Low-Dose Dobutamine and Single-Dose Tocilizumab in Acute Myocardial Infarction With High Risk of Cardiogenic Shock

NCT ID: NCT05350592

Last Updated: 2025-07-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-13
• Study Completion Date: 2025-09-30

Brief Summary

In the present study, we aim to investigate the effects of dobutamine infusion and/or a single intravenous (IV) dose of the IL-6 antagonist Tocilizumab administered after percutaneous coronary intervention (PCI) to patients with acute myocardial infarction (AMI) presenting < 24 hours from onset of chest pain and an intermediate to high risk of cardiogenic shock (CS) by assessment with the ORBI risk score (≥10 - not in overt shock at hospital admission).

Plasma concentrations of pro-B-type natriuretic peptide (proBNP) as a proxy for development of cardiogenic shock (CS) and hemodynamic instability will be sampled for primary endpoint analysis.

Effects on clinical parameters, mortality, morbidity as well as specific indicators of inflammation, cardiac function, and infarct size will secondarily be assessed noninvasively.

The rationale behind the current study is that inflammatory and neurohormonal responses are associated with subclinical hemodynamic instability in patients with AMI with high risk of CS have worse outcomes. The potentially unstable condition may be targeted pharmacologically as an add-on to existing therapy. This is investigated in patients at elevated risk of CS by sampling biomarkers reflecting the inflammatory and neurohormonal responses, as well as determining effects on patient outcomes and infarct size.

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.

Conditions

Acute Myocardial Infarction; Cardiogenic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Tocilizumab + Dobutamine

Tocilizumab IV 280 mg (100mL/hour, 1 hour) Dobutamine IV 5 micrograms/kg/minute (5mL/hour, 24 hours)

Group Type: ACTIVE_COMPARATOR

Tocilizumab

Intervention Type: DRUG

Single bolus

Dobutamine

Intervention Type: DRUG

Continous weight-adjusted infusion

Tocilizumab + Placebo

Tocilizumab IV 280 mg (100mL/hour, 1 hour) NaCl 0,9% IV (5mL/hour, 24 hours)

Group Type: ACTIVE_COMPARATOR

Tocilizumab

Intervention Type: DRUG

Single bolus

NaCl 0.9%

Intervention Type: DRUG

Placebo comparator and diluent

Placebo + Dobutamine

NaCl 0,9% IV (100mL/hour, 1 hour) Dobutamine IV 5 micrograms/kg/minute (5mL/hour, 24 hours)

Group Type: ACTIVE_COMPARATOR

Dobutamine

Intervention Type: DRUG

Continous weight-adjusted infusion

NaCl 0.9%

Intervention Type: DRUG

Placebo comparator and diluent

Placebo + Placebo

NaCl 0,9% IV (100mL/hour, 1 hour) NaCl 0,9% IV (5mL/hour, 24 hours)

Group Type: PLACEBO_COMPARATOR

NaCl 0.9%

Intervention Type: DRUG

Placebo comparator and diluent

Interventions

Tocilizumab

Single bolus

Intervention Type: DRUG

Dobutamine

Continous weight-adjusted infusion

Intervention Type: DRUG

NaCl 0.9%

Placebo comparator and diluent

Intervention Type: DRUG

Other Intervention Names

RoActemra (Actemra); Dobutrex; Saline isotonic

Eligibility Criteria

Inclusion Criteria

• Acute myocardial infarction
• Revascularization with PCI
• Presentation within 24 hours of chest pain
• ORBI risk score ≥ 10
• Age ≥ 18

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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: collaborator

Simon Spies Fonden

UNKNOWN

Sponsor Role: collaborator

Helge Peetz og Verner Peetz og hustru Vilma Peetz Legat

UNKNOWN

Sponsor Role: collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role: lead

Responsible Party

Helle Søholm, MD, PhD

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Helle Søholm, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Dept. of Cardiology, Rigshospitalet

Martin Frydland, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Dept. of Cardiology, Rigshospitalet

Locations

Rigshospitalet, Copenhagen University Hospital

Copenhagen, , Denmark

Countries

Denmark

References

Holle SLD, Kunkel JB, Hassager C, Pecini R, Wiberg S, Palm P, Holmvang L, Bang LE, Kjaergaard J, Thomsen JH, Engstrom T, Moller JE, Lonborg JT, Soholm H, Frydland M. Low-dose dobutamine in acute myocardial infarction with intermediate to high risk of cardiogenic shock development (the DOBERMANN-D trial): study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial. Trials. 2024 Oct 30;25(1):731. doi: 10.1186/s13063-024-08567-y.

Reference Type: BACKGROUND

PMID: 39478521 (View on PubMed)

Kunkel JB, Holle SLD, Hassager C, Pecini R, Wiberg S, Palm P, Holmvang L, Bang LE, Kjaergaard J, Thomsen JH, Engstrom T, Moller JE, Lonborg JT, Frydland M, Soholm H. 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. 2024 Nov 5;25(1):739. doi: 10.1186/s13063-024-08573-0.

Reference Type: BACKGROUND

PMID: 39501388 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2021-002028-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

H-21045751

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1277-8523

Identifier Type: REGISTRY

Identifier Source: secondary_id

RH-CARD-Pharma001

Identifier Type: -

Identifier Source: org_study_id