Early Left Ventricular unLoading by Impella vs Intra-aortic Balloon Pump

Recruiting

• Conditions: Cardiogenic Shock

• Registration Number: NCT06645990
• Lead Sponsor: University Hospital, Montpellier

Brief Summary

Over the past decade, VA-ECMO has become the main mechanical support for cardiogenic shock (CS) unresponsive to medical therapy. However, recent studies failed to show any significant survival benefit at 30 days compared to medical treatment for myocardial infarction-related CS. This could be due to the complications of VA-ECMO, such as LV overload and increased LV distension, which can hinder heart recovery.

To address this, early LV unloading using devices like IABP or Impella (ECMELLA) may help by reducing LV wall stress and oxygen consumption. However, these techniques carry risks, and their benefit is still unclear. A randomized trial is needed to compare these approaches, but observational studies are also contributing to understanding the best strategies

Detailed Description

Over the last decade, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has become the mechanical circulatory support of choice for cardiogenic shock (CS) refractory to medical treatment. VA-ECMO allows to supplement cardiac function until myocardium recovers, or in bridge to long-term left ventricular assist device (LVAD) or to heart transplant. However, recent randomized controlled trials (RCT) and meta-analysis have failed to demonstrate any benefit of VA-ECMO in terms of 30-day survival compared with optimal medical treatment in CS related to myocardial infarction.

Reasons for these disappointing results are multifactorial. The associated risk of temporary mechanical circulatory support (t-MCS)-related complications might counterbalance any hemodynamic benefit. In addition to hemorrhagic and ischemic complications, the significant myocardial impact due to VA-ECMO drawbacks should not be overlooked. Indeed, while VA-ECMO restores systemic perfusion, it can also lead to an increase in left ventricle (LV) loading conditions. Although LV distension is not consistently observed, recent publications strongly suggest that the origin of LV overload seems to be multifactorial and contributes partially to cardiac remodeling through the modulation of cardioprotective cellular pathways, resulting in reduced cardiomyocyte apoptosis. Furthermore, peripheral VA-ECMO affects myocardial contractility and increases myocardial work (potential energy, stroke work, and pressure-volume area), particularly at native low blood flow.

Thus, cardiac recovery may be compromised and weaning from VA-ECMO delayed. This vicious cycle affects the patients overall prognosis, as delayed and possibly failure of VA-ECMO weaning and may convert the initial medical strategy of recovery towards heart transplantation or LVAD. To optimize the chance of VA-ECMO weaning, early LV unloading may be a good therapeutic option. It aims at increasing coronary flow directly and, indirectly, by improving sub-endocardial myocardial perfusion through decreasing LV wall stress and myocardial oxygen consumption. Currently, 2 techniques are mainly used, the intra-aortic balloon pump (IABP) and the microaxial flow pump as Impella device familly (ECMELLA). These invasive techniques carry risks of bleeding and thromboembolic complications, and the benefit/risk ratio of their use for myocardial recovery is not clearly established.

A few retrospective studies suggest that early left ventricular unloading during VA-ECMO could improve prognosis. In the absence of RCT, the choice of the technique (Impella or IABP) is mainly driven by center practice. A multicenter randomized clinical trial would be the best choice to address this question. However, due to the acute poor prognosis of these patients (50% of early deaths), reliable preliminary data about the expected effect size are necessary to design the most efficient clinical trial. Recent epidemiologic developments of observational studies, the emulated trials, allow a better control of immortal time bias and indication bias.

This innovative multicenter study will compare the effectiveness and safety of LV unloading by Impella (ECMELLA) versus IABP in terms of survival with myocardial recovery in patients with refractory CS

Study Timeline

• Study Start: 2010-01-01
• Primary Completion: 2023-01-01
• Status Verified: 2024-10
• Study First Submitted: 2024-10-01
• Study First Submitted QC: 2024-10-15
• Last Update Submitted: 2024-10-15
• Study First Posted: 2024-10-17
• Last Update Posted: 2024-10-17
• Study Completion: 2025-01-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

• Adult patients (more than or =18 years) admitted for cardiogenic shock supported by ECMO+ IABP or ECMELLA between January 1, 2010, and December 31, 2023

Exclusion Criteria

• Ongoing extra-corporeal CardioPulmonary Resuscitation (eCPR) at time of ECMO implantation
• Cardiogenic shock with previous prolonged continuous cardiopulmonary resuscitation (CPR) more than 30 minutes
• Acute irreversible neurological injury
• Previous known severe chronic cardiomyopathy (LVEF less than 25%) or awaiting heart transplantation or LVAD implantation
• Contraindication to the implantation of an Impella or IABP
• Mechanical complications of myocardial infarction
• Moribund patient (SAPS more than 90)
• Previous known severe chronic renal or hepatic failure
• Age less than18 years

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Myocardial recovery	from start of hospitalization until hospital discharge assessed up to 3 month	Hospital Survival without chronic mechanical circulatory support (LVAD) and heart transplantation.

Secondary Outcome Measures

Name	Time	Method
Early mortality	from start of hospitalization until hospital discharge assessed up to 3 month	In-hospital all-cause mortality
Adverse events related to LV unloading technics	from start of hospitalization until hospital discharge assessed up to 3 month	Arterial thromboembolic events; Hemorrhagic events (RBC transfusion); Hemolysis; Bacteremia; Infection of the device insertion site or the device itself
Duration of mechanical ventilation	from start of hospitalization until hospital discharge assessed up to 3 month	Total duration of invasive mechanical ventilation
Duration of temporary MCS support	from start of hospitalization until hospital discharge assessed up to 3 month	Total duration of t-MCS
Lengh of stay	from start of hospitalization until hospital discharge assessed up to 3 month	Total and in intensive care unit lenght of stay
Cardiac long-term project	from start of hospitalization until hospital discharge assessed up to 3 month	Rate and % of patients with myocardial recovery, ventricular assist device or/and heart transplantation

Trial Locations

Locations (1)

CHU Arnaud de Villeneuve; 🇫🇷 Montpellier, France