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

• ClinicalTrials.gov Identifier: NCT04775472
• Recruitment Status: Completed
• First Posted: March 1, 2021
• Last Update Posted: January 12, 2024
• Sponsor: Chonnam National University Hospital
• Information provided by (Responsible Party): Min Chul Kim, Chonnam National University Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cardiogenic Shock	Procedure: Early left atrial septostomy within 12 hours after VA-ECMO implantation; Procedure: Selective left atrial septostomy	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 116 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Early Left Atrial Septostomy Versus Conventional Approach After Venoarterial Extracorporeal Membrane Oxygenation: A Randomized Controlled Study
• Actual Study Start Date: March 4, 2021
• Actual Primary Completion Date: March 14, 2022
• Actual Study Completion Date: October 31, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Cumulative incidence rate of all-cause death [ Time Frame: Up to 30 days ]
   Cumulative incidence rate of all-cause death

Secondary Outcome Measures :

1. Rate of all-cause death or left atrial septostomy in conventional approach group [ Time Frame: Up to 30 days ]
   Rate of all-cause death or left atrial septostomy in conventional approach group
2. Rate of left atrial septostomy in conventional approach group [ Time Frame: Up to 30 days ]
   Rate of left atrial septostomy in conventional approach group
3. Incidence rate of all-cause death during index admission [ Time Frame: Up to 6 months ]
   Incidence rate of all-cause death during index admission
4. Cumulative incidence rate of cardiac death [ Time Frame: Up to 30 days ]
   Cumulative incidence rate of cardiac death
5. Cumulative incidence rate of non-cardiac death [ Time Frame: Up to 30 days ]
   Cumulative incidence rate of non-cardiac death
6. Weaning rate from venoarterial extracorporeal membrane oxygenation during index admission [ Time Frame: Up to 6 months ]
   Weaning rate from venoarterial extracorporeal membrane oxygenation during index admission
7. Rate of disappearance of pulmonary edema on chest X-ray during index admission [ Time Frame: Up to 6 months ]
   Rate of disappearance of pulmonary edema on chest X-ray during index admission
8. Weaning rate from mechanical ventilator during index admission [ Time Frame: Up to 6 months ]
   Weaning rate from mechanical ventilator during index admission
9. Intensive care unit length of stay during index admission [ Time Frame: Up to 6 months ]
   Intensive care unit length of stay during index admission
10. Hospital length of stay [ Time Frame: Up to 6 months ]
    Hospital length of stay
11. Lactate normalization rate [ Time Frame: Up to 30 days ]
    Lactate normalization rate
12. Lactate clearance rate [ Time Frame: Up to 30 days ]
    Lactate clearance rate
13. Rate of renal replacement therapy during index admission [ Time Frame: Up to 6 months ]
    Rate of renal replacement therapy during index admission
14. Rate of limb ischemia during index admission [ Time Frame: Up to 6 months ]
    Rate of limb ischemia during index admission
15. Rate of infection during index admission [ Time Frame: Up to 6 months ]
    Rate of infection during index admission
16. Rate of transient ischemic attack or stroke during index admission [ Time Frame: Up to 6 months ]
    Rate of transient ischemic attack or stroke during index admission
17. Rate of BARC bleeding type 3 or 5 during index admission [ Time Frame: Up to 6 months ]
    Rate of BARC bleeding type 3 or 5 during index admission
18. Rate of bridge to ventricular assist device or heart transplantation during index admission [ Time Frame: Up to 6 months ]
    Rate of bridge to ventricular assist device or heart transplantation during index admission
19. Rate of major vascular injury or cardiac tamponade during left atrial septostomy [ Time Frame: Up to 30 days ]
    Rate of major vascular injury or cardiac tamponade during left atrial septostomy
20. Cumulative incidence rate of all-cause death [ Time Frame: Up to 12 months ]
    Cumulative incidence rate of all-cause death
21. Cumulative incidence rate of cardiac death [ Time Frame: Up to 12 months ]
    Cumulative incidence rate of cardiac death
22. Cumulative incidence rate of non-cardiac death [ Time Frame: Up to 12 months ]
    Cumulative incidence rate of non-cardiac death
23. Re-hospitalization rate due to heart failure [ Time Frame: Up to 12 months ]
    Re-hospitalization rate due to heart failure
24. All-cause death or re-hospitalization rate due to heart failure [ Time Frame: Up to 12 months ]
    All-cause death or re-hospitalization rate due to heart failure

Eligibility Criteria

• Ages Eligible for Study: 19 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Korea, Republic of

Chonnam National University Hospital

Gwangju, Korea, Republic of

Sponsors and Collaborators

Chonnam National University Hospital

Investigators

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

More Information

• Responsible Party: Min Chul Kim, Associate Professor, Chonnam National University Hospital
• ClinicalTrials.gov Identifier: NCT04775472
• Other Study ID Numbers: CNUH-2020-390
• First Posted: March 1, 2021
• Last Update Posted: January 12, 2024
• Last Verified: January 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Min Chul Kim, Chonnam National University Hospital:

Extracorporeal membrane oxygenation; Myocardial Infarction; Heart Diseases; Cardiovascular Diseases; Coronary Disease

Additional relevant MeSH terms:

Shock, Cardiogenic; Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Necrosis; Shock