Clinical trial NCT04763200: Impella®-Supported PCI in High-Risk Patients With Complex Coronary Artery Disease and Reduced Left Ventricular Function
Official title: Impella®-Supported PCI in High-Risk Patients With Complex Coronary Artery Disease and Reduced Left Ventricular Function: The PROTECT IV Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Left Ventricular Dysfunction
Coronary Artery Disease
Keywords: Non-ST Elevated Myocardial Infarction
Cardiovascular Diseases
Heart Diseases
Myocardial Ischemia
Myocardial Infarction
Anterior Wall Myocardial Infarction
Inferior Wall Myocardial Infarction
Lead sponsor: Abiomed Inc.
Sponsor class: INDUSTRY
First posted: 2021-02-21
Enrollment: 1252
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, multicenter, randomized, parallel-controlled, open-label two-arm trial with an adaptive design.
Primary purpose: TREATMENT

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.

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:

Subjects must not meet ANY of the following Exclusion Criteria to participate in the Trial:

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)

Primary outcomes:
measure: The composite of all-cause death, stroke, MI, unplanned clinically driven revascularization, durable LVAD implant or heart transplant, or other hospitalization for cardiovascular (CV) causes.
timeFrame: 3 years
Secondary outcomes:
measure: Death or NYHA Class III or IV
timeFrame: 1 year
measure: Improvement in KCCQ
timeFrame: Baseline to 6 months
measure: 6MWD
timeFrame: 6 months
measure: All CV hospitalizations through 3 years
timeFrame: 3 years
measure: Composite of CV death, stroke, MI, unplanned clinically driven revascularization, durable LVAD implant or heart transplant, or other hospitalization for cardiovascular causes through 3 years
timeFrame: 3 years
measure: CV death or HF hospitalizations through 3 years
timeFrame: 3 years
measure: Improvement in LVEF based on ANCOVA regression with inclusion of baseline LVEF measurement as a covariate
timeFrame: Baseline to 6 months
measure: Achievement of complete anatomic revascularization after the index and planned staged procedures
timeFrame: 3 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Phoenix
country: United States
facility: St. Joseph's Medical Center - Phoenix
state: Arizona
city: Tucson
country: United States
facility: Northwest Medical Center Tucson
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Cardiology
state: Arkansas
city: Glendale
country: United States
facility: Adventist Health Glendale
state: California
city: Los Angeles
country: United States
facility: Keck School of Medicine of USC
state: California
city: Orange
country: United States
facility: St. Joseph Hospital - Orange
state: California
city: San Bernardino
country: United States
facility: Loma Linda University Health
state: California
city: San Diego
country: United States
facility: UCSD Medical Center
state: California
city: Lakewood
country: United States
facility: Colorado Heart and Vascular
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Gainesville
country: United States
facility: The Cardiac & Vascular Institute
state: Florida
city: Gainesville
country: United States
facility: University of Florida Health - Gainesville
state: Florida
city: Jacksonville
country: United States
facility: UF Health Jacksonville
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Lawrenceville
country: United States
facility: Northside Cardiovascular Institute
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Evanston
country: United States
facility: NorthShore University Health System
state: Illinois
city: Evanston
country: United States
facility: Northwestern University
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Wichita
country: United States
facility: Cardiovascular Research Institute of Kansas
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Foundation Hospital
state: Louisiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Detroit
country: United States
facility: Henry Ford St. John Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Health
state: Michigan
city: Coon Rapids
country: United States
facility: Metropolitan Heart and Vascular Institute / Metropolitan Cardiology Consultants
state: Minnesota
city: Saint Cloud
country: United States
facility: CentraCare (St. Cloud Hospital)
state: Minnesota
city: Bridgeton
country: United States
facility: SSM Health DePaul Hospital
state: Missouri
city: Kansas City
country: United States
facility: St. Luke's Hospital
state: Missouri
city: Manchester
country: United States
facility: Catholic Medical Center
state: New Hampshire
city: Englewood
country: United States
facility: Englewood Hospital
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: Ridgewood
country: United States
facility: The Valley Hospital - Ridgewood
state: New Jersey
city: Albuquerque
country: United States
facility: Lovelace/New Mexico Heart Institute
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses
state: New York
city: Buffalo
country: United States
facility: University at Buffalo/Kaleida Health
state: New York
city: Manhasset
country: United States
facility: Northwell University Hospital
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mt. Sinai
state: New York
city: New York
country: United States
facility: Columbia University Medical Cenrer/NYPH
state: New York
city: Roslyn
country: United States
facility: St. Francis Hospital and Heart Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Hospital (SUNY)
state: New York
city: Charlotte
country: United States
facility: Sanger Heart and Vascular Institute
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Raleigh
country: United States
facility: North Carolina Heart and Vascular Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cincinnati
country: United States
facility: Linder Research Center (The Christ Hospital)
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Medical Center
state: Oklahoma
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: York
country: United States
facility: WellSpan York Hospital
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Hospital System
state: South Carolina
city: Kingsport
country: United States
facility: Wellmont Cardiology Services
state: Tennessee
city: Nashville
country: United States
facility: Centennial Heart - Nashville
state: Tennessee
city: Nashville
country: United States
facility: Ascension St. Thomas West
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Presbyterian Hospital Dallas / Texas Health Physicians Group
state: Texas
city: Fort Worth
country: United States
facility: Medical City Fort Worth
state: Texas
city: Houston
country: United States
facility: HCA Houston Healthcare
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Texas Medical Center (UT Health)
state: Texas
city: Houston
country: United States
facility: Texas Heart Institute at Baylor St. Luke's Hospital
state: Texas
city: Kingwood
country: United States
facility: Texas Cardiology Associates of Houston
state: Texas
city: Plano
country: United States
facility: Baylor Scott & White Heart - Plano
state: Texas
city: San Antonio
country: United States
facility: Methodist Hospital - San Antonio
state: Texas
city: Norfolk
country: United States
facility: Sentara Norfolk Health System
state: Virginia
city: Roanoke
country: United States
facility: Carilion Clinic
state: Virginia
city: Seattle
country: United States
facility: University Of Washington Medical Center
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Hospital
state: West Virginia
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montréal
country: Canada
facility: Royal Victoria Hospital
state: Quebec
city: Munich
country: Germany
facility: Klinikum rechts der Isar der TUM
state: Bavaria
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
state: Bayern
city: Karlsburg
country: Germany
facility: Klinikum Karlsburg
state: Mecklenburg-Vorpommern
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
state: NRW
city: Trier
country: Germany
facility: Krankenhaus der Barmherzigen Brüder
state: Rheinland-Pfalz
city: Aachen
country: Germany
facility: University Hospital Aachen
city: Bad Krozingen
country: Germany
facility: Universitätsklinikum Freiburg, Universitäts-Herzzentrum
city: Berlin
country: Germany
facility: Berlin CBF
city: Berlin
country: Germany
facility: CVK Berlin
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
city: Dresden
country: Germany
facility: Herzzentrum Dresden GmbH
city: Frankfurt
country: Germany
facility: University Hopsital Frankfurt
city: Friedrichshafen
country: Germany
facility: Klinikum Friedrichshafen GmbH
city: Gießen
country: Germany
facility: Universitätsklinikum Gießen
city: Köln
country: Germany
facility: St. Vinzenz-Hospital GMBH KÖLN
city: Würzburg
country: Germany
facility: Uniklinik Würzburg
city: Rome
country: Italy
facility: Policlinico Universitario Agostino Gemelli
state: RM
city: San Donato Milanese
country: Italy
facility: Ospedale di San Donato
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis Eindhoven
state: North Brabant
city: Lugano
country: Switzerland
facility: Istituto Cardiocentro Ticino
state: Tessin
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital
city: London
country: United Kingdom
facility: Royal Brompton Hospital
Study officials:
References:
citation: 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.