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

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

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.

Study Overview

• Status: Completed
• Conditions: TIA
• Intervention / Treatment: Other: Non-Interventional Study

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 1150

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Centre
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 1J8
      • Vancouver Island Health Authority

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population includes individuals presenting to the hospital ED or stroke clinic with symptoms suggesting mild ACVS who would be referred to the outpatient stroke clinic. Patients will be recruited primarily from emergency department settings or hospital-based stroke units.

Description

Inclusion Criteria:

1. Time from the neurologic event to study enrollment is within <24 hours of first symptom onset.
2. All planned diagnostic tests for stroke evaluation must be completed, including brain imaging (MRI) within 4-7 days; and 24-hour +/- extended cardiac monitoring.
3. 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.
4. Age ≥18 years.
5. Written informed consent consistent with local regulations governing research in human subjects.

Exclusion Criteria:

1. Stroke severity exceeding 4 on the National Institutes of Health Stroke Severity scale (NIHSS <4).
2. Contraindications to brain imaging.
3. Non-English speaking, unless translator present.
4. Isolated monocular blindness.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Andrew Penn
• Collaborators: Heart and Stroke Foundation of Canada; Genome British Columbia; Vancouver Island Health Authority; British Columbia Centre for Disease Control; Bruker Daltonics; Genome Canada; Genome Alberta; LifeLabs; Stroke Services BC
• Investigators: Principal Investigator: Andrew M Penn, M.D., Vancouver Island Health Authority; Principal Investigator: Christoph Borchers, P.hD, UVic-Genome BC Proteomics Centre

Publications and helpful links

General Publications

• Penn AM, Croteau NS, Votova K, Sedgwick C, Balshaw RF, Coutts SB, Penn M, Blackwood K, Bibok MB, Saly V, Hegedus J, Yu AYX, Zerna C, Klourfeld E, Lesperance ML. Systolic blood pressure as a predictor of transient ischemic attack/minor stroke in emergency department patients under age 80: a prospective cohort study. BMC Neurol. 2019 Oct 25;19(1):251. doi: 10.1186/s12883-019-1466-4.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2015
• Primary Completion (ACTUAL): March 31, 2017
• Study Completion (ACTUAL): March 31, 2017

Study Registration Dates

• First Submitted: February 28, 2017
• First Submitted That Met QC Criteria: February 28, 2017
• First Posted (ACTUAL): March 3, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 18, 2017
• Last Update Submitted That Met QC Criteria: August 15, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: Island Health CREB C2015-042

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