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

Launched by ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS · Jul 25, 2022

Keywords

ClinConnect Summary

This clinical trial is investigating whether combining two medications, colchicine and ticagrelor, can help prevent ischemic strokes in patients who have experienced strokes caused by atherosclerosis, which is the buildup of plaque in the arteries. The study aims to find out if these medications can reduce inflammation and improve outcomes for patients at high risk of having another stroke.

To participate in this trial, patients must be at least 18 years old and have had a documented stroke or transient ischemic attack (TIA), which is a temporary blockage of blood flow to the brain. They should also have specific types of artery blockages confirmed by medical imaging. However, patients with certain health conditions, such as severe digestive disorders or those requiring other treatments that could interfere with the study, may not be eligible. Participants will be closely monitored during the trial and will need to provide informed consent before joining. This study is currently recruiting participants and aims to contribute valuable information about stroke prevention strategies.

Gender

ALL

Eligibility criteria

• Inclusion criteria:
• Patient should have the following:
• Patient with:
• • 1. Cerebral infarction (CI) proven by neuro-imaging (MRI or head-CT), immediately once the neurologic deficit is stabilized (investigator judgement) if the patient 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 the qualifying event (TIA with documented ischemic lesion (MRI or CT) in the appropriate area corresponding to the symptoms will be considered CI, following the current definition)
• • 2. Or TIA lasting more 10 minutes or more (with motor symptoms or aphasia/dysarthria or visual defect), with total resolution and no brain lesion on neuro-imaging (TIA) and with ipsilateral carotid stenosis that was revascularized (endarterectomy or stenting) or with ipsilateral, potentially causal intracranial stenosis ≥70%) if the patient 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 the qualifying event
• 3. and documented atherosclerotic stenosis:
• • 1. presence of carotid atherosclerotic stenosis (on the basis of carotid duplex, CTA, MRA, XRA - only the report will be required to document atherosclerotic disease) ipsilateral to the cerebral ischemic symptoms (stenosis defined by luminal narrowing ≥30%, judgement of the investigator)
• • 2. or presence of atherosclerotic stenosis of another cerebral artery (documented vertebral artery stenosis, basilar artery stenosis, other intracranial artery stenosis) ipsilateral to the ischemic area (stenosis defined by luminal narrowing ≥30%, judgement of the investigator)
• • 3. or presence of atherosclerotic disease of the aortic arch with a plaque ≥4mm in thickness with or without superimposed thrombus, or a plaque \<4 mm with a superimposed mobile thrombus (detected by transesophageal echocardiography or CT angiography)
• • 4. with no clear indication of colchicine treatment (gout, Mediterranean fever) and with an indication to long-term antiplatelet therapy (no clear indication to oral anticoagulant)
• • 5. age equal or above 18
• • 6. Rankin score less than ≤4 (ranges from 0 to 6, with 0 indicating no symptoms, 1 no disability, 2 to 3 needing some help with daily activities, 4 to 5 dependent or bedridden, and 6 death),
• • 7. fully informed and signed inform consent
• • 8. with social security number.
• • 9. medical examination before the participation to the research
• • 10. Under contraception in case of childbearing potential (highly effective: 1) combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation et 2) progestogen-only).
• • 11. 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 digestive tract 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, circulatory assistance)
• • 8. A recent severe sepsis (7 days) or all recent acute reaches
• • 9. Chronic treatment (for more than 6 months) with corticosteroids or NSAIDs (or repeated high-dose intake for less than 7 days).
• • 10. Anticipated concomitant oral or intravenous therapy with strong CYP3A4 inhibitors or CYP3A4 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 the investigator) or due to cardiac source of embolism without documented atherosclerotic disease (e.g., mitral stenosis or endomyocardial fibrosis, endocarditis) a patient with atrial fibrillation, or with a history of myocardial infarction, or with calcified aortic stenosis will be eligible if the above inclusion 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 cerebral hemosiderin deposits -so called "microbleedings" - on gradient echo imaging is not an 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 or that 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 experimental therapy 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 colchicine and/or ticagrelor