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

Coronary Artery Disease Clinical Trial

— PROTECT IV  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04763200
• Other study ID #: VV-TMF-18508
• Status: Recruiting
• Phase: N/A
• Start date: April 13, 2021
• Est. completion date: October 2027

Study information

• Verified date: May 2024
• Source: Abiomed Inc.
• Contact: Charles (Chuck) Simonton, MD FACC FSCAI
• Phone: 978-646-1597
• Email: csimonton[@]abiomed.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1252
• Est. completion date: October 2027
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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)

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Left Ventricular Dysfunction
• Myocardial Ischemia
• Ventricular Dysfunction
• Ventricular Dysfunction, Left

Intervention

Device:
• 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.
• IABP Intra-aortic balloon pump
IABP uses counterpulsation to provide 0.2L/min coronary flow

Locations

Country	Name	City	State
Canada	Toronto General Hospital	Toronto	Ontario
Canada	St. Boniface Hospital	Winnipeg	Manitoba
Germany	University Hospital Aachen	Aachen
Germany	Universitätsklinikum Freiburg, Universitäts-Herzzentrum	Bad Krozingen
Germany	Segeberger Kliniken GmbH	Bad Segeberg
Germany	Berlin CBF	Berlin
Germany	CVK Berlin	Berlin
Germany	Klinikum Chemnitz gGmbH	Chemnitz
Germany	Herzzentrum Dresden GmbH	Dresden
Germany	Universitätsklinikum Düsseldorf	Düsseldorf	NRW
Germany	Universitätsklinikum Erlangen	Erlangen	Bayern
Germany	Universitätsklinikum Essen AöR	Essen
Germany	Klinikum Friedrichshafen GmbH	Friedrichshafen
Germany	Universitätsklinikum Gießen	Gießen
Germany	Klinikum Karlsburg	Karlsburg	Mecklenburg-Vorpommern
Germany	St. Vinzenz-Hospital Gmbh Köln	Köln
Germany	Klinikum rechts der Isar der TUM	Munich	Bavaria
Germany	Krankenhaus der Barmherzigen Brüder	Trier	Rheinland-Pfalz
Germany	Uniklinik Würzburg	Würzburg
Italy	Clinica Mediterranea	Napoli
Italy	Policlinico Universitario Agostino Gemelli	Rome	RM
Italy	Humanitas Clinical & Research Hospital	Rozzano	Lombardy
Netherlands	Catharina Ziekenhuis Eindhoven	Eindhoven	North Brabant
Netherlands	LUMC-Leids Universitair Medisch Centrum	Leiden	Zuid
Switzerland	Inselspital Bern	Bern
Switzerland	Istituto Cardiocentro Ticino	Lugano	Tessin
Switzerland	Luzerner Kantonsspital	Luzern
United Kingdom	Royal Brompton Hospital	London
United States	Lovelace/New Mexico Heart Institute	Albuquerque	New Mexico
United States	Lehigh Valley Health Network	Allentown	Pennsylvania
United States	Emory University Hospital	Atlanta	Georgia
United States	University of Alabama	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	SSM Health DePaul Hospital	Bridgeton	Missouri
United States	Montefiore Medical Center - Moses	Bronx	New York
United States	University at Buffalo/Kaleida Health	Buffalo	New York
United States	Mills-Peninsula Medical Center	Burlingame	California
United States	Sanger Heart and Vascular Institute	Charlotte	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	Linder Research Center (The Christ Hospital)	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Metropolitan Heart and Vascular Institute / Metropolitan Cardiology Consultants	Coon Rapids	Minnesota
United States	Presbyterian Hospital Dallas / Texas Health Physicians Group	Dallas	Texas
United States	Cardiology Associates Research Company	Daytona Beach	Florida
United States	Ascension St. John Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Englewood Hospital	Englewood	New Jersey
United States	NorthShore University Health System	Evanston	Illinois
United States	Northwestern University	Evanston	Illinois
United States	Washington Regional Medical Center - Walker Heart Institute	Fayetteville	Arkansas
United States	Medical City Fort Worth	Fort Worth	Texas
United States	Saint Agnes Medical Center	Fresno	California
United States	The Cardiac & Vascular Institute	Gainesville	Florida
United States	University of Florida Health - Gainesville	Gainesville	Florida
United States	University of Texas Medical Branch (UTMB) Galveston	Galveston	Texas
United States	Adventist Health Glendale	Glendale	California
United States	Spectrum Health	Grand Rapids	Michigan
United States	Greenville Hospital System	Greenville	South Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	The Queen's Medical Center	Honolulu	Hawaii
United States	HCA Houston Healthcare	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	UF Health Jacksonville	Jacksonville	Florida
United States	St. Luke's Hospital	Kansas City	Missouri
United States	Wellmont Cardiology Services	Kingsport	Tennessee
United States	Texas Cardiology Associates of Houston	Kingwood	Texas
United States	Parkwest Medical Center	Knoxville	Tennessee
United States	Cardiovascular Institute of the South (Lafayette General Medical Center)	Lafayette	Louisiana
United States	Colorado Heart and Vascular	Lakewood	Colorado
United States	Northside Cardiovascular Institute	Lawrenceville	Georgia
United States	Arkansas Cardiology	Little Rock	Arkansas
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Norton Healthcare - Norton Heart Specialists	Louisville	Kentucky
United States	Catholic Medical Center	Manchester	New Hampshire
United States	Northwell University Hospital	Manhasset	New York
United States	Wellstar Kennestone Hospital	Marietta	Georgia
United States	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	West Virginia University Hospital	Morgantown	West Virginia
United States	Morristown Medical Center	Morristown	New Jersey
United States	Ascension St. Thomas West	Nashville	Tennessee
United States	Centennial Heart - Nashville	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Jersey Shore University Medical Center	Neptune	New Jersey
United States	Robert Wood Johnson Medical School & Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	Ochsner Foundation Hospital	New Orleans	Louisiana
United States	Columbia University Medical Cenrer/NYPH	New York	New York
United States	Icahn School of Medicine at Mt. Sinai	New York	New York
United States	NYU Langone Health	New York	New York
United States	Sentara Norfolk Health System	Norfolk	Virginia
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	University of Oklahoma Medical Center	Oklahoma City	Oklahoma
United States	St. Joseph Hospital - Orange	Orange	California
United States	Abrazo Arizona Heart	Phoenix	Arizona
United States	St. Joseph's Medical Center - Phoenix	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Baylor Scott & White Heart - Plano	Plano	Texas
United States	Legacy Emanuel Hospital & Health Center	Portland	Oregon
United States	Oregon Health and Science University	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	North Carolina Heart and Vascular Research	Raleigh	North Carolina
United States	Monument Health Clinical Research	Rapid City	South Dakota
United States	VCU Medical Center	Richmond	Virginia
United States	The Valley Hospital - Ridgewood	Ridgewood	New Jersey
United States	Carilion Clinic	Roanoke	Virginia
United States	St. Francis Hospital and Heart Center	Roslyn	New York
United States	CentraCare (St. Cloud Hospital)	Saint Cloud	Minnesota
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Methodist Hospital - San Antonio	San Antonio	Texas
United States	Loma Linda University Health	San Bernardino	California
United States	UCSD Medical Center	San Diego	California
United States	University Of Washington Medical Center	Seattle	Washington
United States	Memorial Medical Center	Springfield	Illinois
United States	Stony Brook University Hospital (SUNY)	Stony Brook	New York
United States	AdventHealth - Tampa	Tampa	Florida
United States	Torrance Memorial Medical Center	Torrance	California
United States	Northwest Medical Center Tucson	Tucson	Arizona
United States	Tucson Medical Center HealthCare	Tucson	Arizona
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	WellSpan York Hospital	York	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Abiomed Inc.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		3 years
Secondary	Death or NYHA Class III or IV		1 year
Secondary	Improvement in KCCQ		Baseline to 6 months
Secondary	6MWD		6 months
Secondary	All CV hospitalizations through 3 years		3 years
Secondary	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		3 years
Secondary	CV death or HF hospitalizations through 3 years		3 years
Secondary	Improvement in LVEF based on ANCOVA regression with inclusion of baseline LVEF measurement as a covariate		Baseline to 6 months
Secondary	Achievement of complete anatomic revascularization after the index and planned staged procedures		3 years