Cardiogenic Shock
Conditions
Keywords
Left ventricular unloading, Venoarterial ExtraCorporeal Membrane Oxygenation (VA ECMO), Cardiogenic shock
Brief summary
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
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: 1. A patient registry that will serve for quality monitoring and observational studies of ECMO patients being treated in participating centers. 2. 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. * LV unloading trial A first trial domain to be initiated within the REMAP ECMO platform will address the effects of left ventricular (LV) unloading, 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. * Physiological substudy on IABP as adjunct to V-A ECMO A nested physiological observational substudy within the ongoing REMAP ECMO RCT, using the trial arms where patients are randomized between receiving V-A ECMO with or without IABP in the Erasmus Medical Center Rotterdam. The substudy aims to evaluate the physiological effects of IABP in conjunction with V-A ECMO on respiratory and hemodynamic parameters. The substudy consists of two parts: 1. Microcirculation and Macrocirculation: This part investigates the impact of IABP on both microcirculation and macrocirculation in the setting of V-A ECMO. 2. PEEP as an Unloading Modality: This part examines the effect of Positive End-Expiratory Pressure (PEEP) as an unloading modality during a decremental PEEP trial in patients receiving V-A ECMO, either with or without IABP. Endpoints in both substudies that can be assessed blindly will be evaluated by an assessor who is blinded to the assigned treatment arm and the objectives of the substudy
Interventions
An IABP is placed percutaneously into the thoracic aorta and supports the heart through synchronized inflation and deflation of a balloon.
Sponsors
Dutch Heart Foundation
Erasmus Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
No masking is possible as the device is visible after placement.
Intervention model description
Adaptive Bayesian Platform Trial evaluating multiple interventions in multiple domains
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ECMO weaning success | 30 days | 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). |
| Physiological substudy: End diastolic volume | within 24 hours after ECMO initiation | End diastolic volume as assessed by echocardiography |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Physiological substudy: microcirculation measurements | 24 and 48 hours after ECMO initiation | Microcirculation measurements: Perfused vessel density (PVD \[mm/mm2\], Total vessel density (TVD \[mm/mm2\] |
| Treatment failure | During ECMO support | 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). |
| 30 day, 90 day and 1 year mortality | 30 days, 90 days and 1 year after ECMO initiation | Mortality rate at 30 days, 90 days and 1 year after ECMO initiation |
| ECMO support duration | Until 30 days after ECMO initiation | The duration of ECMO support in days |
| Physiological substudy: respiratory parameters | 24 and 48 hours after ECMO initiation | Respiratory: FiO2, PEEP, Respiratory System Compliance (CRS) as the ratio between Vt/Dp. |
| Major bleeding events | Until 30 days after ECMO initiation | 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) | Until 30 days after 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. |
| Time to lactate normalization | Until 30 days after ECMO initiation | Time to lactate normalization (\<2 mmol/L). |
| Time to first negative net fluid balance | Until 30 days after ECMO initiation | Time to first negative net fluid balance (calculated per 24 hours). |
| The occurrence of continuous venovenous hemofiltration initiation during ECMO support | Until 30 days after ECMO initiation | The occurrence of continuous venovenous hemofiltration (dialysis) (CVVH(D)) initiation during ECMO support. |
| Physiological substudy: delta NT-pro BNP | 24 and 48 hours after ECMO initiation | delta NT-pro BNP |
| Duration of mechanical ventilation. | Until 30 days after ECMO initiation. | Duration of mechanical ventilation. Patients on mechanical ventilation via tracheostomy need to be 24 hours free of mechanical ventilation. |
| Left ventricular ejection fraction 30 days after ECMO initiation. | At 30 days after ECMO initiation. | Left ventricular ejection fraction 30 days after ECMO initiation. |
| Time course in vasoactive inotropic score (VIS) during ECMO support | Until 30 days after ECMO initiation. | Time course in vasoactive inotropic score (VIS) during ECMO support |
| Time course in NT-pro BNP during ECMO support. | Until 30 days after ECMO initiation. | Time course in NT-pro BNP during ECMO support. |
| Quality of life at 1 year | 1 year after ECMO initiation | Quality of life on basis of EQ5D questionnaires |
| Total health care costs | 6 and 12 months after ECMO initiation | 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 |
| Hospital readmission rate | 1 year | The number of hospital readmissions based on the information provided in the international Medical Consumption Questionnaire (iMCQ) |
| Physiological substudy: Heart rate | 24 and 48 hours after ECMO initiation | The average heart rate measured during 5 minutes |
| Physiological substudy: pulmonary artery catheter parameters | 24 and 48 hours after ECMO initiation | pulmonary artery catheter parameters: pulmonary capillary wedge pressure, cardiac output, central venous pressure |
| Course in PF ratio | Until 30 days after ECMO initiation. | Course in PaO2/FiO2 (PF) ratio (PaO2 divided by FiO2 provided) |
| Physiological substudy: Echocardiography | 24 and 48 hours after ECMO initiation | Echocardiography: LV ejection fraction, TAPSE, VTI LVOT |
Countries
Belgium, Netherlands
Contacts
Primary ContactMyrthe van Steenwijk
Backup ContactChristiaan Meuwese
Outcome results
None listed