Clinical trial NCT07027202: Early Preventive Left Ventricle Unloading After VA-ECMO for Refractory Cardiogenic Shock
Official title: Early Preventive Left Ventricle Unloading After VA-ECMO for Refractory Cardiogenic Shock
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Cardiogenic Shock Acute
Keywords: ECMO
BPIA
Cardiogenic shock acute
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2025-06-18
Enrollment: 298
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, prospective, randomized, comparative open trial
Primary purpose: OTHER

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.


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.

Primary outcomes:
measure: Composite hierarchical outcome assessed at day 30, composed of three components: 1)All-cause mortality, 2)unloading device or strategy related complication 3) time off temporary mechanical circulatory support (tMCS) or invasive mechanical ventilation (
timeFrame: Day 30
Secondary outcomes:
measure: Bleeding (BARC 3 or more)
timeFrame: Day 30
measure: Infection at any MCS insertion site treated by antibiotics
timeFrame: Day 30
measure: Critical limb ischemia (leading to fasciotomy, surgical or endovascular intervention, MCS withdrawal).
timeFrame: Day 30
measure: Stroke (ischemic or hemorrhagic)
timeFrame: Day 30
measure: Any specific complication associated with intraventricular microvascular pump (aortic or mitral valve lesion, severe hemolysis) or atrial septostomy (tamponade, cardiac perforation).
timeFrame: Day 30
measure: All-cause mortality
timeFrame: Day 60
measure: Duration of ECMO support
timeFrame: Day 60
measure: Bridge to durable ventricular assist device (left ventricular assist device type Heartmate3 or a total artificial heart) or heart transplantation
timeFrame: Day 60
measure: Durations of ICU stay
timeFrame: Day 60
measure: Number of days of invasive mechanical ventilation
timeFrame: Day 30
measure: Number of days of renal replacement therapy
timeFrame: Day 30
measure: Number of days alive without organ failure(s)
timeFrame: From randomization to day 30
measure: Number of ventilator-associated pneumonia treated with antibiotics
timeFrame: From randomization to Day 60
measure: Durations of hospitalization
timeFrame: Day 60
measure: Durations of ICU stay
timeFrame: Between inclusion and Day 30
measure: Durations of hospitalization
timeFrame: Between inclusion and Day 30
measure: Major complication specifically related to the unloading device (IABP, microaxial IMPELLA pump) or strategy (atrial septostomy) - Bleeding (BARC 3 or more)
timeFrame: Between inclusion and Day 30
measure: All cause mortality
timeFrame: Day 30
measure: Number of days of ECMO support and days free of ECMO support
timeFrame: Day 30
measure: Delay to overt pulmonary edema (defined by pulmonary capillary wedge pressure (PCWP) >20 mmHg and bilateral infiltrates on Chest X-ray) indicating escalation to an unloading device (IABP, microaxial LV venting pump or atrial septostomy for control group
timeFrame: Day 30
measure: Rate of bridge to durable ventricular assist device or heart transplantation
timeFrame: Day 30
measure: Total number of packed red blood cells and platelet transfused
timeFrame: Day 30
measure: Left ventricular function assessed with Doppler echocardiography for alive patients only
timeFrame: Day 30
Other outcomes:
Locations:
Study officials:
affiliation: Assistance Publique Hôpitaux de Paris - Pitié Salpêtrière Hospital
name: Guillaume LEBRETON, MD
role: STUDY_DIRECTOR
affiliation: Assistance Publique Hôpitaux de Paris - Pitié Salpêtrière Hospital
name: Adrien BOUGLE, MD
role: STUDY_DIRECTOR
References: