Impella®-Supported PCI in High-Risk Patients With Complex Coronary Artery Disease and Reduced Left Ventricular Function (PROTECT IV)
Left Ventricular Dysfunction, Coronary Artery Disease
About this trial
This is an interventional treatment trial for Left Ventricular Dysfunction focused on measuring Non-ST Elevated Myocardial Infarction, Cardiovascular Diseases, Heart Diseases, Myocardial Ischemia, Myocardial Infarction, Anterior Wall Myocardial Infarction, Inferior Wall Myocardial Infarction
Eligibility Criteria
Inclusion Criteria:
- Age ≥18 years and ≤90 years
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.
- Local heart team (interventional cardiologist and cardiac surgeon) has determined that PCI is indicated and is the most appropriate management for the patient
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:
- 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
- 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)
- 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)
- 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:
- 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.)
- 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)
- Subject is presently or recently intubated for the current admission (NOTE: recently intubated patients must be extubated for >24 hours with full neurologic recovery)
- Cardiorespiratory arrest related to the current admission unless subject is extubated for >24 hours with full neurologic recovery and hemodynamically stable
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:
- 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.
- 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
- Iliofemoral stents placed within 6 months of enrollment with planned vascular access through these vascular segments
- 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)
- Known left ventricular thrombus
- Incessant ventricular arrhythmias that would likely preclude stable Impella positioning
- Severe aortic stenosis or severe aortic insufficiency
- Prior mechanical valve or self-expanding TAVR (NOTE: prior bioprosthetic surgical valve or balloon expandable TAVR implanted >24 hours pre-procedure is acceptable)
- Any prior CABG or prior PCI within 12 months, including during the index hospitalization. The one 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
- Prior placement of IABP, Impella or any other MCS device for any reason during the index admission, prior to randomization
- 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
- Moderate or severe RV dysfunction defined as TAPSE <12 mm or RVFAC ≤30% as assessed on baseline TTE (NOTE: these measures may be quantified at the site; if the site determines qualitatively that some degree of RV dysfunction is present or the subject has signs or symptoms of RV dysfunction but the site is unable to quantitate RV function, the echo must be submitted for Core Laboratory assessment prior to subject enrollment)
- Platelet count <75,000 cells/mm3, bleeding diathesis or active bleeding, coagulopathy or unwilling to receive blood transfusions
- On dialysis
- Prior stroke with any permanent neurologic deficit 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
- 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)
- Plan for any surgery within 6 months necessitating discontinuing antiplatelet agents
- Pregnant or child-bearing potential unless negative pregnancy test within 1 week
- 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
- 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
- Any non-cardiac condition with life expectancy <3 years (e.g., cirrhosis, oxygen or oral steroid dependent COPD, cancer not in remission, etc.)
- Subject is currently hospitalized for definite or suspected COVID-19
- Subject has previously been symptomatic with or hospitalized for COVID-19 unless he/she has been discharged (if hospitalized) and asymptomatic for ≥8 weeks and has returned to his/her prior baseline (pre-COVID) clinical condition
- Subject is asymptomatic (never ill) and COVID-19 PCR/antigen test is positive within the prior 4 weeks unless subject remains asymptomatic for ≥4 weeks after the last positive test
- Subject belongs to a vulnerable population (defined as individuals with mental disability, persons in nursing homes, 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)
Sites / Locations
- University of AlabamaRecruiting
- Abrazo Arizona Heart
- St. Joseph's Medical Center - PhoenixRecruiting
- Tucson Medical Center HealthCare
- Northwest Medical Center TucsonRecruiting
- Washington Regional Medical Center - Walker Heart Institute
- Arkansas CardiologyRecruiting
- Mills-Peninsula Medical Center
- Saint Agnes Medical Center
- Adventist Health GlendaleRecruiting
- Cedars-Sinai Medical Center
- St. Joseph Hospital - OrangeRecruiting
- Loma Linda University HealthRecruiting
- UCSD Medical CenterRecruiting
- Torrance Memorial Medical Center
- Colorado Heart and VascularRecruiting
- MedStar Washington Hospital CenterRecruiting
- Cardiology Associates Research Company
- The Cardiac & Vascular InstituteRecruiting
- University of Florida Health - GainesvilleRecruiting
- UF Health JacksonvilleRecruiting
- AdventHealth - Tampa
- Emory University HospitalRecruiting
- Northside Cardiovascular InstituteRecruiting
- Wellstar Kennestone Hospital
- The Queen's Medical Center
- Rush University Medical Center
- NorthShore University Health SystemRecruiting
- Northwestern UniversityRecruiting
- Advocate Christ Medical CenterRecruiting
- Memorial Medical Center
- Norton Healthcare - Norton Heart SpecialistsRecruiting
- Cardiovascular Institute of the South (Lafayette General Medical Center)
- Ochsner Foundation HospitalRecruiting
- Tufts Medical CenterRecruiting
- Massachusetts General HospitalRecruiting
- Beth Israel Deaconess Medical CenterRecruiting
- Henry Ford HospitalRecruiting
- Ascension St. John HospitalRecruiting
- Spectrum HealthRecruiting
- Metropolitan Heart and Vascular Institute / Metropolitan Cardiology ConsultantsRecruiting
- CentraCare (St. Cloud Hospital)Recruiting
- SSM Health DePaul HospitalRecruiting
- St. Luke's HospitalRecruiting
- Missouri Baptist Medical Center
- Catholic Medical CenterRecruiting
- Englewood Hospital
- Hackensack University Medical CenterRecruiting
- Morristown Medical CenterRecruiting
- Jersey Shore University Medical CenterRecruiting
- Robert Wood Johnson Medical School & Robert Wood Johnson University Hospital
- The Valley Hospital - RidgewoodRecruiting
- Lovelace/New Mexico Heart InstituteRecruiting
- Montefiore Medical Center - MosesRecruiting
- University at Buffalo/Kaleida HealthRecruiting
- Northwell University HospitalRecruiting
- NYU Langone HealthRecruiting
- Icahn School of Medicine at Mt. SinaiRecruiting
- Columbia University Medical Cenrer/NYPHRecruiting
- St. Francis Hospital and Heart CenterRecruiting
- Stony Brook University Hospital (SUNY)Recruiting
- Sanger Heart and Vascular Institute
- North Carolina Heart and Vascular ResearchRecruiting
- Wake Forest University Health SciencesRecruiting
- Linder Research Center (The Christ Hospital)Recruiting
- Cleveland Clinic FoundationRecruiting
- University of Oklahoma Medical CenterRecruiting
- Providence St. Vincent Medical CenterRecruiting
- Legacy Emanuel Hospital & Health CenterRecruiting
- Oregon Health and Science University
- Lehigh Valley Health NetworkRecruiting
- Allegheny General HospitalRecruiting
- WellSpan York HospitalRecruiting
- Greenville Hospital System
- Monument Health Clinical ResearchRecruiting
- Wellmont Cardiology ServicesRecruiting
- Parkwest Medical CenterRecruiting
- Centennial Heart - NashvilleRecruiting
- Ascension St. Thomas WestRecruiting
- Vanderbilt University Medical CenterRecruiting
- Presbyterian Hospital Dallas / Texas Health Physicians GroupRecruiting
- Medical City Fort WorthRecruiting
- University of Texas Medical Branch (UTMB) Galveston
- HCA Houston HealthcareRecruiting
- Memorial Hermann Texas Medical Center (UT Health)Recruiting
- Texas Heart Institute at Baylor St. Luke's Hospital
- Texas Cardiology Associates of HoustonRecruiting
- Baylor Scott & White Heart - PlanoRecruiting
- Methodist Hospital - San AntonioRecruiting
- Sentara Norfolk Health SystemRecruiting
- VCU Medical Center
- Carilion ClinicRecruiting
- University Of Washington Medical CenterRecruiting
- West Virginia University HospitalRecruiting
- Aurora St. Luke's Medical CenterRecruiting
- Medical College of Wisconsin
- St. Boniface Hospital
- Toronto General Hospital
- Universitätsklinikum ErlangenRecruiting
- Klinikum KarlsburgRecruiting
- Universitätsklinikum Düsseldorf
- Krankenhaus der Barmherzigen BrüderRecruiting
- University Hospital AachenRecruiting
- Universitätsklinikum Freiburg, Universitäts-HerzzentrumRecruiting
- Segeberger Kliniken GmbH
- Berlin CBFRecruiting
- CVK BerlinRecruiting
- Klinikum Chemnitz gGmbHRecruiting
- Herzzentrum Dresden GmbHRecruiting
- Universitätsklinikum Essen AöRRecruiting
- Klinikum Friedrichshafen GmbHRecruiting
- Universitätsklinikum GießenRecruiting
- St. Vinzenz-Hospital Gmbh KölnRecruiting
- Uniklinik WürzburgRecruiting
- Humanitas Clinical & Research Hospital
- Policlinico Universitario Agostino Gemelli
- Clinica Mediterranea
- Catharina Ziekenhuis EindhovenRecruiting
- LUMC-Leids Universitair Medisch Centrum
- Istituto Cardiocentro TicinoRecruiting
- Inselspital BernRecruiting
- Luzerner KantonsspitalRecruiting
- Royal Brompton Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Impella Arm
Control Arm
Impella CP® or Impella 2.5 placement prior to high-risk PCI
Subjects randomized to the Control group will be treated per standard of care PCI with or without an intra-aortic balloon pump (IABP).