Imaging Guided Patient Selection for Interventional Revascularization Therapy

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.