Evaluation of Low Dose Colchicine and Ticagrelor in Prevention of Ischemic Stroke in Patients With Stroke Due to Atherosclerosis

Inclusion criteria:

Patient should have the following:

Patient with:

1. Cerebral infarction (CI) proven by neuro-imaging (MRI or head-CT), immediately oncethe neurologic deficit is stabilized (investigator judgement) if the patient was onantiplatelet agent monotherapy after the qualifying event, or after 21 days if thepatient was on clopidogrel plus aspirin after the qualifying event, or after 21 to 30 days if the patient was on ticagrelor plus aspirin after the qualifying event (TIA with documented ischemic lesion (MRI or CT) in the appropriate areacorresponding to the symptoms will be considered CI, following the currentdefinition)

2. Or TIA lasting more 10 minutes or more (with motor symptoms or aphasia/dysarthria orvisual defect), with total resolution and no brain lesion on neuro-imaging (TIA) andwith ipsilateral carotid stenosis that was revascularized (endarterectomy orstenting) or with ipsilateral, potentially causal intracranial stenosis ≥70%) if thepatient was on antiplatelet agent monotherapy after the qualifying event, or after 21 days if the patient was on clopidogrel plus aspirin after the qualifying event,or after 21 to 30 days if the patient was on ticagrelor plus aspirin after thequalifying event

3. and documented atherosclerotic stenosis:

4. presence of carotid atherosclerotic stenosis (on the basis of carotid duplex,CTA, MRA, XRA - only the report will be required to document atheroscleroticdisease) ipsilateral to the cerebral ischemic symptoms (stenosis defined byluminal narrowing ≥30%, judgement of the investigator)

5. or presence of atherosclerotic stenosis of another cerebral artery (documentedvertebral artery stenosis, basilar artery stenosis, other intracranial arterystenosis) ipsilateral to the ischemic area (stenosis defined by luminalnarrowing ≥30%, judgement of the investigator)

6. or presence of atherosclerotic disease of the aortic arch with a plaque ≥4mm inthickness with or without superimposed thrombus, or a plaque <4 mm with asuperimposed mobile thrombus (detected by transesophageal echocardiography orCT angiography)

7. with no clear indication of colchicine treatment (gout, Mediterranean fever) andwith an indication to long-term antiplatelet therapy (no clear indication to oralanticoagulant)

8. age equal or above 18

9. Rankin score less than ≤4 (ranges from 0 to 6, with 0 indicating no symptoms, 1 nodisability, 2 to 3 needing some help with daily activities, 4 to 5 dependent orbedridden, and 6 death),

10. fully informed and signed inform consent

11. with social security number.

12. medical examination before the participation to the research

13. Under contraception in case of childbearing potential (highly effective: 1) combined (estrogen and progestogen containing) hormonal contraception associated withinhibition of ovulation et 2) progestogen-only).

14. Pregnancy test for women of childbearing potential

Exclusion Criteria:

1. Colchicine treatment needed (e.g., gout, Mediterranean fever)

2. Hypersensitivity to ticagrelor or any of the excipients.

3. Hypersensitivity to colchicine or any of the excipients.

4. Major digestive disorders (chronic diarrhea, inflammatory disease of the digestivetract as uncontrolled ulcerative colitis or active Crohn disease)

5. Immunosuppression, medullary aplasia

6. Active chronic inflammatory disease, chronic active infection, evolving cancer

7. Hemodynamic instability (need for amines for more than 24 hours, circulatoryassistance)

8. A recent severe sepsis (7 days) or all recent acute reaches

9. Chronic treatment (for more than 6 months) with corticosteroids or NSAIDs (orrepeated high-dose intake for less than 7 days).

10. Anticipated concomitant oral or intravenous therapy with strong CYP3A4 inhibitors orCYP3A4 substrates than cannot be stopped for the course of the course of this study

11. CI/TIA due to arterial dissection (as documented following the judgment of theinvestigator) or due to cardiac source of embolism without documentedatherosclerotic disease (e.g., mitral stenosis or endomyocardial fibrosis,endocarditis) a patient with atrial fibrillation, or with a history of myocardialinfarction, or with calcified aortic stenosis will be eligible if the aboveinclusion criteria are also met]

12. Indication to long-term oral anticoagulant treatment (e.g., atrial fibrillation)

13. Symptomatic hemorrhagic stroke (the mere presence of asymptomatic cerebralhemosiderin deposits -so called "microbleedings" - on gradient echo imaging is notan exclusion criteria)

14. Active pathological bleeding

15. Uncontrolled hypertension (investigator judgement)

16. Follow-up visit impossible or anticipated bad compliance.

17. Intercurrent disease that may interfere with evaluation of the primary end-point orthat may prevent follow-up study visits..

18. Anticipated pregnancy at time of enrollment in the study

19. Breastfeeding woman

20. Patients participating in another pharmaco therapeutic program with an experimentaltherapy that is known to affect the ticagrerlor, colchicine or aspirine therapy.

21. Leukopenia <3000/μl

22. Patients with severe renal impairment (creatinine clearance < 30 ml/min)

23. Patients with severe hepatic impairment

24. Prohibited treatments: All treatments contraindicated during the use of colchicineand/or ticagrelor