Colchicine in High-risk Patients With Acute Minor-to-moderate Ischemic Stroke or Transient Ischemic Attack (CHANCE-3)

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.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke; TIA
• Intervention / Treatment: Drug: Colchicine; Drug: Placebo colchicine

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 Type: Interventional
• Enrollment (Anticipated): 8238
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100070
      • Active, not recruiting
      • Beijing Tiantan Hospital, Capital Medical University
  • Shandong
    • Liaocheng, Shandong, China
      • Recruiting
      • Third People's Hospital of Liaocheng
      • Contact: Liguo Chang; Phone Number: +86-17763559299; Email: chliguo@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Any new stroke events	Incidence of any new ischemic or hemorrhagic stroke	any time within 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
New vascular events	Incidence of any new vascular events, including ischemic stroke, hemorrhagic stroke, TIA, myocardial infarction and vascular death	any time within 90 days
New ischemic stroke	Incidence of any new ischemic stroke	any time within 90 days
Poor functional outcome	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)	at 90 days after randomization
New stroke and TIA	Incidence of any new stroke and TIA	any time within 90 days
Severity of recurrent stroke and TIA	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	within 90 days after randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Any new stroke events	Incidence of any new ischemic or hemorrhagic stroke	any time within 1 year after randomization
New vascular events	Incidence of any new vascular events, including ischemic stroke, hemorrhagic stroke, TIA, myocardial infarction and vascular death	any time within 1 year after randomization
New ischemic stroke	Incidence of any new ischemic stroke	any time within 1 year after randomization
Poor functional outcome	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)	at 1 year after randomization
New stroke and TIA	Incidence of any new stroke and TIA	any time within 1 year after randomization
Severity of recurrent stroke and TIA	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	within 1 year after randomization
Adverse events	Rate of adverse events ( AEs )	within 90 days
Severe adverse events	Rate of serious adverse events ( SAEs )	within 90 days
Increased CK levels or abnormal hepatic function when concomitant high-intensity statin treatment	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	within 90 days
Adverse events	Rate of adverse events ( AEs )	within 1 year
Severe adverse events	Rate of serious adverse events ( SAEs )	within 1 year

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2022
• Primary Completion (Anticipated): April 30, 2024
• Study Completion (Anticipated): January 31, 2025

Study Registration Dates

• First Submitted: June 20, 2022
• First Submitted That Met QC Criteria: June 29, 2022
• First Posted (Actual): June 30, 2022

Study Record Updates

• Last Update Posted (Estimate): May 8, 2023
• Last Update Submitted That Met QC Criteria: May 4, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Ischemic Attack, Transient; Cerebral Infarction; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: NCRC-2022-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No