SpecTRA; A Study of the Validation of Protein Biomarkers in Transient Ischemic Attack

Study Overview
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Brief Summary
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A clinical decision support rule/tool for classification of TIA/mimic that will enable rapid detection of ACVS in hyper-acute settings is being developed. Also under development is a multi-protein test using mass spectrometry (MS). This test will provide TIA results within an hour or two for a fraction of the price of neuroimaging. With guidance provided by this test at their disposal, physicians can inform patients whether they can go home safely or whether they need further testing. The right patients will receive the right treatment, reduce unwarranted imaging risks and costs, and reduce the burden of stroke. The Heart and Stroke Foundation will work to ensure that physicians, allied healthcare providers, the public and other stakeholders are aware of the outcomes and clinical impacts of this project. Further, work is being done to establish the mechanisms to develop a strong phenotype for TIA that includes medical imaging (MRI), cardiac monitoring, cognitive assessments, and surveillance of health outcomes for extended periods of time.

Detailed Description
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Patients who fulfill all inclusion and none of the exclusion criteria after giving informed consent will be enrolled in the Validation study. At enrollment, patients will receive a stroke nurse assessment in the Emergency Department (ED) and clinical information documented on an ACVS Assessment Form/SpecTRA Case Report Form. Patients will provide 6 mL of blood drawn into a purple-top EDTA tube that will be processed for proteomic analyses. These blood draws may or may not occur with the standard-of-care blood draw in the ED or stroke unit. Clinical orders include medical imaging (MRI +/- CT/CTA), cardiac monitoring (24hr +/- extended event monitoring). Patients will be referred by the attending ED physician to a stroke clinic for neurological consultation within 48 hours - 7 days, whereby diagnosis of (i) possible ACVS; (ii) definite ACVS or (iii) mimic will be made. At the stroke clinic a cognitive screening test will be administered either as part of usual clinical care by treating physicians, nurses, or a study coordinator. A re- assessment will be repeated at 90 days by phone. MRI will be reviewed initially for clinical interpretation at the neurological consultation for evidence of brain ischemia (DWI+) and later by neuro-radiologists for definitive diagnosis in study purposes. Final adjudication of TIA and aetiology will be done by the non-blinded principal investigators at each site based on diagnostic results plus 90-day and up to 2-year outcomes.

Official Title
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Spectrometry for TIA Rapid Assessment (SpecTRA) Project: Study 2-Validation of Clinical Features and Protein Biomarkers

Conditions
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TIA

Intervention / Treatment
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* Other: Non-Interventional Study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Time from the neurologic event to study enrollment is within <24 hours of first symptom onset. All planned diagnostic tests for stroke evaluation must be completed, including brain imaging (MRI) within 4-7 days; and 24-hour +/- extended cardiac monitoring. Be able to provide blood samples collected either under standard-of-care presentation in the ED or hospital-based stroke unit, or by a study-specific personnel outside of standard-of-care collections. Age ≥18 years. Written informed consent consistent with local regulations governing research in human subjects. Exclusion Criteria: Stroke severity exceeding 4 on the National Institutes of Health Stroke Severity scale (NIHSS <4). Contraindications to brain imaging. Non-English speaking, unless translator present. Isolated monocular blindness.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Mild ACVS-definite<br>Clinical diagnosis of ACVS, and imaging positive (either DWI+ or CT/CTA+). | Other: Non-Interventional Study<br>* This is a non-interventional study. However, several blood samples will be taken which would not be taken as part of standard of care.<br>|
| Mild ACVS-possible<br>Clinical diagnosis of ACVS, and DWI- and/or CTA-. | Other: Non-Interventional Study<br>* This is a non-interventional study. However, several blood samples will be taken which would not be taken as part of standard of care.<br>|
| Mimic<br>Clinical diagnosis of mimic and imaging negative. | Other: Non-Interventional Study<br>* This is a non-interventional study. However, several blood samples will be taken which would not be taken as part of standard of care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Validation of a Protein Classifier for the Diagnosis of TIA in the Emergency Department | Calculated score for distinguishing ACVS from Mimic based on previously locked-down formula involving 16 proteins measured using multiple reaction monitoring in blood samples taken within 24 hours from onset of symptoms. | 24 Hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Validation of a Clinical Classifier for the Diagnosis of TIA in the Emergency Department. | Calculated score for distinguishing ACVS from Mimic based on previously locked-down formula involving 50 clinical variables recorded on a standardized case report form. | 24 hours |