Acute Ischemic Stroke From Large Vessel Occlusion
Conditions
Keywords
ischemic stroke, large vessel occlusion, mechanical thrombectomy, revascularization, Penumbra System, Separator 3D
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.
Interventions
DEVICEPenumbra System with Separator 3D
The Separator 3D is an additional Separator with a new tip configuration for the Penumbra System.
DEVICEPenumbra 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.
Sponsors
Penumbra Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Angiographic Revascularization of the Occluded Target Vessel | 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 | Within 24 hours post-procedure | — |
| Number of Procedure-related Serious Adverse Event | Within 24 hours post-procedure | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Symptomatic Intracranial Hemorrhage | Within 24 hours post-procedure | — |
| Good Clinical Outcome at 30 Days | 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. |
| Good Neurological Outcome at 90 Days | 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 |
| Number of Participants With 90 Day mRS Score 0-2 | at 90 days post-procedure | — |
| All Cause Mortality | At 90 days post-procedure | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Penumbra System With Separator 3D Penumbra System with Separator 3D: The Separator 3D is an additional Separator with a new tip configuration for the Penumbra System. | 98 |
| Penumbra System Alone 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. | 100 |
| Total | 198 |
Baseline characteristics
| Characteristic | Penumbra System Alone | Total | Penumbra System With Separator 3D |
|---|---|---|---|
| Age, Continuous | 66.5 years STANDARD_DEVIATION 12.5 | 66.9 years STANDARD_DEVIATION 13 | 67.3 years STANDARD_DEVIATION 13.6 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 100 Participants | 198 Participants | 98 Participants |
| Sex: Female, Male Female | 54 Participants | 111 Participants | 57 Participants |
| Sex: Female, Male Male | 46 Participants | 87 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 19 / 98 | 26 / 100 |
| other Total, other adverse events | 81 / 88 | 83 / 93 |
| serious Total, serious adverse events | 38 / 88 | 49 / 93 |
Outcome results
Primary
Number of Device-related Serious Adverse Events
Time frame: Within 24 hours post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Penumbra System With Separator 3D | Number of Device-related Serious Adverse Events | 4 Device-Related Serious Adverse Events |
| Penumbra System Alone | Number of Device-related Serious Adverse Events | 5 Device-Related Serious Adverse Events |
Primary
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
Time frame: At immediate post-procedure
Population: Analysis population demonstrate outcomes of number of subjects that met endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Penumbra System With Separator 3D | Number of Participants With Angiographic Revascularization of the Occluded Target Vessel | 82 Participants |
| Penumbra System Alone | Number of Participants With Angiographic Revascularization of the Occluded Target Vessel | 79 Participants |
Primary
Number of Procedure-related Serious Adverse Event
Time frame: Within 24 hours post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Penumbra System With Separator 3D | Number of Procedure-related Serious Adverse Event | 10 Procedure-related Serious Adverse Events |
| Penumbra System Alone | Number of Procedure-related Serious Adverse Event | 14 Procedure-related Serious Adverse Events |
Secondary
All Cause Mortality
Time frame: At 90 days post-procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Penumbra System With Separator 3D | All Cause Mortality | 19 Participants |
| Penumbra System Alone | All Cause Mortality | 26 Participants |
Secondary
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.
Time frame: 30 days post-procedure
Population: Analysis population demonstrate outcomes of number of subjects that met endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Penumbra System With Separator 3D | Good Clinical Outcome at 30 Days | 58 Participants |
| Penumbra System Alone | Good Clinical Outcome at 30 Days | 55 Participants |
Secondary
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
Time frame: At 90 days post-procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Penumbra System With Separator 3D | Good Neurological Outcome at 90 Days | 56 Participants |
| Penumbra System Alone | Good Neurological Outcome at 90 Days | 55 Participants |
Secondary
Number of Participants With 90 Day mRS Score 0-2
Time frame: at 90 days post-procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Penumbra System With Separator 3D | Number of Participants With 90 Day mRS Score 0-2 | 39 Participants |
| Penumbra System Alone | Number of Participants With 90 Day mRS Score 0-2 | 44 Participants |
Secondary
Number of Symptomatic Intracranial Hemorrhage
Time frame: Within 24 hours post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Penumbra System With Separator 3D | Number of Symptomatic Intracranial Hemorrhage | 3 Symptomatic Intracranial Hemorrhage |
| Penumbra System Alone | Number of Symptomatic Intracranial Hemorrhage | 5 Symptomatic Intracranial Hemorrhage |