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

Phase 3

Recruiting

• Conditions: Stroke, Ischemic; Atherosclerosis; Myocardial Infarction; Cerebral Infarction; Stroke; Coronary Syndrome; TIA; Cardiac Disease
• Interventions: Drug: Colchicine 0.5 MG; Drug: Aspirin 75-300mg; Drug: Ticagrelor 90mg

• Registration Number: NCT05476991
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Study Timeline

• Study First Submitted: 2022-07-25
• Study First Submitted QC: 2022-07-25
• Study First Posted: 2022-07-27
• Study Start: 2023-05-17
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-31
• Last Update Posted: 2024-06-03
• Primary Completion: 2027-09-01
• Study Completion: 2027-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 2800

Inclusion Criteria

Not provided

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Colchine + Aspirine	Aspirin 75-300mg	-
SOC + Aspirine	Aspirin 75-300mg	-
Colchine + Aspirine	Colchicine 0.5 MG	-
Colchicine + Ticagrelor	Colchicine 0.5 MG	-
Colchicine + Ticagrelor	Ticagrelor 90mg	-
SOC + Ticagrelor	Ticagrelor 90mg	-

Primary Outcome Measures

Name	Time	Method
Number of Participants with nonfatal ischemic stroke	36 months	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".
Number of Participants with vascular death including sudden death	36 months	- 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).
Number of Participants with nonfatal myocardial infarction	36 months	* Fatal or nonfatal myocardial infarction (OMS.AHA/ACC definition); o Clinical symptoms + elevated troponin; * Silent myocardial infarction following universal definition
Number of Participants with undetermined stroke	36 months	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".
Number of Participants with urgent coronary or carotid revascularization following new symptoms	36 months	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.

Secondary Outcome Measures

Name	Time	Method
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 death participant (any death)	36 months
Number of Participant with all revascularization procedures (coronary, carotid, peripheral)	36 months
Number of Participants with vascular death	36 months
Number of Participants with any stroke or TIA	36 months	A TIA is defined by sudden onset of neurologic symptoms presumed of ischemic origin, with total resolution, being clearly related to focal cerebral or retinal involvement, and with negative neuro-imaging in the cerebral area corresponding to the symptoms. TIA diagnosis must be confirmed by a neurologist, based on clinical and negative neuro-imaging evaluation (MRI with DWI is recommended).
Number of Participants with major coronary events	36 months
Number of Participants with any coronary end-points (MI, hospitalization for recurrent ACS, coronary revascularization procedure urgent or elective, fatal coronary event)	36 months	ACS: Acute Coronary Syndrome
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 Carotid revascularization	36 months

Trial Locations

Locations (1)

URC Lariboisière-Fernand Widal-Saint Louis; 🇫🇷 Paris, France