基于生物标志物的血液检测（LVOCheck-Opti）敏感性和特异性的优化：一项针对疑似中风患者的多中心前瞻性观察性研究方案
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.
作者信息
Kaffes Maximilian, Bondi Fulvio, Geisler Frederik, Grittner Ulrike, Haacke Lisa, Ihl Thomas, Lorenz Maren, Schehadat Marc S, Schwabauer Eugen, Wendt Matthias, Zuber Martina, Kübler-Weller Dorothee, Lorenz-Meyer Irina, Sanchez Jean-Charles, Montaner Joan, Audebert Heinrich J, Weber Joachim E
机构信息
Department of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
出版信息
Front Neurol. 2024 Feb 2;14:1327348. doi: 10.3389/fneur.2023.1327348. eCollection 2023.
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.
引言
急性缺血性卒中（AIS）是一种对时间要求严格的医疗急症。对于大血管闭塞（LVO）患者，机械取栓术（MT）是金标准治疗方法。移动卒中单元（MSU）通过计算机断层扫描（CT）提供现场诊断能力，并且已被证明可改善卒中患者的功能结局，但仅在城市地区具有成本效益。血液生物标志物最近已成为用于LVO诊断的脑成像的可能替代方法。院前LVO诊断提供了将患者直接转运至具备MT治疗条件的中心的可能性。在本研究中，我们评估将两种生物标志物即心型脂肪酸结合蛋白（HFABP）和N末端脑钠肽前体（NT-proBNP）与临床指标相结合，使用超早期院前血样检测LVO的准确性。该研究已在德国临床试验注册中心注册（注册号：DRKS00030399）。
方法与分析
我们计划进行一项多中心前瞻性观察性研究，纳入800例在症状发作后24小时内疑似卒中的患者。研究参与者将在德国柏林的三个地点（移动卒中单元）招募。血样将在院前现场采集，并检测HFABP和NT-proBNP水平。将收集其他临床数据以及有关最终诊断的信息，并记录在电子病例报告表（eCRF）中。将通过迭代排列-反应计算来计算该组合的敏感性和特异性。
讨论
本研究旨在评估生物标志物HFABP和NT-proBNP的组合在LVO预测中的诊断能力。与迄今为止的大多数其他生物标志物研究不同，通过将移动卒中单元用作研究中心，可以分析生物标志物的超早期水平。在疑似卒中患者中进行即时LVO检测可能会在城市和农村地区都实现更快的治疗，从而在更广泛的范围内改善功能结局。
临床试验注册
德国临床试验注册中心https://drks.de/search/de/trial/DRKS00030399，注册号：DRKS00030399
Zotero 插件