Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC)

• ClinicalTrials.gov Identifier: NCT03153683
• Recruitment Status: Recruiting
• First Posted: May 15, 2017
• Last Update Posted: April 28, 2021
• Sponsor: Justin Fraser
• Collaborator: University of Kentucky
• Information provided by (Responsible Party): Justin Fraser, University of Kentucky

Study Description

Brief Summary:

This is a prospective open enrollment registry to evaluate arterial blood and thrombus removed during the standard thrombectomy procedure, which will then be used for the purposes of identifying biological markers, inflammatory cell infiltrates, and biological states in large vessel occlusive stroke in the human condition. The primary objectives are to evaluate the feasibility of obtaining distal clot blood during thrombectomy; develop a group of biosamples (blood and clots) to evaluate novel proteins, cell types, and cytokines in acute ischemic stroke in the human condition, and evaluate specific biomarkers, proteins, and leukocyte populations in stroke in the human condition. The study population will include up to 250 subjects. Male and female participants 18 years of age and older will be enrolled. Participants must have had a suspected acute ischemic stroke based on clinical and radiographic evidence as determined and documented by the Stroke Neurology team at University of Kentucky. There is no therapeutic intervention involved in this study.

This is the first study to our knowledge that will utilize thrombectomy technique to collect focal blood samples and the clot related brain infarction. This proposal will provide preliminary data needed to understand relationships between the local inflammatory cascade and clinical variables such as age, gender, time from symptoms to thrombectomy, and stroke imaging results. Characterizing these relationships is vital in the formulation of related therapeutics. Issues of gender-differences, age-based variations, and co-morbidities all engender heterogeneity, which plague translation of stroke research from animal to human. By starting with the human condition, the investigators aim to minimize this loss in translation. Overall, this study will have a great impact on our knowledge of stroke pathology. In essence, this could fundamentally change not only how the investigators develop treatment strategies for the stroke patient population but allow us to individualize the treatment dependent on time after stroke, age, sex, and co-morbidities. Molecular techniques that are impractical when delivered systemically could be delivered locally to impede the early inflammation.

Condition or disease	Intervention/treatment
Acute Ischemic Stroke	Other: Registry

Detailed Description:

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.

Study Design

• Study Type: Observational
• Estimated Enrollment: 250 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC)
• Actual Study Start Date: May 11, 2017
• Estimated Primary Completion Date: March 1, 2024
• Estimated Study Completion Date: March 1, 2024

Groups and Cohorts

Group/Cohort	Intervention/treatment
Acute Ischemic Stroke Patients; This is a registry. No above standard of care interventions will take place. Participants must have an acute thromboembolus within an intracranial artery in the anterior circulation (internal carotid, anterior cerebral, middle cerebral), which undergoes mechanical thrombectomy per standard of care.	Other: Registry; Collect standard of care clot and arterial blood during standard of care thrombectomy from Acute Ischemic Stroke Patients for lab analysis.

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: Assessed over the course of the study, an estimated 3 years. ]
   A small amount of blood (from the two specimens) will be sent for blood gas analysis to evaluate the pH, pO2, pCO2, pHCO3 potassium, sodium, and calcium concentrations.

Biospecimen Retention:   Samples With DNA

1 cc of arterial distal blood, thrombus, and 5 cc of peripheral arterial blood

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Sampling Method: Non-Probability Sample

Study Population

The study population will include up to 250 subjects. Male and female participants 18 years of age and older will be enrolled. Participants must have had a suspected acute ischemic stroke based on clinical and radiographic evidence as determined and documented by the Stroke Neurology team at University of Kentucky.

Criteria

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.

Contacts and Locations

Contacts

Contact: Mary F Faulkner, BA; 859-218-5006; mffaul2@uky.edu

Contact: Justin F Fraser, MD; 859-323-0616; jfr235@uky.edu

Locations

United States, Kentucky

University of Kentucky Deparment of Neurosurgery, UK Chandler Hospital; Recruiting

Lexington, Kentucky, United States, 40536-0298

Sponsors and Collaborators

Justin Fraser

University of Kentucky

Investigators

• Principal Investigator: Justin F Fraser, MD; University of Kentucky

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Maglinger B, McLouth CJ, Frank JA, Rupareliya C, Sands M, Sheikhi L, Pahwa S, Dornbos D 3rd, Harp JP, Trout AL, Turchan-Cholewo J, Stowe AM, Fraser JF, Pennypacker KR. Influence of BMI on adenosine deaminase and stroke outcomes in mechanical thrombectomy subjects. Brain Behav Immun Health. 2022 Jan 26;20:100422. doi: 10.1016/j.bbih.2022.100422. eCollection 2022 Mar.

Spears RC, McLouth CJ, Pennypacker KR, Frank JA, Maglinger B, Martha S, Trout AL, Roberts J, Stowe AM, Sheikhi L, Pahwa S, Fraser JF. Alterations in Local Peri-Infarct Blood Gases in Stroke Patients Undergoing Thrombectomy. World Neurosurg. 2021 Oct 30. pii: S1878-8750(21)01682-X. doi: 10.1016/j.wneu.2021.10.171. [Epub ahead of print]

Sands M, Frank JA, Maglinger B, McLouth CJ, Trout AL, Turchan-Cholewo J, Stowe AM, Fraser JF, Pennypacker KR. Antimicrobial protein REG3A and signaling networks are predictive of stroke outcomes. J Neurochem. 2022 Jan;160(1):100-112. doi: 10.1111/jnc.15520. Epub 2021 Oct 14.

Shaw BC, Maglinger GB, Ujas T, Rupareliya C, Fraser JF, Grupke S, Kesler M, Gelderblom M, Pennypacker KR, Turchan-Cholewo J, Stowe AM. Isolation and identification of leukocyte populations in intracranial blood collected during mechanical thrombectomy. J Cereb Blood Flow Metab. 2022 Feb;42(2):280-291. doi: 10.1177/0271678X211028496. Epub 2021 Jul 11.

Armstrong GK, Frank JA, McLouth CJ, Stowe A, Roberts JM, Trout AL, Fraser JF, Pennypacker K. Commentary: Use of BACTRAC Proteomic Database-Uromodulin Protein Expression During Ischemic Stroke. J Exp Neurol. 2021 Mar;2(1):29-33.

Maglinger B, Frank JA, McLouth CJ, Trout AL, Roberts JM, Grupke S, Turchan-Cholewo J, Stowe AM, Fraser JF, Pennypacker KR. Proteomic changes in intracranial blood during human ischemic stroke. J Neurointerv Surg. 2021 Apr;13(4):395-399. doi: 10.1136/neurintsurg-2020-016118. Epub 2020 Jul 8.

Martha SR, Cheng Q, Fraser JF, Gong L, Collier LA, Davis SM, Lukins D, Alhajeri A, Grupke S, Pennypacker KR. Expression of Cytokines and Chemokines as Predictors of Stroke Outcomes in Acute Ischemic Stroke. Front Neurol. 2020 Jan 15;10:1391. doi: 10.3389/fneur.2019.01391. eCollection 2019.

Fraser JF, Collier LA, Gorman AA, Martha SR, Salmeron KE, Trout AL, Edwards DN, Davis SM, Lukins DE, Alhajeri A, Grupke S, Roberts JM, Bix GJ, Pennypacker KR. The Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC) protocol: novel method for evaluating human stroke. J Neurointerv Surg. 2019 Mar;11(3):265-270. doi: 10.1136/neurintsurg-2018-014118. Epub 2018 Jul 31.

• Responsible Party: Justin Fraser, Asst Professor of Cerebrovascular, Endovascular, & Skull Base Surgery; Director, Cerebrovascular Surgery; Depts of Neurological Surgery, Neurology, Radiology, and Anatomy & Neurobiology; Center for Advanced Translational Stroke Science; Univ of KY, University of Kentucky
• ClinicalTrials.gov Identifier: NCT03153683
• Other Study ID Numbers: BACTRAC-17-0019-F1V
• First Posted: May 15, 2017
• Last Update Posted: April 28, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: To be announced.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Justin Fraser, University of Kentucky:

Acute; Ischemic; Stroke; Biomarkers; Proteins; Leukocyte; Inflammatory Cells; Acid/Base Balance

Additional relevant MeSH terms:

Ischemic Stroke; Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases