Low-Dose Dobutamine Infusion and Single-Dose Tocilizumab in Acute Myocardial Infarction Patients with High Risk of Cardiogenic Shock Development (Dobermann)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Rigshospitalet

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

13 Mar 2022 → 30 Sep 2025

Decision date (initial)

2024-09-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novo Nordisk Foundation · Copenhagen University Hospital Rigshospitalet · Simon Spies Fonden · Helge Peetz og Verner Peetz og hustru Vilma Peetz Legat

External identifiers

EU CT number

2024-515999-13-00

EudraCT number

2021-002028-19

WHO UTN

U1111-1277-8523

ClinicalTrials.gov

NCT05350592

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

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).

Secondary objectives 1

1. 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 postprocedure 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.

Conditions and MedDRA coding

Acute Myocardial Infarction with increased risk of Cardiogenic Shock

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Acute myocardial infarction
2. Revascularization with PCI
3. Presentation within 24 hours of chest pain
4. ORBI risk score ≥ 10
5. Age ≥ 18 years

Exclusion criteria 13

1. Comatose after cardiac arrest
2. 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.
3. Other major clinical non-coronary condition (stroke, sepsis etc.), which can explain a high ORBI risk score
4. Referral for acute coronary artery bypass grafting (CABG) (<24 hours) after the CAG, whereas subacute (>24 hours will be included)
5. Contraindications against dobutamine infusion (sustained ventricular tachycardia prior to admission or noted in the cath.lab., known pheochromocytoma, idiopathic hypertrophic subaortic stenosis)
6. Tocilizumab allergy
7. Pregnant- or breastfeeding women
8. Known liver disease/dysfunction
9. Ongoing uncontrollable infection
10. Immune deficiency/treatment with immunosuppressants
11. Known, uncontrolled gastrointestinal (GI) disease predisposing to GI perforation
12. Unwilling to give informed consent to study participation
13. Unable to give consent due to language barrier

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. NTproBNP in blood samples drawn from hospital admission to 48 hours after admission.

Secondary endpoints 11

1. Infarct size measured by cMRi during index admission and after 3 months
2. 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
3. 2D echocardiographic measurements of hemodynamics (VTI) and left ventricular function including strain measurements according to protocol
4. SOFA score (PaO2, FiO2, on medical ventilation, Platelets, GCS, Bilirubin, mean arterial pressure OR administration of vasoactive agents required, Creatinine, COVID-19 status)
5. Development of in-hospital CS and/or in-hospital cardiac arrest and/or transfer to the ICU during index admission
6. Long-term all-cause mortality
7. PCI operator's post-procedure clinical assessment of the patient (survives to discharge 'yes/no')
8. 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)
9. Re-admission (all cause and cardiovascular) during the first year after index hospitalization
10. Re-admission with heart failure and re-infarction during the first year after index hospitalization
11. Quality of Life and mental and cognitive health at baseline and after three months

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rigshospitalet

Sponsor organisation

Rigshospitalet

Address

Blegdamsvej 9

City

Copenhagen Oe

Postcode

2100

Country

Denmark

Scientific contact point

Organisation

Rigshospitalet

Contact name

Helle Søholm

Public contact point

Organisation

Rigshospitalet

Contact name

Helle Søholm

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications