Physiology of Unloading VA ECMO Trial

The goal of this clinical trial is to compare the use of veno-arterial extracorporeal membrane oxygenation (VA ECMO) with and without left ventricular (LV) unloading in patients being treated for cardiogenic shock (CS). The main aims of the study are:

1. To determine the physiologic effects on cardiopulmonary congestion of adding LV unloading to VA ECMO
2. To determine the effects on myocardial function of adding LV unloading to ECMO
3. To test the effects on myocardial recovery of adding LV unloading to VA ECMO

Participants who are being treated with VA ECMO will be randomized to receive or not receive LV unloading in the form of an intra-aortic balloon pump (IABP). Over the course of the study, the investigators will obtain measurements via lab work, echocardiography, and pulmonary artery catheter that will allow comparison of the two groups.

Study Overview

• Status: Recruiting
• Conditions: Cardiogenic Shock
• Intervention / Treatment: Device: IABP

Detailed Description

Although extracorporeal membrane oxygenation (ECMO) for cardiogenic shock (CS) is used in over 3,000 patients per year, the best management strategies are not known. Identifying and improving treatment of CS is critically important, as CS occurs in 160,000 patients per year in the US with a 50% mortality rate. VA ECMO is an increasingly used method of mechanical circulatory support (MCS) for patients with CS refractory to medical therapy. Despite the benefit of full cardiopulmonary support ECMO is also thought to increase after load in the failing heart- which paradoxically reduces cardiac output and may lead to myocardial injury and cardiac congestion. A potential solution is to add a device to VA ECMO that decreases after-load - known as left ventricular (LV) unloading. LV unloading can be achieved with different approaches, directly with transvalvular pumps (known as a peripheral ventricular assist device (pVAD)), or indirectly with an intra-aortic balloon pump (IABP)

Preliminary data suggests that unloading the LV is associated with improved survival. Results from a cohort of VA ECMO patients with medical CS, showed a hospital survival benefit LV unloading (aOR 0.87 (0.79, 094); p=0.001). Data has also shown that the survival benefit of LV unloading was much larger with pVAD (HR 0.6), but with higher complications, including limb ischemia - a potentially catastrophic complication. However, results also show that different unloading approaches have different physiologic effects on the myocardium and on peripheral perfusion - highlighting the uncomfortable observation that it is not known how (physiologically) these unloading devices lead to changes in survival.

There are two potential pathways whereby LV unloading could influence survival, including myocardial effects (distension, injury, ejection fraction ) and peripheral effects (peripheral pulse pressure, lactate clearance, CO2 gap). Determining the physiologic effects from LV unloading according to device type and patient etiology will allow us to match the intervention with the patient's physiology. Data suggests that ECMO patients with acute myocardial infarction (AMI) have different mortality and different physiologic changes than patients with decompensated chronic heart failure (CHF) when unloaded.

The ultimate goal is to reduce morbidity and mortality in cardiogenic shock. This study will define the physiologic benefit of LV unloading during CS.

• Study Type: Interventional
• Enrollment (Estimated): 104
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • University of Utah
      • Contact: Joseph E. Tonna, MD, FAAEM; Phone Number: 801.587.9373; Email: joseph.tonna@hsc.utah.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients (age 18 years or older)
• Diagnosis of acute cardiogenic shock (CS)

• Patients failing medical therapy, defined as 1 or more of the following:

  1. Society for Coronary Angiography and Interventions (SCAI) Stage C or greater
  2. 2 or more inotropic medications and not improving
  3. IABP in place and clinically worsening
  4. Placed on VA ECMO for CS
  5. In the opinion of the attending physician, patient has worsening CS and could require VA ECMO support in the near-term

Exclusion Criteria:

• Metastatic or stage 4 cancer
• Atrial septostomy
• Planned LV unloading on ECMO
• Anticipated death <72 hours
• Existing durable left ventricular assist device (dLVAD)
• Unwillingness to randomize
• Patients who are pregnant

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: With LV Unloading; Patients on VA ECMO who randomize to receive LV unloading	Device: IABP; LV unloading via intra-aortic balloon pump (IABP); Other Names: LV unloading
No Intervention: Without LV Unloading; Patients on VA ECMO who randomize to receive no LV unloading

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pulmonary capillary wedge pressure	Change in pulmonary capillary wedge pressure (PCWP) from ECMO start to ECMO day 5 (Day 5 - Baseline) with and without LV unloading	ECMO start, ECMO day 5, ECMO decannulation up to 3 months, day of ICU discharge up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pulmonary artery diastolic pressure	Change in pulmonary artery diastolic pressure (PADP) from ECMO start to ECMO day 5 (Day 5 - baseline) with and without LV unloading	ECMO start, ECMO days 1-5, ECMO decannulation up to 3 months, day of ICU discharge up to 6 months
Change in left ventricular end diastolic diameter	Change in left ventricular end diastolic diameter (LVEDd) from ECMO start to ECMO day 5 (Day 5 - baseline) with and without LV unloading	ECMO start, ECMO day 5, ECMO decannulation up to 3 months, day of ICU discharge up to 6 months
Change in N-terminal pro b-type natriuretic peptide	Change in N-terminal pro b-type natriuretic peptide (NT-pro BNP) from ECMO start to ECMO day 5 (Day 5 - baseline) with and without LV unloading	ECMO start, ECMO days 1-5, ECMO decannulation up to 3 months, day of ICU discharge up to 6 months
Hemodynamic stability	Hemodynamic stability (defined as a change in mean arterial pressure [MAP] from prior to turn down until 2 minutes of wean) at ECMO day 5 with and without LV unloading	ECMO start, ECMO day 5
Global cardiovascular function	Global cardiovascular function is defined as arterial pulse pressure during the protocoled wean. To assess this outcome, the investigators will calculate the change in pulse pressure from prior to wean to 2 minutes during wean.	ECMO start, ECMO days 1-5
Difference in partial pressure of carbon dioxide (pCO2)	As part of assessing global cardiovascular function, the investigators will measure, via lab draw, pCO2, which is the difference in CO2 between arterial and central venous blood. This is a marker of peripheral perfusion.	ECMO start, q12 hours ECMO days 1-3, ECMO decannulation up to 3 months, day of ICU discharge up to 6 months
Lactate	As part of assessing global cardiovascular function, the investigators will measure, via lab draw, arterial lactate. This is a marker of peripheral perfusion.	ECMO start, ECMO days 1-5, ECMO decannulation up to 3 months, day of ICU discharge up to 6 months
Cardiac BIN1	Change in Cardiac BIN1 (cBIN1) serum level from Baseline to Day 5 (Day 5 - Baseline). cBIN1is a validated marker of myocardial recovery in heart failure.	ECMO start, ECMO day 5, day of ICU discharge up to 6 months
Troponin I	Change in troponin I from ECMO start to ECMO day 5 (Day 5 - Baseline)	ECMO start, ECMO days 1-5, ECMO decannulation up to 3 months, day of ICU discharge up to 6 months
Tumor necrosis factor alpha	Change in tumor necrosis factor alpha (TNFa) from ECMO start to ECMO day 5 (Day 5 - Baseline)	ECMO start, ECMO day 5, ECMO decannulation up to 3 months, day of ICU discharge up to 6 months
Ejection fraction percentage	Assessment of heart function via echocardiography	ECMO start, ECMO day 5, ECMO decannulation up to 3 months, day of ICU discharge up to 6 months
Interferon gamma	Predictor of myocardial recovery assessed from baseline through ICU discharge	ECMO start, ECMO day 5, ECMO decannulation up to 3 months, day of ICU discharge up to 6 months
Limb ischemia	Ischemia in the ipsilateral limb as the IABP will be tracked from baseline until 48 hours after the intervention is removed.	Randomization, 48 hours post-device removal
Mortality	Assessment of patient mortality status at hospital discharge	Hospital discharge up to 6 months

Collaborators and Investigators

• Sponsor: University of Utah
• Collaborators: University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2024
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: March 8, 2024
• First Submitted That Met QC Criteria: March 27, 2024
• First Posted (Actual): March 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: cardiogenic shock; extracorporeal membrane oxygenation; left ventricular unloading
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infarction; Necrosis; Myocardial Ischemia; Myocardial Infarction; Ischemia; Shock; Pathological Conditions, Signs and Symptoms; Shock, Cardiogenic
• Other Study ID Numbers: 153309

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No