Early Preventive Left Ventricle Unloading After VA-ECMO for Refractory Cardiogenic Shock

NCT ID: NCT07027202

Last Updated: 2025-06-18

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 298 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-30
• Study Completion Date: 2027-08-31

Brief Summary

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly being used worldwide to treat severe cardiogenic shock. The survival rate of these patients has increased in the last decade, reaching 45-50% for patients with acute myocardial infarction (AMI), the most frequent indication of the technique, 50-60% for patients with end-stage dilated cardiomyopathy bridged to heart transplantation or long-term left ventricle assist device (LVAD) surgery, 60-70% for fulminant myocarditis, while it remains lower for post-cardiotomy cardiogenic shock (25-35%) and after cardiac arrest (20-40%). However, peripherally inserted VA-ECMO increases left ventricular (LV) afterload, that may lead to poorer clinical outcomes by fostering left ventricular distension, blood stagnation, aortic valve closure, all of which increasing pulmonary congestion and the need for mechanical ventilation and compromising myocardial recovery whenever it is possible, or delaying a bridge to a heart transplantation or long-term left ventricle assist device (LVAD) surgery for patients with end-stage cardiac dysfunction. Several methods have been proposed to reduce afterload after VA-ECMO, including the use of an intra-aortic balloon pump (IABP), balloon atrial septostomy, transseptal left atrial cannula insertion, and use of the left-sided Impella device (Abiomed, Danvers, MA, USA). The clinical benefits of left ventricular unloading have been suggested by many retrospective case-control studies, including a study by our group that showed that associating an IABP with peripheral VA-ECMO was independently associated with a lower frequency of hydrostatic pulmonary edema under ECMO and more days off mechanical ventilation. More recently, unloading the left ventricle with an IABP was associated with the best survival rate and security profile as compared to no unloading or unloading with a microaxial pump in 12,734 VA-ECMO patients included in the Extracorporeal Life Support Organization registry. It should also be mentioned that another large registry study showed that the greatest benefit of LV unloading under ECMO was observed with early versus delayed insertion of the unloading device. Lastly, the EARLY-UNLOAD randomized trial in which a transseptal left atrial cannula was used for LV unloading yielded negative results. However, it is important to note that 50% of control patients were rapidly transitioned to LV unloading, thereby compromising the opportunity to demonstrate a mortality benefit. It was also underpowered for the primary outcome of D30 mortality since it included only 116 patients As a result, the recourse to systematic early LV unloading remains highly heterogeneous in clinical practice. For example, , while IABP was EULODIA - Protocol, version 1.0 dated 24/01/2025 Page 6 sur 54 This document is the property of DRCI/AP-HP. All reproduction is strictly prohibited.

Version no. 4.0 of 31/05/2019 associated to ECMO in >70% of the cases in our series of AMI CS patients, only 5.8% of the patients included in the ECMO arm of the recent ECLS-Shock trial received an unloading device, which may have contributed to the neutral result of the study and the only randomized trial to date was underpowered and flawed by a very high rate of early cross-over. Indeed, there is large heterogeneity in current clinical practice, where decisions on whether to add an additional mechanical unloading device during VA-ECMO support vary widely.

Therefore, a new and adequately powered trial comparing systematic early left ventricular unloading to a conventional approach, with rescue left ventricular unloading only in case of clear and urgent indication, i.e. if overt hydrostatic cardiogenic pulmonary edema occurs, is urgently needed. The EULODIA trial is designed to test the hypothesis that early preventive left ventricle unloading with an IABP improves clinical outcomes as compared to conventional care with delayed curative unloading in patients under VA-ECMO for refractory cardiogenic shock.

Conditions

Cardiogenic Shock Acute

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Early Left Ventricle unloading arm

An Intraortic balloon pump will be systematically inserted as soon as possible, within 12 hours post-randomization.

• A pulmonary artery catheter (PAC) will enable hemodynamic monitoring of cardiac filling pressures, cardiac output and pulmonary artery pressures.
• Doppler Echocardiography will be performed at least daily to monitor LV ejection, LV dimension, appearance of LV blood stagnation, aortic time-velocity integral (VTI) and aortic valve opening.
• Escalation to a microaxial LV venting pump, central ECMO or atrial septostomy will be possible and discussed by the Shock team (as suggested by international recommendations) in case of
• Overt cardiogenic pulmonary edema requiring invasive mechanical ventilation
• Persisting more than 6 hours despite IABP support and optimization of patient's management (titration of ECMO blood flow, inotropes, non-invasive mechanical ventilation with PEEP, diuretics or hemofiltration).

Group Type: EXPERIMENTAL

Early Left Ventricle unloading

Intervention Type: PROCEDURE

An Intraortic balloon pump will be systematically inserted as soon as possible, within 12 hours post-randomization.

• A pulmonary artery catheter (PAC) will enable hemodynamic monitoring of cardiac filling pressures, cardiac output and pulmonary artery pressures.
• Doppler Echocardiography will be performed at least daily to monitor LV ejection, LV dimension, appearance of LV blood stagnation, aortic time-velocity integral (VTI) and aortic valve opening.
• Escalation to a microaxial LV venting pump, central ECMO or atrial septostomy will be possible and discussed by the Shock team (as suggested by international recommendations) in case of
• Overt cardiogenic pulmonary edema requiring invasive mechanical ventilation
• Persisting more than 6 hours despite IABP support and optimization of patient's management (titration of ECMO blood flow, inotropes, non-invasive mechanical ventilation with PEEP, diuretics or hemofiltration).

Standard management of VA-ECMO cardiogenic shock patients.

A pulmonary artery catheter will enable hemodynamic monitoring of cardiac filling pressures, cardiac output, and pulmonary artery pressures. - Doppler Echocardiography will be performed at least daily to monitor LV ejection, LV dimension, appearance of LV blood stagnation, aortic VTI and aortic valve opening. - Optimization of patient's management in case of signs of cardiogenic pulmonary edema occurring under VA-ECMO (titration of ECMO blood flow, inotropes, non-invasive ventilation mechanical ventilation with PEEP, diuretics or hemofiltration). - LV unloading (IABP, microaxial LV venting pump, central ECMO or atrial septostomy) (as suggested by international recommendations) discussed by the Shock team in case of overt cardiogenic pulmonary edema persisting more than 6 hours despite the aforementioned measure and the recourse to invasive mechanical ventilation AND o PCWP \>20 mmHg OR o Aortic valve opening less than 50% of electric systole and VTI \< 4cm

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Early Left Ventricle unloading

An Intraortic balloon pump will be systematically inserted as soon as possible, within 12 hours post-randomization.

• A pulmonary artery catheter (PAC) will enable hemodynamic monitoring of cardiac filling pressures, cardiac output and pulmonary artery pressures.
• Doppler Echocardiography will be performed at least daily to monitor LV ejection, LV dimension, appearance of LV blood stagnation, aortic time-velocity integral (VTI) and aortic valve opening.
• Escalation to a microaxial LV venting pump, central ECMO or atrial septostomy will be possible and discussed by the Shock team (as suggested by international recommendations) in case of
• Overt cardiogenic pulmonary edema requiring invasive mechanical ventilation
• Persisting more than 6 hours despite IABP support and optimization of patient's management (titration of ECMO blood flow, inotropes, non-invasive mechanical ventilation with PEEP, diuretics or hemofiltration).

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

1. Patient on peripheral femoro-femoral VA ECMO for severe Cardiogenic shock for ≤24h

2. Initiation of LV unloading possible within 12 hours after randomization.

3. Consent obtained from a close relative or surrogate. Should such a person be absent, eligible patients will be randomized according to the specifications of emergency consent and the patient will be asked to give his/her consent for the continuation of the trial when his/her condition will allow.

4. Social security registration (AME excluded)

Exclusion Criteria

1. Age <18 years

2. Pregnancy

3. Onset of VA-ECMO >24 h

4. Overt pulmonary edema despite optimization of patient's management (titration of ECMO blood flow, inotropes, non-invasive mechanical ventilation with PEEP, diuretics or hemofiltration) requiring urgent LV unloading

5. ECMO for massive pulmonary embolism or primary RV failure

6. ECMO after heart transplant

7. ECMO after LVAD surgery

8. Resuscitation >30 minutes before ECMO (cumulative low-flow time), except if the patient has fully recover consciousness at the time of randomization.

9. ECMO for refractory cardiac arrest (E-CPR)

10. Grade 3-4 aortic regurgitation

11. Mechanical complication of acute myocardial infarction (massive mitral regurgitation, pericardium drainage required, septal ventricular defect)

12. Patient moribund on the day of randomization

13. Cerebral deficit with fixed dilated pupils or Irreversible neurological pathology

14. Other severe concomitant disease with limited life expectancy <1 year

15. Patient has a durable ventricular assist device, an IABP or another temporary mechanical circulatory support (other than ECMO) prior to enrollment.

16. Severe peripheral artery disease or previous aortic or ilio-femoral surgery precluding IABP or IMPELLA insertion.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guillaume LEBRETON, MD

Role: STUDY_DIRECTOR

Assistance Publique Hôpitaux de Paris - Pitié Salpêtrière Hospital

Adrien BOUGLE, MD

Role: STUDY_DIRECTOR

Assistance Publique Hôpitaux de Paris - Pitié Salpêtrière Hospital

Central Contacts

Alain COMBES, MD

Role: CONTACT

alain.combes@aphp.fr

0142163818

Other Identifiers

IDRCB Number

Identifier Type: OTHER

Identifier Source: secondary_id

APHP240927

Identifier Type: -

Identifier Source: org_study_id