Aureva Transcranial Ultrasound Device With tPA in Patients With Acute Ischemic Stroke

The primary objective of this study is to assess the safety and efficacy of TUS using the
Sonolysis Headframe in combination with systemic tPA (Treatment group) compared to systemic
tPA alone (Control group) in subjects with acute ischemic stroke.

Number of Subjects Required:

Lead-in Phase: 40 subjects in the U.S.; Primary Phase: 556 total enrolled subjects (278 per
arm)

Number of Study Centers:

Lead-in Phase: Up to 20 Institutions in U.S.; Primary Phase: Up to 70 Institutions worldwide

Inclusion Criteria:

1. Subjects with acute ischemic stroke

2. Subjects that initially present at non-EVT treating hospitals that have established
transport services in place to transfer subjects to hospitals capable of performing
EVT

3. Males or females 18 - 80 years of age

4. Subjects presenting within time window for IV tPA treatment approved by local
regulatory authorities but no more than 4.5 hours from onset of symptoms

5. No signs of intracranial bleeding on assessment by non-contrast CT

6. Subjects that in the opinion of the treating physician require treatment with full
dose of IV tPA (0.9mg/kg) as standard of care per institutional standards

7. SBP ≤ 185 mmHg and DBP ≤ 105 mmHg at baseline or after treatment of hypertension with
medications prior to tPA bolus

8. Pre-morbid mRS of 0-1

9. Arterial occlusion in the middle cerebral artery (MCA) M1 or proximal M2, intracranial
carotid T, anterior cerebral artery (ACA) A1, basilar, proximal posterior cerebral
artery (PCA) P1 or intracranial tandem lesions in these locations visible on CT
angiography (CTA)

10. Provision of informed consent as demonstrated by the subject's signature or by the
signature of the subject's authorized legal representative on the Informed Consent
Form in accordance with all local and national regulations and no later than 15
minutes after standard of care tPA administration

Exclusion Criteria:

1. Tandem lesions where one lesion is extracranial (carotid or vertebral artery)

2. ASPECTS score < 6 on non contrast CT or ischemic changes that in the opinion of the
investigator would be medically inappropriate for reperfusion therapy

3. Poor collateral circulation defined as minimal or no pial collaterals in >50% of the
ischemic territory

4. Expected time between activation of Sonolysis Headframe and initiation of EVT < 90
minutes

5. Pregnant or breast feeding women, clinical signs of pericarditis, sepsis or any other
serious medical illness likely to interact with treatment, confounding preexistent
neurological or psychiatric disease or test values that, in the opinion of the
investigator, pose significant risk to the subject and warrant exclusion from the
study

6. Impaired renal function defined as eGFR < 60 mL/min/1.73 m2

7. No permanent address or phone number

8. Any investigational drug <14 days prior to study participation

9. Subjects with known allergy to x-ray contrast material

10. Subjects with any standard contraindication for intravenous tPA therapy as per local
or national guidelines