Left Ventricular Unloading to Improve Outcome in Cardiogenic Shock Patients on VA-ECMO

Study Overview
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Brief Summary
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Prospective, multi-center, randomized (1:1), controlled trial of Impella for active left ventricular unloading on top of veno-arterial extracorporeal membrane oxygenation vs. veno-arterial extracorporeal membrane oxygenation alone for the treatment of cardiogenic shock.

Detailed Description
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In the past years extensive efforts in developing treatment strategies for patients with cardiogenic shock have been performed. One promising such strategy is active unloading of the left ventricle while simultaneously supporting the circulatory system with veno-arterial extracorporeal membrane oxygenation. Recently, in a multinational, multicenter, retrospective registry, it has been shown that this approach might be associated with lower mortality . The investigators now seek to extend the evidence on this topic and to test this approach in a prospective, randomized, controlled, multicenter trial. A power calculation has been conducted based on the data from the registry. N=198 patients with cardiogenic shock will be randomized 1:1 to be either treated with an Impella for active left ventricular unloading on top of veno-arterial extracorporeal membrane oxygenation or with veno-arterial extracorporeal membrane oxygenation alone. A blinded interim analysis will be performed, which might lead to an adjustment of the enrollment target. The primary endpoint of this study will be death from any cause 30 days after randomization.

Official Title
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UNLOAD ECMO - Left Ventricular Unloading to Improve Outcome in Cardiogenic Shock Patients on VA-ECMO - a Prospective, Randomized, Controlled, Multi-center Trial

Conditions
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Cardiogenic Shock

Intervention / Treatment
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* Device: Impella
* Device: VA-ECMO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe cardiogenic shock due to severe left ventricular dysfunction: Systolic blood pressure <90 mmHg or need for catecholamines to maintain such blood pressure Signs of impaired organ perfusion with at least one of the following: altered mental status OR cold, clammy skin OR oliguria with urine output <30 ml/h Arterial lactate >5 mmol/l Exclusion Criteria: Post-cardiotomy cardiogenic shock. Cardiogenic shock due to acute rejection in heart transplant recipients. Obstructive cardiogenic shock (e.g. cardiogenic shock due to fulminant pulmonary embolism) Cardiogenic shock due to other causes (e.g. bleeding, hypothermia) Pre-existing Impella treatment. Onset of shock >12 hours. Mechanical complication of acute myocardial infarction. Prolonged resuscitation (>60 minutes). Severe peripheral artery disease with infeasibility for Impella or veno-arterial extracorporeal membrane oxygenation implantation. Age <18 or >80 years. Other severe concomitant disease with life expectancy <6 months. Participation in another trial with an intervention or pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Impella + VA-ECMO<br> | Device: Impella<br>* To provide active left ventricular unloading in the experimental arm<br>Device: VA-ECMO<br>* To provide circulatory support in both arms<br>|
| Active Comparator: VA-ECMO only<br> | Device: VA-ECMO<br>* To provide circulatory support in both arms<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to death from any-cause within 30 days after randomization | Time to death from any-cause within 30 days after randomization | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death from any-cause at 6 and 12 months as well as time to death at these time points | Cardiovascular death at day 30, 6 months and 12 months as well as time to death at these time points | 6 and 12 months | 
| Cardiovascular death at day 30, 6 months and 12 months as well as time to death at these time points | Cardiovascular death at day 30, 6 months and 12 months as well as time to death at these time points | 30 days, 6 and 12 months | 
| Length of veno-arterial extracorporeal membrane oxygenation therapy, mechanical ventilation, inotrope therapy and stay at the intensive care unit (in days). | Length of veno-arterial extracorporeal membrane oxygenation therapy, mechanical ventilation, inotrope therapy and stay at the intensive care unit (in days). | 12 months | 
| Days free from veno-arterial extracorporeal membrane oxygenation therapy in 30 days | Days free from veno-arterial extracorporeal membrane oxygenation therapy in 30 days | 30 days | 
| Need for renal replacement therapy until day 30, 6 months and 12 months | Need for renal replacement therapy, intermittent or ongoing, until day 30, 6 months and 12 months | 30 days, 6 and 12 months | 
| Neurological function (per Cerebral Performance Category) at day 30, 6 months and 12 months | Neurological function (per Cerebral Performance Category) at day 30, 6 months and 12 months | 30 days, 6 and 12 months | 
| Rate of incidence of hospitalization for heart failure (hospitalization for more than 24 hours with heart failure as the main reason) as well as time to first event after 6 months and 12 months and recurrent events within 12 months | Rate of incidence of hospitalization for heart failure (hospitalization for more than 24 hours with heart failure as the main reason) as well as time to first event after 6 months and 12 months and recurrent events within 12 months | 6 and 12 months | 
| Left ventricular function assessed by echocardiography at day 30, 6 months and 12 months | Left ventricular function assessed by echocardiography at day 30, 6 months and 12 months | 30 days, 6 and 12 months | 
| Quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire at 30-days and at 12 months | Quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire at 30-days and at 12 months | 30 days and 6 months | 
| 6-Minute Walking Distance at day 30, 6 months and 12 months | 6-Minute Walking Distance at day 30, 6 months and 12 months | 30 days, 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Active left ventricular unloading, VA-ECMO, Impella, Cardiogenic shock