A Randomized, Concurrent Controlled Trial to Assess the Safety and Effectiveness of the Separator 3D as a Component of the Penumbra System in the Revascularization of Large Vessel Occlusion in Acute Ischemic Stroke

Study Overview
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Brief Summary
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This is a prospective, randomized, single blind, concurrent controlled, multi-center study. Patients presenting with symptoms of acute ischemic stroke who have evidence of a large vessel (2.5mm or greater in diameter) occlusion in the cerebral circulation will be assigned to either the Penumbra System with the Separator 3D or the Penumbra System without the Separator 3D. Each treated patient will be followed and assessed for 3 months after randomization. Up to 230 evaluable patients at up to 50 centers presenting with acute ischemic stroke in vessels accessible to the Penumbra Separator 3D System for revascularization within 8 hours of symptom onset. The hypothesis to be tested is that the safety and effectiveness of the Penumbra System with the Separator 3D for the revascularization of large vessel occlusion is not inferior to the Penumbra System alone.

Official Title
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A Randomized, Concurrent Controlled Trial to Assess the Safety and Effectiveness of the Separator 3D as a Component of the Penumbra System in the Revascularization of Large Vessel Occlusion in Acute Ischemic Stroke

Conditions
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Acute Ischemic Stroke From Large Vessel Occlusion

Intervention / Treatment
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* Device: Penumbra System with Separator 3D
* Device: Penumbra System alone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: From 18 to 85 years of age Present with symptoms consistent with an acute ischemic stroke for revascularization within 8 hours from symptom onset Refractory to or not eligible for IV rtPA therapy., e.g., presenting between 0 and 3 hours from symptom onset AND contraindicated for IV rtPA, or presenting between 3 and 8 hours of symptom onset, or evidence of persistent occlusion from vascular imaging after IV rtPA Evidence of a large vessel (2.5mm or greater in diameter) occlusion in the cerebral circulation NIH Stroke Scale (NIHSS) score 8 or more points Signed informed consent Exclusion Criteria: History of stroke in the past 3 months. Females who are pregnant Pre-existing neurological or psychiatric disease that could confound the study results such as a pre-stroke mRS score 1 or higher Known severe allergy to contrast media Uncontrolled hypertension (defined as systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg) CT evidence of the following conditions at randomization: Significant mass effect with midline shift Large infarct region >1/3 of the middle cerebral artery territory Evidence of intracranial hemorrhage Angiographic evidence of an arterial stenosis proximal to the occlusion that could prevent thrombus removal Angiographic evidence of preexisting arterial injury Rapidly improving neurological status prior to enrollment Bilateral stroke Intracranial tumors Known history of cerebral aneurysm or arteriovenous malformation Known hemorrhagic diathesis, coagulation deficiency, or on anticoagulant therapy with an International Normalized Ratio (INR) of >1.7 Baseline platelets <50,000 Use of IV heparin in the past 48 hours with PTT >1.5 times the normalized ratio Baseline glucose <50mg/dL or >300mg/dL Life expectancy less than 90 days prior to stroke onset Participation in another clinical investigation that could confound the evaluation of the study device

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Penumbra System with Separator 3D<br> | Device: Penumbra System with Separator 3D<br>* The Separator 3D is an additional Separator with a new tip configuration for the Penumbra System.<br>|
| Active Comparator: Penumbra System alone<br> | Device: Penumbra System alone<br>* The Penumbra System® is a new generation of neuro-embolectomy devices specifically designed to remove thrombus through aspiration.The treatment paradigm of this System involves the introduction of the Reperfusion Catheter through a guide catheter into the intracranial vasculature, and guided over an appropriate guidewire to the site of primary occlusion. The Reperfusion Catheter is used in parallel with the Separator and an aspiration source (Aspiration Pump) to separate the thrombus and aspirate it from the occluded vessel.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Angiographic Revascularization of the Occluded Target Vessel | Number of Participants with Angiographic revascularization of the occluded target vessel defined by mTICI grade 2-3 | At immediate post-procedure | 
| Number of Device-related Serious Adverse Events |  | Within 24 hours post-procedure | 
| Number of Procedure-related Serious Adverse Event |  | Within 24 hours post-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Good Clinical Outcome at 30 Days | Defined by a 10 points or more improvement in the NIHSS at Discharge, a NIHSS score of 0-1 at Discharge; or a 30-day mRS score of 0-2. The NIHSS is a stroke scale that measures impairment caused by stroke. The Modified Rankin scale (mRS) measures neurological disability or dependence for stroke patients. | 30 days post-procedure | 
| Number of Participants With 90 Day mRS Score 0-2 |  | at 90 days post-procedure | 
| All Cause Mortality |  | At 90 days post-procedure | 
| Number of Symptomatic Intracranial Hemorrhage |  | Within 24 hours post-procedure | 
| Good Neurological Outcome at 90 Days | Defined by an mRS score of 0-2, or equal to the pre-stroke mRS score if the pre-stroke mRS score was higher than 2, or an improvement of 10 or more points on the NIHSS score | At 90 days post-procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ischemic stroke, large vessel occlusion, mechanical thrombectomy, revascularization, Penumbra System, Separator 3D