Impella®-Supported PCI in High-Risk Patients with Complex Coronary Artery Disease and
Reduced Left Ventricular Function: The PROTECT IV Trial

Inclusion Criteria:
Subjects must meet all of the following Inclusion Criteria to participate in
the Trial
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 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%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)

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:
a. 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.
b. 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 mmHg 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. Medical contraindication to discontinue vitamin K anatonists (for at least
72 hours) or the NOACs (new oral anticoagulants) (for at least 48 hours).
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 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.The subject is unable to give adequate consent.