Optimization of sensitivity and specificity of a biomarker-based blood test (LVOCheck-Opti): A protocol for a multicenter prospective observational study of patients suspected of having a stroke

Maximilian Kaffes; Fulvio Bondi; Frederik Geisler; Ulrike Grittner; Lisa Haacke; Thomas Ihl; Maren Lorenz; Marc S Schehadat; Eugen Schwabauer; Matthias Wendt; Martina Zuber; Dorothee Kübler-Weller; Irina Lorenz-Meyer; Jean-Charles Sanchez; Joan Montaner; Heinrich J Audebert; Joachim E Weber

doi:10.3389/fneur.2023.1327348

Optimization of sensitivity and specificity of a biomarker-based blood test (LVOCheck-Opti): A protocol for a multicenter prospective observational study of patients suspected of having a stroke

Front Neurol. 2024 Feb 2:14:1327348. doi: 10.3389/fneur.2023.1327348. eCollection 2023.

Authors

Maximilian Kaffes^{1

2}, Fulvio Bondi¹, Frederik Geisler¹, Ulrike Grittner³, Lisa Haacke¹, Thomas Ihl^{1

2}, Maren Lorenz¹, Marc S Schehadat¹, Eugen Schwabauer⁴, Matthias Wendt⁵, Martina Zuber¹, Dorothee Kübler-Weller¹, Irina Lorenz-Meyer^{1

2}, Jean-Charles Sanchez⁶, Joan Montaner^{7

8

9}, Heinrich J Audebert^{1

2}, Joachim E Weber^#^{1

2

10

11}

Affiliations

¹ Department of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
² Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
³ Institute of Biometry and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁴ Department of Neurology, Vivantes Klinikum Neukölln, Berlin, Germany.
⁵ Department of Neurology, Unfallkrankenhaus Berlin, Berlin, Germany.
⁶ Department of Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
⁷ Institute de Biomedicine of Seville, IBiS/Hospital Universitario Virgen del Rocío/CSIC/University of Seville, Seville, Spain.
⁸ Department of Neurology, Hospital Universitario Virgen Macarena, Seville, Spain.
⁹ Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (VHIR), Barcelona, Spain.
¹⁰ Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹¹ German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.

^# Contributed equally.

Abstract

Introduction: Acute ischemic stroke (AIS) is a time-critical medical emergency. For patients with large-vessel occlusions (LVO), mechanical thrombectomy (MT) is the gold-standard treatment. Mobile Stroke Units (MSUs) provide on-site diagnostic capabilities via computed tomography (CT) and have been shown to improve functional outcomes in stroke patients, but are cost-efficient only in urban areas. Blood biomarkers have recently emerged as possible alternative to cerebral imaging for LVO diagnosis. Prehospital LVO diagnosis offers the potential to transport patients directly to centers that have MT treatment available. In this study, we assess the accuracy of combining two biomarkers, HFABP and NT-proBNP, with clinical indicators to detect LVO using ultra-early prehospital blood samples. The study was registered in the German Clinical Trials Register (DRKS-ID: DRKS00030399).

Methods and analysis: We plan a multicenter prospective observational study with 800 patients with suspected stroke enrolled within 24 h of symptom onset. Study participants will be recruited at three sites (MSUs) in Berlin, Germany. Blood-samples will be taken pre-hospitally at the scene and tested for HFABP and NT-proBNP levels. Additional clinical data and information on final diagnosis will be collected and documented in an electronic case report form (eCRF). Sensitivity and specificity of the combination will be calculated through iterative permutation-response calculations.

Discussion: This study aims to evaluate the diagnostic capabilities of a combination of the biomarkers HFABP and NT-proBNP in LVO prediction. In contrast to most other biomarker studies to date, by employing MSUs as study centers, ultra-early levels of biomarkers can be analyzed. Point-of-care LVO detection in suspected stroke could lead to faster treatment in both urban and rural settings and thus improve functional outcomes on a broader scale.

Clinical trial registration: Deutsches Register klinischer Studien https://drks.de/search/de/trial/DRKS00030399, DRKS00030399.

Keywords: biomarkers; cerebrovascular disease; emergency medicine; large vessel occlusion; mobile stroke units; prehospital emergency medicine; stroke; stroke mimics.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The project is supported by a Grant within the framework of the funding line Eurostars of the Eureka Association. The funding of the national sub-program is provided by the German Ministry for Education and Research (BMBF) (01QE2219C). The funding body is not involved in the design of the study, collection, analysis, and interpretation of data and in writing the manuscript.