Tirzepatide in Thrombectomy-Treated Acute Ischemic Stroke: A Randomized Trial

Participants must meet all of the following criteria:

1. Age >18 years and ≤80 years;

2. Acute ischemic stroke with imaging-confirmed anterior large vessel occlusion at:

3. NIHSS score between 6 and 25 prior to randomization;

4. Alberta Stroke Program Early CT Score (ASPECTS) of 6-10 before randomization;

5. Time from symptom onset (or last known well) to planned endovascular thrombectomy within 24 hours;

6. Pre-stroke mRS score of 0-1;

7. Patients presenting within 6 hours of symptom onset are eligible for direct EVT. Patients presenting between 6 and 24 hours after symptom onset must undergo advanced imaging demonstrating a salvageable perfusion mismatch and meet the DEFUSE-3 criteria: an infarct core volume <70 mL, a mismatch volume >15 mL, and a mismatch ratio >1.8;

8. Written informed consent provided by the participant or a legally authorized representative.

Participants meeting any of the following criteria will be excluded:

1. Posterior-circulation large vessel occlusion stroke;

2. Receipt of intravenous thrombolysis prior to randomization;

3. Simultaneous bilateral anterior-circulation occlusions or concurrent anterior- and posterior-circulation occlusions;

4. Intracranial hemorrhage on baseline CT or MRI, including subarachnoid hemorrhage or intracerebral hemorrhage; evidence of large established infarction, defined as:

5. Active bleeding within the previous month (e.g., gastrointestinal, genitourinary, or retinal hemorrhage), major organ surgery or biopsy within 14 days before stroke onset, or known bleeding diathesis;

6. Refractory hypertension despite treatment, defined as persistent systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg;

7. Severe hepatic or renal impairment, including:

8. Blood glucose <2.7 mmol/L or >22.2 mmol/L; platelet count <80 × 10⁹/L; or international normalized ratio (INR) >1.7;

9. Previous use of GLP-1 receptor agonists or GIP receptor agonists, or known hypersensitivity to these agents;

10. Personal or family history of medullary thyroid carcinoma (MTC) or diagnosis of Multiple Endocrine Neoplasia Type 2 (MEN2);

11. History of severe anxiety or depression prior to stroke onset;

12. Severe underlying disease with life expectancy <1 year, such as advanced malignancy;

13. Pregnancy or breastfeeding;

14. Participation in another clinical trial.