REMAP ECMO: A Study on the Effects of Left Ventricular Unloading in the Setting of VA ECMO Support
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
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:
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A patient registry that will serve for quality monitoring and observational studies of ECMO patients being treated in participating centers.
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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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: IABP unloading arm 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
An IABP is placed percutaneously into the thoracic aorta and supports the heart through synchronized inflation and deflation of a balloon.
Other Names:
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| No Intervention: ECMO alone arm This group of patients will receive VA ECMO support without left ventricular unloading device after randomization. |
Outcome Measures
Primary Outcome Measures
- 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).
Secondary Outcome Measures
- 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
- 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.
- Course in PF ratio [Until 30 days after ECMO initiation.]
Course in PaO2/FiO2 (PF) ratio (PaO2 divided by FiO2 provided)
- 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)
Eligibility Criteria
Criteria
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):
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Cardiogenic shock
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Having received VA ECMO support for severe circulatory (and respiratory insufficiency).
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Age ≥ 18 years
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Initiation of LV unloading (IABP or Impella) possible ≤ 8 hours after ECMO initiation
Exclusion criteria for the registry backbone
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Objection to participation in the registry by the patient and/or proxy
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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)
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No (deferred) informed consent provided by the patient and/or proxy.
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Pregnancy
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ECMO usage confined to the period during surgery or another intervention (the ECMO was removed at the end of the intervention).
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Isolated right ventricular failure (e.g. due to pulmonary embolism).
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Left ventricular assist device (LVAD), Impella or IABP in situ.
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Ventricular septal defect or papillary muscle rupture as the cause of shock.
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Thoracic or abdominal aortic dissection.
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Moderate or severe aortic regurgitation
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Mechanical prosthesis in mitral valve position
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Amphia hospital | Breda | Brabant | Netherlands | 4818 CK |
| 2 | Catharina hospital | Eindhoven | Brabant | Netherlands | 5623 EJ |
| 3 | Amsterdam University Medical Center | Amsterdam | Noord Holland | Netherlands | 1105 AZ |
| 4 | Antonius hospital | Nieuwegein | Utrecht | Netherlands | 3435 CM |
| 5 | Haga ziekenhuis | Den Haag | Zuid Holland | Netherlands | 2545 AA |
| 6 | Leiden University Medical Center | Leiden | Zuid Holland | Netherlands | 2333 ZA |
| 7 | Erasmus Medical Center | Rotterdam | Zuid Holland | Netherlands | 3015 GD |
| 8 | University Medical Center Utrecht | Utrecht | Netherlands | 3584 CX |
Sponsors and Collaborators
- Erasmus Medical Center
- Dutch Heart Foundation
Investigators
- Principal Investigator: Christiaan Meuwese, Erasmus Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
- Cheng R, Hachamovitch R, Kittleson M, Patel J, Arabia F, Moriguchi J, Esmailian F, Azarbal B. Complications of extracorporeal membrane oxygenation for treatment of cardiogenic shock and cardiac arrest: a meta-analysis of 1,866 adult patients. Ann Thorac Surg. 2014 Feb;97(2):610-6. doi: 10.1016/j.athoracsur.2013.09.008. Epub 2013 Nov 8.
- Grandin EW, Nunez JI, Willar B, Kennedy K, Rycus P, Tonna JE, Kapur NK, Shaefi S, Garan AR. Mechanical Left Ventricular Unloading in Patients Undergoing Venoarterial Extracorporeal Membrane Oxygenation. J Am Coll Cardiol. 2022 Apr 5;79(13):1239-1250. doi: 10.1016/j.jacc.2022.01.032.
- Keebler ME, Haddad EV, Choi CW, McGrane S, Zalawadiya S, Schlendorf KH, Brinkley DM, Danter MR, Wigger M, Menachem JN, Shah A, Lindenfeld J. Venoarterial Extracorporeal Membrane Oxygenation in Cardiogenic Shock. JACC Heart Fail. 2018 Jun;6(6):503-516. doi: 10.1016/j.jchf.2017.11.017. Epub 2018 Apr 11.
- Na SJ, Yang JH, Yang JH, Sung K, Choi JO, Hahn JY, Jeon ES, Cho YH. Left heart decompression at venoarterial extracorporeal membrane oxygenation initiation in cardiogenic shock: prophylactic versus therapeutic strategy. J Thorac Dis. 2019 Sep;11(9):3746-3756. doi: 10.21037/jtd.2019.09.35.
- Russo JJ, Aleksova N, Pitcher I, Couture E, Parlow S, Faraz M, Visintini S, Simard T, Di Santo P, Mathew R, So DY, Takeda K, Garan AR, Karmpaliotis D, Takayama H, Kirtane AJ, Hibbert B. Left Ventricular Unloading During Extracorporeal Membrane Oxygenation in Patients With Cardiogenic Shock. J Am Coll Cardiol. 2019 Feb 19;73(6):654-662. doi: 10.1016/j.jacc.2018.10.085.
- Schrage B, Becher PM, Bernhardt A, Bezerra H, Blankenberg S, Brunner S, Colson P, Cudemus Deseda G, Dabboura S, Eckner D, Eden M, Eitel I, Frank D, Frey N, Funamoto M, Gossling A, Graf T, Hagl C, Kirchhof P, Kupka D, Landmesser U, Lipinski J, Lopes M, Majunke N, Maniuc O, McGrath D, Mobius-Winkler S, Morrow DA, Mourad M, Noel C, Nordbeck P, Orban M, Pappalardo F, Patel SM, Pauschinger M, Pazzanese V, Reichenspurner H, Sandri M, Schulze PC, H G Schwinger R, Sinning JM, Aksoy A, Skurk C, Szczanowicz L, Thiele H, Tietz F, Varshney A, Wechsler L, Westermann D. Left Ventricular Unloading Is Associated With Lower Mortality in Patients With Cardiogenic Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation: Results From an International, Multicenter Cohort Study. Circulation. 2020 Dec;142(22):2095-2106. doi: 10.1161/CIRCULATIONAHA.120.048792. Epub 2020 Oct 9.
- Thiele H, Zeymer U, Thelemann N, Neumann FJ, Hausleiter J, Abdel-Wahab M, Meyer-Saraei R, Fuernau G, Eitel I, Hambrecht R, Bohm M, Werdan K, Felix SB, Hennersdorf M, Schneider S, Ouarrak T, Desch S, de Waha-Thiele S; IABP-SHOCK II Trial (Intraaortic Balloon Pump in Cardiogenic Shock II) Investigators; IABP-SHOCK II Investigators. Intraaortic Balloon Pump in Cardiogenic Shock Complicating Acute Myocardial Infarction: Long-Term 6-Year Outcome of the Randomized IABP-SHOCK II Trial. Circulation. 2019 Jan 15;139(3):395-403. doi: 10.1161/CIRCULATIONAHA.118.038201. Epub 2018 Nov 11.
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