REMAP ECMO - Beta Receptor Modulation Trial
- Registration Number
- NCT06522594
- Lead Sponsor
- Erasmus Medical Center
- Brief Summary
In this phase 2, single center, randomized clinical pilot trial, investigators will study the effect of a strategy involving a reduction of beta receptor (BR) stimulation (by decreasing dobutamine dosages) and subsequent BR inhibition (through ultra-short acting betablockers), versus a (routine) strategy with continued BR stimulation through dobutamine infusion, on heart rate in patients with cardiogenic shock due to left- or bi-ventricular failure being supported by V-A ECMO.
- Detailed Description
Despite the great benefits of Venoarterial ExtraCorporeal Membrane Oxygenation (V-A ECMO) and its rapidly increasing usage, even today, 30 till 70 percent of patients cannot be weaned from ECMO support and up to 50 percent of patients will eventually die in the first year. These high incidences of mortality and failure to wean from V-A ECMO support seem largely attributable to failure of the heart to recover in the context of inotropic drug administration and high sympathetic drive due to severe illness (further stressing an already failing heart). As V-A ECMO support creates a "safety window" where organ perfusion no longer relies on native cardiac output, therapeutic focus could be shifted to cardioprotective treatments. Cardioprotective treatments typically include beta blockers (BB) which have unequivocally shown benefits on mortality and morbidity in other patient categories with heart failure with reduced ejection fraction (HFrEF).
The investigators hypothesize that, in selected patients with cardiogenic shock undergoing V-A ECMO support, application of BBs is feasible and safe, and can effectively reduce heart rate.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 20
- Age ≥ 18 years,
- Having received V-A ECMO support for severe circulatory insufficiency due to left- or bi-ventricular failure.
- ≤ 16 hours after initiation of V-A ECMO support
- Receiving ≥ 2 mcg/kg/min of dobutamine.
- Norepinephrine infusion ≤ 0.4 mcg/kg/min
- Heart rate ≥ 80 bpm (being sinus rhythm, atrial fibrillation or atrial flutter) after V-A ECMO initiation
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Objection during the deferred consent procedure
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V-A ECMO usage confined to the period during surgery or another intervention (the ECMO was removed at the end of the intervention).
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Concomitant durable Left Ventricular Assist Device (LVAD)
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Polymorphic ventricular tachycardia necessitating BB therapy
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Isolated right ventricular failure (e.g. due to pulmonary embolism)
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Need of high dose dobutamine > 6.0 mcg/kg/min
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Epinephrine infusion
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Signs of insufficient trans cardiac flow:
- Absence of aortic valve opening
- Pulse pressure <10 mmHg (with intra-aortic balloon pump (IABP) standby)
- Spontaneous contrast in the heart at echocardiography
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Contraindications for-, intolerance to- or allergy to esmolol
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Second- or third- degree AV block
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Pregnancy
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Life expectancy of less than 24 hours
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Participation in another randomized clinical trial (e.g. On Scene trial or Left Ventricular unloading trial)
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Inability to start study treatment within 4 hours after randomization
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Post heart transplantation patients
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Beta receptor inhibition arm Esmolol In the "beta receptor (BR) inhibition arm", patients are randomized to a biphasic strategy where BR stimulation is phased out and esmolol (BR blockade) is initiated in a sequential way. During a first phase, milrinone (a phosphodiesterase inhibitor which is routinely used in V-A ECMO supported patients) infusion will be initiated (if not already being given) at 0.25 mcg/kg/min and dobutamine dosages will be decreased every hour and eventually stopped according to the following sequence; 6 - 4 - 2 - 1 - 0 mcg/kg/min. In a second phase, esmolol is initiated with a dosage of 25 mcg/kg/min. The dose of the BB will be increased with increments of 25 mcg/kg/min every hour until reaching a heart rate between 50 and 70 bpm or a maximum dose of 200 mcg/kg/min. Prior to each dosage escalation, a reassessment of the hemodynamic situation will be done. The BR inhibition strategy will be continued until 48 hours after randomization or earlier when deemed necessary by the treating physician.
- Primary Outcome Measures
Name Time Method Change (delta) in heart rate 24 hours after randomization. 24 hours after randomization The average heart rate on basis of all observations during 5 minutes at both time points (t=0 and t=24h).
- Secondary Outcome Measures
Name Time Method Myocardial oxygen consumption At 24 and 48 hours after randomization Estimated by calculating the pressure volume (PV) area on basis of non-invasive PV loop assessments using echocardiography and pulmonary artery catheter measurements
Vasopressor score at baseline, 24 and 48 hours using the calculation as described in literature, excluding inotropic medication
Stroke volume index at baseline, 24 and 48 hours Pulmonary arterial catheter parameter
Maximum median dosages of esmolol after 48 hours Tricuspid annular plane systolic excursion (TAPSE). at baseline, 24 and 48 hours Echocardiography parameters
Left ventricular outflow tract velocity time integral (LVOT VTI) at baseline, 24 and 48 hours Echocardiography parameters
Lactate level at baseline, 24 and 48 hours Plasma NT-proBNP levels At baseline and 48 hours after randomization Biomarker for cardiac stretch
Plasma Creatine Kinase MB levels At baseline and 48 hours after randomization Biomarker for cardiac injury
Plasma metanephrine levels At baseline and 24 after randomization Plasma normetanephrines levels At baseline and 24 after randomization Positive End Expiratory Pressure (PEEP) level At 24 and 48 hours after randomization Percentage of patients having received esmolol after 48 hours Occurrence of new onset ventricular and/or atrial arrhythmias after randomization during the first 48 hours Cardiac output at baseline, 24 and 48 hours Pulmonary arterial catheter parameter
Pulmonary capillary wedge pressure at baseline, 24 and 48 hours Pulmonary arterial catheter parameter
Troponin At 24 and 48 hours after randomization measured at baseline, 24- and 48- hours after randomization, and Area Under the Curve (AUC)
Central venous pressure at baseline, 24 and 48 hours Pulmonary arterial catheter parameter
Mixed venous oxygen saturation (SvO2) at baseline, 24 and 48 hours Pulmonary arterial catheter parameter
FiO2 suppletion At 24 and 48 hours after randomization Ejection fraction (EF) at baseline, 24 and 48 hours Echocardiography parameters
Trial Locations
- Locations (1)
Erasmus Medical Center
🇳🇱Rotterdam, Zuid Holland, Netherlands