This study evaluates the safety and efficacy of early versus delayed initiation of direct oral anticoagulants (DOACs) in patients with acute ischemic stroke related to atrial fibrillation who develop hemorrhagic transformation after endovascular treatment.

This is a multicenter, prospective, open-label, randomized controlled trial evaluating the safety and efficacy of different initiation timings of direct oral anticoagulants (DOACs) therapy in patients with acute ischemic stroke related to atrial fibrillation who develop hemorrhagic transformation after emergency endovascular therapy (EVT).

Inclusion Criteria:

1. Aged 18 years or over.

2. Clinical diagnosis of large vessel occlusion acute ischemic stroke.

3. Emergency endovascular treatment was performed within 24 hours of stroke onset.

4. Atrial fibrillation (including paroxysmal, persistent or permanent atrial fibrillation), confirmed by at least one of the following:

   1. 12-lead ECG recording;
   2. Inpatient ECG telemetry;
   3. Prolonged ECG monitoring (e.g. Holter monitor);
   4. Previously established diagnosis of atrial fibrillation verified by medical records.

5. CT or MRI demonstrating one of the following findings:

   1. Parenchymatous hematoma type 1: defined as hematoma occupying less than 30% of the infarcted tissue, no substantive mass effect (Heidelberg classification);
   2. Parenchymatous hematoma type 2: defined as heamtoma occupying 30% or more of the infarcted tissue, with obvious mass effect (Heidelberg classification);
   3. Intracerebral hemorrhage outside the infarcted brain tissue or intracranial-extracerebral hemorrhage (Heidelberg classification).

6. Time from stroke onset to randomization ranged from 7 days to 4 weeks.

7. Written informed consent obtained from the patient or a legally authorized representative.

Exclusion Criteria:

1. Atrial fibrillation due to reversible causes (e.g. thyrotoxicosis, pericarditis, recent surgery, or myocardial infarct).

2. Contraindication to the use of direct oral anticoagulants (DOACs):

   1. Known allergy or intolerance to both factor Xa inhibitors and direct thrombin inhibitors;
   2. Definite indication for vitamin K antagonist (VKA) treatment (e.g. mechanical heart valve, valvular atrial fibrillation);
   3. Severe renal impairment (defined as creatinine exceeding 1.5 times of the upper limit of normal range) and significant hepatic dysfunction (defined as ALT or AST > twice the upper limit of normal range) ;
   4. Concomitant use of medications with significant interactions with DOACs, including azole antifungals, HIV protease inhibitors, or strong CYP3A4 inducers;
   5. Baseline platelet count < 100 x 109/L;
   6. History of coagulopathy or systemic hemorrhage.

3. Prior DOAC use within 48 hours of stroke onset, or recent treatment with vitamin K antagonist (VKA) leading to INR ≥1.7 at randomization.

4. Pregnant or breastfeeding women, or positive pregnancy test at admission.

5. History of major surgery or severe trauma within 1 month prior to stroke onset.

6. History of active bleeding within 1 month prior to stroke onset (e.g. gastrointestinal bleeding, urinary tract bleeding).

7. Dual antiplatelet therapy at baseline, or strong likelihood of requiring dual antiplatelet therapy during the trial.

8. Evidence of cerebral amyloid angiopathy.

9. CT or MRI evidence of non-stroke pathology likely to account for the presenting clinical symptoms (e.g. mass lesion, encephalitis).

10. Modified Rankin scale (mRS) score > 1 prior to stroke onset.

11. Inability to complete the 90-day follow-up.

12. Currently participating in another drug clinical trial.

13. Any other reason deemed by the investigator to make the patient unsuitable for participation in the trial.

The study is proceeding.