sCLEC-2 in Stroke Study

Study Overview
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Brief Summary
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Any platelet function tests have not been widely used in the clinical practice of acute cerebrovascular disease because of the concerns in repeatability, economic performance, and simplicity. Soluble C-type lectin-like receptor 2 (sCLEC-2) is a new marker for platelet activation, which can be easily measured by usual blood collection in routine clinical practice. We planned the sCLEC-2 in Stroke (CLECSTRO), which is a prospective cohort study in patients with acute ischemic stroke (AIS) and transient ischemic attack (TIA). We planned the sCLEC-2 in Stroke (CLECSTRO), which is a prospective cohort study in patients with acute ischemic stroke (AIS) and transient ischemic attack (TIA). The purpose of this study is to evaluate the clinical utility of sCLEC-2 as a biomarker for pathophysiology, differential diagnosis, prediction of prognosis, and monitoring of antiplatelet therapy in patients with AIS and TIA. Subjects are patients with AIS or TIA and control patients required for differentiation from AIS or TIA. The target population is 600 including the patients and the controls. The outcomes include difference in plasma sCLEC-2 level between patients with AIS or TIA and patient controls, correlation between sCLEC-2 after antithrombotic therapy and recurrence or worsening of stroke, difference in sCLEC-2/D-dimer ratio between non-cardioembolic and cardioembolic AIS or TIA, and correlation between baseline sCLEC-2 and outcome (modified Rankin scale score) after 3 months. sCLEC-2 could be a widely useful biomarker to contribute to the progress of precision medicine in clinical practice of AIS and TIA.

Detailed Description
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The study design is a multicenter prospective cohort study across Japan including 8 stroke centers. Patients are male or female at age of 20 years or older. The inclusion criteria are (1) AIS within 24 hours of onset and mRS 0 to 2, (2) TIA without MRI positivity within 7 days of onset, and (3) contemporary patients with neurological symptoms, who are required for differentiation from AIS or TIA (served as controls). The main exclusion criteria are (1) platelet or coagulation abnormalities, (2) hemorrhagic stroke, head or other trauma, post-surgery, and hemorrhagic tendency, (3) severe infection, (4) inappropriate patients who were judged by doctors, and (5) poor status of blood samples. The target population is 600 in total (AIS 400, TIA 100 and control 100). The plasma levels of sCLEC-2 are measured with D-dimer, soluble fibrin, and thrombin-antithrombin complex. sCLEC-2 is determined before starting treatment on admission. The modified Rankin Scale (mRS) and NIH Stroke Scale (NIHSS) are evaluated at registration as baseline data. sCLEC-2 as well as mRS and NIHSS are measured at Day 7 or at discharge. mRS is finally evaluated at 3 months. In the controls, plasma levels of sCLEC-2 and the baseline data are collected at entry. The sCLEC-2 levels are measured for the difference between patients with AIS or TIA and controls, correlation with severity of stroke, correlation with size of infarct, correlation with Age, Blood pressure, Clinical feature, Diabetes, Duration of symptoms (ABCD2) score in TIA, relationship between treatment effect and worsening or recurrence, difference in the sCLEC-2/D-dimer ratio between cardiogenic and non-cardiogenic etiologies, and difference between TOAST subtypes of ischemic stroke. The study protocol has been approved in each ethical committee at stroke centers.

Official Title
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Soluble C-type Lectin-Like Receptor 2 in Stroke Study

Conditions
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Acute Ischemic Stroke, Transient Ischemic Attack

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ischemic stroke within 24 hours of onset and modified Rankin Scale 0 to 2 Transient ischemic attack without MRI positivity within 7 days of onset Contemporary patients required for differentiation from ischemic stroke or transient ischemic attack Exclusion Criteria: Platelet or coagulation abnormalities Hemorrhagic stroke, head or other trauma, post-surgery, and hemorrhagic tendency Severe infection Inappropriate patients who were judged by doctors Poor status of blood samples

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Acute Ischemic Stroke<br>Ischemic stroke within 24 hours of onset and modified Rankin Scale 0 to 2 | |
| Transient ischemic attack<br>Transient ischemic attack without MRI positivity within 7 days of onset | |
| Patient Control<br>Contemporary patients with neurological symptoms required for differentiation from ischemic stroke or transient ischemic attack | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnosis of Acute Ischemic Stroke and TIA | The ischemic stroke group and TIA group will be compared with the control group to evaluate whether the sCLEC-2 level contributes to the improvement of the diagnostic accuracy of ischemic stroke and TIA. | On admission before treatment | 
| Evaluation of Antithrombotic Therapy | The post-treatment sCLEC-2 levels in patients with acute ischemic cerebrovascular disorders will be compared between patients without worsening/recurrence (effective treatment group) and those with worsening/recurrence during treatment (ineffective treatment group) to evaluate whether sCLEC-2 measurements contribute to the evaluation of the efficacy of antithrombotic therapy. | On 7+/-1 days after admission | 
| Comparison of sCLEC-2 /D-dimer ratio between cardiogenic and non-cardiogenic etiologies | The ischemic stroke group and TIA group will be classified into cardiogenic and non-cardiogenic etiologies based on the TOAST classification to evaluate whether the sCLEC-2/ D-dimer ratio contributes to the accuracy of subtype classification. | On admission before treatment | 
| Correlation of sCLEC-2 levels on admission with outcome of ischemic stroke and TIA at 3 months | The relationships between the sCLEC-2 levels on admission and outcomes at 3 months in the ischemic stroke and TIA groups will be evaluated. | On admission before treatment and 3 months after onset | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of sCLEC-2 levels on admission with severity of ischemic stroke or TIA | (1) Correlation with ischemic stroke severity (NIHSS), (2) correlation with size of infarct, (3) correlation with ABCD2 score in TIA will be evaluated. | On admission before treatment | 
| Difference of sCLEC-2 levels among TOAST subtypes of ischemic stroke | sCLEC-2 levels on admission among subtypes of ischemic stroke will be evaluated. | On admission before treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Platelet Activation, Soluble C-Type Lectin-Like Receptor 2