"Comparison between norepinephrine and dobutamine in patients with cardiogenic shock"

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Unita' Sanitaria Locale Toscana Sud Est

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

3 Feb 2025 → ongoing

Decision date (initial)

2025-02-03

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-520399-84-00

EudraCT number

2020-004881-20

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

Evaluate the difference in lactate variation associated with one of the two therapeutic schemes, norepinephrine versus dobutamine plus norepinephrine.

Secondary objectives 1

1. Evaluate the incidence of Death or Extracorporeal Oxygenation Implantation or Left Ventricular Assiste Device at 72 hours and at discharge.

Conditions and MedDRA coding

Cardiogenic shock

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. - Cardiogenic shock with: systolic systemic arterial pressure (SBP) < 90 mmHg or mean arterial pressure (MAP) < 60 mmHg for at least 30 consecutive minutes and need for pharmacological support (inotropes and/or vasopressors) to maintain an SBP > 90 mmHg or MAP > 60 mmHg; - Age over 18 years; - Enrollment within 3 hours of the acute event; - Written informed consent; - SOFA score < 2

Exclusion criteria 1

1. - Current pregnancy (possibly confirmed by serum B-Hcg dosage); - Presence of at least moderate aortic and/or mitral valve disease; - Septic or hypovolemic shock; - Mechanical complications of acute myocardial infarction (free wall rupture, ventricular septal defect, papillary rupture. - Arrhythmic storm, persistent or chronic tachycardic atrial fibrillation. - Infusion of inotropes/vasoconstrictors already in progress at the time of randomization. - Hypersensitivity to the active substance or any of the excipients - Patients with inotrope-dependent chronic heart failure - Participation in a clinical trial in which an investigational drug was administered within 30 days of screening or 5 half-lives of the study drug, whichever is longer - Any previous or ongoing medical condition or clinically significant laboratory value at screening that, in the opinion of the investigator, may pose a risk to patient safety, interfere with study compliance and follow-up, or confound the interpretation of the data throughout the study period. - Noradrenaline should not be administered concomitantly with: - Anesthetics such as cyclopropane and halothane: may increase cardiac excitability which may cause ventricular tachycardia or fibrillation; - tricyclic antidepressants: may enhance the effects of noradrenaline causing hypertension, cardiac arrhythmias and tachycardia. If it is necessary to administer these drugs together, careful monitoring must be performed and the dose of noradrenaline must be reduced; - MAO antidepressants and other MAO inhibitors: may increase the hypertensive effect by reducing sympathomimetic metabolism. - Neuroleptics: may decrease the effectiveness of noradrenaline. If it is necessary to administer these drugs together, an adjustment of the dose of noradrenaline is necessary to maintain or achieve the expected therapeutic effect. It is recommended to monitor blood pressure. - Dihydroergotamine: an extreme increase in blood pressure may occur; - Antibiotics (linezolid): a hypertensive crisis may be triggered or worsened. Therefore, it is necessary to reduce the dose of noradrenaline and adjust it to achieve the desired effect; - COMT inhibitors (entacapone): may increase tachycardia, hypertension and arrhythmia; - Guanethidine: may cause an increase in blood pressure and risk of arrhythmias. - Noradrenaline should not be administered intravenously together with: - Basic buffered antibiotics. Noradrenaline is labile in an alkaline environment and caution should be exercised in preparations when a final pH greater than 6 is reached; - Cefamandole, cefoxitin, moxalactam, nitrofurantoin, secobarbital, phenobarbital, thiopental; - Dobutamine should be administered with caution at the same time as: halothane and cyclopropane as ventricular arrhythmia has been reported - Dobutamine is inactivated by alkaline solutions; therefore it should not be mixed with 5% sodium bicarbonate or other alkaline solutions

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. - Change in blood lactate concentration measured as the difference between the maximum value at baseline: 0-1 hours after randomization and 72 hours after randomization, in the two treatment arms. - In case of death: change in blood lactate concentration measured as the difference between the maximum value at baseline: 0-1h after randomization and the last available lactate value from randomization, in the two treatment arms.

Secondary endpoints 1

1. - death or need for ECMO/LVAD at 72 hours - death or need for ECMO/LVAD at discharge - change in SOFA score between baseline (0-1 hour from randomization) and 72 hours from randomization and between baseline (0-1 hour from randomization) and 7 days from randomization - lactate AUC (0-72 hours) - need for additional extra-trial inotrope at 72 hours

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Unita' Sanitaria Locale Toscana Sud Est

Sponsor organisation

Azienda Unita' Sanitaria Locale Toscana Sud Est

Address

Via Senese 169

City

Grosseto

Postcode

58100

Country

Italy

Scientific contact point

Organisation

Azienda Unita' Sanitaria Locale Toscana Sud Est

Contact name

Valentina Fabbrini

Public contact point

Organisation

Azienda Unita' Sanitaria Locale Toscana Sud Est

Contact name

Valentina Fabbrini

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 17 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