Testing of Identification Markers for Stroke (TIME)

• ClinicalTrials.gov Identifier: NCT04292600
• Recruitment Status: Recruiting
• First Posted: March 3, 2020
• Last Update Posted: April 20, 2022
• Sponsor: POCKiT diagnostics Ltd
• Collaborators: University of Alabama at Birmingham; University of Mississippi Medical Center; Bay Area Consulting Telemedicine
• Information provided by (Responsible Party): POCKiT diagnostics Ltd

Study Description

Brief Summary:

Stroke is the third leading cause of death and the first cause of physical disability and dementia worldwide. Ischemic stroke caused by large vessel occlusion (LVO) is responsible for the vast majority of deaths and disabilities. A very effective and safe treatment, called mechanical thrombectomy (MT) is available for LVO patients. Nevertheless, no blood biomarkers able to identify LVO patients rapidly and to direct them to CT angiography and thrombectomy currently exist.

The TIME study is an observational prospective cohort study. All Patients referred to the emergency department or stroke unit with a suspected stroke as identified by paramedics, nurses or clinicians will be enrolled in the study. A panel of blood biomarkers will be analysed retrospectively via standard laboratory assays.

The main outcome of the TIME study will be the evaluation of the clinical diagnostic performance of a panel of blood biomarkers, in conjunction with clinical data, for the identification of large vessel occlusion ischemic stroke subtype. This study will allow the identification and evaluation of a final panel of biomarkers and will prompt the development of a test for LVO stroke diagnosis.

Condition or disease	Intervention/treatment
Stroke, Ischemic; Infarction, Middle Cerebral Artery; Infarction, Anterior Circulation, Brain	Diagnostic Test: POCKiT diagnostics' algorithm for LVO detection

Detailed Description:

Stroke affects 16M people in the world every year and 100K in the UK only. More than 30% of these patients die and 90% of survivors develop permanent disabilities as a consequence of stroke. There are two main types of stroke, ischemic and haemorrhagic. Ischemic stroke is caused by the formation of a clot in a blood vessel in the brain and represents ~85% of stroke patients. Haemorrhagic stroke is due to the rupture of a blood vessel in the brain, with consequent bleeding, and it represents ~15% of stroke patients. Both stroke subtypes cause brain damage and their symptoms are very similar. In addition to these two types of stroke, among the population of suspected stroke patients, there are the so-called stroke "mimics". These are conditions that appear with stroke-like symptoms (e.g. migraine, epilepsy, encephalitis, etc) but that are not stroke.

The deadliest stroke subtype is the one caused by occlusion of large vessels (LVO) in the brain. For these patients, a new treatment is available, called thrombectomy, which is a surgical procedure that mechanically removes the clot via a probe inserted at the level of the groin. Treatment of LVO patients with mechanical thrombectomy (MT) significantly increases the chances of survival, as well as decreases the extent of disability1. MT is only available in comprehensive stroke centres (CSC), and LVO patients have to be transported specifically to CSC in order to be treated and increase their chances of survival. MT has been proven a safe and effective treatment for LVO stroke until 24 hours from stroke onset2, indicating that detection of LVO strokes several hours after onset can significantly aid the stroke care pathway.

Current treatment of stroke patients is dependent on diagnosis via computerised tomography (CT) scan to the head. CT is highly accurate for detection of brain haemorrhages, but is very inaccurate for detection of ischemic stroke or LVOs3. In case of a negative result from CT, neurologists can order a further MRI scan to confirm ischemic stroke. If LVO is suspected, patients are transported to the nearest CSC where a further procedure, called CT angiography, is performed. The identification of LVO patients can be a very lengthy process that wastes precious time and makes stroke patients worse.

Fast diagnosis of stroke patients at their first point of admission (i.e. ambulance or emergency department) able to identify LVO patients could quickly direct patients to CSC and significantly improve treatment of the most dangerous stroke subtype. Several studies have investigated the ability of pre-hospital assessment scores based on patient symptoms to be performed in the ambulance4-7. Despite this, these scoring scales lack the accuracy required for triaging LVO patients with confidence. A more accurate diagnostic test able to complement these assessment scores and direct LVO patients to CSC and CT angiography is much needed8.

POCKiT DX are developing a novel device for stroke diagnosis that combines accurate blood biomarkers with ultra-rapid (<20 minutes) biomarker detection within a point-of-care device. The panel of blood biomarkers identified by POCKiT DX was tested in 80 patients with suspected stroke and accuracy of 83% (CI 95%: 74-92%), sensitivity of 86% (CI 95%: 74-98%), and specificity of 82% (CI 95%: 68-95%) was observed for LVO identification.

The aim of the TIME study is to evaluate the clinical diagnostic performance of a panel of blood biomarkers identified by POCKiT diagnostics in the identification of LVO stroke patients among the population of suspected stroke. Diagnostic performance of blood biomarkers alone, and in conjunction with clinical data, including pre-hospital stroke assessment scores (e.g. EMSA), will be evaluated. Results of this study will direct the development of a diagnostic test for directing stroke patients to the right treatment, more rapidly, improving patient outcomes.

Study Design

• Study Type: Observational
• Estimated Enrollment: 400 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Testing of Identification Markers for Stroke
• Actual Study Start Date: May 1, 2021
• Estimated Primary Completion Date: August 31, 2022
• Estimated Study Completion Date: August 31, 2022

Groups and Cohorts

Group/Cohort	Intervention/treatment
UMMC; Cohort recruited at University of Mississippi Medical Center	Diagnostic Test: POCKiT diagnostics' algorithm for LVO detection; Measurement of blood biomarkers and integration within Pockit diagnostics' algorithm for LVO detection
UAB; Cohort recruited at University of Alabama in Birmingham	Diagnostic Test: POCKiT diagnostics' algorithm for LVO detection; Measurement of blood biomarkers and integration within Pockit diagnostics' algorithm for LVO detection
BRH; Cohort recruited at Brandon Regional Hospital by Bay Area Consulting Telemedicine	Diagnostic Test: POCKiT diagnostics' algorithm for LVO detection; Measurement of blood biomarkers and integration within Pockit diagnostics' algorithm for LVO detection

Outcome Measures

Primary Outcome Measures :

1. Diagnostic accuracy measures for LVO detection vs non-LVO stroke activations [ Time Frame: 1 year ]
   Accuracy of pre-defined algorithm thresholds for LVO identification from the population of all suspected strokes (Ischemics non-LVO, Hemorrhagic, Mimics, TIAs)

Secondary Outcome Measures :

1. Optimisation of the cut-off points of the diagnostic algorithm for LVO detection [ Time Frame: 1 year ]
   Determine optimal cut-off points for diagnostic algorithm for detection of LVO vs non-LVO

Biospecimen Retention:   Samples Without DNA

Plasma and whole blood

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

Patients admitted to the ambulance and ED with suspected stroke will be recruited in the study. Patient population is expected to be composed of ~50% ischemic strokes (of which ~30-40% could have LVOs), ~40% stroke mimics, and ~10% haemorrhagic strokes.

Criteria

Inclusion Criteria:

• Referred to the ambulance or emergency department for suspected stroke.
• Time from stroke onset < 18 hours

Exclusion Criteria:

• Received thrombolytic therapy (e.g. tPA, Alteplase) before collection of blood;
• (Anticipated) inability to provide a blood sample;
• Time from stroke onset > 18 hours.
• At time of consent participating in a Clinical Trial Investigational Medicinal Product (CTIMP)

Contacts and Locations

Contacts

Contact: Edoardo gaude, PhD; +447548131982; edoardo.gaude@pockitdx.co.uk

Contact: Gonzalo Ladreda; 07548131982; gonzalo.ladreda@pockitdx.co.uk

Locations

United States, Alabama

University of Alabama in Birmingham Comprehensive Stroke Center; Not yet recruiting

Birmingham, Alabama, United States, 35294

Contact: Toby Gropen, MD 205-975-7571 tgropen@uabmc.edu

United States, Florida

BAC Telemed - Brandon Regional Hospital; Recruiting

Brandon, Florida, United States, 33511

Contact: Allauddin Khan, MD

United States, Mississippi

University of Mississippi Medical Center; Not yet recruiting

Jackson, Mississippi, United States, 39216

Contact: Shashank Shekar, MD 601-984-5514 sshekhar@umc.edu

Sponsors and Collaborators

POCKiT diagnostics Ltd

University of Alabama at Birmingham

University of Mississippi Medical Center

Bay Area Consulting Telemedicine

Investigators

• Principal Investigator: Shashank Shekar, MD; University of Mississippi Medical Center
• Principal Investigator: Toby Gropen, MD; University of Alabama in Birmingham Comprehensive Stroke Center
• Principal Investigator: Allauddin Khan, MD; BAC Telemed (Brandon Regional Hospital)

  Study Documents (Full-Text)

Documents provided by POCKiT diagnostics Ltd:

Study Protocol and Statistical Analysis Plan  [PDF] February 19, 2021

Informed Consent Form  [PDF] January 21, 2020

More Information

Publications:

Malhotra K, Gornbein J, Saver JL. Ischemic Strokes Due to Large-Vessel Occlusions Contribute Disproportionately to Stroke-Related Dependence and Death: A Review. Front Neurol. 2017 Nov 30;8:651. doi: 10.3389/fneur.2017.00651. eCollection 2017. Review.

Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, Yavagal DR, Ribo M, Cognard C, Hanel RA, Sila CA, Hassan AE, Millan M, Levy EI, Mitchell P, Chen M, English JD, Shah QA, Silver FL, Pereira VM, Mehta BP, Baxter BW, Abraham MG, Cardona P, Veznedaroglu E, Hellinger FR, Feng L, Kirmani JF, Lopes DK, Jankowitz BT, Frankel MR, Costalat V, Vora NA, Yoo AJ, Malik AM, Furlan AJ, Rubiera M, Aghaebrahim A, Olivot JM, Tekle WG, Shields R, Graves T, Lewis RJ, Smith WS, Liebeskind DS, Saver JL, Jovin TG; DAWN Trial Investigators. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. N Engl J Med. 2018 Jan 4;378(1):11-21. doi: 10.1056/NEJMoa1706442. Epub 2017 Nov 11.

Gropen TI, Boehme A, Martin-Schild S, Albright K, Samai A, Pishanidar S, Janjua N, Brandler ES, Levine SR. Derivation and Validation of the Emergency Medical Stroke Assessment and Comparison of Large Vessel Occlusion Scales. J Stroke Cerebrovasc Dis. 2018 Mar;27(3):806-815. doi: 10.1016/j.jstrokecerebrovasdis.2017.10.018. Epub 2017 Nov 22.

• Responsible Party: POCKiT diagnostics Ltd
• ClinicalTrials.gov Identifier: NCT04292600
• Other Study ID Numbers: POCKiT
• First Posted: March 3, 2020
• Last Update Posted: April 20, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

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

Keywords provided by POCKiT diagnostics Ltd:

large vessel occlusion strokes

Additional relevant MeSH terms:

Stroke; Ischemic Stroke; Infarction, Middle Cerebral Artery; Brain Infarction; Infarction; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Ischemia; Pathologic Processes; Necrosis; Cerebral Infarction; Brain Ischemia; Cerebral Arterial Diseases; Intracranial Arterial Diseases