TY - JOUR
T1 - Interleukin-6 receptor antibodies (tocilizumab) in acute myocardial infarction with intermediate to high risk of cardiogenic shock development (DOBERMANN-T)
T2 - study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial
AU - Kunkel, Joakim Bo
AU - Holle, Sarah Louise Duus
AU - Hassager, Christian
AU - Pecini, Redi
AU - Wiberg, Sebastian
AU - Palm, Pernille
AU - Holmvang, Lene
AU - Bang, Lia Evi
AU - Kjærgaard, Jesper
AU - Thomsen, Jakob Hartvig
AU - Engstrøm, Thomas
AU - Møller, Jacob Eifer
AU - Lønborg, Jacob Thomsen
AU - Frydland, Martin
AU - Søholm, Helle
N1 - © 2024. The Author(s).
PY - 2024/11/5
Y1 - 2024/11/5
N2 - 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.
AB - 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.
KW - Humans
KW - Antibodies, Monoclonal, Humanized/therapeutic use
KW - Double-Blind Method
KW - Myocardial Infarction/blood
KW - Shock, Cardiogenic/etiology
KW - Percutaneous Coronary Intervention/adverse effects
KW - Randomized Controlled Trials as Topic
KW - Natriuretic Peptide, Brain/blood
KW - Biomarkers/blood
KW - Treatment Outcome
KW - Receptors, Interleukin-6/antagonists & inhibitors
KW - Peptide Fragments/blood
KW - Time Factors
KW - Male
KW - Middle Aged
KW - Risk Factors
KW - Aged
KW - Female
KW - Anti-Inflammatory Agents/therapeutic use
KW - Adult
KW - Risk Assessment
KW - Ventricular Function, Left/drug effects
UR - http://www.scopus.com/inward/record.url?scp=85208603479&partnerID=8YFLogxK
U2 - 10.1186/s13063-024-08573-0
DO - 10.1186/s13063-024-08573-0
M3 - Journal article
C2 - 39501388
SN - 1745-6215
VL - 25
SP - 739
JO - Trials
JF - Trials
IS - 1
M1 - 739
ER -