Colchicine in High-risk Patients With Acute MiNor-to-moderate IschemiC Stroke or TransiEnt Ischemic Attack (CHANCE-3)

Sponsor

Beijing Tiantan Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05439356

Collaborator

(none)

8,238

Enrollment

Locations

Arms

29.7

Anticipated Duration (Months)

4119

Patients Per Site

138.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ischemic Stroke TIA	Drug: Colchicine Drug: Placebo colchicine	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

8238 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Colchicine in High-risk Patients With Acute MiNor-to-moderate IschemiC Stroke or TransiEnt Ischemic Attack (CHANCE-3)

Actual Study Start Date :

Aug 10, 2022

Anticipated Primary Completion Date :

Apr 30, 2024

Anticipated Study Completion Date :

Jan 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Colchicine Group Patients in this arm will receive colchicine for 90 days in addition to standard medical care	Drug: Colchicine 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.
Placebo Comparator: Placebo Colchicine Group Patients in this arm will receive placebo colchicine for 90 days in addition to standard medical care	Drug: Placebo colchicine 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.

Arm

Intervention/Treatment

Experimental: Colchicine Group

Patients in this arm will receive colchicine for 90 days in addition to standard medical care

Drug: Colchicine

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.

Placebo Comparator: Placebo Colchicine Group

Patients in this arm will receive placebo colchicine for 90 days in addition to standard medical care

Drug: Placebo colchicine

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.

Outcome Measures

Primary Outcome Measures

Any new stroke events [any time within 90 days]
Incidence of any new ischemic or hemorrhagic stroke

Secondary Outcome Measures

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 Outcome Measures

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
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)
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
Adverse events [within 90 days]
Rate of adverse events ( AEs )
Severe adverse events [within 90 days]
Rate of serious adverse events ( SAEs )
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
Adverse events [within 1 year]
Rate of adverse events ( AEs )
Severe adverse events [within 1 year]
Rate of serious adverse events ( SAEs )

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

40 years or older than 40 years；
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)；
With a hsCRP level of ≥2mg/L at randomization;
Can be treated with study drug within 24 hours of symptoms onset*(*Symptom onset is defined by the "last seen normal" principle)；
Informed consent signed.

Exclusion Criteria:

Malformation, tumor, abscess or other major non-ischemic brain disease (e.g., multiple sclerosis) on baseline head CT or MRI.
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.
Iatrogenic causes (angioplasty or surgery) of stroke or TIA.
Presumed cardiac source of embolus, such as atrial fibrillation or prosthetic cardiac valve).
A score of ≥ 2 on the modified Rankin scale immediately before the occurrence of the index event.
Usage of colchicine within 30 days before randomization or planning to take colchicine therapy for other indications.
Known allergy or sensitivity or intolerance to colchicine.
Inflammatory bowel disease (Crohn's or ulcerative colitis) or chronic diarrhea.
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.
A history of cirrhosis, chronic active hepatitis or severe hepatic disease.
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.
Anemia (haemoglobin <10g/dL), thrombocytopenia (platelet count <100×109/L) or leucopenia (white blood cell <3×109/L) at randomization.
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.
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.
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.
Planned surgery or interventional treatment requiring cessation of the study drug during the study.
Participating in another clinical trial with an investigational drug or device concurrently or during the last 30 days.
Women of childbearing age who were not practicing reliable contraception and did not have a documented negative pregnancy test or severe noncardiovascular coexisting condition.
Severe non-cardiovascular comorbidity with a life expectancy of less than 3 months.
With a history of clinically significant drug or alcohol abuse.
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.