Efficacy of Colchicine in Preventing Recurrent Stroke in the Patients With Acute Atherothrombotic Ischemic Stroke During Hospitalization

Study Overview
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Brief Summary
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This study is two-center, prospective, randomized, open-label, controlled, investigator-sponsored study that aims to investigate the efficacy of low-dose colchicine in preventing recurrent stroke in the patients with acute atherothrombotic minor-to-moderate ischemic stroke during hospitalization.

Detailed Description
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This study is two-center, prospective, randomized, open-label, controlled, investigator-sponsored study that aims to investigate the efficacy of low-dose colchicine in preventing recurrent stroke in the patients with acute atherothrombotic minor-to-moderate ischemic stroke during hospitalization. Patients who were eligible to the inclusion criteria and ineligible to the exclusion criteria will be randomly assigned into two groups by a 1:1 ratio. Patients in one arm will receive colchicine initiated with a dose of 0.5 mg per day during on days 1 through 14. Study visits will be performed on the day of randomization and at discharge. The outcomes were stroke, neurological deterioration, сombined endpoint events (stroke, myocardial infarction and death), bleeding during 14 days of follow-up in an intention-to treat analysis.

Official Title
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Two-center, Prospective, Randomized, Open-label, Controlled Clinical Trial With Endpoint Evaluation

Conditions
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Ischemic Stroke

Intervention / Treatment
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* Drug: Colchicine
* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form by patient prior to any study-specific procedure. Patient age over 18 years Presence of ipsilateral lesion of the extracranial artery ≥50% according to the European measurement method ECST or its occlusion, as well as stenosis < 50% with signs of morphological instability of the atherosclerotic plaque (ulceration, hemorrhage into the plaque, intimal flotation, mural thrombus, etc.). Minor neurological deficit (NIHSS score ≤5). The duration of development of stroke symptoms before colchicine taken is no more than 48 hours. Confirmation of the presence of a focus of acute ischemia in the brain according to computed tomography or magnetic resonance imaging of the brain. Exclusion Criteria: The presence of risk factors and conditions that determine a different pathogenetic subtype of ischemic stroke (atrial fibrillation/flutter, ventricular aneurysm, ets.). Hemorrhagic stroke NIHSS score ≤5. Hospitalization of the patient more than 48 hours from the onset of the disease. Severe anemia, thrombocytopenia, leukopenia. Course of an infectious/viral disease. Concomitant treatment with moderate or strong CYP3A4 inhibitors (clarithromycin, erythromycin, telithromycin, other macrolide antibiotics, ketoconazole, itraconazole, voriconazole, ritonavir, atazanavir, indinavir, other HIV protease inhibitors, verapamil or pilitin disulfazole) inhibitors (cyclosporine) at randomization. Concomitant severe degenerative disease of the nervous system. Concomitant inflammatory or autoimmune disease. Dementia, established mental illness. History of malignancy, known hepatitis B or C, or HIV infection. Swallowing impairment interfering with oral administration of the study drug. Pregnancy or breastfeeding. Women of child-bearing potential who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the Investigator. Participation in another clinical study with an investigational product at any time during the 30 days prior to randomization Previous enrolment or randomization in the present study. Decrease renal function with creatinine clearance < 30 ml/min. Presence of contraindications to taking colchicine, acetylsalicylic acid and clopidogrel.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Colchicine Group<br>All patients in this arm will receive colchicine for 14 days in addition to standard medical care without clopidogrel (acetylsalicylic acid, lipid-lowering, antihypertensive, gastroprotective, hypoglycemic drugs if necessary, lifestyle recommendations, early rehabilitation activities). | Drug: Colchicine<br>* Oral colchicine will be initiated with a dose of 0.5 mg per day during 14 days. Acetylsalicylic acid was used as an antiplatelet agent (300 mg on days 1 and continuing with 100 mg/day).<br>|
| Active Comparator: Clopidogrel treatment group<br>All patients in this arm will receive standard treatment including clopidogrel. | Drug: Clopidogrel<br>* Dual antiplatelet therapy includes ASA (300 mg on days 1 and continuing with 100 mg/day) and clopidogrel (300 mg on days 1 and continuing with 75 mg/day).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Any new stroke events | Incidence of any new ischemic stroke. | any time within 14 days | 
| Neurological deterioration | Neurological deterioration, defined as an increase in The National Institutes of Health Stroke Scale (NIHSS) of 2 or more. The NIHSS provides a quantitative measure of stroke-related neurologic deficit. The higher the score, the more severe the neurological deficit. | any time within 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| New vascular events | Incidence of any new vascular events, including ischemic stroke, myocardial infarction and vascular death | any time within 14 days | 
| Bleeding event | Bleeding event that is categorised as severe according to GUSTO (Global Utilization Of Streptokinase And Tpa For Occluded Arteries) bleeding criteria. | any time within 14 days | 
| Positive functional outcome | A positive functional outcome within 14 days is determined if the Modified Rankin Score (mRS) improves to 0-1 and/or Rivermead Mobility Index (RMI) to 14 -15 points and/or Rehabilitation Routing Scale 0 -1 points. The mRS is a 6 point disability scale with possible scores ranging from 0 to 5. A separate category of 6 is usually added for patients who expire. The RMI includes fifteen mobility items. A maximum score of 15 is possible: higher scores indicate better mobility performance. The rehabilitation routing scale is needed by the doctor to understand whether the patient requires rehabilitation. The maximum number of points is 6. The more points the patient scores, the more severe his condition. | any time within 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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clopidogrel, ischemic stroke, low-dose colchicine