• Endovascular Therapy (EVT)
• Medical Management (MM)

1. LVO patients with mild deficits/low NIHSS (NIHSS 0-5)
2. MVO patients with Non-dominant/Co-dominant M2 occlusion
3. DMVO patients with M3,4 or A1,2,3 or P1,2,3 occlusion.

1. Age 18 years or older
2. Pre-stroke modified Rankin Scale score 0-2
3. Within 24 hours of last known well
4. Has any one or more of the following presentations:
   1. Low NIHSS Patient (must have both):
      1. Mild presenting neurologic deficits - NIHSS 0-5
      2. Occlusion of the intracranial ICA or M1 MCA
   2. Medium/Distal Vessel Occlusion (must have all 3):
      1. Lumen diameter >/= 0.75 mm
      2. Non-dominant/Co-dominant M2 or M3,4 or A1,2,3 or P1,2,3
      3. Less than 50% core in the territory supplied by the occluded vessel as evident by hypodensity and loss of grey-white border on NCCT or ADC <620 mm2/s on diffusion MRI or rCBF<30% on CTP after 6h of symptom onset.
         1. Time from CTA/MRA imaging to arterial puncture should be within 2 hours. Vessel imaging should be repeated if more than 120 minutes have elapsed.¹

Domain-Specific Exclusions

1. Clinical
1. Presumed septic embolus; suspicion of bacterial endocarditis
2. Seizure at stroke onset or between onset and enrollment
3. Allergy to contrast material that precludes endovascular reperfusion therapy
4. Intracranial occlusion suspected to be chronic, based on history and/or imaging
5. Intracranial dissection, based on history and/or imaging
6. Cerebral vasculitis, based on history and/or imaging
7. Known pregnancy
8. Known pre-existing medical, neurological or psychiatric disease that would confound the neurological or functional evaluations
9. Known serious, advanced, or terminal illness or life expectancy less than 6 months in the investigator judgment.
2. Laboratory
1. Known platelet count < 100,000/uL
3. Imaging
1. Unfavorable vascular anatomy that limits access to the occluded artery precluding endovascular reperfusion therapy.
2. Acute occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior/posterior circulation)
3. Significant mass effect with midline shift (>5mm)
4. Evidence of intra-axial tumor (except small meningioma)
5. Evidence of acute intracranial hemorrhage

Primary Endpoints

Efficacy

• 90-day global disability assessed with the modified Rankin Scale

Safety

• Symptomatic intracranial hemorrhage (sICH) (per modified Heidelberg criteria)

Secondary Endpoints

Clinical Efficacy

For all EVT INDICATION EXPANSION DOMAIN patients, secondary clinical efficacy endpoints will be:

• mRS 0-2 (functional independence) at 90 days
• Level of disability [mRS 6-level (0,1,2,3,4,5/6) ordinal distribution]
• NIHSS (neurologic deficit) at 24 hours

In addition, for the subsets of patients with low NIHSS and/or target MVO occlusion site, secondary clinical efficacy endpoints will also include:

• mRS 0-1 (freedom from disability) at 90 days

Technical Efficacy

Technical efficacy endpoints (analyzed only in EVT patients) will be:

• eTICI 2b50-3 (substantial reperfusion) at end of procedure
• eTICI 2c-3 (excellent reperfusion) at end of procedure
• eTICI 2c-3 (excellent reperfusion) on first device pass

Safety

Secondary safety endpoints analyzed in both EVT and MM patients will be:

• Any radiologic intracranial hemorrhage
• Mortality by 90 days
• Serious adverse events (SAEs)

An additional secondary safety endpoint analyzed in the EVT group will be:

• Unanticipated adverse device effects (UADEs)
• Arterial access complications requiring surgical intervention
• Intracranial vessel perforation or dissection
• Embolization to previously uninvolved territory