Clinical trial NCT03431467: Impella CP With VA ECMO for Cardiogenic Shock
Official title: A Prospective Randomised Trial of Early LV Venting Using Impella CP for Recovery in Patients With Cardiogenic Shock Managed With VA ECMO
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Cardiogenic Shock
Keywords: ECMO
Heart Failure
RCT
Mechanical unloading
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2018-02-13
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised controlled trial at three U Penn Sites
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Recovery from cardiogenic shock.
timeFrame: At thirty days.
Secondary outcomes:
measure: Survival to hospital discharge.
timeFrame: At discharge from hospital, an average of 60 days
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Hospital of The University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Christian Bermudez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Michael Ibrahim, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: