E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Myocardial Infarction with increased risk of Cardiogenic Shock. |
Akut myokardieinfarkt med høj risiko for kardiogent shock. |
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E.1.1.1 | Medical condition in easily understood language |
Acute myocardial infarction presenting within 24 hours from onset of symptoms and intermidate to high risk of developing cardiogenic shock. |
Akut blodprop i hjertet med debut af symptomer inden for 24 timer og intermediær til høj risiko for kardiogent shock. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000891 |
E.1.2 | Term | Acute myocardial infarction |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
In the present study, we aim to investigate the effects of dobutamine infusion and a or single post-PCI intravenous (IV) dose of Tocilizumab on plasma concentration of NTproBNP as a proxy for development of hemodynamic instability / CS in patients with acute myocardial infarction (AMI) presenting < 24 hours from chest pain plus intermediate to high risk of CS assessed by the ORBI risk score (≥11 – not in overt shock at hospital admission). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to determine the effects on development of in-hospital CS and/or in-hospital cardiac arrest and/or transfer to the ICU during index admission, infarct size measured by cMRi, long-term all-cause mortality, biomarkers reflecting neurohormonal activation, endothelial function/damage, inflammation, connective tissue damage, organ dysfunction, PCI operators post-procedure clinical assessment of the patient, development of non-cardiac arrest arrythmia, 2D echocardiographic findings of hemodynamics and left ventricular function, re-admission during the first year after index hospitalization, re-admission with heart failure and re-infarction, SOFA score, quality of life and mental and cognitive health at baseline and after three months. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Acute myocardial infarction; Revascularization with PCI; Presentation within 24 hours of chest pain; ORBI risk score ≥ 11; Age ≥ 18. |
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E.4 | Principal exclusion criteria |
Unwilling to give informed consent to study participation; Unable to give consent due to language barrier; Comatose after cardiac arrest; Cardiogenic shock with systolic blood pressure < 100 mmHg for more than 30 minutes or need for vasopressor to maintain blood pressure and arterial lactate > 2,5 (2,0) mmol/L developed before leaving the cath. lab.; Other major clinical non-coronary condition (stroke, sepsis etc.), which can explain a high ORBI risk score; Referral for acute coronary artery bypass grafting (CABG) (< 24 hours) after the CAG, whereas subacute (>24 hours will be included) ; In patients with coronary biomarkers without dynamic elevation (‘rise-and-fall’) reflecting other condition than AMI, treatment with the assigned study drug(s) will be completed and the patient will be included in sensitivity analyses but will not have MRi performed; Contraindications against dobutamine infusion (sustained ventricular tachycardia prior to admission or noted in the cath.lab., known pheochromocytoma, idiopathic hypertrophic subaortic stenosis); Tocilizumab allergy; Pregnant- or breastfeeding women; Known liver disease/dysfunction; Ongoing uncontrollable infection; Immune deficiency/treatment with immunosuppressants; Known, uncontrolled gastrointestinal (GI) disease predisposing to GI perforation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
NTproBNP in blood samples drawn from hospital admission to 48 hours after admission. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
NTproBNP will be measured on admission and at 3, 12, 24, 36 and 48 hours from admission. |
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E.5.2 | Secondary end point(s) |
Paraclinical endpoints: Infarct size measured by cMRi during index admission and after 3 months; Biomarkers reflecting neurohormonal activation, endothelial function/damage, inflammation (pro- and anti-inflammatory processes – including IL-6 and C-reactive peptide (CRP)), connec-tive tissue damage, organ dysfunction, and other relevant processes; 2D echocardiographic measurements of hemodynamics (VTI) and left ventricular function including strain measurements according to protocol; SOFA score (PaO2, FiO2, on medical ventilation, Platelets, GCS, Bilirubin, mean arterial pressure OR administration of vasoactive agents required, Creatinine, COVID-19 status).
Clinical endpoints: Development of in-hospital CS and/or in-hospital cardiac arrest and/or transfer to the ICU during index admission; Long-term all-cause mortality; PCI operator’s post-procedure clinical assessment of the patient (survives to discharge ‘yes/no’); Development of non-cardiac arrest arrythmia (sustained ventricular tachycardia, atrial fibrillation with a frequency above 120 for more than 30 minutes) during index admission (safety); Re-admission (all cause and cardiovascular) during the first year after index hospitalization; Re-admission with heart failure and re-infarction during the first year after index hospitalization; Quality of Life and mental and cognitive health at baseline and after three months. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Evaulation of paraclinical endpoints during index admission. Evaluation of paraclinical endpoints at follow-up at 3 months. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last contact to the subject will be 3 months (+/- 4 weeks) after last randomization. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |