Safety and Efficacy of Intravenous Thrombolysis in Patients With Ischemic Stroke and Direct Oral Anticoagulants Intake

Inclusion Criteria:

• Informed consent (deferred consent when possible according to national legislation)

• AIS eligible to receive intravenous alteplase/tenecteplase as per standard of caredisabling according to the judgement of the treating physician

• DOAC ingestion within 48 hours prior to enrollment, or patient with an ongoingprescription of DOAC but exact time point of last intake is unknown.

• Either

• Can be randomized within 4 hours 15 minutes and treated within 4 hours 30minutes of last known well time OR

• MRI showing a pattern of "DWI-FLAIR-mismatch", i.e. acute ischemic lesionvisibly on DWI ("positive DWI") but no marked parenchymal hyperintensityvisible on FLAIR ("negative FLAIR") indicative of an acute ischemic lesion ≤4.5hours of age AND Treatment can be started within 4.5 hours of symptomrecognition (e.g., awakening).

Exclusion Criteria:

• Contra-indications to IVT by the current standard of care of the treating physicianswith the exception of recent DOAC intake as specified above.

• Intended reversal by specific or unspecific reversal agents

• Pregnancy or lactating women. To be reasonable sure to exclude women with ongoingpregnancy, women are not considered of childbearing potential if they fulfill thefollowing criteria

• Age > 55 years OR

• Age < 55 years and at least 12 months since last menstrual period OR

• Have had a documented surgical sterilization

• Patient < 18 years of age (since the benefit of IVT is unproven in this population)

Since the benefit of IVT might be smaller in patients in which additional endovascular treatment is planned, the investigators will cap patients with intended mechanical thrombectomy at 20% of the trial population. If this number is reached, the following additional exclusion criterion will be applied:

• Intended treatment with endovascular reperfusion strategies