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

NCT ID: NCT05476991

Last Updated: 2025-09-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 2800 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-17
• Study Completion Date: 2027-09-01

Brief Summary

REDUCING INFLAMMATION IN ISCHEMIC STROKE WITH COLCHICINE, AND TICAGRELOR IN HIGH-RISK PATIENTS-EXTENDED TREATMENT IN ISCHEMIC STROKE.

Detailed Description

Our main hypothesis is that low-dose colchicine (0.5 mg/day) on top of best medical care, in patients with an ischemic stroke with ipsilateral atherosclerotic stenosis, will reduce the risk of major vascular events after 36-60 months of treatment as compared to no colchicine.

Our second main hypothesis, tested in 2x2 factorial design, is that ticagrelor 90 mg bid in the same patients, will reduce the long-term risk of major vascular events (after 36-60 months of treatment) as compared to aspirin 75-300 mg/day.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Colchicine + Ticagrelor

Group Type: EXPERIMENTAL

Colchicine 0.5 MG

Intervention Type: DRUG

Colchicine is a medication used to treat gout and Behçet's disease. In gout, it is less preferred to NSAIDs or steroids. Other uses for colchicine include the management of pericarditis and familial Mediterranean fever.

Ticagrelor 90mg

Intervention Type: DRUG

Ticagrelor, sold under the brand name Brilinta among others, is a medication used for the prevention of stroke, heart attack and other events in people with acute coronary syndrome, meaning problems with blood supply in the coronary arteries. It acts as a platelet aggregation inhibitor by antagonising the P2Y 12 receptor.

Colchine + Aspirine

Group Type: EXPERIMENTAL

Colchicine 0.5 MG

Intervention Type: DRUG

Colchicine is a medication used to treat gout and Behçet's disease. In gout, it is less preferred to NSAIDs or steroids. Other uses for colchicine include the management of pericarditis and familial Mediterranean fever.

Aspirin 75-300mg

Intervention Type: DRUG

Also known as Aspirin, acetylsalicylic acid (ASA) is a commonly used drug for the treatment of pain and fever due to various causes. Acetylsalicylic acid has both anti-inflammatory and antipyretic effects. This drug also inhibits platelet aggregation and is used in the prevention of blood clots stroke, and myocardial infarction (MI).

SOC + Ticagrelor

Group Type: EXPERIMENTAL

Ticagrelor 90mg

Intervention Type: DRUG

Ticagrelor, sold under the brand name Brilinta among others, is a medication used for the prevention of stroke, heart attack and other events in people with acute coronary syndrome, meaning problems with blood supply in the coronary arteries. It acts as a platelet aggregation inhibitor by antagonising the P2Y 12 receptor.

SOC + Aspirine

Group Type: ACTIVE_COMPARATOR

Aspirin 75-300mg

Intervention Type: DRUG

Also known as Aspirin, acetylsalicylic acid (ASA) is a commonly used drug for the treatment of pain and fever due to various causes. Acetylsalicylic acid has both anti-inflammatory and antipyretic effects. This drug also inhibits platelet aggregation and is used in the prevention of blood clots stroke, and myocardial infarction (MI).

Interventions

Colchicine 0.5 MG

Colchicine is a medication used to treat gout and Behçet's disease. In gout, it is less preferred to NSAIDs or steroids. Other uses for colchicine include the management of pericarditis and familial Mediterranean fever.

Intervention Type: DRUG

Ticagrelor 90mg

Ticagrelor, sold under the brand name Brilinta among others, is a medication used for the prevention of stroke, heart attack and other events in people with acute coronary syndrome, meaning problems with blood supply in the coronary arteries. It acts as a platelet aggregation inhibitor by antagonising the P2Y 12 receptor.

Intervention Type: DRUG

Aspirin 75-300mg

Also known as Aspirin, acetylsalicylic acid (ASA) is a commonly used drug for the treatment of pain and fever due to various causes. Acetylsalicylic acid has both anti-inflammatory and antipyretic effects. This drug also inhibits platelet aggregation and is used in the prevention of blood clots stroke, and myocardial infarction (MI).

Intervention Type: DRUG

Other Intervention Names

Brilinta; Acetylsalicylic acid

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

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

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

URC Lariboisière-Fernand Widal-Saint Louis

Paris, Paris, France

Site Status: RECRUITING

Countries

France

Central Contacts

Pierre Amarenco, Pr

Role: CONTACT

pierre.amarenco@gmail.com

140258725 ext. +33

Facility Contacts

Brahim M Elarbi

Role: primary

brahim.mohamed-elarbi@aphp.fr

01 40 05 43 60 ext. +33

Other Identifiers

APHP211055

Identifier Type: -

Identifier Source: org_study_id