Clinical trial NCT05913622: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cardiogenic Shock
Keywords: Left ventricular unloading
Venoarterial ExtraCorporeal Membrane Oxygenation (VA ECMO)
Cardiogenic shock
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: Dutch Heart Foundation
First posted: 2023-06-22
Enrollment: 430
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Adaptive Bayesian Platform Trial evaluating multiple interventions in multiple domains
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: ECMO weaning success
timeFrame: 30 days
measure: Physiological substudy: End diastolic volume
timeFrame: within 24 hours after ECMO initiation
Secondary outcomes:
measure: Treatment failure
timeFrame: During ECMO support
measure: 30 day, 90 day and 1 year mortality
timeFrame: 30 days, 90 days and 1 year after ECMO initiation
measure: ECMO support duration
timeFrame: Until 30 days after ECMO initiation
measure: Major bleeding events
timeFrame: Until 30 days after ECMO initiation
measure: Unplanned surgical or catheter based intervention of the leg(s)
timeFrame: Until 30 days after ECMO initiation
measure: Time to lactate normalization
timeFrame: Until 30 days after ECMO initiation
measure: Time to first negative net fluid balance
timeFrame: Until 30 days after ECMO initiation
measure: The occurrence of continuous venovenous hemofiltration initiation during ECMO support
timeFrame: Until 30 days after ECMO initiation
measure: Course in PF ratio
timeFrame: Until 30 days after ECMO initiation.
measure: Duration of mechanical ventilation.
timeFrame: Until 30 days after ECMO initiation.
measure: Left ventricular ejection fraction 30 days after ECMO initiation.
timeFrame: At 30 days after ECMO initiation.
measure: Time course in vasoactive inotropic score (VIS) during ECMO support
timeFrame: Until 30 days after ECMO initiation.
measure: Time course in NT-pro BNP during ECMO support.
timeFrame: Until 30 days after ECMO initiation.
measure: Quality of life at 1 year
timeFrame: 1 year after ECMO initiation
measure: Total health care costs
timeFrame: 6 and 12 months after ECMO initiation
measure: Hospital readmission rate
timeFrame: 1 year
measure: Physiological substudy: Heart rate
timeFrame: 24 and 48 hours after ECMO initiation
measure: Physiological substudy: pulmonary artery catheter parameters
timeFrame: 24 and 48 hours after ECMO initiation
measure: Physiological substudy: Echocardiography
timeFrame: 24 and 48 hours after ECMO initiation
measure: Physiological substudy: microcirculation measurements
timeFrame: 24 and 48 hours after ECMO initiation
measure: Physiological substudy: respiratory parameters
timeFrame: 24 and 48 hours after ECMO initiation
measure: Physiological substudy: delta NT-pro BNP
timeFrame: 24 and 48 hours after ECMO initiation
Other outcomes:
Locations:
city: Breda
country: Netherlands
facility: Amphia hospital
state: Brabant
city: Eindhoven
country: Netherlands
facility: Catharina hospital
state: Brabant
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Center
state: Noord Holland
city: Nieuwegein
country: Netherlands
facility: Antonius hospital
state: Utrecht
city: Den Haag
country: Netherlands
facility: Haga ziekenhuis
state: Zuid Holland
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
state: Zuid Holland
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
state: Zuid Holland
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
affiliation: Erasmus Medical Center
name: Christiaan Meuwese
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.