Physiology of Unloading VA ECMO Trial

Cardiogenic Shock Clinical Trial

Official title:

Physiology of Unloading VA ECMO Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06336655
• Other study ID #: 153309
• Status: Recruiting
• Phase: Phase 2
• Start date: April 15, 2024
• Est. completion date: February 1, 2029

Study information

• Verified date: March 2024
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 non-postoperative 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 104
• Est. completion date: February 1, 2029
• Est. primary completion date: February 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiogenic Shock
• Shock, Cardiogenic

Intervention

Device:
• IABP
LV unloading via intra-aortic balloon pump (IABP)

Locations

Country	Name	City	State
United States	University of Utah	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
University of Utah	University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Mortality	Assessment of patient mortality status at hospital discharge	Hospital discharge up to 6 months