LOW-DOSE DOBUTAMINE INFUSION AND SINGLE-DOSE TOCILIZUMAB IN ACUTE MYOCARDIAL INFARCTION PATIENTS WITH HIGH RISK OF CARDIOGENIC SHOCK DEVELOPMENT (DOBERMANN)

Phase 4

Active, not recruiting

• Conditions: Acute Myocardial Infarction with increased risk of Cardiogenic Shock

• Registration Number: 2024-515999-13-00
• Lead Sponsor: Rigshospitalet

Brief Summary

In the present study, we aim to investigate the effects of dobutamine infusion and/or a 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).

Detailed Description

The planned study is an investigator-initiated, randomized, double blinded clinical trial.

Consecutive patients at Copenhagen University Hospital, Rigshospitalet admitted with AMI \< 24 hours from chest pain will be screened.

Patients eligible for trial inclusion will be randomized 2:2 to receive a continuous IV dobutamine infusion of 5 mcg/kg/minute versus placebo for 24 hours and to receive a single IV dose of tocilizumab (1-hour infusion) versus placebo administered after PCI.

Treatment with the investigational drug will be initiated as soon as possible but no later than 2 hours after transfer to the coronary care unit (CCU) and after informed consent. All included patients will follow usual treatment according to current guidelines.

The biomarker proBNP will be measured in blood samples drawn upon hospital admission in patients with ORBI risk score ≥10, and after 12, 24, 36 and 48 hours from admission.

After treatment termination, 2D-echocardiography will be performed acutely and within 2 days to evaluate left ventricular ejection fraction (LVEF), and cardiac magnetic resonance imaging (cMRi) with late gadolinium enhancement technique prior to hospital discharge as close to 48 hours post-MI and after 3 months after discharge will be performed to calculate area at risk and salvage index after AMI.Blood samples (40 mL) will be obtained and stored in a biobank for subsequent measurement of biomarkers reflecting inflammation, neurohormonal activation, neuronal injury, connective tissue function and other relevant pathophysiological processes.

These biomarkers will solely have research interest and no clinical implications. Furthermore, no genetic biomarkers and markers associated with malignancy development will be measured. Any leftover blood from the research biobank will be transferred to a biobank for future research and stored for up to 10 years solely for research purposes. After this period blood samples will be destroyed.

Study Timeline

• Study First Submitted: 2022-03-08
• Study Start: 2022-03-13
• Study First Submitted QC: 2022-04-21
• Study First Posted: 2022-04-28
• Primary Completion: 2025-06-30
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-16
• Last Update Posted: 2025-07-17
• Study Completion: 2025-09-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Not specified
• Target Recruitment: 100

Inclusion Criteria

Acute myocardial infarction

Revascularization with PCI

Presentation within 24 hours of chest pain

ORBI risk score ≥ 10

Age ≥ 18 years

Exclusion Criteria

Comatose after cardiac arrest

Immune deficiency/treatment with immunosuppressants

Known, uncontrolled gastrointestinal (GI) disease predisposing to GI perforation

Unwilling to give informed consent to study participation

Unable to give consent due to language barrier

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)

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Primary Outcome Measures

Name	Time	Method
NTproBNP in blood samples drawn from hospital admission to 48 hours after admission.		NTproBNP in blood samples drawn from hospital admission to 48 hours after admission.

Secondary Outcome Measures

Name	Time	Method
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)		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)
Infarct size measured by cMRi during index admission and after 3 months		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		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		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)		SOFA score (PaO2, FiO2, on medical ventilation, Platelets, GCS, Bilirubin, mean arterial pressure OR administration of vasoactive agents required, Creatinine, COVID-19 status)
Development of in-hospital CS and/or in-hospital cardiac arrest and/or transfer to the ICU during index admission		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		Long-term all-cause mortality
PCI operator's post-procedure clinical assessment of the patient (survives to discharge 'yes/no')		PCI operator's post-procedure clinical assessment of the patient (survives to discharge 'yes/no')
Re-admission (all cause and cardiovascular) during the first year after index hospitalization		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		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		Quality of Life and mental and cognitive health at baseline and after three months

Trial Locations

Locations (1)

Rigshospitalet, Copenhagen University Hospital; 🇩🇰 Copenhagen, Denmark