Early Insertion of Axillary Impella® With VA ECMO

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT04084015
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arm: 1
• Actual Duration (Months): 17.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Veno-arterial extra-corporeal membrane oxygenation (VA-ECMO) is used as a rescue strategy for patients in acute hemodynamic deterioration such as cardiogenic shock and cardiopulmonary arrest with severe pulmonary congestion. VA ECMO is the fastest way to stabilize a patient with cardiogenic shock and improve end-organ perfusion. However, one of the major disadvantages of peripheral VA-ECMO is that it provides no left ventricular unloading and increases left ventricular (LV) afterload secondary to the retrograde blood flow. Therefore, LV wall tension and myocardial oxygen demand may actually increase in the setting of VA ECMO.

The Impella® device is a miniature rotary blood pump which can be inserted retrograde across the aortic valve. In this configuration, it withdraws blood from the LV and ejects it into the ascending aorta. It unloads the left ventricle, reducing LV wall tension and myocardial oxygen demand and increasing myocardial blood flow. The Impella® 5.0 is an FDA approved pump designed for intermediate support in patients with severe, cardiogenic shock. The axillary positioning allows for early extubation and ambulation and is more stable than groin placement.

In present practice, the decision to place an Impella® pump in VA-ECMO patients is based on the perceived need for direct LV unloading or when a bridge device is required to transition off ECMO support. Patients with peripheral VA ECMO are managed with inotropic agents at the beginning and once patients develop pulmonary edema mechanical LV unloading is considered electively. The advantage of LV unloading with Impella® has been demonstrated in recent studies. We also reported that concomitant implantation of Impella® with VA ECMO for LV unloading resulted in improved survival and recovery of ventricular performance in patients with cardiogenic shock. Compared to delayed elective LV unloading, early LV unloading could lead to decreased pulmonary edema, improved oxygenation delivery to the myocardium, increased chance of LV recovery and improved survival.

The objective of this prospective study is to assess whether the early direct ventricular unloading using axillary Impella® leads to higher rates of cardiac recovery, defined as survival free from mechanical circulatory support, heart transplantation or inotropic support at thirty days, compared with the conventional, elective placement of Impella® after developing significant pulmonary congestion.

Condition or Disease	Intervention/Treatment	Phase
Cardiogenic Shock	Device: Axillary Impella®	N/A

Detailed Description

This prospective, single-arm trial will include all consecutive patients undergoing cannulation of peripheral VA ECMO at the Massachusetts General Hospital (MGH) from April 2019 to March 2020. All enrolled patients will undergo surgical placement of Impella® via axillary artery within 48 hours after peripheral VA ECMO initiation and be managed with early extubation and ambulation strategy.

After Impella® placement, there will be no research procedures performed. Subjects will receive standard of care and the subject's progress will be documented throughout the 30 days study follow-up. The data obtained from the electronic medical record in Epic health record system at MGH will be reviewed throughout the study.

The primary outcome of this study will be survival at 30 days. Prespecified secondary end points will include the rate of death from cardiovascular causes, New York Heart Association (NYHA) functional class, LV function (assessed by echocardiography), and the rate of stroke, neurological functional status, acute kidney injury, vascular complications, and bleeding.

The enrolled subjects (early Impella®) would be compared with patients who underwent current elective placement of Impella® after cannulation of VA ECMO (elective Impella®) in the past two years. Student's t-test (for continuous variables) or Fisher exact test (for categorical variables) will be used for between-group comparisons. The primary endpoint in the data analysis is binary: 30-day survival. The null hypothesis of no difference between early Impella® and elective Impella® will be tested using logistic regression. The secondary endpoint, the rate of death from cardiovascular causes, NYHA functional class, LV function, and the rate of stroke, neurological functional status, acute kidney injury, vascular complications, and bleeding, will be addressed using competing risks hazard regression models. This is a pilot study for the future multicenter study. If this study demonstrates no inferiority or any significant superiority, we will proceed to do multicenter prospective study. Power analysis will be assessed based on the result of this preliminary study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: This prospective, single-arm trial will include all consecutive patients undergoing cannulation of peripheral VA ECMO at the Massachusetts General Hospital from April 2019 to March 2020. Approximately 20 subjects are anticipated to be enrolled during this time.This prospective, single-arm trial will include all consecutive patients undergoing cannulation of peripheral VA ECMO at the Massachusetts General Hospital from April 2019 to March 2020. Approximately 20 subjects are anticipated to be enrolled during this time.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Early Insertion of Axillary Impella® for LV Recovery in Patients With Veno-arterial Extracorporeal Membrane Oxygenation
• Actual Study Start Date: Oct 1, 2019
• Actual Primary Completion Date: Mar 23, 2021
• Actual Study Completion Date: Mar 23, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Early axillary Impella® Early placement of axillary Impella® for LV unloading and LV recovery in patients with VA ECMO	Device: Axillary Impella®; All enrolled patients will undergo surgical placement of Impella® via axillary artery within 48 hours after peripheral VA ECMO initiation and be managed with early extubation and ambulation strategy

Outcome Measures

Primary Outcome Measures

1. Survival [30 days after cannulation of VA ECMO]

   Patient survival at 30-days post VA ECMO cannulation timepoint. Collected through patient chart review.

Secondary Outcome Measures

1. Death From Cardiovascular Causes [30 days after cannulation of VA ECMO or Discharge]

   Death from cardiovascular cases at 30-days post VA ECMO cannulation timepoint. Collected from review of patient charts.

2. New York Heart Association Functional Status [30 days after cannulation of VA ECMO or Discharge]

   Retrospective review in a patient chart

3. Number of Participants With a Neurological Event [30 days after cannulation of VA ECMO or Discharge]

   Neurological event up to 30-days post VA-ECMO cannulation or Discharge. Includes hypoxic brain damage, intracerebral bleeding, hemorrhagic stroke, or ischemic stroke. Data collected through patient chart review.

4. Left Ventricular Function [30 days after cannulation of VA ECMO or Discharge]

   Measured by Echocardiogram study.

Other Outcome Measures

1. Number of Participants With Acute Kidney Injury [Within 30 days after cannulation of VA ECMO]

   Retrospective review in a patient chart

2. Vascular Complication [Within 30 days after cannulation of VA ECMO]

   Retrospective review in a patient chart

3. Number of Participants With Bleeding [Within 30 days after cannulation of VA ECMO]

   Moderate bleeding in hospital. Defined by transfusion of red blood cells without hemodynamic impairment. Collected through review of patient chart.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age ≥18

• Impaired LV systolic function with ≤35% of left ventricular ejection fraction (LVEF)

• Enlarged LV with ≥50mm of left ventricular diastolic diameter (LVEDD) on echocardiogram

Exclusion Criteria:

• Non-cardiac etiology

• Surgically correctable cardiac abnormality

• Recent significant pulmonary embolism

• Severe pulmonary hypertension

• Acute aortic dissection

• Presence of mechanical aortic valve prosthesis

• Presence of left ventricle thrombus

• Pre-existing Impella® 5.0

• Critical aortic stenosis

• Uncorrectable system malperfusion under ECMO support

• Significant cerebrovascular accident

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital

Investigators

• Principal Investigator: David D'Alessandro, MD, Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 11, 2019

More Information

Publications

None provided.

• Responsible Party: David A. D'Alessandro, M.D., Associate Professor, Principal Investigator, Surgical Director, Heart Transplantation and Mechanical Circulatory Support, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT04084015
• Other Study ID Numbers: 2019P000668
• First Posted: Sep 10, 2019
• Last Update Posted: Jun 29, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by David A. D'Alessandro, M.D., Associate Professor, Principal Investigator, Surgical Director, Heart Transplantation and Mechanical Circulatory Support, Massachusetts General Hospital: Extracorporeal membrane oxygenation; Left ventricular unloading; Impella®
• Additional relevant MeSH terms: Shock, Cardiogenic

Study Results

Participant Flow

Recruitment Details	Patients were recruited from inpatient medical units at Massachusetts General Hospital. The recruitment period was from August 2019-March 2021.

Arm/Group Title	Early Axillary Impella®
Arm/Group Description	Early placement of axillary Impella® for LV unloading and LV recovery in patients with VA ECMO Axillary Impella®: All enrolled patients will undergo surgical placement of Impella® via axillary artery within 48 hours after peripheral VA ECMO initiation and be managed with early extubation and ambulation strategy
Period Title: Overall Study
STARTED	2
COMPLETED	2
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Early Axillary Impella®
Arm/Group Description	Early placement of axillary Impella® for LV unloading and LV recovery in patients with VA ECMO Axillary Impella®: All enrolled patients will undergo surgical placement of Impella® via axillary artery within 48 hours after peripheral VA ECMO initiation and be managed with early extubation and ambulation strategy
Overall Participants	2
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47 (15.6)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	2 100%
Race and Ethnicity Not Collected (Count of Participants)

Outcome Measures

1. Primary Outcome

Title	Survival
Description	Patient survival at 30-days post VA ECMO cannulation timepoint. Collected through patient chart review.
Time Frame	30 days after cannulation of VA ECMO

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Early Axillary Impella®
Arm/Group Description	Early placement of axillary Impella® for LV unloading and LV recovery in patients with VA ECMO Axillary Impella®: All enrolled patients will undergo surgical placement of Impella® via axillary artery within 48 hours after peripheral VA ECMO initiation and be managed with early extubation and ambulation strategy
Measure Participants	2
Count of Participants [Participants]	1 50%

2. Secondary Outcome

Title	Death From Cardiovascular Causes
Description	Death from cardiovascular cases at 30-days post VA ECMO cannulation timepoint. Collected from review of patient charts.
Time Frame	30 days after cannulation of VA ECMO or Discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Early Axillary Impella®
Arm/Group Description	Early placement of axillary Impella® for LV unloading and LV recovery in patients with VA ECMO Axillary Impella®: All enrolled patients will undergo surgical placement of Impella® via axillary artery within 48 hours after peripheral VA ECMO initiation and be managed with early extubation and ambulation strategy
Measure Participants	2
Count of Participants [Participants]	1 50%

3. Secondary Outcome

Title	New York Heart Association Functional Status
Description	Retrospective review in a patient chart
Time Frame	30 days after cannulation of VA ECMO or Discharge

Outcome Measure Data

Analysis Population Description

Data were not collected. NYHA Assessment was not done at 30-days post VA-ECMO cannulation per standard of care.

Arm/Group Title	Early Axillary Impella®
Arm/Group Description	Early placement of axillary Impella® for LV unloading and LV recovery in patients with VA ECMO Axillary Impella®: All enrolled patients will undergo surgical placement of Impella® via axillary artery within 48 hours after peripheral VA ECMO initiation and be managed with early extubation and ambulation strategy
Measure Participants	0

4. Secondary Outcome

Title	Number of Participants With a Neurological Event
Description	Neurological event up to 30-days post VA-ECMO cannulation or Discharge. Includes hypoxic brain damage, intracerebral bleeding, hemorrhagic stroke, or ischemic stroke. Data collected through patient chart review.
Time Frame	30 days after cannulation of VA ECMO or Discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Early Axillary Impella®
Arm/Group Description	Early placement of axillary Impella® for LV unloading and LV recovery in patients with VA ECMO Axillary Impella®: All enrolled patients will undergo surgical placement of Impella® via axillary artery within 48 hours after peripheral VA ECMO initiation and be managed with early extubation and ambulation strategy
Measure Participants	2
Count of Participants [Participants]	1 50%

5. Secondary Outcome

Title	Left Ventricular Function
Description	Measured by Echocardiogram study.
Time Frame	30 days after cannulation of VA ECMO or Discharge

Outcome Measure Data

Analysis Population Description

Neither of the subjects who were enrolled had an echocardiogram done at the 30 day post VA-ECMO cannulation or Discharge timepoints so LVEF could not be collected.

Arm/Group Title	Early Axillary Impella®
Arm/Group Description	Early placement of axillary Impella® for LV unloading and LV recovery in patients with VA ECMO Axillary Impella®: All enrolled patients will undergo surgical placement of Impella® via axillary artery within 48 hours after peripheral VA ECMO initiation and be managed with early extubation and ambulation strategy
Measure Participants	0

6. Other Pre-specified Outcome

Title	Number of Participants With Acute Kidney Injury
Description	Retrospective review in a patient chart
Time Frame	Within 30 days after cannulation of VA ECMO

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Early Axillary Impella®
Arm/Group Description	Early placement of axillary Impella® for LV unloading and LV recovery in patients with VA ECMO Axillary Impella®: All enrolled patients will undergo surgical placement of Impella® via axillary artery within 48 hours after peripheral VA ECMO initiation and be managed with early extubation and ambulation strategy
Measure Participants	2
Count of Participants [Participants]	2 100%

7. Other Pre-specified Outcome

Title	Vascular Complication
Description	Retrospective review in a patient chart
Time Frame	Within 30 days after cannulation of VA ECMO

Outcome Measure Data

Analysis Population Description

Data not collected for either subject

Arm/Group Title	Early Axillary Impella®
Arm/Group Description	Early placement of axillary Impella® for LV unloading and LV recovery in patients with VA ECMO Axillary Impella®: All enrolled patients will undergo surgical placement of Impella® via axillary artery within 48 hours after peripheral VA ECMO initiation and be managed with early extubation and ambulation strategy
Measure Participants	0

8. Other Pre-specified Outcome

Title	Number of Participants With Bleeding
Description	Moderate bleeding in hospital. Defined by transfusion of red blood cells without hemodynamic impairment. Collected through review of patient chart.
Time Frame	Within 30 days after cannulation of VA ECMO

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Early Axillary Impella®
Arm/Group Description	Early placement of axillary Impella® for LV unloading and LV recovery in patients with VA ECMO Axillary Impella®: All enrolled patients will undergo surgical placement of Impella® via axillary artery within 48 hours after peripheral VA ECMO initiation and be managed with early extubation and ambulation strategy
Measure Participants	2
Count of Participants [Participants]	1 50%

Adverse Events

Time Frame	Adverse event data were collected up to 30-days post VA-ECMO cannulation/Impella Insertion, whichever came first.
Adverse Event Reporting Description	Each subject will be followed through 30 days post VA-ECMO cannulation/Impella Insertion. Adverse events data will be collected throughout this time period. Adverse events will be determined and assessed only through medical chart review.
Arm/Group Title	Early Axillary Impella®
Arm/Group Description	Early placement of axillary Impella® for LV unloading and LV recovery in patients with VA ECMO Axillary Impella®: All enrolled patients will undergo surgical placement of Impella® via axillary artery within 48 hours after peripheral VA ECMO initiation and be managed with early extubation and ambulation strategy
All Cause Mortality
	Early Axillary Impella®
	Affected / at Risk (%)	# Events
Total	1/2 (50%)
Serious Adverse Events
	Early Axillary Impella®
	Affected / at Risk (%)	# Events
Total	1/2 (50%)
Cardiac disorders
Death	1/2 (50%)
Other (Not Including Serious) Adverse Events
	Early Axillary Impella®
	Affected / at Risk (%)	# Events
Total	0/2 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.