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

1. LVO patients with mild deficits/low NIHSS
2. MVO/DMVO patients with Non-dominant/Co-dominant M2 and M3 occlusions

1. Age 18 years or older
2. Pre-stroke modified Rankin Scale score 0-2
3. Presentation to enrolling hospital within 24 hours of last known well/stroke onset
4. Able to initiate arterial puncture within 2 hours from qualifying CTA/MRA or CTP/MRP imaging *CT/MR and qualifying CTA/MRA or CTP/MRP should be repeated if more than 120 minutes have elapsed since the imaging and randomization has not been performed1. The exception is for LVO Mild deficit/Low NIHSS 0-5 for which imaging would only need to be repeated if there has been significant improvement in the NIHSS prior to randomization.Has any one or more of the following presentations:
   1. LVO patients with mild deficits/low NIHSS (must have both):
      1. Mild presenting neurologic deficits - NIHSS 0-5 (Must have some focal neurological deficit attributable to the target occlusion if NIHSS 0)
      2. 2. Complete occlusion of the intracranial ICA or M1 MCA
   2. Medium/Distal Vessel Occlusion:
      1. Visualized complete occlusion or perfusion deficit (Tmax > 4s) supportive of a cortical branch occlusion in one of the following vessels
         1. Non-dominant/Co-dominant M2 (defined as serving < 50% of entire overall MCA territory)
         2. M3
      2. If symptom onset is > 6h, the core must be less than 50% of the territory supplied by the occluded vessel as evident by either:
         1. Hypodensity and loss of grey-white border on NCCT or
         2. ADC <620 mm2/s on diffusion MRI or rCBF<30% on CTP
      3. NIHSS > 8

Domain-Specific Exclusions

1. Clinical
1. Presumed septic embolus; suspicion of bacterial endocarditis
2. Seizure at stroke onset or between onset and enrollment
3. Known anaphylactic reaction 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.
10. Known intracranial atherosclerotic disease (ICAD)
2. Laboratory
1. Known platelet count < 100,000/uL
3. Imaging
1. CT ASPECT score <6 (MRI ASPECT score <7)
2. Unfavorable vascular anatomy that limits access to the occluded artery precluding endovascular reperfusion therapy.
3. Acute occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior/posterior circulation)
4. Tandem occlusions
5. Significant mass effect with midline shift (>5mm)
6. Evidence of intra-axial tumor (except small meningioma)
7. 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
• Ordinal analysis of the 10-level mRS (0/1A/1B/2A/2B/3A/3B/4/5/6)
• AMC (Academic Medical Center) linear disability score (ALDS)

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 within 36 hours after randomization
• Mortality by 90 days
• Serious adverse events (SAEs)
• Early Clinical Deterioration within 36 hours of randomization
• Early Clinical Deterioration within 36 hours of randomization

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

• Unanticipated adverse device effects (UADEs) before hospital discharge
• Arterial access complications requiring surgical intervention
• Intracranial vessel perforation or dissection
• Embolization to previously uninvolved territory before the end of EVT procedure

1. N=1,000 patients with LVO mild deficits/low NIHSS
2. N=600 patients with Medium/Distal Vessel occlusion