Blood And Clot Thrombectomy Registry And Collaboration

This study represents the first time that clot and blood will be evaluated for the markers,
proteins, and cytokines listed in the protocol in human subjects undergoing thrombectomy for
emergent large vessel occlusion stroke. The study is an open, unblinded, clinical and
biologic registry to evaluate specific questions that are novel to understanding stroke in
the human condition. There is no therapeutic intervention involved in this study. The study
population will include up to 250 subjects enrolled at the University of Kentucky. The
primary endpoints of the study will be evaluation of specific proteins and leukocyte
populations in the human stroke clot and blood. Secondary endpoints include: Acid/Base
Balance: Evaluate pH of blood as a marker of acid/base balance in distal blood and proximal
blood, and correlate to interval of time between Last Known Normal and vessel recanalization;
Inpatient Biomarker; Protein, RNA, expression with Clinical Correlation.

Participants will be recruited from patients evaluated at University of Kentucky Chandler
Hospital for acute ischemic stroke. Participants with impaired capacity may be included as
the pathology to be studied (stroke) may impair their capacity.

The study events occur during the acute hospitalization for the subject's condition (acute
ischemic stroke).

Baseline (Day 0):

- Verify inclusion/exclusion criteria

- The patient or the Legally Authorized Representative (LAR) will be consented within 24
hours following the standard of care thrombectomy procedure.

- Medical history taken from medical record, participant and family to determine
eligibility based on inclusion/exclusion criteria (Standard of Care)

- Medication history (Standard of Care)

- Baseline physical examination to include vital signs (Standard of Care)

- Premorbid Modified Ranking Score (mRS)

- NIH Stroke Scale (Standard of Care)

- BMI (Body Mass Index) (Standard of Care)

- Obtain consent from the patient or Legally Authorized Representative (LAR)

- Cerebral angiogram with Endovascular Thrombectomy (Standard of Care)

- Study Specimen Collection as detailed below

Datapoints recorded will include the vessel location of the thrombus and time from Last Known
Normal to vessel recanalization, along with TICI (Thrombolysis in Cerebral Infarction) score.

Study Specimen Collection

1. Once a subject is determined by clinical staff to require thrombectomy, the thrombectomy
pager will be activated. Since potential subjects arrive at any time of day,
approximately 10 researchers will share call responsibilities. Once paged, the on-call
researcher will attend the thrombectomy procedure.

2. During the procedure, the neurointerventionalist will retain three samples, which are
removed during the thrombectomy procedure:

1. 1 cc of blood obtained from the microcatheter distal to the clot prior to thrombectomy
(see Figure 1) 2. The thrombus itself (normally discarded) 3. 5 cc of whole blood from
arterial guide catheter placed for the thrombectomy procedure. This represents a small amount
of the blood typically removed/lost during the suction aspiration performed at the guide
catheter. No separate venipuncture or arterial puncture will be necessary.

3. The on-call researcher will retrieve the blood samples and thrombus. The samples will be
collected, processed, and aliquoted by the researcher in a manner that will not delay or slow
the thrombectomy procedure. In addition to the samples, a separate researcher will enter
clinical data points on each subject into a REDCap (Research Electronic Data Capture)
database.

All endpoints listed below are standard of care for followup after thrombectomy.

The following clinical endpoints will be captured:

1. Date of Birth

2. Age at enrollment

3. Gender

4. Race/ethnicity

5. Height

6. Weight

7. Body Mass Index (BMI)

8. Premorbid Modified Rankin Score (mRS)

9. Location of the thrombus (e.g. M1 segment of middle cerebral artery) and source of the
thrombus (cardioembolic, intracranial stenosis, dissection, carotid occlusion,
infection, unknown).

10. Presence of tandem occlusion of the cervical artery proximal to the thrombus

11. Time from last known normal to thrombectomy completion (reopening of the vessel)

12. Thrombectomy success as rated by TICI score

13. NIH Stroke Scale prior to discharge

14. Modified Rankin Score (mRS): premorbid, discharge, 90 days (Standard of Care)

15. Mini-Montreal Cognitive Assessment (Mini-MoCA) or similar cognitive scale prior to
discharge (Standard of Care)

16. Medical comorbidities including hypertension, diabetes and hypercholesterolemia

17. Volume of infarct

18. Significant intracranial hemorrhage (defined as intracranial hemorrhage resulting in
4-point increase in NIH Stroke Scale or requiring surgical intervention)

19. Petechial hemorrhages.

20. Proximal (systemic) blood (pH - potential of hydrogen/acidity or basicity, pCO2 - carbon
dioxide partial pressure, pO2 - oxygen partial pressure, pHCO3 - bicarbonate partial
pressure, Na - sodium, K - potassium, Ca - Calcium)

21. Distal blood (pH, pCO2, pO2, pHCO3, Na, K, Ca)

22. Concomitant medications

Visit 1 (Within 48 hours)

MRI or CT is performed typically within 48 hours after thrombectomy as standard of care.
Radiographic endpoints that will be captured include:

1. Volume of infarct

2. Significant intracranial hemorrhage (defined as intracranial hemorrhage resulting in
4-point increase in NIH Stroke Scale or requiring surgical intervention)

3. Petechial hemorrhages.

For the purposes of this study, the central clinical endpoint will be time from Last Known
Normal to thrombectomy completion. The other data points will be captured for exploratory
purposes as correlations and associations with immune cell and cytokine levels may lead to
future studies beyond the scope of this grant.

Visit 2 (By and At Discharge) Data collection by Discharge: discharge destination; NIHSS;
Mini-Montreal Cognitive Assessment (MiniMoCA) or similar cognitive scale outcome variables.
(Standard of Care) Data collection at Discharge: mRS. (Standard of Care)

Visit 3 (90 Day Standard of Care Follow-Up) Data Collection: mRS and Montreal Cognitive
Assessment (MoCA). (Standard of Care)

Laboratory Procedures/Evaluations The three biospecimen samples described will be banked, and
may be used for pH analysis and electrolyte analysis, serum biomarker analysis, protein and
RNA levels, and leukocyte populations. These analyses may be correlated to clinical factors
including but not limited to age/gender, interval from Last Known Normal, location of the
thrombus, medical co-morbidities, and source of the thrombus.

Inclusion Criteria:

1. Patient or the Legally Authorized Representative (LAR) as recognized by the State of
Kentucky will be consented for the study within 24 hours post procedure.

2. Male or female, aged 18 years or older.

3. Suspected acute ischemic stroke based on clinical and radiographic evidence as
determined and documented by the Stroke Neurology team at University of Kentucky.

4. Participants must meet criteria for intra-arterial thrombectomy as determined and
documented by Interventional Radiology attending physician at University of Kentucky.

5. Participants must have an acute thromboembolus within an intracranial artery in the
anterior circulation (internal carotid, anterior cerebral, middle cerebral), which
undergoes mechanical thrombectomy.

6. Participants with impaired capacity may be included as the pathology to be studied
(stroke) may impair their capacity.

7. Participant must undergo thrombectomy procedure.

8. For females of reproductive potential: Negative urine pregnancy test at baseline.

Exclusion Criteria:

- There are no specific exclusion criteria outside of meeting the inclusion criteria.