REMAP ECMO - Beta Receptor Modulation Trial

NCT06522594 | Recruiting Phase 2

• 1 other identifier: EUCT 2024-511805-42
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure; Cardiogenic Shock

Keywords

Veno-Arterial ExtraCorporeal Membrane Oxygenation; Betablocker; Esmolol; Cardiogenic shock

Outcome Measures

Primary Outcomes (1)

• Change (delta) in heart rate 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).

  24 hours after randomization

Secondary Outcomes (21)

• Percentage of patients having received esmolol

  after 48 hours

• Vasopressor score

  at baseline, 24 and 48 hours

• Occurrence of new onset ventricular and/or atrial arrhythmias after randomization

  during the first 48 hours

• Left ventricular outflow tract velocity time integral (LVOT VTI)

  at baseline, 24 and 48 hours

• Cardiac output

  at baseline, 24 and 48 hours

Study Arms (2)

Beta receptor inhibition arm

EXPERIMENTAL

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.

Drug: Esmolol

Routine care arm

NO INTERVENTION

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.

Interventions

Esmolol DRUG

A vey cardioselective, short-acting betablocker, with an ultra-short half life time.

Beta receptor inhibition arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Erasmus Medical Center: lead

Study Sites (1)

Erasmus Medical Center

Rotterdam, South Holland, 3015GD, Netherlands

RECRUITING

Related Publications (5)

• Meuwese CL, Hermens JA, de Haan M, Braithwaite SA, Ramjankhan F, Buijsrogge MP, de Jonge N, Kirkels JH, de Jong M, Pasma W, Vromen-Wijsman JLP, Kraaijeveld AO, de Waal EE, Torn E, Platenkamp M, van der Heijden JJ, Cremer OL, van Dijk D, Donker DW. Twelve years of circulatory extracorporeal life support at the University Medical Centre Utrecht. Neth Heart J. 2021 Jul;29(7-8):394-401. doi: 10.1007/s12471-021-01552-z. Epub 2021 Mar 6.

  PMID: 33675521 BACKGROUND

• McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. No abstract available.

  PMID: 34447992 BACKGROUND

• Flather MD, Gollop ND. Understanding Mechanisms of Action of Beta-Blockers in Heart Failure With Reduced and Preserved Ejection Fraction. JACC Heart Fail. 2016 Feb;4(2):150-151. doi: 10.1016/j.jchf.2015.12.009. No abstract available.

  PMID: 26823116 BACKGROUND

• Rahhal A, Omar AS, Aljundi A, Kasem M, Mahfouz A, Alyafei S. Successful Use of Intravenous B-blocker Therapy in Cardiogenic Shock Supported With Venoarterial Extracorporeal Membrane Oxygenation: A Case Series. Curr Probl Cardiol. 2022 Nov;47(11):101071. doi: 10.1016/j.cpcardiol.2021.101071. Epub 2021 Nov 26.

  PMID: 34838902 BACKGROUND

• Brugts JJ, Manintveld O, Constantinescu A, Donker DW, van Thiel RJ, Nieman K, Jewbali LS, Zijlstra F, Caliskan K. Preventing LVAD implantation by early short-term mechanical support and prolonged inodilator therapy : A case series with acute refractory cardiogenic shock treated with veno-arterial extracorporeal membrane oxygenation and optimised medical strategy. Neth Heart J. 2014 Apr;22(4):176-81. doi: 10.1007/s12471-013-0509-5.

  PMID: 24424723 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Shock, Cardiogenic

Interventions

esmolol

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Myocardial Infarction; Myocardial Ischemia; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Shock

Study Officials

• Christiaan L. Meuwese

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christiaan L. Meuwese, MD, PhD

CONTACT

0631135752; c.meuwese@erasmusmc.nl

Myrthe PJ van Steenwijk, MD

CONTACT

0650162551; m.p.j.vansteenwijk@erasmusmc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Cardiologist-Intensivist

Study Record Dates

• First Submitted: July 17, 2024
• First Posted: July 26, 2024
• Study Start: June 1, 2024
• Primary Completion: December 1, 2025
• Study Completion: December 3, 2025
• Last Updated: July 26, 2024

Record last verified: 2024-07

Locations

NL (1)