Esmolol hydrochloride for Cardiogenic shock

Inclusion criteria

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

Exclusion criteria

• {"criterion_text":"- Objection during the deferred consent procedure"}
• {"criterion_text":"- Second- or third- degree AV block"}
• {"criterion_text":"- Pregnancy"}
• {"criterion_text":"- Estimated life expectancy of < 24 hours"}
• {"criterion_text":"- Participation in another randomized clinical trial"}
• {"criterion_text":"- Inability to start study treatment within 4 hours after randomization"}
• {"criterion_text":"- Post heart transplantation patients"}
• {"criterion_text":"- V-A ECMO usage confined to the period during surgery or another intervention (the ECMO was removed at the end of the intervention)"}
• {"criterion_text":"- Concomittant durable LVAD"}
• {"criterion_text":"- Polymorphic ventricular tachycardia necessitating betablocker therapy"}
• {"criterion_text":"- Isolated right ventricular failure (e.g. due to pulmonary embolism)"}
• {"criterion_text":"- Need of high dose dobutamine > 6.0 mcg/kg/min"}
• {"criterion_text":"- Epinephrine infusion"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Contraindications for-, intolerance to- or allergy to esmolol"}

Primary endpoints

• {"endpoint_text":"- Change (delta) in heart rate 24 hours after randomization. The average heart rate will be calculated based on all observations during 5 minutes.","definition_or_measurement_approach":"Average heart rate calculated based on all observations during 5 minutes; change (delta) measured at 24 hours after randomization."}

Secondary endpoints

• {"endpoint_text":"- Percentage of patients having received esmolol and the maximum median dosages after 48 hours.","definition_or_measurement_approach":"Proportion of patients who received esmolol; report maximum median dosages at 48 hours."}
• {"endpoint_text":"- Vasopressor score at baseline, 24 and 48 hours after randomization, using the calculation as described in literature, excluding inotropic medication","definition_or_measurement_approach":"Vasopressor score calculated per published method (excluding inotropic medication) at baseline, 24h, 48h."}
• {"endpoint_text":"- Occurrence of new onset ventricular and/or atrial arrhythmias during the first 48 hours after randomization","definition_or_measurement_approach":"Record incidence of new ventricular and/or atrial arrhythmias within 48 hours after randomization."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Echocardiographic measures (LVOT VTI, EF, TAPSE) at baseline, 24h, 48h."}
• {"endpoint_text":"- Cardiac output, pulmonary capillary wedge pressure, central venous pressure (measured by pulmonary artery catheter), SVO2 at baseline, 24 and 48 hours after randomization","definition_or_measurement_approach":"Hemodynamic parameters including CO, PCWP, CVP (via pulmonary artery catheter) and SVO2 measured at baseline, 24h, 48h."}
• {"endpoint_text":"- Lactate level at baseline, 24 and 48 hours after randomization","definition_or_measurement_approach":"Blood lactate measured at baseline, 24h, 48h."}
• {"endpoint_text":"- Troponin at 24 and 48 hours after randomization and Area Under the Curve (AUC)","definition_or_measurement_approach":"Troponin measured at 24h and 48h and AUC calculated."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Estimate myocardial O2 consumption by calculating PV area from non-invasive PV loop assessments using echocardiography and pulmonary artery catheter data at 24h and 48h."}
• {"endpoint_text":"- Biomarkers on cardiac stretch and cardiac injury at baseline and 48 hours after randomization","definition_or_measurement_approach":"Measure biomarkers of cardiac stretch and injury at baseline and 48h."}
• {"endpoint_text":"- FiO2 suppletion and PEEP level at 24 and 48 hours after randomization","definition_or_measurement_approach":"Record FiO2 supplementation and PEEP at 24h and 48h."}
• {"endpoint_text":"- Plasma metanephrines and normetanephrine levels at baseline and 24 hours after randomization","definition_or_measurement_approach":"Measure plasma metanephrines and normetanephrines at baseline and 24h."}

Netherlands

Earliest CTIS Part Ii Submission Date

02-05-2024

Latest Decision Or Authorization Date

10-05-2024

Processing Time Days

8

Number Of Sites

1

Number Of Participants

20

Primary sponsor

Full Name

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands