Early Left Atrial Septostomy Versus Conventional Approach After Venoarterial Extracorporeal Membrane Oxygenation (EARLY-UNLOAD)

Early Left Atrial Septostomy Versus Conventional Approach After Venoarterial Extracorporeal Membrane Oxygenation: A Randomized Controlled Study

The use of venoarterial-extracorporeal membrane oxygenation(VA-ECMO) was associated with lower in-hospital mortality in patients with cardiogenic shock. However, VA-ECMO has a deleterious effect for hemodynamics. It can increase left ventricular end-diastolic pressure(LVEDP), followed by left ventricular dilatation, abnormal opening of aortic valve and jeopardizes of myocardial recovery. Therefore, several methods have been used to reduce LVEDP. Among these, left atrial septostomy is effective, but less invasive than surgical left ventricular unloading. However, there is few data regarding this issue. Therefore, the investigators will evaluate the effect of routine, early left atrial septostomy in patients with VA-ECMO for the treatment of cardiogenic shock.

Study Overview

• Status: Completed
• Conditions: Cardiogenic Shock
• Intervention / Treatment: Procedure: Early left atrial septostomy within 12 hours after VA-ECMO implantation; Procedure: Selective left atrial septostomy

Detailed Description

Study Objectives:

To determine the effect of early left atrial septostomy versus conventional approach(left atrial septostomy only in cases of significant changes due to left ventricular end-diastolic pressure increase) in patients who received venoarterial-extracorporeal membrane oxygenation(VA-ECMO) for the treatment of cardiogenic shock.

Study Background:

Cardiogenic shock is due to myocardial dysfunction from multifactorial causes, which has high mortality. The treatment for cardiogenic shock includes early coronary revascularization, inotropes, vasopressors, or mechanical circulatory support, such as intraaortic balloon pump(IABP), VA-ECMO. However, the routine use of IABP is not recommended for the treatment of cardiogenic shock in recent guidelines. VA-ECMO can be easily implanted, and can maintain high cardiac output. In several studies, The use of VA-ECMO was associated with lower in-hospital mortality in patients with cardiogenic shock.

However, VA-ECMO has a deleterious effect for hemodynamics. It can increase left ventricular end-diastolic pressure(LVEDP), followed by left ventricular dilatation, abnormal opening of aortic valve and jeopardizes of myocardial recovery. Therefore, several methods have been used to reduce LVEDP. Among these, left atrial septostomy is effective, but less invasive than surgical left ventricular unloading. However, there is few data regarding this issue. Therefore, the investigators will evaluate the effect of routine, early left atrial septostomy in patients with VA-ECMO for the treatment of cardiogenic shock.

Study Hypothesis:

Early, routine left atrial septostomy for left heart unloading is superior compared to conventional approach to reduce in-hospital mortality and the duration of VA-ECMO.

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gwangju, Korea, Republic of
    • Chonnam National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1) Age more than 18 years old 2) Cardiogenic shock* 3) Successful VA-ECMO implantation

• The definition of cardiogenic shock All these criteria should be met

  1. Systolic blood pressure < 90 mmHg for 30 minutes, or needing inotrope or vasopressor to maintain systolic blood pressure > or = 90 mmHg
  2. Pulmonary congestion on chest X-ray or increased left ventricular filling pressure by cardiac catheterization

  3. At least one criteria of organ dysfunction

     - mental obtundation, clammy skin, oliguria, renal dysfunction, increased level of blood lactate

     Exclusion Criteria:

  1. VA-ECMO after open heart surgery
  2. VA-ECMO for the treatment of non-cardiac shock
  3. Severe bleeding*
  4. Terminal malignancy
  5. Irreversible brain damage
  6. Pregnancy or lactation

• The definition of severe bleeding Hemoglobin decrease after VA-ECMO or cannulation site bleeding is not a exclusion criteria

  1. Hypovolemic shock due to definite bleeding cause
  2. Identifiable bleeding causes: gastrointestinal bleeding, hemothorax, traumatic bleeding, central nervous system hemorrhage, pulmonary hemorrhage

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early left atrial septostomy group; Early left atrial septostomy group will routinely receive left atrial septostomy within 12 hours after VA-ECMO implantation.	Procedure: Early left atrial septostomy within 12 hours after VA-ECMO implantation; Early left atrial septostomy group will routinely receive left atrial septostomy within 12 hours after VA-ECMO implantation. Left atrial septostomy will be done using percutaneous technique.
Active Comparator: Conventional approach group; Conventional approach group will receive left atrial septostomy in cases of deleterious effect of increased LVEDP after VA-ECMO implantation, such as refractory pulmonary edema, abnormal opening of aortic valve, left ventricular dilatation, refractory ventricular tachycardia or fibrillation.	Procedure: Selective left atrial septostomy; Left atrial septostomy will be done in cases of deleterious effect of increased LVEDP after VA-ECMO implantation, such as refractory pulmonary edema, abnormal opening of aortic valve, left ventricular dilatation, refractory ventricular tachycardia or fibrillation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence rate of all-cause death	Cumulative incidence rate of all-cause death	Up to 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence rate of all-cause death	Cumulative incidence rate of all-cause death	Up to 12 months
Cumulative incidence rate of cardiac death	Cumulative incidence rate of cardiac death	Up to 12 months
Rate of all-cause death or left atrial septostomy in conventional approach group	Rate of all-cause death or left atrial septostomy in conventional approach group	Up to 30 days
Rate of left atrial septostomy in conventional approach group	Rate of left atrial septostomy in conventional approach group	Up to 30 days
Incidence rate of all-cause death during index admission	Incidence rate of all-cause death during index admission	Up to 6 months
Cumulative incidence rate of cardiac death	Cumulative incidence rate of cardiac death	Up to 30 days
Cumulative incidence rate of non-cardiac death	Cumulative incidence rate of non-cardiac death	Up to 30 days
Weaning rate from venoarterial extracorporeal membrane oxygenation during index admission	Weaning rate from venoarterial extracorporeal membrane oxygenation during index admission	Up to 6 months
Rate of disappearance of pulmonary edema on chest X-ray during index admission	Rate of disappearance of pulmonary edema on chest X-ray during index admission	Up to 6 months
Weaning rate from mechanical ventilator during index admission	Weaning rate from mechanical ventilator during index admission	Up to 6 months
Intensive care unit length of stay during index admission	Intensive care unit length of stay during index admission	Up to 6 months
Hospital length of stay	Hospital length of stay	Up to 6 months
Lactate normalization rate	Lactate normalization rate	Up to 30 days
Lactate clearance rate	Lactate clearance rate	Up to 30 days
Rate of renal replacement therapy during index admission	Rate of renal replacement therapy during index admission	Up to 6 months
Rate of limb ischemia during index admission	Rate of limb ischemia during index admission	Up to 6 months
Rate of infection during index admission	Rate of infection during index admission	Up to 6 months
Rate of transient ischemic attack or stroke during index admission	Rate of transient ischemic attack or stroke during index admission	Up to 6 months
Rate of BARC bleeding type 3 or 5 during index admission	Rate of BARC bleeding type 3 or 5 during index admission	Up to 6 months
Rate of bridge to ventricular assist device or heart transplantation during index admission	Rate of bridge to ventricular assist device or heart transplantation during index admission	Up to 6 months
Rate of major vascular injury or cardiac tamponade during left atrial septostomy	Rate of major vascular injury or cardiac tamponade during left atrial septostomy	Up to 30 days
Cumulative incidence rate of non-cardiac death	Cumulative incidence rate of non-cardiac death	Up to 12 months
Re-hospitalization rate due to heart failure	Re-hospitalization rate due to heart failure	Up to 12 months
All-cause death or re-hospitalization rate due to heart failure	All-cause death or re-hospitalization rate due to heart failure	Up to 12 months

Collaborators and Investigators

• Sponsor: Chonnam National University Hospital
• Investigators: Principal Investigator: Min Chul Kim, Professor, Chonnam National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2021
• Primary Completion (Actual): March 14, 2022
• Study Completion (Actual): October 31, 2023

Study Registration Dates

• First Submitted: February 24, 2021
• First Submitted That Met QC Criteria: February 25, 2021
• First Posted (Actual): March 1, 2021

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: January 10, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Cardiovascular Diseases; Myocardial Infarction; Heart Diseases; Extracorporeal membrane oxygenation; Coronary Disease
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Shock; Myocardial Infarction; Infarction; Shock, Cardiogenic
• Other Study ID Numbers: CNUH-2020-390

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