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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Cardiogenic Shock
• Intervention / Treatment: Device: Impella; Device: VA-ECMO

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 198
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dirk Westermann, Prof.; Phone Number: 0049 40 7410 0; Email: d.westermann@uke.de
• Study Contact Backup: Name: Benedikt Schrage, Dr.; Email: b.schrage@uke.de

Study Locations

• Germany
  • Hamburg, Germany, 20251
    • Recruiting
    • University Heart and Vascular Center Hamburg
    • Contact: Benedikt Schrage, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Universitätsklinikum Hamburg-Eppendorf

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2022
• Primary Completion (Anticipated): November 30, 2024
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: October 10, 2022
• First Submitted That Met QC Criteria: October 10, 2022
• First Posted (Actual): October 13, 2022

Study Record Updates

• Last Update Posted (Estimate): December 29, 2022
• Last Update Submitted That Met QC Criteria: December 28, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Impella; Cardiogenic shock; VA-ECMO; Active left ventricular unloading
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Shock; Shock, Cardiogenic
• Other Study ID Numbers: UNLOAD ECMO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No