A Study on the Effects of Left Ventricular Unloading in the Setting of VA ECMO Support (REMAP ECMO)

Randomized Embedded Multifactorial Adaptive Platform in ExtraCorporeal Membrane Oxygenation (REMAP ECMO) - Left Ventricular Unloading Study

REMAP ECMO is a registry based platform in which multiple response adaptive randomized clinical trials (trial domains) will be embedded. These trial domains will, in a perpetual way, study the effects of a range of patient management strategies which aim to improve VA ECMO weaning success. A first trial domain will address the effects of left ventricular (LV) unloading through intra-aortic balloon pumping on weaning succes in VA ECMO supported patients.

ExtraCorporeal Membrane Oxygenation (ECMO) is increasingly used but remains associated with high weaning failure- and mortality- rates. This seems in part attributable to a knowledge gap on how to properly manage ECMO and its related therapies as current knowledge and treatment protocols are based on observational studies and expert opinions. The "Randomized Embedded Multifactorial Adaptive Platform in ECMO" (REMAP ECMO) study was developed to study, in an efficient and randomized way, different ECMO related patient management issues and will consist of two parts: A patient registry that will serve for quality monitoring and observational studies of ECMO patients being treated in participating centers. Embedded within the registry, multiple response adaptive randomized clinical trials (trial domains) which aim to evaluate the effectiveness of a range of therapeutic interventions on ECMO weaning success. These interventions all have in common that they are all already used in ECMO care but their use depends on center and/or doctors preferences as no high quality (randomized) evidence guiding their indication, timing and management exists. A first trial domain to be initiated within the REMAP ECMO platform will address the effects of different left ventricular (LV) unloading techniques, through application of an intra-aortic balloon pump (IABP), on weaning success in the setting of venoarterial (VA) ECMO. The rationale of this trial domain is based on the increase in LV loading conditions, as induced by VA ECMO, which could lead to pulmonary edema, intracardiac thrombosis and even death. These serious sequelae could possibly be prevented by adding IABP as adjunct to VA ECMO therapy.

Left ventricular unloading, Venoarterial ExtraCorporeal Membrane Oxygenation (VA ECMO), Cardiogenic shock

This group of patients will receive an intra-aortic balloon pump (IABP) as an adjunct to VA ECMO support. When allocated to the IABP unloading arm, patients must receive an IABP within 8 hours after VA ECMO initiation.

This group of patients will receive VA ECMO support without left ventricular unloading device after randomization.

An IABP is placed percutaneously into the thoracic aorta and supports the heart through synchronized inflation and deflation of a balloon.

Proportion of patients successfully weaned from VA ECMO at 30 days being defined by; a) being alive, b) without ECMO, IABP or Impella support, and c) not having received a heart transplantation or left ventricular assist device (LVAD).

The proportion of patients in whom LV unloading therapy was escalated. Escalation is defined by the insertion of an IABP (only in the VA ECMO alone arm), or Impella or left vent (IABP unloading arm or VA ECMO alone arm).

The occurrence of major bleeding events (fatal, in a critical area (intracranial, intraspinal, or intraocular), requiring intervention (coiling or surgery) and/or transfusion of ≥3 packed cells) until 30 days after VA ECMO initiation.

Unplanned surgical or catheter based intervention of the leg(s) in which ECMO and/or IABP or Impella was inserted until 30 days after ECMO initiation.

The occurrence of continuous venovenous hemofiltration (dialysis) (CVVH(D)) initiation during ECMO support.

Duration of mechanical ventilation. Patients on mechanical ventilation via tracheostomy need to be 24 hours free of mechanical ventilation.

Total healthcare costs in euros are determined by using the International Medical Consumption Questionnaire (iMCQ) and the calculated costs after 6 and 12 months of follow up

The number of hospital readmissions based on the information provided in the international Medical Consumption Questionnaire (iMCQ)

Inclusion criteria for the registry backbone: Having received ECMO support for severe circulatory and/or respiratory insufficiency Inclusion Criteria for the LV unloading trial domain (VA ECMO + IABP vs VA ECMO alone): Cardiogenic shock Having received VA ECMO support for severe circulatory (and respiratory insufficiency). Age ≥ 18 years Initiation of LV unloading (IABP or Impella) possible ≤ 8 hours after ECMO initiation Exclusion criteria for the registry backbone Objection to participation in the registry by the patient and/or proxy VA ECMO usage confined to the period during surgery or another intervention (the VA ECMO was removed at the end of the intervention in the operation room). Exclusion criteria for the LV unloading trial domain (VA ECMO + IABP vs VA ECMO alone) No (deferred) informed consent provided by the patient and/or proxy. Pregnancy ECMO usage confined to the period during surgery or another intervention (the ECMO was removed at the end of the intervention). Isolated right ventricular failure (e.g. due to pulmonary embolism). Left ventricular assist device (LVAD), Impella or IABP in situ. Ventricular septal defect or papillary muscle rupture as the cause of shock. Thoracic or abdominal aortic dissection. Moderate or severe aortic regurgitation Mechanical prosthesis in mitral valve position

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