Efficacy of Colchicine in Preventing Recurrent Stroke in the Patients With Acute Atherothrombotic Ischemic Stroke During Hospitalization (COLCHIDA)

Two-center, Prospective, Randomized, Open-label, Controlled Clinical Trial With Endpoint Evaluation

This study is two-center, prospective, randomized, open-label, controlled, investigator-sponsored study that aims to investigate the efficacy of low-dose colchicine in preventing recurrent stroke in the patients with acute atherothrombotic minor-to-moderate ischemic stroke during hospitalization.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke
• Intervention / Treatment: Drug: Colchicine; Drug: Clopidogrel

Detailed Description

This study is two-center, prospective, randomized, open-label, controlled, investigator-sponsored study that aims to investigate the efficacy of low-dose colchicine in preventing recurrent stroke in the patients with acute atherothrombotic minor-to-moderate ischemic stroke during hospitalization. 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 0.5 mg per day during on days 1 through 14. Study visits will be performed on the day of randomization and at discharge. The outcomes were stroke, neurological deterioration, сombined endpoint events (stroke, myocardial infarction and death), bleeding during 14 days of follow-up in an intention-to treat analysis.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• Russian Federation
  • Kemerovo Region
    • Kemerovo, Kemerovo Region, Russian Federation, 650002
      • Recruiting
      • Research Institute for Complex Issues of Cardiovascular Diseas
      • Contact: Mikhail Zykov, PhD; Phone Number: +79183062959; Email: mvz83@mail.ru
  • Krasnodar Refion
    • Sochi, Krasnodar Refion, Russian Federation, 354057
      • Recruiting
      • Sochi City Hospital #4
      • Contact: Mikhail Zykov, PhD; Phone Number: +79183062959; Email: mvz83@mail.ru
      • Sub-Investigator: Vadim Butsev
      • Sub-Investigator: Natalia Ryazanova
      • Sub-Investigator: Daria Zykova
      • Principal Investigator: Mikhail Zykov, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed informed consent form by patient prior to any study-specific procedure.
2. Patient age over 18 years
3. Presence of ipsilateral lesion of the extracranial artery ≥50% according to the European measurement method ECST or its occlusion, as well as stenosis < 50% with signs of morphological instability of the atherosclerotic plaque (ulceration, hemorrhage into the plaque, intimal flotation, mural thrombus, etc.).
4. Minor neurological deficit (NIHSS score ≤5).
5. The duration of development of stroke symptoms before colchicine taken is no more than 48 hours.
6. Confirmation of the presence of a focus of acute ischemia in the brain according to computed tomography or magnetic resonance imaging of the brain.

Exclusion Criteria:

1. The presence of risk factors and conditions that determine a different pathogenetic subtype of ischemic stroke (atrial fibrillation/flutter, ventricular aneurysm, ets.).
2. Hemorrhagic stroke
3. NIHSS score ≤5.
4. Hospitalization of the patient more than 48 hours from the onset of the disease.
5. Severe anemia, thrombocytopenia, leukopenia.
6. Course of an infectious/viral disease.
7. Concomitant treatment with moderate or strong CYP3A4 inhibitors (clarithromycin, erythromycin, telithromycin, other macrolide antibiotics, ketoconazole, itraconazole, voriconazole, ritonavir, atazanavir, indinavir, other HIV protease inhibitors, verapamil or pilitin disulfazole) inhibitors (cyclosporine) at randomization.
8. Concomitant severe degenerative disease of the nervous system.
9. Concomitant inflammatory or autoimmune disease.
10. Dementia, established mental illness.
11. History of malignancy, known hepatitis B or C, or HIV infection.
12. Swallowing impairment interfering with oral administration of the study drug.
13. Pregnancy or breastfeeding. Women of child-bearing potential who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the Investigator.
14. Participation in another clinical study with an investigational product at any time during the 30 days prior to randomization
15. Previous enrolment or randomization in the present study.
16. Decrease renal function with creatinine clearance < 30 ml/min.
17. Presence of contraindications to taking colchicine, acetylsalicylic acid and clopidogrel.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Colchicine Group; All patients in this arm will receive colchicine for 14 days in addition to standard medical care without clopidogrel (acetylsalicylic acid, lipid-lowering, antihypertensive, gastroprotective, hypoglycemic drugs if necessary, lifestyle recommendations, early rehabilitation activities).	Drug: Colchicine; Oral colchicine will be initiated with a dose of 0.5 mg per day during 14 days. Acetylsalicylic acid was used as an antiplatelet agent (300 mg on days 1 and continuing with 100 mg/day).
Active Comparator: Clopidogrel treatment group; All patients in this arm will receive standard treatment including clopidogrel.	Drug: Clopidogrel; Dual antiplatelet therapy includes ASA (300 mg on days 1 and continuing with 100 mg/day) and clopidogrel (300 mg on days 1 and continuing with 75 mg/day).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Any new stroke events	Incidence of any new ischemic stroke.	any time within 14 days
Neurological deterioration	Neurological deterioration, defined as an increase in The National Institutes of Health Stroke Scale (NIHSS) of 2 or more. The NIHSS provides a quantitative measure of stroke-related neurologic deficit. The higher the score, the more severe the neurological deficit.	any time within 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
New vascular events	Incidence of any new vascular events, including ischemic stroke, myocardial infarction and vascular death	any time within 14 days
Bleeding event	Bleeding event that is categorised as severe according to GUSTO (Global Utilization Of Streptokinase And Tpa For Occluded Arteries) bleeding criteria.	any time within 14 days
Positive functional outcome	A positive functional outcome within 14 days is determined if the Modified Rankin Score (mRS) improves to 0-1 and/or Rivermead Mobility Index (RMI) to 14 -15 points and/or Rehabilitation Routing Scale 0 -1 points. The mRS is a 6 point disability scale with possible scores ranging from 0 to 5. A separate category of 6 is usually added for patients who expire. The RMI includes fifteen mobility items. A maximum score of 15 is possible: higher scores indicate better mobility performance. The rehabilitation routing scale is needed by the doctor to understand whether the patient requires rehabilitation. The maximum number of points is 6. The more points the patient scores, the more severe his condition.	any time within 14 days

Collaborators and Investigators

• Sponsor: Mikhail Zykov

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2023
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: October 22, 2023
• First Submitted That Met QC Criteria: October 25, 2023
• First Posted (Actual): October 26, 2023

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 2, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: ischemic stroke; clopidogrel; low-dose colchicine
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Ischemia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Clopidogrel; Colchicine
• Other Study ID Numbers: COLCHIDA_1

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