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

• Sponsor: Penumbra Inc.
• Information provided by (Responsible Party): Penumbra Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Acute Ischemic Stroke From Large Vessel Occlusion	Device: Penumbra System with Separator 3D; Device: Penumbra System alone	Not Applicable

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	198 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Participant)
Primary Purpose:	Treatment
Official Title:	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 Start Date :	April 2012
Actual Primary Completion Date :	June 2017
Actual Study Completion Date :	December 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Penumbra System with Separator 3D	Device: Penumbra System with Separator 3D; The Separator 3D is an additional Separator with a new tip configuration for the Penumbra System.
Active Comparator: Penumbra System alone	Device: Penumbra System alone; 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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Good Clinical Outcome at 30 Days [ Time Frame: 30 days post-procedure ]
   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.
2. Number of Participants With 90 Day mRS Score 0-2 [ Time Frame: at 90 days post-procedure ]
3. All Cause Mortality [ Time Frame: At 90 days post-procedure ]
4. Number of Symptomatic Intracranial Hemorrhage [ Time Frame: Within 24 hours post-procedure ]
5. Good Neurological Outcome at 90 Days [ Time Frame: At 90 days post-procedure ]
   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

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 85 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Locations

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United States, California
Hoag Hospital
Newport Beach, California, United States, 92658
United States, Colorado
Swedish Medical Center
Denver, Colorado, United States, 80112
United States, Connecticut
Hartford Hospital
Hartford, Connecticut, United States, 6106
United States, Georgia
Grady Health System
Atlanta, Georgia, United States, 30303
United States, Minnesota
St. Joseph Hospital- Healtheast
Saint Paul, Minnesota, United States, 55102
United States, New York
Kaleida Health
Buffalo, New York, United States, 14209
Stony Brook University Hospital
Stony Brook, New York, United States, 11794-8122
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232

Sponsors and Collaborators

Penumbra Inc.

Investigators

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Principal Investigator:	Don Frei, MD	Swedish Medical Center, Denver, CO

  Study Documents (Full-Text)

Documents provided by Penumbra Inc.:

Study Protocol  [PDF] June 27, 2012

Statistical Analysis Plan  [PDF] February 5, 2013

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Nogueira RG, Frei D, Kirmani JF, Zaidat O, Lopes D, Turk AS 3rd, Heck D, Mason B, Haussen DC, Levy EI, Mehta S, Lazzaro M, Chen M, Dörfler A, Yoo AJ, Derdeyn CP, Schwamm L, Langer D, Siddiqui A; Penumbra Separator 3D Investigators. Safety and Efficacy of a 3-Dimensional Stent Retriever With Aspiration-Based Thrombectomy vs Aspiration-Based Thrombectomy Alone in Acute Ischemic Stroke Intervention: A Randomized Clinical Trial. JAMA Neurol. 2018 Mar 1;75(3):304-311. doi: 10.1001/jamaneurol.2017.3967.

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Responsible Party:	Penumbra Inc.
ClinicalTrials.gov Identifier:	NCT01584609 History of Changes
Other Study ID Numbers:	CLP 4853; CLP 4853 ( Other Identifier: Penumbrainc )
First Posted:	April 25, 2012
Results First Posted:	September 13, 2018
Last Update Posted:	September 13, 2018
Last Verified:	August 2018

Keywords provided by Penumbra Inc.:

ischemic stroke; large vessel occlusion; mechanical thrombectomy	revascularization; Penumbra System; Separator 3D

Additional relevant MeSH terms:

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Stroke; Ischemia; Cerebral Infarction; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases	Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia