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

NCT05476991 | Recruiting Phase 3 DMC

• 1 other identifier: APHP211055
• Study Type: interventional
• Target: 2,800
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

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

Keywords

Stroke; Colchicine; Atherosclerosis; Aspirin; Ticagrelor

Outcome Measures

Primary Outcomes (5)

• Number of Participants with nonfatal ischemic stroke

  Sudden onset of focal neurologic symptoms related to impaired cerebral circulation. ASCOD phenotyping will be used. TIAs will not be part of strokes. However, any focal neurologic symptoms associated with positive DWI or hypodensity on the CT scan in an appropriate area in relation with these symptoms will be considered a cerebral infarction and be part of "strokes".

  36 months

• Number of Participants with undetermined stroke

  Sudden onset of focal neurologic symptoms related to impaired cerebral circulation. ASCOD phenotyping will be used. TIAs will not be part of strokes. However, any focal neurologic symptoms associated with positive DWI or hypodensity on the CT scan in an appropriate area in relation with these symptoms will be considered a cerebral infarction and be part of "strokes".

  36 months

• Number of Participants with nonfatal myocardial infarction

  * Fatal or nonfatal myocardial infarction (OMS.AHA/ACC definition) o Clinical symptoms + elevated troponin * Silent myocardial infarction following universal definition

  36 months

• Number of Participants with urgent coronary or carotid revascularization following new symptoms

  Revascularization Procedure * Coronary : Angioplasty or stenting or CABG * Carotid : angioplasty or stenting, surgical endarterectomy * Peripheral: angioplasty or stenting including aorta, surgical by-pass or endarterectomy of a peripheral artery.

  36 months

• Number of Participants with vascular death including sudden death

  \- Vascular death * Death due to cardiac or vascular cause * Death due to systemic hemorrhage * Death due to pulmonary embolism * Sudden death: death occurring within 24 hours, unexpected in a patient in apparent healthy condition or condition that was stable or improved * Death without documented nonvascular cause * Fatal stroke: death occurring within 30 days of stroke onset (whether ischemic or hemorrhagic).

  36 months

Secondary Outcomes (11)

• Number of Participants with recurrent fatal and nonfatal ischemic stroke

  36 months

• Number of Participants with urgent carotid revascularization following a new transient ischemic attack with negative neuro-imaging

  36 months

• Number of Participants with fatal and nonfatal myocardial infarction

  36 months

• Number of Participants with fatal and nonfatal myocardial infarction or urgent coronary revascularization following a new acute coronary syndrome

  36 months

• Number of Participants with vascular death

  36 months

Study Arms (4)

Colchicine + Ticagrelor

EXPERIMENTAL

Drug: Colchicine 0.5 MG; Drug: Ticagrelor 90mg

Colchine + Aspirine

EXPERIMENTAL

Drug: Colchicine 0.5 MG; Drug: Aspirin 75-300mg

SOC + Ticagrelor

EXPERIMENTAL

Drug: Ticagrelor 90mg

SOC + Aspirine

ACTIVE COMPARATOR

Drug: Aspirin 75-300mg

Interventions

Colchicine 0.5 MG 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.

Colchicine + Ticagrelor; Colchine + Aspirine

Ticagrelor 90mg 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.

Also known as: Brilinta

Colchicine + Ticagrelor; SOC + Ticagrelor

Aspirin 75-300mg 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).

Also known as: Acetylsalicylic acid

Colchine + Aspirine; SOC + Aspirine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient should have the following:
• Patient with:
• 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)
• 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
• and documented atherosclerotic stenosis:
• 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)
• 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)
• 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)
• 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)
• age equal or above 18
• 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),
• fully informed and signed inform consent
• with social security number.
• medical examination before the participation to the research
• 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).

You may not qualify if:

• Colchicine treatment needed (e.g., gout, Mediterranean fever)
• Hypersensitivity to ticagrelor or any of the excipients.
• Hypersensitivity to colchicine or any of the excipients.
• Major digestive disorders (chronic diarrhea, inflammatory disease of the digestive tract as uncontrolled ulcerative colitis or active Crohn disease)
• Immunosuppression, medullary aplasia
• Active chronic inflammatory disease, chronic active infection, evolving cancer
• Hemodynamic instability (need for amines for more than 24 hours, circulatory assistance)
• A recent severe sepsis (7 days) or all recent acute reaches
• Chronic treatment (for more than 6 months) with corticosteroids or NSAIDs (or repeated high-dose intake for less than 7 days).
• 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
• Indication to long-term oral anticoagulant treatment (e.g., atrial fibrillation)
• Active pathological bleeding
• Uncontrolled hypertension (investigator judgement)
• Follow-up visit impossible or anticipated bad compliance.
• Intercurrent disease that may interfere with evaluation of the primary end-point or that may prevent follow-up study visits..

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

URC Lariboisière-Fernand Widal-Saint Louis

Paris, Paris, 75010, France

RECRUITING

MeSH Terms

Conditions

Stroke; Ischemic Stroke; Atherosclerosis; Myocardial Infarction; Angina, Unstable; Heart Diseases; Cerebral Infarction

Interventions

Colchicine; Ticagrelor; Aspirin

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Myocardial Ischemia; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Angina Pectoris; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Brain Infarction; Brain Ischemia

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Central Study Contacts

Pierre Amarenco, Pr

CONTACT

140258725; pierre.amarenco@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2022
• First Posted: July 27, 2022
• Study Start: May 17, 2023
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: September 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)