• Age 18 years or older.

• Clinically diagnosed with acute ischemic stroke.

• DOACs intake within 48 hours prior to enrollment, or on an ongoing DOACs therapy but the exact time of last intake is unknown.

⁃ To ensure a representative study population, the investigators will limit the number of patients who took DOACs within 24-48 hours before enrollment or those with unknown last intake time to 50% of the planned sample size. If this number is reached, the inclusion criterion 3 will be modified:

• DOACs intake within 24 hours prior to enrollment.

• Study intervention (IVT or placebo) can be started

‣ within 4.5 hours of last known well (LKW). OR

⁃ within 4.5 to 24 hours of LKW (including wake-up stroke) AND evidence of target mismatch profile on CT perfusion or MR perfusion (ischemic core volume \< 50mL, hypoperfused volume to ischemic core volume ratio \> 1.6, mismatch volume ≥10ml).

∙ Hypoperfused tissue is defined as Tmax \>6s on CT perfusion or MR perfusion. Ischemic core is defined as rCBF \<30% on CT perfusion or ADC\<620μm\^2/s on diffusion MRI.

• Baseline National Institutes of Health Stroke Scale (NIHSS) 4-25. OR Disabling stroke with baseline NIHSS of 0-3, including complete hemianopia, aphasia, measurable deficit on motor power, or other disabling neurological deficit judged by the investigator.

• Written informed consent signed by patients or their legally authorized representatives.