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

NCT05350592 | Active Not Recruiting Phase 2 DMC

• 4 other identifiers: RH-CARD-Pharma0012021-002028-19H-21045751U1111-1277-8523
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Myocardial Infarction; Cardiogenic Shock

Keywords

acute myocardial infarction; cardiogenic shock; AMI; inflammation; proBNP; AMI-CS; infarct size; STEMI

Outcome Measures

Primary Outcomes (1)

• ProBNP

  ProBNP plasma concentration being assessed at multiple time points (including the primary endpoint) will be analyzed by application of a linear mixed model of covariance. As the biomarker will be measured prior to initiation of the study drug, the models will be baseline corrected (i.e., constrained linear mixed models, CLMM). The main result of these analyses will be the treatment-by-time interaction as a marker of whether the proBNP levels change differently over time in the treatment versus the placebo arm.

  48 hours

Secondary Outcomes (13)

• CS and/or cardiac arrest

  Index admission

• Acute Infarct Size

  Admission

• Post-infarction Salvaged Myocardium

  3 months

• Additional biomarkers

  Index admission

• Post-procedure assessment

  Index admission

Study Arms (4)

Tocilizumab + Dobutamine

ACTIVE COMPARATOR

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

Drug: Tocilizumab; Drug: Dobutamine

Tocilizumab + Placebo

ACTIVE COMPARATOR

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

Drug: Tocilizumab; Drug: NaCl 0.9%

Placebo + Dobutamine

ACTIVE COMPARATOR

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

Drug: Dobutamine; Drug: NaCl 0.9%

Placebo + Placebo

PLACEBO COMPARATOR

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

Drug: NaCl 0.9%

Interventions

Tocilizumab DRUG

Single bolus

Also known as: RoActemra (Actemra)

Tocilizumab + Dobutamine; Tocilizumab + Placebo

Dobutamine DRUG

Continous weight-adjusted infusion

Also known as: Dobutrex

Placebo + Dobutamine; Tocilizumab + Dobutamine

NaCl 0.9% DRUG

Placebo comparator and diluent

Also known as: Saline isotonic

Placebo + Dobutamine; Placebo + Placebo; Tocilizumab + Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Novo Nordisk A/S: collaborator
• Simon Spies Fonden: collaborator
• Helge Peetz og Verner Peetz og hustru Vilma Peetz Legat: collaborator

Study Sites (1)

Rigshospitalet, Copenhagen University Hospital

Copenhagen, 2100, Denmark

Location

Related Publications (2)

• 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.

  PMID: 39478521 BACKGROUND

• 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.

  PMID: 39501388 BACKGROUND

MeSH Terms

Conditions

Shock, Cardiogenic; Inflammation; ST Elevation Myocardial Infarction

Interventions

tocilizumab; Dobutamine; Sodium Chloride

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Shock

Intervention Hierarchy (Ancestors)

Catecholamines; Amines; Organic Chemicals; Phenethylamines; Ethylamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Helle Søholm, MD, PhD

  Dept. of Cardiology, Rigshospitalet

  PRINCIPAL INVESTIGATOR

• Martin Frydland, MD, PhD

  Dept. of Cardiology, Rigshospitalet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Model Details: 2x2

Study Record Dates

• First Submitted: March 8, 2022
• First Posted: April 28, 2022
• Study Start: March 13, 2022
• Primary Completion: June 30, 2025
• Study Completion: September 30, 2025
• Last Updated: July 17, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Access and final IPD criteria is pending final, complete publication of the study.
• Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA)

Locations

DK (1)