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Impella CP With VA ECMO for Cardiogenic Shock (REVERSE)

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ClinicalTrials.gov Identifier: NCT03431467
Recruitment Status : Recruiting
First Posted : February 13, 2018
Last Update Posted : April 5, 2021
Sponsor:
Information provided by (Responsible Party):
Michael Ibrahim, University of Pennsylvania

Brief Summary:

Veno-arterial extra-corporeal membrane oxygenation (VA-ECMO) is indicated as a haemodynamic rescue strategy in decompensated acute or chronic heart failure presenting as cardiogenic shock. It has been used across aeitologies including post-myocardial infarction, dilated cardiomyopathy, acute myocarditis and in post-cardiotomy shock. VA ECMO has a number of effects on the circulation including improved end-organ perfusion and possibly improved coronary perfusion, and is a bridge to further therapies including permanent advanced mechanical circulatory support, cardiac transplantation and to cardiac recovery.

Left ventricular assist devices (LVADs) provide long-term mechanical circulatory support and also profoundly mechanically unload the left ventricle. Multiple clinical studies have documented cardiac recovery using LVAD therapy, with a rate between 10-60% in selected populations. A large body of basic science has documented the pivotal role of mechanical load in determining ventricular contractile performance across species. Therefore both clinical data and basic laboratory studies support the notion that profound ventricular unloading may result in improved cardiac performance through a variety of mechanisms ranging from triggered de novo cardiomyocyte proliferation, subcellular calcium handling reverse remodeling, changes to the extracellular matrix of the heart, reverse remodeling of the neurohormal milleu, amongst many others.

One of the major deficiencies of peripheral VA-ECMO is its lack of left ventricular unloading, with associated pulmonary congestion, which can derail clinical improvement and hamper cardiac recovery. Indeed, percutaneous VA-ECMO increases LV afterload due to the retrograde blood flow, and because of the lack of venting, there may be progressive LV distension. These conditions can result in a congested, pressure-overloaded ventricle, even in the absence of echocardiographic ventricular distension. This may be ameliorated with the addition of ventricular mechanical unloading using percutaneous therapies including the percutaneous left ventricular device, Impella CP.

On the platform of VA-ECMO, the addition of an Impella device to reduce ventricular loading results in improved survival and recovery of ventricular performance in the setting of cardiogenic shock. In a number of small studies, the use of additional means to unload the ventricle, principally Impella, results in cardiac recovery and less ventricular distension. In chronic heart failure, direct ventricular unloading is critical to cardiac recovery.

The objective of this randomized study is to determine whether the addition of early direct ventricular unloading using Impella CP leads to higher rates of cardiac recovery, defined as survival free from mechanical circulatory support, heart transplantation or inotropic support at thirty days. This study will also examine the clinical, biochemical, echocardiographic and radiologic effects of VA ECMO with and without the addition of Impella CP to directly vent the left ventricle to address adjunct important questions such as the effects on pulmonary congestion.


Condition or disease Intervention/treatment Phase
Cardiogenic Shock Device: Impella-CP LV Vent Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomised controlled trial at three U Penn Sites
Masking: Single (Outcomes Assessor)
Masking Description: All data will be masked as far as possible. For example, Echo data will be masked
Primary Purpose: Treatment
Official Title: A Prospective Randomised Trial of Early LV Venting Using Impella CP for Recovery in Patients With Cardiogenic Shock Managed With VA ECMO
Actual Study Start Date : March 19, 2018
Estimated Primary Completion Date : January 1, 2025
Estimated Study Completion Date : January 1, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Shock

Arm Intervention/treatment
No Intervention: Control
VA-ECMO alone per standard clinical protocol.
Experimental: Experimental
VA-ECMO with early institution of Impella CP LV venting
Device: Impella-CP LV Vent
Patients randomised to the experimental arm will have an Impella-CP implanted in addition to VA-ECMO within a maximum of 10 hours of institution of VA-ECMO




Primary Outcome Measures :
  1. Recovery from cardiogenic shock. [ Time Frame: At thirty days. ]
    Proportion of subjects treated with this standardized ECMO protocol with either (i) no additional therapy or (ii) Impella CP for LV mechanical unloading who experience myocardial recovery defined as: survival free from mechanical circulatory support, heart transplantation or inotropic support.


Secondary Outcome Measures :
  1. Survival to hospital discharge. [ Time Frame: At discharge from hospital, an average of 60 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Cardiogenic shock: Including refractory to conventional therapy, including systolic blood pressure < 90mm Hg, Cardiac Index < 1.8 or a cardiac index < 2.0 on moderate to high doses of inotropes and vasopressors for greater than 30 mins, or systemic signs of tissue hypoxia.
  • Post-acute myocardial infarction cardiogenic shock: excluding mechanical complications requiring surgical intervention after extracorpeal membrane oxygenator (ECMO) such as post-ischaemic ventricular septal defect (VSD).
  • Drug overdose-induced cardiogenic shock.
  • Early graft failure: post orthotropic heart transplantation cardiogenic shock, excluding immediate intra-operative failure.
  • Acute on chronic cardiomyopathy with progressive shock and decompensation unresponsive to medical therapies.

Exclusion Criteria:

  • Recent Significant Pulmonary Embolus
  • Moderate to severe aortic valve insufficiency (AI)
  • Ongoing significant sepsis
  • Severe pulmonary hypertension & shock
  • Hypothermia
  • Post-cardiotomy cardiogenic shock
  • Continuous cardiopulmonary resuscitation (CPR) >20-30 minutes, except if neurological status is satisfactory
  • Transfer from outside hospital on VA ECMO or with history of CPR
  • Listed for cardiopulmonary transplantation or being evaluated for cardiopulmonary transplantation or permanent mechanical circulatory support
  • Known or suspected chronic heart failure with echocardiogram documenting left ventricular diastolic diameter >6.5cm
  • Known or suspected chronic heart failure with echocardiogram documenting left ventricular ejection fraction < 25%
  • Mechanical aortic valve replacement
  • Presence of left ventricular thrombus
  • Pre-existing Impella 2.5, CP, 3.5 or 5.0
  • Cardiogenic shock due to primary respiratory failure
  • Mechanical complications requiring surgical intervention after ECMO such as post-ischaemic VSD.
  • Severe liver failure
  • Active malignancy
  • Acute aortic dissection
  • Intracranial hemorrhage
  • Neurological injury including recent cerebrovascular accident or suspected severe neurologic injury

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03431467


Contacts
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Contact: Michael Ibrahim, MD PhD 2677605502 michael.ibrahim@uphs.upenn.edu

Locations
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United States, Pennsylvania
Hospital of The University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Michael Ibrahim, MD PhD       michael.ibrahim@uphs.upenn.edu   
Contact: Michael Ibrahim       michael.ibrahim@uphs.upenn.edu   
Sponsors and Collaborators
University of Pennsylvania
Investigators
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Principal Investigator: Christian Bermudez, MD University of Pennsylvania
Principal Investigator: Michael Ibrahim, MD PhD University of Pennsylvania
  Study Documents (Full-Text)

Documents provided by Michael Ibrahim, University of Pennsylvania:
Study Protocol  [PDF] December 20, 2017
Statistical Analysis Plan  [PDF] December 20, 2017

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Responsible Party: Michael Ibrahim, Co-Principal Investogator, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT03431467    
Other Study ID Numbers: 828198
First Posted: February 13, 2018    Key Record Dates
Last Update Posted: April 5, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Deidentiifed data will be used within the research team

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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.: Yes
Keywords provided by Michael Ibrahim, University of Pennsylvania:
ECMO
Heart Failure
RCT
Mechanical unloading
Additional relevant MeSH terms:
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Shock, Cardiogenic
Shock
Pathologic Processes
Myocardial Infarction
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Infarction
Ischemia
Necrosis