Aureva Transcranial Ultrasound Device With tPA in Patients With Acute Ischemic Stroke
Aureva Transcranial Ultrasound Device With tPA in Patients With Acute Ischemic Stroke
This is a randomized, placebo controlled, double-blind phase 3 clinical study to evaluate the
 efficacy and safety of transcranial ultrasound (TUS) using the Sonolysis Headframe as an
 adjunctive therapy to intravenous (IV) tissue plasminogen activator (tPA) therapy in subjects
 with acute ischemic stroke that initially present at non-endovascular (EVT) treating
 hospitals that have established transport services in place to transfer subjects to hospitals
 capable of performing EVT.
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