Acute Ischemic Stroke
Conditions
Keywords
Acute stroke, Large cerebral vessel occlusion, Core infarct volume, Penumbra System, Revascularization, Intracerebral hemorrhage, mRS, NIHSS, Procedural serious adverse events, All cause mortality
Brief summary
The primary objective of this clinical evaluation is to determine the safety and effectiveness of the Penumbra System in a stroke cohort who presents within 8 hours from symptom and with a known core infarct volume at admission. The secondary objective is to determine if there is a correlation between infarct volume and functional outcome in treated patients at 90 days post-procedure.
Detailed description
Study Title: The START Trial: Clinical Outcome in Acute Stroke Treatment after Imaging Guided Patient Selection for Interventional Revascularization Therapy Study Objective: The objective of this clinical evaluation is to determine the safety and effectiveness of the Penumbra System in a stroke cohort who presents within 8 hours from symptom onset and with a known core infarct volume at admission. The data will also be used to determine if there is a correlation between infarct volume and functional outcome at 90 days post-procedure. Safety is defined by the procedural serious adverse events, and effectiveness is defined by the rate of revascularization (TIMI 2-3/TICI 2a-3) and good functional outcome. Good functional outcome is defined by a modified Rankin scale (mRS) score of 2 or less at 90 days post-procedure. Core infarct volume at admission will be assessed by computed tomography perfusion (CTP), computed tomography angiography (CTA) or magnetic resonance DWI scans. The core infarct volumes will be sub-grouped by \<50cc, 50-100cc and \>100cc to determine the correlation with patient functional outcome. Study Design: A prospective, single arm, multi-center trial. Up to 200 patients at up to 45 centers will be enrolled in the study. It is anticipated that up to 150 evaluable patients will be needed for analysis. Patient Population: Patients presenting with symptoms of acute ischemic stroke within 8 hours from symptom onset and with a known imaging-defined infarct volume will be enrolled for interventional treatment by the Penumbra System to achieve revascularization of the target vessel territory. Indication: The Penumbra System is intended for use in the revascularization of patients with acute ischemic stroke secondary to intracranial large vessel occlusive disease (within the internal carotid, middle cerebral - M1 and M2 segments, basilar, and vertebral arteries) within 8 hours of symptom onset. Sample Size Justification: Up to 200 subjects will be enrolled in order to obtain up to 150 evaluable patients. Assuming a post-procedure angiographic success (TIMI 2-3/TICI 2a-3) rate of 80% (120/150), the expected two-sided exact binomial 95% confidence interval is (72.7%, 86.1%). Assuming a 90-day mRS success (mRS 0-2) rate of 30%, the expected two-sided exact binomial 95% confidence interval is (22.8%, 38.0%). Additionally, the study results will be used for sample size estimates for a potential future randomized, concurrent controlled trial. Core Laboratory and Clinical Event Committee An independent Core Lab will review and score all imaging scans for infarct volume, TIMI, TICI and ICH. A Clinical Event Committee will adjudicate all Serious Adverse Events for severity and causality (disease-, procedure-, drug-, or device-relatedness. Study Rationale: Use of interventional revascularization techniques offer several potential clinical benefits by improving cerebral perfusion to the target vascular territory in certain patients. The validation of a simple, pragmatic, and executable image guided patient selection paradigm may identify a cohort of acute stroke patients who will benefit from interventional treatment by the Penumbra System and in whom revascularization as a treatment for acute stroke will be indicated.
Interventions
DEVICEPenumbra System
The Penumbra System is used to revascularize clotted cerebral blood vessels.
Sponsors
Penumbra Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* From 18 to 85 years of age. * Evidence of proximal anterior circulation large vessel occlusion (TIMI /TICI 0-1) (Tables 2A & B). Target vessel occlusion may include the supra-clinoid segment of the ICA through the M1 segment of the MCA. * Presented with symptoms consistent with acute ischemic stroke within 8 hours of symptom onset. Patients who presented within 3 hours must be ineligible or refractory to IV rtPA therapy. * At time of enrollment, neurological deficit resulting in an NIH Stroke Scale (NIHSS) score of 10 or greater. * Core infarct volume assessed by CTP, CTA or DWI scans within 60 minutes to arterial puncture. * Signed informed consent.
Exclusion criteria
* History of stroke in the past 3 months. * Vessel tortuosity too difficult to allow endovascular access. * Pre-existing neurological or psychiatric disease that could confound the study results such as a pre-stroke mRS score of 1 or greater. * Known severe allergy to contrast media. * Uncontrolled hypertension (defined as systolic blood pressure \> 185 mmHg or diastolic blood pressure \> 110 mmHg). * Noncontrast CT evidence of the following conditions before enrollment: * Significant mass effect with midline shift; * 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. * Life expectancy less than 90 days. * Participation in another clinical investigation that could confound the evaluation of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Functional Outcome as Defined by a mRS of 0-2 at 90 Days Post-procedure | At 90 days post-procedure | Modified Rankin Scale (mRS) ranges from 0 to 5, with higher scores being worse. |
| Angiographic Assessment of Vessel Patency as Measured by TIMI Score | At immediate post-procedure | Defined by Number of participants with Thrombolysis in Myocardial Infarction (TIMI) 2-3. A lower score means a worse outcome and higher scores means better outcome on a scale of 0-3. |
| Angiographic Assessment of Vessel Patency as Measured by Modified TICI Score | At immediate post-procedure | Defined by number of participants with modified thrombolysis in cerebral infarction (TICI) 2-3. A lower score means a worse outcome and higher scores means better outcome on a scale of 0-3. |
| Procedural Serious Adverse Events During the Procedure | During the procedure, approximately 24 hours | Defined by serious adverse events (SAEs) within 24 hours of the procedure |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of Symptomatic and Asymptomatic Hemorrhage Based on the ECASS Criteria and Patient Neurological Status Within 24 Hours of the Procedure | Within 24 hours of the procedure |
| All Cause Mortality at 90 Days Post-procedure | At 90 days post-procedure |
| Good Neurological Recovery Post-procedure as Defined by a 10 Points or More Improvement on the NIHSS at Discharge | At Discharge, an average of 7 days |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Penumbra Device Arm Penumbra System: The Penumbra System is used to revascularize clotted cerebral blood vessels. | 146 |
| Total | 146 |
Baseline characteristics
| Characteristic | Penumbra Device Arm |
|---|---|
| Age, Continuous | 66 Years STANDARD_DEVIATION 14 |
| Baseline NIHSS | 19 units on a scale |
| Sex: Female, Male Female | 82 Participants |
| Sex: Female, Male Male | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 37 / 146 |
| other Total, other adverse events | 14 / 146 |
| serious Total, serious adverse events | 8 / 146 |
Outcome results
Primary
Angiographic Assessment of Vessel Patency as Measured by Modified TICI Score
Defined by number of participants with modified thrombolysis in cerebral infarction (TICI) 2-3. A lower score means a worse outcome and higher scores means better outcome on a scale of 0-3.
Time frame: At immediate post-procedure
Population: One subject had two sites of occlusion
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Penumbra Device Arm | Angiographic Assessment of Vessel Patency as Measured by Modified TICI Score | 122 Participants |
Primary
Angiographic Assessment of Vessel Patency as Measured by TIMI Score
Defined by Number of participants with Thrombolysis in Myocardial Infarction (TIMI) 2-3. A lower score means a worse outcome and higher scores means better outcome on a scale of 0-3.
Time frame: At immediate post-procedure
Population: One subject had two sites of occlusion
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Penumbra Device Arm | Angiographic Assessment of Vessel Patency as Measured by TIMI Score | 122 Participants |
Primary
Functional Outcome as Defined by a mRS of 0-2 at 90 Days Post-procedure
Modified Rankin Scale (mRS) ranges from 0 to 5, with higher scores being worse.
Time frame: At 90 days post-procedure
Population: 16 subjects with missing 90-day mRS assessment and 3 withdrew consent.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Penumbra Device Arm | Functional Outcome as Defined by a mRS of 0-2 at 90 Days Post-procedure | 57 Participants |
Primary
Procedural Serious Adverse Events During the Procedure
Defined by serious adverse events (SAEs) within 24 hours of the procedure
Time frame: During the procedure, approximately 24 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Penumbra Device Arm | Procedural Serious Adverse Events During the Procedure | 40 events |
Secondary
All Cause Mortality at 90 Days Post-procedure
Time frame: At 90 days post-procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Penumbra Device Arm | All Cause Mortality at 90 Days Post-procedure | 37 Participants |
Secondary
Good Neurological Recovery Post-procedure as Defined by a 10 Points or More Improvement on the NIHSS at Discharge
Time frame: At Discharge, an average of 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Penumbra Device Arm | Good Neurological Recovery Post-procedure as Defined by a 10 Points or More Improvement on the NIHSS at Discharge | 47 Participants |
Secondary
Incidence of Symptomatic and Asymptomatic Hemorrhage Based on the ECASS Criteria and Patient Neurological Status Within 24 Hours of the Procedure
Time frame: Within 24 hours of the procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Penumbra Device Arm | Incidence of Symptomatic and Asymptomatic Hemorrhage Based on the ECASS Criteria and Patient Neurological Status Within 24 Hours of the Procedure | 18 Participants |