Endovascular Therapy for Low NIHSS Ischemic Strokes (ENDOLOW)

Inclusion Criteria:

1. Age 18 years or older
2. Acute ischemic stroke based on clinical diagnosis (NIHSS 0-5) and presence of an objective neurological deficit
3. Patients eligible for intravenous rt-PA should receive this therapy as soon as possible and no later than 4.5 hours from symptom onset

4. Proximal Intracranial Artery Occlusion on Imaging by NCCT/CTA or MRI/MRA showing complete occlusion of the intracranial ICA, M1, or an "M1-like" M2 vessel with or without tandem cervical lesion. Notably, "M1-like" M2 vessel occlusions are defined functionally for the trial as following:

   1. On CTA: Occlusion of both branches after MCA division (both M2s occluded) or occlusion of the larger diameter M2 branch . In case of trifurcations, either the two largest M2 branches are occluded or the occluded M2 has a larger diameter than the combined diameter of the two other M2s . Notably, the M2 origins are defined by the first branching point in the MCA other than the anterior temporal artery rather than by anatomic landmarks (e.g., horizontal versus insular location).

      or

   2. If mCTA or CTP performed (optional): a M2 occlusion which supplies a large proportion of the MCA territory by evidence of either:

   i. The bulk (>2/3) of the MCA territory has evidence of delayed washout on multiphase CT or ii. Perfusion imaging shows a hypoperfusion lesion volume involving a significant proportion of the MCA territory defined as Tmax >4 sec lesion of ≥100 mL

5. Baseline Infarct Core of either:

   1. Baseline ASPECTS ≥6 on non-contrast CT (NCCT), or
   2. Baseline Infarct Core Volume of < 70cc on either CTP (Volume of rCBF <30%) or DWI if quantitative software tools are available (neither test is mandatory for study)

Exclusion Criteria:

1. NIHSS ≥6
2. Any sign of intracranial hemorrhage on baseline CT/MR (SDH/SAH/ICH)
3. Any imaging findings suggestive of futile recanalization in the judgment of the local investigator
4. High degree of suspicion of intracranial arterial disease (ICAD), such as evidence of multifocal ICAD
5. Premorbid disability (mRS ≥3)
6. Inability to randomize within 8 hours of last known well
7. Seizures at stroke onset if it precludes obtaining an accurate baseline NIHSS
8. Baseline blood glucose of <50 mg/dL (2.78 mmol) or >400 mg/dL (22.20 mmol)
9. Known coagulation disorders as defined as platelet count <100,000/uL
10. Known renal failure as defined as serum creatinine levels > 3.0 mg/dL
11. Presumed septic embolus or suspicion of bacterial endocarditis
12. Any other condition that, in the opinion of the investigator, precludes an endovascular procedure or poses a significant hazard to the subject if an endovascular procedure was performed.
13. Participation in another investigational treatment study in the previous 30 days
14. Intubation and mechanical ventilation prior to study enrollment is medically indicated
15. History of drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
16. Site investigator does not have equipoise towards the ideal treatment concept (thrombectomy vs. best medical management)
17. Known pregnancy
18. Prisoner or incarceration
19. Known acute symptomatic COVID-19 infection