Stroke
Conditions
Keywords
stroke, colchicine, secondary prevention
Brief summary
The role of colchicine in the secondary prevention of ischemic stroke has not been determinded. This multicenter, randomized, double-blind, placebo-controlled, event-driven clinical trial of CHANCE-3 EX was aimed to assess the efficacy and safety of low-dose colchicine versus placebo on reducing the risk of recurrent ischemic stroke, myocardial infarction and vascular death in patients with minor-to-moderate ischemic stroke.
Interventions
DRUGColchicine 0.5 mg
Oral colchicine will be initiated with a dose of 0.5 mg per day.
Oral placebo colchicine will be initiated with a dose of 0.5 mg per day.
Sponsors
Shenzhen Medical Academy of Research and Translation
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
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. An age of 18-80 years old 2. Minor-to-moderate ischemic stroke (NIHSS\<15 at randomization; confirmed by CT or MRI) 3. Within 7-30 days after the most recent qualifying stroke onset 4. Informed consent signed
Exclusion criteria
1. Iatrogenic causes (angioplasty or surgery) of stroke 2. mRS\>3 at randomization 3. Known allergy, sensitivity or intolerance to colchicine 4. Inflammatory bowel disease (Crohn's or ulcerative colitis) or chronic diarrhea 5. 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 6. A history of cirrhosis, chronic active hepatitis or severe hepatic disease 7. Impaired hepatic (ALT or AST \> three times 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 8. Anemia (haemoglobin \<10g/dL), thrombocytopenia (platelet count \<100×109/L) or leucopenia (white blood cell count \<3×109/L) at randomization 9. Comorbid gout or other indications for colchicine use 10. Active infection at randomization (including respiratory tract infection, urinary tract infection, or gastroenteritis) 11. Requiring chronic immunosuppressant, glucocorticoid, or nonsteroidal anti-inflammatory drugs therapy (except aspirin) during the study 12. Usage of contraindicated medications for colchicine at randomization: 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) 13. Participating in another clinical trial with an investigational drug or device concurrently or during the last 30 days 14. Women of childbearing age who were not practicing reliable contraception and did not have a documented negative pregnancy test 15. Severe non-cardiovascular comorbidity, active malignant tumors or terminal-stage illnesses, with a life expectancy of less than 2 years 16. Clinically significant drug or alcohol abuse in the past year 17. Any other conditions deemed unsuitable for participation in this study or inability to complete study procedures, including but not limited to mental disorders, cognitive or emotional impairments, or physical conditions that may compromise compliance with study protocols and follow-up visits
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| First Event of ischemic stroke, myocardial infarction and vascular death | From randomization to occurrence of the first event, with a median follow-up time of 24 months | The descriptive statistics are the number of participants having at least one of the composites of the primary endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ischemic stroke | From randomization to event, with a median follow-up time of 24 months. | The descriptive statistics are presented as the number of participants having had ischemic stroke. |
| Myocardial Infarction | From randomization to event, with a median follow-up time of 24 months. | The descriptive statistics are presented as the number of participants having had myocardial infarction. |
| Vascular death | From randomization to death, with a median follow-up time of 24 months. | The descriptive statistics are presented as the number of participants having had a vascular death. |
| mRS 0-1 at 1 year or ≥1-point improvement in mRS score from baseline to 1 year | At 1 year | The descriptive statistics are presented as the number of participants having had mRS 0-1 at 1 year or ≥1-point improvement in mRS score from baseline to 1 year. |
| mRS shift | At 1 year | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Any serious adverse event | Through study completion, a median follow-up time of 24 months. | The descriptive statistics are presented as the number of serious adverse events. |
| Adverse events of special interest | Through study completion, a median follow-up time of 24 months. | The descriptive statistics are presented as the number of adverse events of special interest, including gastrointestinal events (diarrhea, flatulence, nausea, vomiting), infection, impaired hepatic function, moderate or severe impaired renal function, myalgia, myopathy, peripheral neuropathy, myelosuppression, orthostatic hypotension, syncope, rash and alopecia. |
Contacts
Primary ContactJiejie Li, Ph.D
Outcome results
None listed