Ischemic Stroke, TIA
Conditions
Brief summary
This study is a multicentre, randomized, double-blind, placebo-controlled, investigator-sponsored study that aims to investigate the efficacy of colchicine in preventing recurrent stroke in the patients with acute minor-to-moderate ischemic stroke or TIA and a hsCRP level of ≥2mg/L.
Detailed description
This is a multicentre, randomized, double-blind, placebo-controlled trial that aims to investigate the efficacy of colchicine in preventing recurrent stroke in the patients with acute minor-to-moderate ischemic stroke or TIA and a hsCRP level of ≥2mg/L. 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 1mg per day on days 1 through 3, and continuing with 0.5 mg per day on days 4 through 90, and those in the other arm will receive an equivalent placebo drug. Study visits will be performed on the day of randomization, at discharge, at day 90 and at 1 year. The primary outcome was stroke (ischemic or hemorrhagic) during 90 days of follow-up in an intention-to treat analysis.
Interventions
DRUGColchicine
Oral colchicine will be initiated with a dose of 1mg per day (one tablet of 0.5mg initially followed by another tablet of 0.5 mg at least four hours later) on days 1 through 3, and continuing with 0.5 mg (one tablet) per day on days 4 through 90.
Oral placebo colchicine will be initiated with a dose of 1mg per day (one tablet of 0.5mg initially followed by another tablet of 0.5 mg at least four hours later) on days 1 through 3, and continuing with 0.5 mg (one tablet) per day on days 4 through 90.
Sponsors
Beijing Tiantan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 40 years or older than 40 years； 2. Acute cerebral ischemic event due to： Acute minor-to-moderate ischemic stroke (NIHSS≤5 at the time of randomization) or TIA with moderate-to-high risk of stroke (ABCD2 score ≥ 4 at the time of randomization)； 3. With a hsCRP level of ≥2mg/L at randomization; 4. Can be treated with study drug within 24 hours of symptoms onset\*(\*Symptom onset is defined by the last seen normal principle)； 5. Informed consent signed.
Exclusion criteria
1. Malformation, tumor, abscess or other major non-ischemic brain disease (e.g., multiple sclerosis) on baseline head CT or MRI. 2. Isolated or pure sensory symptoms (e.g., numbness), isolated visual changes, or isolated dizziness/vertigo without evidence of acute infarction on baseline head CT or MRI. 3. Iatrogenic causes (angioplasty or surgery) of stroke or TIA. 4. Presumed cardiac source of embolus, such as atrial fibrillation or prosthetic cardiac valve). 5. A score of ≥ 2 on the modified Rankin scale immediately before the occurrence of the index event. 6. Usage of colchicine within 30 days before randomization or planning to take colchicine therapy for other indications. 7. Known allergy or sensitivity or intolerance to colchicine. 8. Inflammatory bowel disease (Crohn's or ulcerative colitis) or chronic diarrhea. 9. Symptomatic peripheral neuropathy or pre-existing progressive neuromuscular disease or with creatine kinase (CK) level \> 3 times the upper limit of normal as measured within the past 30 days and determined to be non-transient through repeat testing. 10. A history of cirrhosis, chronic active hepatitis or severe hepatic disease. 11. Impaired hepatic (ALT or AST \> twice the upper limit of normal range) or kidney (creatinine exceeding 1.5 times of the upper limit of normal range or eGFR less than 50 ml/min) function at randomization. 12. Anemia (haemoglobin \<10g/dL), thrombocytopenia (platelet count \<100×109/L) or leucopenia (white blood cell \<3×109/L) at randomization. 13. In the acute phase of respiratory tract infection, urinary tract infection, and gastro-enteritis, or currently using or planning to receive oral or intravenous anti-infective therapy for any other infection. 14. Currently using or planning to begin long-term (\>7 days) systemic anti-inflammatory drugs (NSAIDs except for aspirin, oral or intravenous steroid therapy) during the study. 15. Planning to use moderate or strong CYP3A4 inhibitors (clarithromycin, erythromycin, telithromycin, other macrolide antibiotics, ketoconazole, itraconazole, voriconazole, ritonavir, atazanavir, indinavir, other HIV protease inhibitors, verapamil, diltiazem, quinidine, digoxin, disulfiram, etc) or P-gp inhibitors (cyclosporine) at randomization. 16. Planned surgery or interventional treatment requiring cessation of the study drug during the study. 17. Participating in another clinical trial with an investigational drug or device concurrently or during the last 30 days. 18. Women of childbearing age who were not practicing reliable contraception and did not have a documented negative pregnancy test or severe noncardiovascular coexisting condition. 19. Severe non-cardiovascular comorbidity with a life expectancy of less than 3 months. 20. With a history of clinically significant drug or alcohol abuse. 21. Inability to understand and/or follow research procedures due to mental, cognitive, or emotional disorders, or to be an unsuitable candidate for the study for any other considered by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Any new stroke events | any time within 90 days | Incidence of any new ischemic or hemorrhagic stroke |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| New vascular events | any time within 90 days | Incidence of any new vascular events, including ischemic stroke, hemorrhagic stroke, TIA, myocardial infarction and vascular death |
| New ischemic stroke | any time within 90 days | Incidence of any new ischemic stroke |
| Poor functional outcome | at 90 days after randomization | Rate of poor functional outcome defined as a Modified Rankin Scale score of \>1 (Modified Rankin Scale score ranges from 0 (no symptoms) to 6 (death) and higher score means worse outcome) |
| New stroke and TIA | any time within 90 days | Incidence of any new stroke and TIA |
| Severity of recurrent stroke and TIA | within 90 days after randomization | Severity is measured using a six-level ordered categorical scale that incorporates the mRS: fatal stroke \[mRS 6\]/severe non-fatal stroke \[mRS 4 or 5\]/moderate stroke \[mRS 2 or 3\]/mild stroke \[mRS 0 or 1\]/TIA/no stroke-TIA |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | within 90 days | Rate of adverse events ( AEs ) |
| Poor functional outcome | at 1 year after randomization | Rate of poor functional outcome defined as a Modified Rankin Scale score of \>1 (Modified Rankin Scale score ranges from 0 (no symptoms) to 6 (death) and higher score means worse outcome) |
| Increased CK levels or abnormal hepatic function when concomitant high-intensity statin treatment | within 90 days | Rate of increased CK levels (≥ 5 times the upper limit of normal) or abnormal hepatic function (ALT or AST ≥ 3 times the upper limit of normal range) within 90 days when concomitant high-intensity statin treatment |
| Severe adverse events | within 90 days | Rate of serious adverse events ( SAEs ) |
| Any new stroke events | any time within 1 year after randomization | Incidence of any new ischemic or hemorrhagic stroke |
| New vascular events | any time within 1 year after randomization | Incidence of any new vascular events, including ischemic stroke, hemorrhagic stroke, TIA, myocardial infarction and vascular death |
| New ischemic stroke | any time within 1 year after randomization | Incidence of any new ischemic stroke |
| New stroke and TIA | any time within 1 year after randomization | Incidence of any new stroke and TIA |
| Severity of recurrent stroke and TIA | within 1 year after randomization | Severity is measured using a six-level ordered categorical scale that incorporates the mRS: fatal stroke \[mRS 6\]/severe non-fatal stroke \[mRS 4 or 5\]/moderate stroke \[mRS 2 or 3\]/mild stroke \[mRS 0 or 1\]/TIA/no stroke-TIA |
Countries
China
Outcome results
None listed