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

Phase 3

Completed

• Conditions: Ischemic Stroke; TIA
• Interventions: Drug: Placebo colchicine; Drug: Colchicine

• Registration Number: NCT05439356
• Lead Sponsor: Beijing Tiantan Hospital

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.

Study Timeline

• Study First Submitted: 2022-06-20
• Study First Submitted QC: 2022-06-29
• Study First Posted: 2022-06-30
• Study Start: 2022-08-11
• Primary Completion: 2023-07-13
• Study Completion: 2024-04-12
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-24
• Last Update Posted: 2024-06-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8343

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Colchicine Group	Placebo colchicine	Patients in this arm will receive placebo colchicine for 90 days in addition to standard medical care
Colchicine Group	Colchicine	Patients in this arm will receive colchicine for 90 days in addition to standard medical care

Primary Outcome Measures

Name	Time	Method
Any new stroke events	any time within 90 days	Incidence of any new ischemic or hemorrhagic stroke

Secondary Outcome Measures

Name	Time	Method
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
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
New ischemic stroke	any time within 90 days	Incidence of any new ischemic stroke

Trial Locations

Locations (244)

Linquan County People's Hospital; 🇨🇳 Fuyang, Anhui, China

Huangshan City People's Hospital; 🇨🇳 Huangshan, Anhui, China

The First Affiliated Hospital of Wannan Medical College; 🇨🇳 Wuhu, Anhui, China

The First People's Hospital of Wuhu; 🇨🇳 Wuhu, Anhui, China

Beijing Tiantan Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

Beijing Shunyi Airport Hospital; 🇨🇳 Beijing, Beijing, China

Beijing Shunyi Hospital; 🇨🇳 Beijing, Beijing, China

Fuxing Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

The First Hospital of Fangshan District, Beijing; 🇨🇳 Beijing, Beijing, China

Chongqing Sanbo Chang 'an Hospital; 🇨🇳 Chongqing, Chongqing, China

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