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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Cardiogenic Shock

Intervention / Treatment
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* Device: Intra-aortic balloon pump


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Adaptive Bayesian Platform Trial evaluating multiple interventions in multiple domains
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IABP unloading arm<br>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. | Device: Intra-aortic balloon pump<br>* An IABP is placed percutaneously into the thoracic aorta and supports the heart through synchronized inflation and deflation of a balloon.<br>* Other names: IABP;|
| No Intervention: ECMO alone arm<br>This group of patients will receive VA ECMO support without left ventricular unloading device after randomization. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ECMO weaning success | 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). | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment failure | 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). | During ECMO support | 
| 30 day, 90 day and 1 year mortality | Mortality rate at 30 days, 90 days and 1 year after ECMO initiation | 30 days, 90 days and 1 year after ECMO initiation | 
| ECMO support duration | The duration of ECMO support in days | Until 30 days after ECMO initiation | 
| Major bleeding events | 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. | Until 30 days after ECMO initiation | 
| Unplanned surgical or catheter based intervention of the leg(s) | 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. | Until 30 days after ECMO initiation | 
| Time to lactate normalization | Time to lactate normalization (<2 mmol/L). | Until 30 days after ECMO initiation | 
| Time to first negative net fluid balance | Time to first negative net fluid balance (calculated per 24 hours). | Until 30 days after ECMO initiation | 
| The occurrence of continuous venovenous hemofiltration initiation during ECMO support | The occurrence of continuous venovenous hemofiltration (dialysis) (CVVH(D)) initiation during ECMO support. | Until 30 days after ECMO initiation | 
| Course in PF ratio | Course in PaO2/FiO2 (PF) ratio (PaO2 divided by FiO2 provided) | Until 30 days after ECMO initiation. | 
| Duration of mechanical ventilation. | Duration of mechanical ventilation. Patients on mechanical ventilation via tracheostomy need to be 24 hours free of mechanical ventilation. | Until 30 days after ECMO initiation. | 
| Left ventricular ejection fraction 30 days after ECMO initiation. | Left ventricular ejection fraction 30 days after ECMO initiation. | At 30 days after ECMO initiation. | 
| Time course in vasoactive inotropic score (VIS) during ECMO support | Time course in vasoactive inotropic score (VIS) during ECMO support | Until 30 days after ECMO initiation. | 
| Time course in NT-pro BNP during ECMO support. | Time course in NT-pro BNP during ECMO support. | Until 30 days after ECMO initiation. | 
| Quality of life at 1 year | Quality of life on basis of EQ5D questionnaires | 1 year after ECMO initiation | 
| Total health care costs | 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 | 6 and 12 months after ECMO initiation | 
| Hospital readmission rate | The number of hospital readmissions based on the information provided in the international Medical Consumption Questionnaire (iMCQ) | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Left ventricular unloading, Venoarterial ExtraCorporeal Membrane Oxygenation (VA ECMO), Cardiogenic shock