Identifying patients with cerebral infarction within the time window compatible with reperfusion therapy, diagnostic performance of glutathione S-transferase-π (GST-π) and peroxiredoxin 1 (PRDX1): exploratory prospective multicentre study FLAG-1 protocol

Introduction Plasma biomarkers may be useful in diagnosing acute cerebral infarction requiring urgent reperfusion, but their performance remains to be confirmed. If confirmed, these molecules could be used to develop rapid and reliable decentralised measurement methods, making it possible to initiat...

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Main Authors: Nicolas Girerd, Arif Karakus, Jean-Charles Sanchez, Sophie Marchal, Anne Aubertin, Sanae Bouali, Kevin Duarte, Sandrine Reymond
Format: Article
Language:English
Published: BMJ Publishing Group 2021-08-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/11/8/e046167.full
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author Nicolas Girerd
Arif Karakus
Jean-Charles Sanchez
Sophie Marchal
Anne Aubertin
Sanae Bouali
Kevin Duarte
Sandrine Reymond
author_facet Nicolas Girerd
Arif Karakus
Jean-Charles Sanchez
Sophie Marchal
Anne Aubertin
Sanae Bouali
Kevin Duarte
Sandrine Reymond
author_sort Nicolas Girerd
collection DOAJ
description Introduction Plasma biomarkers may be useful in diagnosing acute cerebral infarction requiring urgent reperfusion, but their performance remains to be confirmed. If confirmed, these molecules could be used to develop rapid and reliable decentralised measurement methods, making it possible to initiate reperfusion therapy before hospital admission. The FLAG-1 large prospective study will constitute a plasma bank to assess the diagnostic performance of two biomarkers: glutathione S-transferase-π and peroxiredoxin 1. These molecules are involved in the oxidative stress response and could identify cerebral infarction within a therapeutic window of less than 4.5 hours following the onset of symptoms. Secondary objectives include assessing performance of these biomarkers within 3-hour and 6-hour windows; identifying additional biomarkers diagnosing cerebral infarction and significant criteria guiding therapeutic decisions: ischaemic features of stroke, presence of diffusion/fluid-attenuated inversion recovery mismatch, volume of cerebral infarction and penumbra on cerebral MRI.Methods and analysis The exploratory, prospective, multicentre FLAG-1 Study will include 945 patients with acute stroke symptoms (onset ≤12 hours, National Institute of Health Stroke Scale score ≥3). Each patient’s 25 mL blood sample will be associated with cerebral MRI data. Two patient groups will be defined based on the time of blood collection (before and after 4.5 hours following onset). Receiver operating characteristic analysis will determine the diagnostic performance of each biomarker, alone or in combination, for the identification of cerebral infarction <4.5 hours.Ethics and dissemination The protocol has been approved by an independent ethics committee. Biological samples are retained in line with best practices and procedures, in accordance with French legislation. Anonymised data and cerebral imaging records are stored using electronic case report forms and a secure server, respectively, registered with the French Data Protection Authority (Commission Nationale de l'Informatique et des Libertés (CNIL)). Results will be disseminated through scientific meetings and publication in peer-reviewed medical journals.Trial registration number ClinicalTrials.gov Registry (NCT03364296).
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spelling doaj-art-45ea611dfc784f92b3d6d6b9ddea1f8b2025-08-20T02:25:45ZengBMJ Publishing GroupBMJ Open2044-60552021-08-0111810.1136/bmjopen-2020-046167Identifying patients with cerebral infarction within the time window compatible with reperfusion therapy, diagnostic performance of glutathione S-transferase-π (GST-π) and peroxiredoxin 1 (PRDX1): exploratory prospective multicentre study FLAG-1 protocolNicolas Girerd0Arif Karakus1Jean-Charles Sanchez2Sophie Marchal3Anne Aubertin4Sanae Bouali5Kevin Duarte6Sandrine Reymond7Université de Lorraine, Inserm, Centre d’Investigation Clinique Plurithématique 1433, U1116, CHRU de Nancy, F-CRIN INI-CRCT, Nancy, FranceDepartment of Neurology, Stroke Unit, University Hospital Centre Nancy, 54035 Nancy, FranceDepartment of Specialities of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, SwitzerlandStroke Unit, Verdun Hospital Centre, 55100 Verdun, FranceStroke Unit, Hospital Centre Troyes, CS 20718, 10003 Troyes, FrancePlurithematic Clinical Investigation Center, CIC-P 1433, INSERM U1116, University Hospital Centre Nancy, 54500 Vandoeuvre-lès-Nancy, FranceCentre d`Investigations Cliniques-Plurithématique 1433 (CIC-P), INI-CRCT-Cardiovascular and Renal Clinical Trialists, CHRU de Nancy, Nancy, FranceDepartment of Human Protein Sciences, University of Geneva Medical Centre, 1206 Geneva, SwitzerlandIntroduction Plasma biomarkers may be useful in diagnosing acute cerebral infarction requiring urgent reperfusion, but their performance remains to be confirmed. If confirmed, these molecules could be used to develop rapid and reliable decentralised measurement methods, making it possible to initiate reperfusion therapy before hospital admission. The FLAG-1 large prospective study will constitute a plasma bank to assess the diagnostic performance of two biomarkers: glutathione S-transferase-π and peroxiredoxin 1. These molecules are involved in the oxidative stress response and could identify cerebral infarction within a therapeutic window of less than 4.5 hours following the onset of symptoms. Secondary objectives include assessing performance of these biomarkers within 3-hour and 6-hour windows; identifying additional biomarkers diagnosing cerebral infarction and significant criteria guiding therapeutic decisions: ischaemic features of stroke, presence of diffusion/fluid-attenuated inversion recovery mismatch, volume of cerebral infarction and penumbra on cerebral MRI.Methods and analysis The exploratory, prospective, multicentre FLAG-1 Study will include 945 patients with acute stroke symptoms (onset ≤12 hours, National Institute of Health Stroke Scale score ≥3). Each patient’s 25 mL blood sample will be associated with cerebral MRI data. Two patient groups will be defined based on the time of blood collection (before and after 4.5 hours following onset). Receiver operating characteristic analysis will determine the diagnostic performance of each biomarker, alone or in combination, for the identification of cerebral infarction <4.5 hours.Ethics and dissemination The protocol has been approved by an independent ethics committee. Biological samples are retained in line with best practices and procedures, in accordance with French legislation. Anonymised data and cerebral imaging records are stored using electronic case report forms and a secure server, respectively, registered with the French Data Protection Authority (Commission Nationale de l'Informatique et des Libertés (CNIL)). Results will be disseminated through scientific meetings and publication in peer-reviewed medical journals.Trial registration number ClinicalTrials.gov Registry (NCT03364296).https://bmjopen.bmj.com/content/11/8/e046167.full
spellingShingle Nicolas Girerd
Arif Karakus
Jean-Charles Sanchez
Sophie Marchal
Anne Aubertin
Sanae Bouali
Kevin Duarte
Sandrine Reymond
Identifying patients with cerebral infarction within the time window compatible with reperfusion therapy, diagnostic performance of glutathione S-transferase-π (GST-π) and peroxiredoxin 1 (PRDX1): exploratory prospective multicentre study FLAG-1 protocol
BMJ Open
title Identifying patients with cerebral infarction within the time window compatible with reperfusion therapy, diagnostic performance of glutathione S-transferase-π (GST-π) and peroxiredoxin 1 (PRDX1): exploratory prospective multicentre study FLAG-1 protocol
title_full Identifying patients with cerebral infarction within the time window compatible with reperfusion therapy, diagnostic performance of glutathione S-transferase-π (GST-π) and peroxiredoxin 1 (PRDX1): exploratory prospective multicentre study FLAG-1 protocol
title_fullStr Identifying patients with cerebral infarction within the time window compatible with reperfusion therapy, diagnostic performance of glutathione S-transferase-π (GST-π) and peroxiredoxin 1 (PRDX1): exploratory prospective multicentre study FLAG-1 protocol
title_full_unstemmed Identifying patients with cerebral infarction within the time window compatible with reperfusion therapy, diagnostic performance of glutathione S-transferase-π (GST-π) and peroxiredoxin 1 (PRDX1): exploratory prospective multicentre study FLAG-1 protocol
title_short Identifying patients with cerebral infarction within the time window compatible with reperfusion therapy, diagnostic performance of glutathione S-transferase-π (GST-π) and peroxiredoxin 1 (PRDX1): exploratory prospective multicentre study FLAG-1 protocol
title_sort identifying patients with cerebral infarction within the time window compatible with reperfusion therapy diagnostic performance of glutathione s transferase π gst π and peroxiredoxin 1 prdx1 exploratory prospective multicentre study flag 1 protocol
url https://bmjopen.bmj.com/content/11/8/e046167.full
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