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

• ClinicalTrials.gov Identifier: NCT01584609
• Recruitment Status: Completed
• First Posted: April 25, 2012
• Results First Posted: September 13, 2018
• Last Update Posted: September 13, 2018
• Sponsor: Penumbra Inc.
• Information provided by (Responsible Party): Penumbra Inc.

Tracking Information

• First Submitted Date: April 23, 2012
• First Posted Date: April 25, 2012
• Results First Submitted Date: May 17, 2018
• Results First Posted Date: September 13, 2018
• Last Update Posted Date: September 13, 2018
• Study Start Date: April 2012
• Actual Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 11, 2018)

• 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
• Number of Device-related Serious Adverse Events [ Time Frame: Within 24 hours post-procedure ]
• Number of Procedure-related Serious Adverse Event [ Time Frame: Within 24 hours post-procedure ]

Original Primary Outcome Measures (submitted: April 24, 2012)

• Angiographic revascularization of the occluded target vessel at immediate post-procedure as defined by a TIMI/TICI score of 2 or 3 [ Time Frame: At immediate post-procedure ]
• Incidence of device-related and procedure-related serious adverse event [ Time Frame: During the procedure ]

Current Secondary Outcome Measures (submitted: September 11, 2018)

• 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.
• Number of Participants With 90 Day mRS Score 0-2 [ Time Frame: at 90 days post-procedure ]
• All Cause Mortality [ Time Frame: At 90 days post-procedure ]
• Number of Symptomatic Intracranial Hemorrhage [ Time Frame: Within 24 hours post-procedure ]
• 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

Original Secondary Outcome Measures (submitted: April 24, 2012)

• Good clinical outcome at 30 days post-procedure as defined by a 10 points or more improvement in the NIHSS at Discharge, a NIHSS score of 0-1at Discharge; or a 30-day mRS score of 0-2 [ Time Frame: 30 days post-procedure ]
• The proportion of patients with a modified Rankin Scale (mRS) of ≤ 2 at 90 days post treatment [ Time Frame: at 90 days post-procedure ]
• All cause mortality [ Time Frame: At 90 days post-procedure ]
• Incidence of symptomatic hemorrhage [ Time Frame: At 90 days post-procedure ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief 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
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Treatment
• Condition: Acute Ischemic Stroke From Large Vessel Occlusion

Intervention

• Device: Penumbra System with Separator 3D
  The Separator 3D is an additional Separator with a new tip configuration for the Penumbra System.
• 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.

Study Arms

• Experimental: Penumbra System with Separator 3D
  Intervention: Device: Penumbra System with Separator 3D
• Active Comparator: Penumbra System alone
  Intervention: Device: Penumbra System alone

• Publications *: 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, Dorfler 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 11, 2018): 198
• Original Estimated Enrollment (submitted: April 24, 2012): 164
• Actual Study Completion Date: December 2017
• Actual Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01584609
• Other Study ID Numbers: CLP 4853; CLP 4853 ( Other Identifier: Penumbrainc )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Penumbra Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Penumbra Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Penumbra Inc.
• Verification Date: August 2018