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

Official title

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

Overview

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

• 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.

Primary outcome measures

• ECMO weaning success [Time frame: 30 days]
• Physiological substudy: End diastolic volume [Time frame: within 24 hours after ECMO initiation]

Secondary outcome measures (12)

• Treatment failure [Time frame: During ECMO support]
• 30 day, 90 day and 1 year mortality [Time frame: 30 days, 90 days and 1 year after ECMO initiation]
• ECMO support duration [Time frame: Until 30 days after ECMO initiation]
• Major bleeding events [Time frame: Until 30 days after ECMO initiation]
• Unplanned surgical or catheter based intervention of the leg(s) [Time frame: Until 30 days after ECMO initiation]
• Time to lactate normalization [Time frame: Until 30 days after ECMO initiation]
• Time to first negative net fluid balance [Time frame: Until 30 days after ECMO initiation]
• The occurrence of continuous venovenous hemofiltration initiation during ECMO support [Time frame: Until 30 days after ECMO initiation]
• Course in PF ratio [Time frame: Until 30 days after ECMO initiation.]
• Duration of mechanical ventilation. [Time frame: Until 30 days after ECMO initiation.]
• Left ventricular ejection fraction 30 days after ECMO initiation. [Time frame: At 30 days after ECMO initiation.]
• Time course in vasoactive inotropic score (VIS) during ECMO support [Time frame: Until 30 days after ECMO initiation.]

Eligibility 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):

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Netherlands · 11 centers

• Amphia hospital — Breda
• Catharina hospital — Eindhoven
• Amsterdam University Medical Center — Amsterdam
• Leiden University Medical Center — Leiden
• Erasmus Medical Center — Rotterdam
• Haga ziekenhuis — The Hague
• Antonius hospital — Nieuwegein
• University Medical Center Utrecht — Utrecht
• … and 3 more centers

Belgium · 3 centers

• AZ Sint-Jan Brugge — Bruges
• ZOL Genk — Genk
• UZ Gent — Ghent

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. PMID 24210621
• 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. PMID 29655828
• 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 PMID 33032450
• 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 Myo PMID 30586721
• 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. PMID 35361346
• 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. PMID 30765031
• 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. PMID 31656647
• van Steenwijk MPJ, van Rosmalen J, Elzo Kraemer CV, Donker DW, Hermens JAJM, Kraaijeveld AO, Maas JJ, Akin S, Montenij LJ, Vlaar APJ, van den Bergh WM, Oude Lansink-Hartgring A, de Metz J, Voesten N, Boersma E, Scholten E, Beishuizen A, Lexis CPH, Peperstraete H, Schiettekatte S, Lorusso R, Gommers DAMPJ, Tibboel D, de Boer RA, Van Mieghem NMDA, Meuwese CL; REMAP ECMO LV unloading study group. A r PMID 39447716

Identifiers

NCT: NCT05913622 · NL82979.078.23

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗