COLCHICINE for Ischemic stroke | Transient ischaemic attack | Atherosclerosis | Myocardial infarction | Coronary syndrome

Inclusion criteria

• {"criterion_text":"- 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)\n- medical examination before the participation to the research\n- 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)\n- Pregnancy test for women of childbearing potential\n- 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 -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 -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)\n- OR with a history of symptomatic coronary artery disease\n- 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) 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 with ipsilateral carotid stenosis that was revascularized (endarterectomy or stenting) -OR with ipsilateral, potentially causal intracranial stenosis ≥70%\n- with no clear indication of colchicine treatment (gout, Mediterranean fever)\n- age equal or above 18\n- 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)\n- fully informed and signed inform consent\n- with social security number"}

Exclusion criteria

• {"criterion_text":"- Hypersensitivity to colchicine or any of the excipients.\n- Patients participating in another pharmaco therapeutic program with an experimental therapy that is known to affect colchicine therapy.\n- Leukopenia <3000UI/μl\n- Major digestive disorders (chronic diarrhea, inflammatory disease of the digestive tract as uncontrolled ulcerative colitis or active Crohn disease)\n- Patients with severe renal impairment (creatinine clearance < 30 ml/min)\n- Patients with severe hepatic impairment (Prothrombin Time < 50%),\n- Immunosuppression (all immunosuppressive treatments are forbidden, except for inhaled form corticosteroids),, medullary aplasia\n- Active chronic inflammatory disease with chronically elevated blood CRP/hsCRP levels (as in lupus or Horton's disease; patients with asthma or COPD are eligible),\n- Chronic active infection (e.g. tuberculosis). HIV is accepted if treatments taken do not interact with experimental treatments,\n- Evolving cancer with a life expectancy less than 3 years,\n- Hemodynamic instability (need for amines for more than 24 hours, circulatory assistance)\n- Anticipated concomitant oral or intravenous therapy with strong CYP3A4 inhibitors than cannot be stopped for the course of the course of this study\n- A recent severe sepsis (7 days) or all recent acute reaches\n- Chronic treatment (for more than 6 months) with corticosteroids (oral or intravenous) or NSAIDs (or repeated high-dose intake for less than 7 days).\n- Prohibited treatments: All treatments contraindicated during the use of colchicine for a few clinical cases, such as chronic inflammatory diseases and chronic infectious diseases, we will ask the coordinating investigator to validate the patient's eligibility.\n- 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]\n- Symptomatic hemorrhagic stroke (the mere presence of asymptomatic cerebral hemosiderin deposits –so called “microbleedings”\n- Uncontrolled hypertension (investigator judgement)\n- Follow-up visit impossible or anticipated bad compliance.\n- Intercurrent disease that may interfere with evaluation of the primary end-point or that may prevent follow-up study visits\n- Anticipated pregnancy at time of enrollment in the study\n- Breastfeeding woman"}

Primary endpoints

• {"endpoint_text":"- Composite of: nonfatal ischemic stroke or nonfatal hemorrhagic stroke or undetermined stroke, nonfatal myocardial infarction, urgent coronary or carotid revascularization following new symptoms, and vascular death including sudden death during the study (from 36 to 60 months)","definition_or_measurement_approach":"Composite of recurrent major vascular events (nonfatal ischemic stroke, nonfatal hemorrhagic stroke, undetermined stroke, nonfatal myocardial infarction, urgent coronary or carotid revascularization after new symptoms, and vascular death). Timeframe specified: from 36 to 60 months of follow-up."}

Secondary endpoints

• {"endpoint_text":"- Recurrent fatal and nonfatal ischemic stroke or urgent carotid revascularization following a new transient ischemic attack with negative neuro-imaging during the study","definition_or_measurement_approach":"Assessed during the study (as written)."}
• {"endpoint_text":"- Recurrent fatal and nonfatal ischemic stroke during the study","definition_or_measurement_approach":"Assessed during the study (as written)."}
• {"endpoint_text":"- Fatal and nonfatal myocardial infarction or urgent coronary revascularization following a new acute coronary syndrome during the study","definition_or_measurement_approach":"Assessed during the study (as written)."}
• {"endpoint_text":"- Fatal and nonfatal myocardial infarction during the study","definition_or_measurement_approach":"Assessed during the study (as written)."}
• {"endpoint_text":"- Vascular death during the study","definition_or_measurement_approach":"Assessed during the study (as written)."}
• {"endpoint_text":"- Any stroke during the study","definition_or_measurement_approach":"Assessed during the study (as written)."}
• {"endpoint_text":"- Any stroke or TIA during the study","definition_or_measurement_approach":"Assessed during the study (as written)."}
• {"endpoint_text":"- Major coronary events (including MI) during the study","definition_or_measurement_approach":"Assessed during the study (as written)."}
• {"endpoint_text":"- Any coronary end-points (MI, hospitalization for recurrent ACS, coronary revascularization procedure urgent or elective, fatal coronary event) during the study","definition_or_measurement_approach":"Assessed during the study (as written)."}
• {"endpoint_text":"- Any death during the study","definition_or_measurement_approach":"Assessed during the study (as written)."}
• {"endpoint_text":"- Fatal and non-fatal stroke with mRS>1","definition_or_measurement_approach":"Assessed during the study (as written); mRS refers to modified Rankin Scale."}
• {"endpoint_text":"- All revascularization procedures (coronary, carotid, peripheral) during the study","definition_or_measurement_approach":"Assessed during the study (as written)."}
• {"endpoint_text":"- Carotid revascularization during the study","definition_or_measurement_approach":"Assessed during the study (as written)."}

France

Earliest CTIS Part Ii Submission Date

13-09-2024

Latest Decision Or Authorization Date

10-04-2026

Processing Time Days

574

Number Of Sites

43

Number Of Participants

1400

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France