Assess the Penumbra System in the Treatment of Acute Stroke

Current therapies for acute stroke are limited to the intravenous administration of a
intravenous (IV) recombinant human tissue plasminogen activator (rtPA) for thrombolysis of
the affected cerebral arteries within 3-4.5 hours from symptom onset, and the use of
intra-arterial (IA) endovascular mechanical clot retrieval devices within 8 hours from
ictus, all of which have limitations as mono therapies. For example, IV rtPA may not be very
efficacious in large vessel occlusion and the long term effects of mechanical thrombectomy
devices on patient functional outcome is unknown. This is a randomized, concurrent
controlled study to assess the safety and effectiveness of the Penumbra System as adjunctive
therapy to IV rtPA in the acute intervention of acute ischemic stroke. Patients presenting
with symptoms of acute ischemic stroke who have evidence of a large clot burden (clot length
> 8mm) in the anterior circulation will be assigned to either IV rtPA therapy alone
(0.9mg/kg to a maximum of 90mg) or a combined IV rtPA therapy (0.9mg/kg to a maximum of
90mg) and intra-arterial (IA) adjunctive treatment with the Penumbra System. Each treated
patient will be followed and assessed for 3 months after enrollment.

Inclusion Criteria:

1. From 18 to 85 years of age

2. Present with symptoms consistent with an acute ischemic stroke and eligible for IV
rtPA therapy

3. Evidence of a large vessel occlusion in the anterior circulation with a clot length
of 8mm or longer

4. NIH Stroke Scale (NIHSS) score 8 or greater or aphasic at presentation

5. Signed informed consent

Exclusion Criteria:

1. History of stroke in the past 3 months.

2. Females who are pregnant

3. Pre-existing neurological or psychiatric disease that could confound the study
results such as a pre-stroke mRS score 1 or greater

4. Known severe allergy to contrast media

5. Uncontrolled hypertension (defined as systolic blood pressure >185 mmHg or diastolic
blood pressure >110 mmHg)

6. 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

7. Angiographic evidence of an arterial stenosis proximal to the occlusion that could
prevent thrombus removal

8. Angiographic evidence of preexisting arterial injury

9. Rapidly improving neurological status prior to randomization

10. Bilateral stroke

11. Intracranial tumors

12. Known history of cerebral aneurysm or arteriovenous malfunction

13. Known hemorrhagic diathesis, coagulation deficiency, or on anticoagulant therapy with
an International Normalized Ratio (INR) of >1.7

14. Baseline platelets <50,000

15. Use of IV heparin in the past 48 hours with PPT >1.5 times the normalized ratio

16. Baseline glucose <50mg/dL or >300mg/dL

17. Life expectancy less than 90 days prior to stroke onset

18. Participation in another clinical investigation that could confound the evaluation of
the study device