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

Cardiogenic Shock Clinical Trial

— REMAP ECMO  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05913622
• Other study ID #: NL82979.078.23
• Status: Recruiting
• Phase: N/A
• Start date: June 8, 2023
• Est. completion date: June 1, 2028

Study information

• Verified date: June 2023
• Source: Erasmus Medical Center
• Contact: Myrthe van Steenwijk
• Phone: +31627535136
• Email: m.p.j.vansteenwijk[@]erasmusmc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 430
• Est. completion date: June 1, 2028
• Est. primary completion date: July 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiogenic Shock
• Shock, Cardiogenic

Intervention

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.

Locations

Country	Name	City	State
Netherlands	Amsterdam University Medical Center	Amsterdam	Noord Holland
Netherlands	Amphia hospital	Breda	Brabant
Netherlands	Haga ziekenhuis	Den Haag	Zuid Holland
Netherlands	Catharina hospital	Eindhoven	Brabant
Netherlands	Leiden University Medical Center	Leiden	Zuid Holland
Netherlands	Antonius hospital	Nieuwegein	Utrecht
Netherlands	Erasmus Medical Center	Rotterdam	Zuid Holland
Netherlands	University Medical Center Utrecht	Utrecht

Sponsors (2)

Lead Sponsor	Collaborator
Erasmus Medical Center	Dutch Heart Foundation

Country where clinical trial is conducted

Netherlands, 

References & Publications (7)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	ECMO support duration	The duration of ECMO support in days	Until 30 days after ECMO initiation
Secondary	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
Secondary	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
Secondary	Time to lactate normalization	Time to lactate normalization (<2 mmol/L).	Until 30 days after ECMO initiation
Secondary	Time to first negative net fluid balance	Time to first negative net fluid balance (calculated per 24 hours).	Until 30 days after ECMO initiation
Secondary	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
Secondary	Course in PF ratio	Course in PaO2/FiO2 (PF) ratio (PaO2 divided by FiO2 provided)	Until 30 days after ECMO initiation.
Secondary	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.
Secondary	Left ventricular ejection fraction 30 days after ECMO initiation.	Left ventricular ejection fraction 30 days after ECMO initiation.	At 30 days after ECMO initiation.
Secondary	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.
Secondary	Time course in NT-pro BNP during ECMO support.	Time course in NT-pro BNP during ECMO support.	Until 30 days after ECMO initiation.
Secondary	Quality of life at 1 year	Quality of life on basis of EQ5D questionnaires	1 year after ECMO initiation
Secondary	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
Secondary	Hospital readmission rate	The number of hospital readmissions based on the information provided in the international Medical Consumption Questionnaire (iMCQ)	1 year