Beta receptor modulation trial in cardiogenic shock patients supported by V-A ECMO

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

23 May 2024 → ongoing

Decision date (initial)

2024-05-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Erasmus Medical Center Rotterdam

External identifiers

EU CT number

2024-511805-42-00

WHO UTN

U1111-1304-2119

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

1. To demonstrate safety and feasibility of a strategy involving a reduction in BR stimulation and subsequent inhibition through application of an intravenous BB (BR inhibition).
2. To study the effect of a beta receptor inhibition strategy versus a strategy to continue beta receptor stimulation (as is done in routine clinical care) on heart rate.

Secondary objectives 1

1. To study the effect of a strategy involving a reduction and subsequent inhibition of the BR versus a strategy to continue BR stimulation (as is routine care at this moment) on myocardial oxygen consumption, cardiac function, and cardiac markers.

Conditions and MedDRA coding

Cardiogenic shock

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age ≥ 18 years
2. Having received V-A ECMO support for severe circulatory insufficiency due to left- or bi-ventricular failure
3. ≤ 16 hours after initiation of V-A ECMO support
4. Receiving ≥ 2 mcg/kg/min of dobutamine
5. Norepinephrine infusion ≤ 0.6 mcg/kg/min
6. Heart rate of ≥ 80 bpm (being sinus rhythm, atrial fibrillation or atrial flutter) after V-A ECMO initiation

Exclusion criteria 15

1. Objection during the deferred consent procedure
2. V-A ECMO usage confined to the period during surgery or another intervention (the ECMO was removed at the end of the intervention)
3. Concomittant durable LVAD
4. Polymorphic ventricular tachycardia necessitating betablocker therapy
5. Isolated right ventricular failure (e.g. due to pulmonary embolism)
6. Need of high dose dobutamine > 6.0 mcg/kg/min
7. Epinephrine infusion
8. Signs of insufficient trans cardiac flow (Absence of aortic valve opening, pulse pressure <10 mmHg (with IABP standby), spontaneous contrast in the heart at echocardiography)
9. Contraindications for-, intolerance to- or allergy to esmolol
10. Second- or third- degree AV block
11. Pregnancy
12. Estimated life expectancy of < 24 hours
13. Participation in another randomized clinical trial
14. Inability to start study treatment within 4 hours after randomization
15. Post heart transplantation patients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change (delta) in heart rate 24 hours after randomization. The average heart rate will be calculated based on all observations during 5 minutes.

Secondary endpoints 11

1. Percentage of patients having received esmolol and the maximum median dosages after 48 hours.
2. Vasopressor score at baseline, 24 and 48 hours after randomization, using the calculation as described in literature, excluding inotropic medication
3. Occurrence of new onset ventricular and/or atrial arrhythmias during the first 48 hours after randomization
4. Left ventricular outflow tract velocity time integral (LVOT VTI), ejection fraction (EF), tricuspid annular plane systolic excursion (TAPSE) at baseline, 24 and 48 hours after randomization
5. Cardiac output, pulmonary capillary wedge pressure, central venous pressure (measured by pulmonary artery catheter), SVO2 at baseline, 24 and 48 hours after randomization
6. Lactate level at baseline, 24 and 48 hours after randomization
7. Troponin at 24 and 48 hours after randomization and Area Under the Curve (AUC)
8. Myocardial oxygen consumption estimated by calculating the pressure volume (PV) area on basis of non-invasive PV loop assessments using echocardiography and pulmonary artery catheter measurements at 24 and 48 hours after randomization
9. Biomarkers on cardiac stretch and cardiac injury at baseline and 48 hours after randomization
10. FiO2 suppletion and PEEP level at 24 and 48 hours after randomization
11. Plasma metanephrines and normetanephrine levels at baseline and 24 hours after randomization

Investigational products

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

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Sponsor organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015 GD

Country

Netherlands

Scientific contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

C.L. Meuwese

Public contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

C.L. Meuwese

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 3 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