Using colchicine and ticagrelor to prevent ischemic stroke in patients with atherosclerosis

Reducing Inflammation in Ischemic Stroke With Colchicine, and Ticagrelor in High-risk Patients-extended Treatment in Ischemic Stroke

This study is testing if a combination of low-dose colchicine and ticagrelor can help prevent future strokes in people with atherosclerosis who have already had an ischemic stroke.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 2800 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (Academic / other)
• Locations: 1 site (Paris, Paris)
• Trial ID: NCT05476991 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of low-dose colchicine combined with ticagrelor in preventing major vascular events in patients who have experienced an ischemic stroke due to atherosclerosis. The study employs a 2x2 factorial design to compare the outcomes of patients receiving colchicine versus those who do not, as well as ticagrelor versus aspirin. Participants will be monitored over a period of 36 to 60 months to assess the long-term benefits of these treatments. The goal is to determine if these medications can significantly reduce the risk of subsequent strokes or other vascular complications.

Who should consider this trial

Good fit: Ideal candidates include patients who have experienced a cerebral infarction or TIA with documented ischemic lesions and have significant atherosclerotic stenosis.

Not a fit: Patients who have not experienced a stroke or TIA, or those with non-atherosclerotic causes of stroke, may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option that significantly reduces the risk of recurrent strokes in high-risk patients.

How similar studies have performed: Other studies have explored the use of anti-inflammatory agents and antiplatelet therapies in stroke prevention, indicating potential success, but this specific combination is novel.

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

Where this trial is running

Paris, Paris

• URC Lariboisière-Fernand Widal-Saint Louis — Paris, Paris, France (Recruiting)

Study contacts

• Study coordinator: Pierre Amarenco, Pr

Conditions Stroke; Stroke, Ischemic; Atherosclerosis; Myocardial Infarction; Coronary Syndrome; TIA; Cardiac Disease; Cerebral Infarction