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

Abiomed Inc.102 sites in 5 countries1,252 target enrollmentApril 13, 2021

ConditionsLeft Ventricular Dysfunction Coronary Artery Disease

InterventionsImpella CP® / Impella CP® with SmartAssist® / Impella 2.5®IABP Intra-aortic balloon pump

Overview

Phase: N/A
Intervention: Impella CP® / Impella CP® with SmartAssist® / Impella 2.5®
Conditions: Left Ventricular Dysfunction
Sponsor: Abiomed Inc.
Enrollment: 1252
Locations: 102
Primary Endpoint: 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.
Status: Active, Not Recruiting
Last Updated: last month

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

April 13, 2021

End Date

October 1, 2027

Last Updated

last month

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Abiomed Inc.

Responsible Party

Sponsor

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.
•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 \[i.e., not a branch vessel\])
•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)
•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

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)
•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)

Arms & Interventions

Impella Arm

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

Intervention: Impella CP® / Impella CP® with SmartAssist® / Impella 2.5®

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).

Intervention: IABP Intra-aortic balloon pump

Outcomes

Primary Outcomes

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.

Time Frame: 3 years

Secondary Outcomes

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