Imatinib in Acute Ischaemic Stroke

Inclusion Criteria:

1. Clinical diagnosis of acute ischaemic stroke with a neurological deficit correspondingto 6 points or higher on the NIHSS score

2. at the time of randomization if no recanalisation therapy performed

3. prior to iv thrombolysis therapy alone or prior to thrombectomy alone ifperformed

4. prior to iv thrombolysis if both iv thrombolysis and thrombectomy performedIschaemic stroke is defined as an event characterised by sudden onset of acutefocal neurological deficit, presumed to be caused by cerebral ischaemia and animaging scan excluding any intracranial haemorrhage.

5. Age 18-85 years

6. Patients should be randomized as soon as possible but not later than 8 hours ofsymptom onset.

7. If the patient receives iv thrombolysis alone, patient should be randomized andstudy drug should be given within one hour after completion of iv thrombolysisinfusion

8. If the patient receives endovascular thrombectomy (with or without prior ivthrombolysis), patient should be randomized within two hours after completion ofendovascular thrombectomy and study drug given as soon as possible afterrandomization.

9. iv thrombolysis, if performed, is done in agreement with European Stroke Organisationguidelines and has been initiated within 4.5 hours of stroke onset (see below separatecriteria for indications / contraindications)

10. Endovascular thrombectomy, if performed, is done in agreement with recently publishedAmerican Stroke Association guidelines, and fulfilling the following criteria

11. Confirmed diagnosis on Computed Tomography Angiography (CTA) or MagneticResonance Angiography (MRA) of acute occlusion of either of the first twosegments of the Middle Cerebral Artery (M1 or M2), terminal Carotid Artery, firstsegment of the Anterior Cerebral Artery (A1), or Basilar Artery, consistent withthe clinical symptoms.

12. thrombectomy has been initiated within 8 hours of symptom onset (defined as startwith femoral artery (groin) puncture)

13. Patient is competent to make a decision and has provided informed consent with regardto participation in the study, retrieval and storage of data and follow up procedures

Exclusion Criteria: General

1. Imaging scans show signs of large current infarction as defined by more than 1/3 ofthe Middle Cerebral Artery territory or ½ of other vascular territories

2. ) Known significant pre-stroke disability (mRS ≥2)

3. Severe comorbidities such as advanced dementia (estimate pre-stroke if otherwisehealthy), terminal illness, and other severe medical conditions with anticipated lifeexpectancy less than 6 months.

4. Acute pancreatitis

5. Severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis

6. Ongoing treatment with chemotherapy

7. Drugs which may increase the plasma concentration of Imatinib - ketokonazol,itrakonazol, erythromycin and claritomycin

8. Drugs which may decrease the plasma concentration of Imatinib: Dexametason, phenytoin,karbamazepin, rifampizin, phenobarbital, fosphenytoin, primidon, Hypericum perforatum (Johannesört, St John's wort)

9. Female patients with childbearing potential, if pregnancy cannot be excluded bypregnancy test (urine point-of-care pregnancy test).

10. Patient is participating in other interventional study Additional Exclusion criteria for patients treated with intravenous thrombolysis (IVT)

11. Severe stroke as assessed clinically by NIHSS>25

12. Administration of heparin within the previous 48 hours preceding the onset of strokewith an elevated activated thromboplastin time (aPTT) at presentation, orcorresponding low-molecular heparin.

13. Patients receiving oral anticoagulants, e.g. warfarin sodium (INR>1.7) or direct oralanticoagulation: dabigatran ( aPTT>40s), apixaban, rivaroxaban.

14. Platelet count below 100,000/mm3. Significant bleeding disorder at present or withinthe past 6 months, known haemorrhagic diathesis.

15. History or evidence or suspicion of intracranial haemorrhage including sub-arachnoidhaemorrhage

16. Systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg, in spite ofrepeated doses of i.v. medication to reduce blood pressure below these limits.

17. History of the following conditions: prior ischemic stroke within 3 months,intra-axial neoplasm, intracranial or spinal surgery within the prior 3 months, recentsevere head trauma within 3 months or unruptured intracranial aneurysm>5 mm.

18. Major surgery or significant trauma in the past 10 days