricular area at risk, final infarct size, and the derived salvage index and (2) biochemical markers of inflammation (C-reactive protein and leukocyte counts) and cardiac injury (troponin T and creatinine kinase MB). Discussion Modulation of interleukin-6-mediated inflammation in patients with AMI, treated with acute PCI, and at intermediate to high risk of in-hospital CS may lead to increased hemodynamic stability and reduced left ventricular infarct size, which will be assessed using blood biomarkers with proBNP as the primary outcome and inflammatory markers, troponin T, and CMR with myocardial salvage index as the secondary endpoints. Trial registration Registered with the Regional Ethics Committee (H-21045751), EudraCT (2021–002028-19), ClinicalTrials.gov (NCT05350592). Study registration date: 2022-03-08, Universal Trial Number U1111-1277–8523.
Document Type: Article
Other literature type
File Description: application/pdf
Language: English
ISSN: 1745-6215
DOI: 10.1186/s13063-024-08573-0
Access URL: https://pubmed.ncbi.nlm.nih.gov/39501388
https://doaj.org/article/cc0311fa571748c7ae1243f0f04615cf
https://curis.ku.dk/ws/files/412387809/s13063_024_08573_0.pdf
https://portal.findresearcher.sdu.dk/da/publications/26bb7167-6b1c-4983-9f26-2bc65bb288c0
https://doi.org/10.1186/s13063-024-08573-0
Rights: CC BY
Accession Number: edsair.doi.dedup.....d28d6e573926e4dd72a40d661b8b1c8c
Database: OpenAIRE
Description
Abstract:Background Inflammation and neurohormonal activation play a significant role in the adverse outcome seen in acute myocardial infarction (AMI) and the development of cardiogenic shock (CS), which is associated with a mortality rate up to 50%. Treatment with anti-inflammatory drugs such as tocilizumab, an interleukin-6 receptor antagonist, has been shown to reduce troponin release and reduce the myocardial infarct size in AMI patients and it may therefore have cardioprotective properties. Methods This is a double-blind, placebo-controlled, single-center randomized clinical trial, including adult AMI patients without CS at hospital arrival, undergoing percutaneous coronary intervention (PCI) within 24 h from symptom onset, and at intermediate to high risk of developing CS (ORBI risk score ≥ 10). A total of 100 participants will be randomized to receive a single intravenous dose of tocilizumab (280 mg) or placebo (normal saline). The primary outcome is peak plasma pro-B-type natriuretic peptide (proBNP) within 48 h, assessed using serial measurements at intervals: before infusion, 12, 24, 36, and 48 h after infusion. Secondary endpoints include the following: (1) cardiac magnetic resonance imaging (CMR) during 24–48 h after admission and at follow-up after 3 months with assessment of left ventricular area at risk, final infarct size, and the derived salvage index and (2) biochemical markers of inflammation (C-reactive protein and leukocyte counts) and cardiac injury (troponin T and creatinine kinase MB). Discussion Modulation of interleukin-6-mediated inflammation in patients with AMI, treated with acute PCI, and at intermediate to high risk of in-hospital CS may lead to increased hemodynamic stability and reduced left ventricular infarct size, which will be assessed using blood biomarkers with proBNP as the primary outcome and inflammatory markers, troponin T, and CMR with myocardial salvage index as the secondary endpoints. Trial registration Registered with the Regional Ethics Committee (H-21045751), EudraCT (2021–002028-19), ClinicalTrials.gov (NCT05350592). Study registration date: 2022-03-08, Universal Trial Number U1111-1277–8523.
ISSN:17456215
DOI:10.1186/s13063-024-08573-0