Personalized Antiplatelet Secondary Stroke PRevenTion

Study Overview
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Brief Summary
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This is a descriptive study designed to evaluate the safety and feasibility of a precision medicine approach to antiplatelet selection for secondary stroke prevention.

Detailed Description
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Subjects meeting inclusion/exclusion criteria will be randomly assigned to: (1) the treatment group where antiplatelet medications will be selected using platelet function phenotype and/or key pharmacogene genotypes (2) the control group where participants will receive standard care for antiplatelet therapy (without knowledge of phenotype or genotype).

Official Title
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Personalized Antiplatelet Secondary Stroke PRevenTion (PASSPoRT). A Randomized, Phase II, Open Label, Trial in High Risk Transient Ischemic Attack (TIA) and Ischemic Stroke Survivors Age 18 Years and Older

Conditions
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TIA, Ischemic Stroke

Intervention / Treatment
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* Drug: tailored antiplatelet selection
* Drug: standard of care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide signed and dated informed consent form. Willing to comply with all study procedures and be available for the duration of the study. Meet criteria for a mild or moderate ischemic stroke or high-risk TIA Ability to randomize within 30 hours of stroke symptom onset/last seen normal time Exclusion Criteria: Evidence of new or prior non-traumatic intracerebral hemorrhage, subarachnoid hemorrhage, or subdural hemorrhage on initial head CT Evidence of a central nervous system tumor, abscess, intracranial aneurysm or vascular/structural malformation, or any neuro-inflammatory, neuro-infectious, or neurodegenerative disorder on neuroimaging or exam that could confound a participant's functional outcome Isolated or pure sensory symptoms (e.g., numbness), visual changes, or dizziness/vertigo without evidence of acute ischemic stroke on baseline head CT or MRI. Qualifying ischemic event is believed to be iatrogenic or procedure related Required to take a specific antiplatelet medication for an indication other than ischemic stroke during the study period that would prevent the investigator from following the study algorithm Etiology of qualifying ischemic event is known to be cardioembolic High likelihood that anticoagulation will be needed during the study period. High likelihood that carotid endarterectomy or carotid stenting will occur during the period of the study. Pre-stroke modified Rankin scale (mRS) score ≥ 3 Evidence of frailty Contraindication to aspirin, clopidogrel, Aggrenox®, or ticagrelor Known allergy or hypersensitivity that would prevent the investigator from following the study algorithm Any history of moderate to severe drug-induced adverse events Renal insufficiency or history of kidney transplant Hepatic impairment, international normalized ratio (INR) > 1.5, physical manifestations of liver disease, or history of liver transplant Class II, III, or IV New York Heart Association (NYHA) functional heart failure Any history of bradycardia without pacemaker placement Active obstructive lung disease Any active hematologic disorder Active bleeding diathesis Any systemic hemorrhage or GI bleed in the 3 months prior to the qualifying stroke Active peptic ulcer disease Women who self-report that they are pregnant or breastfeeding Active alcohol or substance abuse or dependence Inability or failure to provide informed consent. Inability of the patient to adhere to study procedures and/or follow-up, in the opinion of the investigative team Inability to swallow oral medications Not willing or able to discontinue prohibited concomitant medications Ongoing participation in another non-observational clinical study Life expectancy < 1 year, in the opinion of the investigative team

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>Intervention group | Drug: tailored antiplatelet selection<br>* antiplatelet selection guided by platelet function phenotype and/or key pharmacogene genotypes<br>|
| Active Comparator: Control Group<br>Standard of Care group | Drug: standard of care<br>* antiplatelet selection using standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility - Recruitment and Platelet Reactivity | ability to recruit participants and achieve platelet reactivity target using platelet function assays | 90 days | 
| Safety - Bleeding Complications | bleeding questionnaire | 90 days | 
| Safety - Bleeding Complications | bleeding questionnaire | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient-centered Outcomes - Satisfaction | consumer assessment of healthcare providers and systems | 90 days | 
| Patient-centered Outcomes - Satisfaction | consumer assessment of healthcare providers and systems | 1 year |