Imaging Guided Patient Selection for Interventional Revascularization Therapy (START)

• Functional outcome as defined by a mRS of 0-2 at 90 days post-procedure [ Time Frame: At 90 days post-procedure ] [ Designated as safety issue: No ]
• Angiographic assessment of vessel patency as measured by TIMI and modified TICI scores at immediate post-procedure [ Time Frame: At immediate post-procedure ] [ Designated as safety issue: No ]
• Procedural serious adverse events during the procedure [ Time Frame: During the procedure ] [ Designated as safety issue: Yes ]

• Good neurological recovery post-procedure as defined by a 10 points or more improvement on the NIHSS at Discharge [ Time Frame: At Discharge ] [ Designated as safety issue: No ]
• 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 ] [ Designated as safety issue: Yes ]
• All cause mortality at 90 days post-procedure [ Time Frame: At 90 days post-procedure ] [ Designated as safety issue: Yes ]

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.

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.

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.