Impella®-Supported PCI in High-Risk Patients With Complex Coronary Artery Disease and Reduced Left Ventricular Function

NCT ID: NCT04763200

Last Updated: 2025-07-22

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 1252 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-13
• Study Completion Date: 2027-10-31

Brief Summary

The purpose of this study is to assess if using the Impella® CP (or Impella® 2.5) device during high-risk PCI in patients with reduced left-sided heart function will result in an improvement in symptoms, heart function and health after a heart procedure compared to the current standard of care.

Detailed Description

To demonstrate that in high-risk patients with complex CAD and reduced left ventricular function undergoing PCI, PCI with Impella MCS is superior to PCI without Impella MCS in reducing the composite rate of all-cause death, stroke, MI, unplanned clinically driven revascularization, durable LVAD implant or heart transplant, or other hospitalization for cardiovascular causes at 3-year follow-up.

Conditions

Left Ventricular Dysfunction; Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Impella Arm

Impella CP® or Impella 2.5 placement prior to high-risk PCI

Group Type: EXPERIMENTAL

Impella CP® / Impella CP® with SmartAssist® / Impella 2.5®

Intervention Type: DEVICE

Impella CP / Impella CP with SmartAssist will be used in most patients randomized to the Impella arm. Impella 2.5 may be used in patients with small body size (BMI \<20 kg/m2 or body weight \<60 kg) or if the iliofemoral vasculature is able to accommodate the smaller Impella 2.5 device but not the Impella CP device.

Control Arm

Subjects randomized to the Control group will be treated per standard of care PCI with or without an intra-aortic balloon pump (IABP).

Group Type: ACTIVE_COMPARATOR

IABP Intra-aortic balloon pump

Intervention Type: DEVICE

IABP uses counterpulsation to provide 0.2L/min coronary flow

Interventions

Impella CP® / Impella CP® with SmartAssist® / Impella 2.5®

Impella CP / Impella CP with SmartAssist will be used in most patients randomized to the Impella arm. Impella 2.5 may be used in patients with small body size (BMI \<20 kg/m2 or body weight \<60 kg) or if the iliofemoral vasculature is able to accommodate the smaller Impella 2.5 device but not the Impella CP device.

Intervention Type: DEVICE

IABP Intra-aortic balloon pump

IABP uses counterpulsation to provide 0.2L/min coronary flow

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Age ≥18 years and ≤90 years

2. Clinical presentation and baseline left ventricular function are as follows: Either 2A or 2B must be present

A. Subject has CCS or NSTEMI with an LVEF ≤40% NOTE: The LVEF must be quantitatively measured as ≤40% by echo within 30 days assuming no change in clinical condition. If multiple echos have been performed within 30-days, the most recent test must be used to qualify the patient. NOTE: Subject qualifies if the quantitative site read LVEF is ≤30%; if the quantitative site read is >30% - ≤40% the Echo Core Lab must confirm the LVEF is ≤40% before subject enrollment (Core Lab will provide <48-hour turnaround). Similarly, if the site read is qualitative only (i.e., only provides broad ranges without detailed LVEF quantification), the Echo Core Lab must confirm the LVEF is ≤40% before subject enrollment.

OR

B. Subject has STEMI ≥24 hours and <30 days after symptom onset with an LVEF ≤30% NOTE: In patients qualifying with recent STEMI, the LVEF must be demonstrated to be ≤30% by quantitative echocardiography after the primary PCI procedure (if performed) and within 72-hours prior to the planned randomization. If primary PCI was not performed, the qualifying echocardiogram will be the one taken during the index hospitalization closest to the index procedure. If the site read is qualitative only (i.e., only provides broad ranges without detailed LVEF quantification), the Echo Core Lab must confirm the LVEF is ≤30% before subject enrollment.

3. Local heart team (interventional cardiologist and cardiac surgeon) has determined that PCI is indicated and is the most appropriate management for the patient

4. Complex PCI will be performed: Either 4A or 4B must be met

A. One of the following must be present:

i. Triple vessel disease is present (visually-assessed angiographic DS ≥80% [or ≥40% if non-invasive evidence of ischemia on a localizing stress test or invasive evidence of ischemia (FFR ≤0.80 or iFR ≤0.89)] is present in all 3 epicardial coronary artery distributions in a main vessel or branch with visually-assessed reference vessel diameter ≥2.5 mm) with PCI planned in ≥2 of these vessels in the proximal or mid LAD, proximal or mid-LCX or proximal, mid- or distal RCA [i.e., not a branch vessel])

OR

ii. Left main distal bifurcation or trifurcation disease (visually-assessed DS ≥50% [or DS ≥30% if non-invasive evidence of ischemia in both the anterior and posterolateral distributions or left main IVUS MLA ≤6.0 mm2 or FFR ≤0.80 or iFR ≤0.89] is present) with planned intervention of the left main plus at least 2 branch vessels (i.e., the ostial LAD, ostial LCX or ostial ramus)

OR

iii. Left main equivalent disease with both ostial LAD and ostial LCX having visually-assessed angiographic DS ≥80% [or ≥40% if non-invasive evidence of ischemia on a localizing stress test or invasive evidence of ischemia (FFR ≤0.80 or iFR ≤0.89] and requiring intervention in both branches

OR

iv. Intervention of the last remaining vessel (native coronary artery or bypass graft)

OR

B. Multivessel disease is present (visually-assessed angiographic DS ≥80% [or ≥40% if non-invasive or invasive evidence of ischemia is present] in ≥2 of the 3 epicardial coronary artery distributions in a main vessel or branch with visually-assessed reference vessel diameter ≥2.5 mm) and PCI is planned of at least 2 separate complex lesions in main vessels or branch vessels each having one or more of the following characteristics:

i. Long lesion (≥28 mm visually assessed) requiring ≥30 mm stent length (single or multiple)

ii. Severe angiographic calcification (see Protocol definition) or requiring atheroablation

iii. Any left main morphology not in Criterion A requiring intervention (e.g., isolated ostial or mid-shaft left main lesion or distal left main bifurcation lesion with a planned single provisional stent technique)

iv. Non-left main bifurcation lesion requiring intervention in both the main branch and side branch

v. CTO (TIMI 0 Flow)

vi. Giant thrombus (length ≥3x vessel diameter)

vii. SVG (other than focal (<5 mm) disease of the proximal or distal anastomosis or in-stent restenosis)

NOTES:

1. The multiple lesions can be in the same vessel if separated by ≥10 mm - however, each separate lesion has to have one or more of the above characteristics

2. PCI may be performed on additional non-qualifying lesions (i.e., without 1 or more of the above high-risk characteristics) as long as there are at least two lesions also undergoing PCI with each having 1 or more of the above characteristics)

3. There are 2 exceptions to the rule that each separate lesion must have one or more of the above characteristics (as in Inclusion Criterion 4B above): The subject may qualify if undergoing complex PCI of a single lesion that has 2 or more of the above complex characteristics (as in Inclusion Criterion 4B above) if also:

i. There is a CTO of a proximal or mid-LAD, proximal or mid-LCX or proximal, mid- or distal RCA (i.e., not a branch vessel) that will not be treated

OR

ii. The subject qualifies with recent STEMI with an LVEF ≤30% and the complex PCI is planned in a non-infarct vessel (i.e., a complex PCI in the infarct vessel does not qualify)

5. Subject or legal guardian (permitted at US sites only) agrees to randomization and to follow all study procedures and provides informed, written consent

Exclusion Criteria

1. STEMI ≤24 hours from the onset of ischemic symptoms or at any time if mechanical complications of transmural infarction are present (e.g., VSD, papillary muscle rupture, etc.)

2. Cardiogenic shock (SBP <80 mmHg for ≥30 mins and not responsive to intravenous fluids or hemodynamic deterioration for any duration requiring pressors or mechanical circulatory support, including IABP)

3. Subject is presently or recently intubated for the current admission (NOTE: recently intubated patients must be extubated for >24 hours with full neurologic recovery)

4. Cardiorespiratory arrest related to the current admission unless subject is extubated for >24 hours with full neurologic recovery and hemodynamically stable

5. Any contraindication or inability to Impella placement in both the left and right common femoral artery based on clinical or imaging findings, including iliofemoral artery diameter <5 mm, tortuous vascular anatomy or severe bilateral peripheral vascular disease of the iliac or femoral arteries that can't be adequately treated (e.g., with intravascular lithotripsy)

NOTES:

1. Computed tomography (CT), magnetic resonance angiography (MRA) or contrast angiography to assess the aorta and iliofemoral vasculature to ensure Impella compatibility must be performed within 90 days prior to randomization. It is recommended that this evaluation be performed prior to the index procedure. Absent a qualifying pre-procedure imaging study, contrast angiography of the potential Impella access vessel(s) must be performed in the Cath Lab before the planned enrollment after which the subject may be randomized if he/she still qualifies. Of note, if pre-procedure imaging was performed and after this test but before randomization there was a worsening in PVD symptoms, repeat imaging must be performed prior to randomization.

2. If iliofemoral peripheral vascular disease is present precluding Impella use that can be adequately treated with angioplasty, atherectomy or lithotripsy (without a stent), the subject can be enrolled if such treatment is undertaken and is successful and uncomplicated - randomization must not be performed until such successful and uncomplicated treatment

6. Iliofemoral stents placed within 6 months of enrollment with planned vascular access through these vascular segments

7. Vascular access for Impella is required in any location other than the left or right common femoral artery (i.e., axillary access, transcaval access, etc., for Impella access are not permitted)

8. Known left ventricular thrombus

9. Incessant ventricular arrhythmias that would likely preclude stable Impella positioning

10. Severe aortic stenosis or severe aortic insufficiency

11. Prior mechanical valve or self-expanding TAVR (NOTE: prior bioprosthetic surgical valve or balloon expandable TAVR implanted >24 hours pre-procedure is acceptable)

12. Prior CABG within three (3) months or successful prior PCI of at least one (1) attempted lesion within 12 months (including during the index hospitalization prior to randomization), that has not experienced stent thrombosis or restenosis during that 12-month period; the one (1) exception is that patients may be enrolled if a primary PCI for STEMI was performed during the index hospitalization without MCS and that was ≥24 hours and <30 days prior to randomization.

NOTE: Successful PCI for this exclusion criterion is defined as a visually-assessed angiographic DS ≤50% in at least one (1) attempted lesion.

13. Prior placement of IABP, Impella or any other MCS device for any reason during the index admission, prior to randomization

14. Known severe pulmonary hypertension (right ventricular systolic pressure (RVSP) on echo or pulmonary artery systolic pressure (PASP) on right heart catheterization) >70 mm Hg unless active vasodilator therapy in the Cath Lab is able to reduce the pulmonary vascular resistance (PVR) to <3 Wood Units or between 3 and 4.5 Wood Units with v-wave less than twice the mean of the pulmonary capillary wedge pressure

15. Symptoms or signs of severe RV dysfunction, such as anasarca (NOTE: Leg edema alone does not necessarily indicate severe RV dysfunction if the investigator believes it is due to LV dysfunction)

16. Severe tricuspid insufficiency

17. Platelet count <75,000 cells/mm3, bleeding diathesis or active bleeding, coagulopathy or unwilling to receive blood transfusions

18. On dialysis

19. Prior stroke with any permanent neurologic deficit within the previous three (3) months, or any prior intracranial hemorrhage or any prior subdural hematoma or known intracranial pathology pre-disposing to intracranial bleeding, such as an arteriovenous malformation or mass

20. Taking a chronic oral anticoagulant that cannot be safely discontinued for at least 72-hours before and 72-hours after the index procedure (if a vitamin K antagonist) or that cannot be safely discontinued for at least 48 hours before and 48 hours after the index procedure (for a direct acting oral anticoagulant)

21. Plan for any surgery within 6 months necessitating discontinuing antiplatelet agents

22. Pregnant or child-bearing potential unless negative pregnancy test within 1 week

23. Participation in the active treatment or follow-up phase of another clinical study of an investigational drug or device that has not reached its primary endpoint

24. Any medical or psychiatric condition such as dementia, alcoholism or substance abuse which may preclude informed consent or interfere with any of the study procedures, including follow-up visits

25. Any non-cardiac condition with life expectancy <3 years (e.g., cirrhosis, oxygen or oral steroid dependent COPD, cancer not in remission, etc.)

26. Subject is currently hospitalized for definite or suspected COVID-19

27. Subject has previously been symptomatic with or hospitalized for COVID-19 unless he/she has been discharged (if hospitalized) and asymptomatic for ≥4 weeks and has returned to his/her prior baseline (pre-COVID) clinical condition

28. Subject is asymptomatic (never ill) and COVID-19 PCR/antigen test is positive within the prior four (4) weeks unless a) subject remains asymptomatic for ≥2 weeks after the last positive test or b) the positive test occurred within six (6) months after the subject received a COVID vaccine

29. Subject belongs to a vulnerable population (defined as individuals with mental disability, impoverished persons, homeless persons, nomads, refugees and those permanently incapable of giving informed consent; vulnerable populations also may include members of a group with a hierarchical structure such as university students, subordinate hospital and laboratory personnel, employees of the Sponsor, members of the armed forces and persons kept in detention)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Abiomed Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Alabama

Birmingham, Alabama, United States

St. Joseph's Medical Center - Phoenix

Phoenix, Arizona, United States

Northwest Medical Center Tucson

Tucson, Arizona, United States

Arkansas Cardiology

Little Rock, Arkansas, United States

Adventist Health Glendale

Glendale, California, United States

Keck School of Medicine of USC

Los Angeles, California, United States

St. Joseph Hospital - Orange

Orange, California, United States

Loma Linda University Health

San Bernardino, California, United States

UCSD Medical Center

San Diego, California, United States

Colorado Heart and Vascular

Lakewood, Colorado, United States

Hartford Hospital

Hartford, Connecticut, United States

The Cardiac & Vascular Institute

Gainesville, Florida, United States

University of Florida Health - Gainesville

Gainesville, Florida, United States

UF Health Jacksonville

Jacksonville, Florida, United States

Emory University Hospital

Atlanta, Georgia, United States

Northside Cardiovascular Institute

Lawrenceville, Georgia, United States

Rush University Medical Center

Chicago, Illinois, United States

NorthShore University Health System

Evanston, Illinois, United States

Northwestern University

Evanston, Illinois, United States

Advocate Christ Medical Center

Oak Lawn, Illinois, United States

Cardiovascular Research Institute of Kansas

Wichita, Kansas, United States

Ochsner Foundation Hospital

New Orleans, Louisiana, United States

Tufts Medical Center

Boston, Massachusetts, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Henry Ford Hospital

Detroit, Michigan, United States

Henry Ford St. John Hospital

Detroit, Michigan, United States

Corewell Health

Grand Rapids, Michigan, United States

Metropolitan Heart and Vascular Institute / Metropolitan Cardiology Consultants

Coon Rapids, Minnesota, United States

CentraCare (St. Cloud Hospital)

Saint Cloud, Minnesota, United States

SSM Health DePaul Hospital

Bridgeton, Missouri, United States

St. Luke's Hospital

Kansas City, Missouri, United States

Catholic Medical Center

Manchester, New Hampshire, United States

Englewood Hospital

Englewood, New Jersey, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Morristown Medical Center

Morristown, New Jersey, United States

Jersey Shore University Medical Center

Neptune City, New Jersey, United States

The Valley Hospital - Ridgewood

Ridgewood, New Jersey, United States

Lovelace/New Mexico Heart Institute

Albuquerque, New Mexico, United States

University at Buffalo/Kaleida Health

Buffalo, New York, United States

Northwell University Hospital

Manhasset, New York, United States

NYU Langone Health

New York, New York, United States

Icahn School of Medicine at Mt. Sinai

New York, New York, United States

Columbia University Medical Cenrer/NYPH

New York, New York, United States

St. Francis Hospital and Heart Center

Roslyn, New York, United States

Stony Brook University Hospital (SUNY)

Stony Brook, New York, United States

Montefiore Medical Center - Moses

The Bronx, New York, United States

Sanger Heart and Vascular Institute

Charlotte, North Carolina, United States

Duke University

Durham, North Carolina, United States

North Carolina Heart and Vascular Research

Raleigh, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Linder Research Center (The Christ Hospital)

Cincinnati, Ohio, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

University of Oklahoma Medical Center

Oklahoma City, Oklahoma, United States

Providence St. Vincent Medical Center

Portland, Oregon, United States

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

WellSpan York Hospital

York, Pennsylvania, United States

Greenville Hospital System

Greenville, South Carolina, United States

Wellmont Cardiology Services

Kingsport, Tennessee, United States

Centennial Heart - Nashville

Nashville, Tennessee, United States

Ascension St. Thomas West

Nashville, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Presbyterian Hospital Dallas / Texas Health Physicians Group

Dallas, Texas, United States

Medical City Fort Worth

Fort Worth, Texas, United States

HCA Houston Healthcare

Houston, Texas, United States

Houston Methodist Hospital

Houston, Texas, United States

Memorial Hermann Texas Medical Center (UT Health)

Houston, Texas, United States

Texas Heart Institute at Baylor St. Luke's Hospital

Houston, Texas, United States

Texas Cardiology Associates of Houston

Kingwood, Texas, United States

Baylor Scott & White Heart - Plano

Plano, Texas, United States

Methodist Hospital - San Antonio

San Antonio, Texas, United States

Sentara Norfolk Health System

Norfolk, Virginia, United States

Carilion Clinic

Roanoke, Virginia, United States

University Of Washington Medical Center

Seattle, Washington, United States

West Virginia University Hospital

Morgantown, West Virginia, United States

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Toronto General Hospital

Toronto, Ontario, Canada

Royal Victoria Hospital

Montreal, Quebec, Canada

Universitätsklinikum Erlangen

Erlangen, Bavaria, Germany

Klinikum rechts der Isar der TUM

Munich, Bavaria, Germany

Klinikum Karlsburg

Karlsburg, Mecklenburg-Vorpommern, Germany

Universitätsklinikum Düsseldorf

Düsseldorf, North Rhine-Westphalia, Germany

Krankenhaus der Barmherzigen Brüder

Trier, Rhineland-Palatinate, Germany

University Hospital Aachen

Aachen, , Germany

Universitätsklinikum Freiburg, Universitäts-Herzzentrum

Bad Krozingen, , Germany

Berlin CBF

Berlin, , Germany

CVK Berlin

Berlin, , Germany

Klinikum Chemnitz gGmbH

Chemnitz, , Germany

St. Vinzenz-Hospital GMBH KÖLN

Cologne, , Germany

Herzzentrum Dresden GmbH

Dresden, , Germany

University Hopsital Frankfurt

Frankfurt, , Germany

Klinikum Friedrichshafen GmbH

Friedrichshafen, , Germany

Universitätsklinikum Gießen

Giessen, , Germany

Uniklinik Würzburg

Würzburg, , Germany

Policlinico Universitario Agostino Gemelli

Rome, RM, Italy

Ospedale di San Donato

San Donato Milanese, , Italy

Catharina Ziekenhuis Eindhoven

Eindhoven, North Brabant, Netherlands

Istituto Cardiocentro Ticino

Lugano, Canton Ticino, Switzerland

Inselspital Bern

Bern, , Switzerland

Luzerner Kantonsspital

Lucerne, , Switzerland

Royal Brompton Hospital

London, , United Kingdom

Countries

United States; Canada; Germany; Italy; Netherlands; Switzerland; United Kingdom

References

Lusebrink E, Kellnar A, Krieg K, Binzenhofer L, Scherer C, Zimmer S, Schrage B, Fichtner S, Petzold T, Braun D, Peterss S, Brunner S, Hagl C, Westermann D, Hausleiter J, Massberg S, Thiele H, Schafer A, Orban M. Percutaneous Transvalvular Microaxial Flow Pump Support in Cardiology. Circulation. 2022 Apr 19;145(16):1254-1284. doi: 10.1161/CIRCULATIONAHA.121.058229. Epub 2022 Apr 18.

Reference Type: DERIVED

PMID: 35436135 (View on PubMed)

Other Identifiers

VV-TMF-18508

Identifier Type: -

Identifier Source: org_study_id