REMAP ECMO - Beta Receptor Modulation Trial

Erasmus University

Status and phase: Enrolling; Phase 2

Conditions: Heart Failure; Cardiogenic Shock

Treatments: Drug: Esmolol

Study type: Interventional

Funder types: Other

Identifiers

NCT06522594

EUCT 2024-511805-42

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• Objection during the deferred consent procedure

• V-A ECMO usage confined to the period during surgery or another intervention (the ECMO was removed at the end of the intervention).

• Concomitant durable Left Ventricular Assist Device (LVAD)

• Polymorphic ventricular tachycardia necessitating BB therapy

• Isolated right ventricular failure (e.g. due to pulmonary embolism)

• Need of high dose dobutamine > 6.0 mcg/kg/min

• Epinephrine infusion

• 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

• Contraindications for-, intolerance to- or allergy to esmolol

• Second- or third- degree AV block

• Pregnancy

• Life expectancy of less than 24 hours

• Participation in another randomized clinical trial (e.g. On Scene trial or Left Ventricular unloading trial)

• Inability to start study treatment within 4 hours after randomization

• Post heart transplantation patients

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

Beta receptor inhibition arm

Experimental group

Description:

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.

Treatment:

Drug: Esmolol

Routine care arm

No Intervention group

Description:

The dosage of dobutamine infusion is at the discretion of the treating physician but is typically continued until 48 hours after randomization. All other medication will be managed according to the needs of the patient at the discretion of the treating physician.