Prospective collection of blood plasma samples to identify potential biomarkers for the prehospital stroke diagnosis (ProGrEss-Bio): study protocol for a multicenter prospective observational study

Abstract

Introduction: Intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are well-established, evidence-based, time-critical therapies that reduce morbidity and mortality in acute ischemic stroke (AIS) patients. The exclusion of intracerebral hemorrhage (ICH) is mandatory and has been performed by cerebral imaging to date. Mobile stroke units (MSUs) have been shown to improve functional outcomes by bringing cerebral imaging and IVT directly to the patient, but they have limited coverage. Blood biomarkers clearly distinguishing between AIS, ICH, and stroke mimics (SM) could provide an alternative to cerebral imaging if concentration changes are detectable in the hyperacute phase after stroke with high diagnostic accuracy. In this study, we will take blood samples in a prehospital setting to evaluate potential biomarkers. The study was registered in the German Clinical Trials Register (https://drks.de/search/de) with the identifier DRKS00023063.

Methods and analysis: We plan a prospective, observational study involving 300 patients with suspected stroke and symptom onset of ≤4.5 h before the collection of biomarkers. Study participants will be recruited from three sites in Berlin, Germany during MSU deployments. The focus of the study is the collection of blood samples from participants at the prehospital scene and from participants with AIS or ICH at a second-time point. All samples will be analyzed using targeted and untargeted analytical approaches. Study-related information about participants, including medical information and discharge diagnoses from the subsequent treating hospital, will be collected and documented in an electronic case report form (eCRF).

Discussion: This study will evaluate whether a single blood biomarker or a combination of biomarkers can distinguish patients with AIS and ICH from patients with stroke and SM in the early phase after symptom onset in the prehospital setting. In addition, the kinetics of blood biomarkers in AIS and ICH patients will be investigated. Our goal is to evaluate new ways to reliably diagnose stroke in the prehospital setting and thus accelerate the application of evidence-based therapies to stroke patients.

Keywords: biomarkers; cerebrovascular disease; emergency medicine; intracerebral hemorrhage; mobile stroke units; prehospital emergency medicine; stroke; stroke mimics.

Figure 1

Timeline. The timeline for the study from 2020 to 2023 is shown. The parts of the planning, administrative, and recruitment phases are depicted in the blue and green boxes. The analysis and publication phases are found in the red and yellow box. At the bottom of the graphic, the months and years are shown.

Figure 2

Conduction of the study. Procedure for including patients in the study is shown in chronological order from left to right. Boxes in red describe procedures during routine emergency treatment, and boxes in blue describe study-specific procedures. Blood samples will only be analyzed in cases where the patient or legal representative gives written informed consent. The blood sample is temporarily stored in the fire or rescue station and later in a biobank.

Figure 3

Handling of blood samples. The process of handling blood samples is described here. Details of the exact procedure can be found in the text “collection and processing of blood samples.”