Biological Dating of Cerebral Ischemia With GST-π/PRDX1 to Detect Patients With Stroke of Unknown Onset Within the Therapeutic Window of Thrombolysis (FLAG1)

Biological Dating of Cerebral Ischemia With Glutathion S-Transferase-π (GST-π) and Peroxyredoxin 1 (PRDX1) to Detect Patients With Stroke of Unknown Onset Within the Therapeutic Window of Thrombolysis

The FLAG1 study will assess the diagnostic performance of biomarkers Glutathion S-Transferase-π (GST-π) and Peroxyredoxin 1 (PRDX1) to identify cerebral infarction of less than 4,5 hours in a population of patients with neurological deficiency of less than 12 hours.

Study Overview

• Status: Recruiting
• Conditions: Stroke, Acute
• Intervention / Treatment: Other: Blood Samples

• Study Type: Interventional
• Enrollment (Estimated): 930
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sébastien RICHARD, MD; Phone Number: 0033383852256; Email: s.richard@chru-nancy.fr
• Study Contact Backup: Name: Sanae BOUALI, PhD; Email: s.bouali@chru-nancy.fr

Study Locations

• France
  • Bar-le-Duc, France, 55000
    • Recruiting
    • Centre Hospitalier de Bar-Le-Duc
    • Contact: Karine LAVANDIER, MD
    • Principal Investigator: Karine LAVANDIER, MD
  • Nancy, France, 54000
    • Recruiting
    • Hôpital Central
    • Contact: Sébastien RICHARD, Professor; Email: s.richard@chru-nancy.fr
    • Principal Investigator: Sébastien RICHARD, Professor
  • Paris, France, 75019
    • Recruiting
    • Fondation Adolphe de Rothschild
    • Contact: Candice SABBEN, MD
    • Principal Investigator: Candice SABBEN, MD
  • Troyes, France, 10003
    • Recruiting
    • Centre Hospitalier de Troyes
    • Contact: Anne AUBERTIN, MD
    • Principal Investigator: Anne AUBERTIN, MD
  • Verdun, France, 55300
    • Recruiting
    • Centre Hospitalier de Verdun
    • Contact: Sophie Marchal, MD
    • Principal Investigator: Sophie Marchal, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients over 18 years old
• Patients with symptoms consistent with stroke and a National Institute of Health Stroke Score ≥3 at the inclusion time

• Time symptom onset ≤ 24 hours at inclusion:

  • For patients with time of symptom onset is <4.5h at inclusion, the time of symptom onset has to be precisely known, with a margin of error not exceeding 30 minutes (through patient or witness interview)
  • For patients with time of symptom onset is >4.5h at inclusion, knowledge of precise time of symptom onset is not required. For these patients, to ensure onset-to-inclusion time is between 4.5 and 24 hours at inclusion:
• last time patient presented no deficit must be less than 24 hours,
• symptoms must have been first recognized more than 4.5 hours before blood draw.
• Possibility to perform MRI within the 30 minutes following blood collection
• Person affiliated to or beneficiary of a social security plan

Exclusion Criteria:

• Persons referred in articles L.1121-5, L.1121-7, L.1121-8 and L.1122-2 of the French Public Health Code: Pregnant, parturient or breastfeeding woman ; Minor person (non-emancipated) ; Adult person under legal protection (any form of public guardianship) ; Adult person incapable of giving consent and not under legal protection.
• Persons deprived of liberty for judicial or administrative decision.
• Persons subject to psychiatric care under articles L.3212-1 and L.3213-1 of the French Public Health Code.
• Known cancer in progression.
• Known cirrhosis.
• Myocardial Infarctions, stroke, Subarachnoid hemorrhage or intracranial injury within 3 months prior to enrolment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patients hospitalized for stroke	Other: Blood Samples; Blood sample retrieved for biological assessment and biobanking

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time (<4.5 hours) between cerebral infarction onset and blood sample for determination for GST-π level	ROC analysis will be performed to determine diagnostic performance (sensitivity, specificity) of GST-π plasmatic level to identify cerebral infarction of less than 4.5 hours.	Population will be dichotomized in patients with blood sample performed <4.5 hours and >4.5 hours after stroke onset to determine diagnostic performance of GST-π plasmatic level to identify cerebral infarction of less than 4.5 hours.
Time (<4.5 hours) between cerebral infarction onset and blood sample for determination for PRDX1 levels	ROC analysis will be performed to determine diagnostic performance (sensitivity, specificity) of PRDX1 plasmatic level to identify cerebral infarction of less than 4.5 hours.	Population will be dichotomized in patients with blood sample performed <4.5 hours and >4.5 hours after stroke onset to determine diagnostic performance of PRDX1 plasmatic level to identify cerebral infarction of less than 4.5 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time (<3 and 6 hours) between cerebral infarction onset and blood sample for determination for GST-π and PRDX1 levels	ROC analysis will be performed to determine diagnostic performance (sensitivity, specificity) of GST-π and PRDX1 plasmatic levels to identify cerebral infarction of less than 3 and 6 hours.	Patient will be dichotomized with blood sample performed <3 and >3 hours, and <6 and >6 hours after stoke onset to determine diagnostic performance of GST-π and PRDX1 plasmatic levels to identify cerebral infarction of less than 3 hours, and < 6 hours
Blood sample for determination for GST-π and PRDX1 levels Cerebral MRI for Diffusion/Perfusion mismatch defining ischemic penumbra	ROC analysis will be performed to determine diagnostic performance (sensitivity, specificity) of GST-π and PRDX1 plasmatic levels to identify and quantify ischemic penumbra.	The patient will be included within the 12 hours following stroke onset with one blood sample (defining GST-π and PRDX1 plasmatic levels), and cerebral MRI (defining Diffusion/Perfusion mismatch or penumbra) within the 30 minutes following blood sample.
Blood sample for determination for GST-π and PRDX1 levels Cerebral MRI for diagnosis of stroke vs. other diagnosis	ROC analysis will be performed to determine diagnostic performance (sensitivity, specificity) of GST-π and PRDX1 plasmatic levels to identify stroke.	The patient will be included within the 12 hours following neurological deficiency onset with one blood sample (defining GST-π and PRDX1 plasmatic levels), and cerebral MRI (defining stroke) within the 30 minutes following blood sample.
Blood sample for determination for GST-π and PRDX1 levels Cerebral MRI for diagnosis of ischemic stroke vs. other diagnosis	ROC analysis will be performed to determine diagnostic performance (sensitivity, specificity) of GST-π and PRDX1 plasmatic levels to identify cerebral infarction.	The patient will be included within the 12 hours following neurological deficiency onset with one blood sample (defining GST-π and PRDX1 plasmatic levels), and cerebral MRI (defining stroke) within the 30 minutes following blood sample.
Blood sample for determination for GST-π and PRDX1 levels Cerebral MRI for diagnosis of hemorrhagic stroke vs. other diagnosis	ROC analysis will be performed to determine diagnostic performance (sensitivity, specificity) of GST-π and PRDX1 plasmatic levels to identify hemorrhagic stroke.	The patient will be included within the 12 hours following neurological deficiency onset with one blood sample (defining GST-π and PRDX1 plasmatic levels), and cerebral MRI (defining stroke) within the 30 minutes following blood sample.
MRI Diffusion/FLAIR mismatch (yes versus no)		The patient will be included within the 12 hours following stroke onset with one blood sample (defining GST-π and PRDX1 plasmatic levels), and cerebral MRI (defining Diffusion/Perfusion mismatch or penumbra) within the 30 minutes following blood sample.
Volume of cerebral infarction assessed by MRI diffusion weighted imaging.		The patient will be included within the 12 hours following stroke onset with one blood sample (defining GST-π and PRDX1 plasmatic levels), and cerebral MRI (defining Diffusion/Perfusion mismatch or penumbra) within the 30 minutes following blood sample.

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France

Publications and helpful links

General Publications

• Karakus A, Girerd N, Sanchez JC, Sabben C, Wietrich A, Lavandier K, Marchal S, Aubertin A, Humbertjean L, Mione G, Bouali S, Duarte K, Reymond S, Gory B, Richard S. Identifying patients with cerebral infarction within the time window compatible with reperfusion therapy, diagnostic performance of glutathione S-transferase-pi (GST-pi) and peroxiredoxin 1 (PRDX1): exploratory prospective multicentre study FLAG-1 protocol. BMJ Open. 2021 Aug 20;11(8):e046167. doi: 10.1136/bmjopen-2020-046167.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2018
• Primary Completion (Estimated): September 13, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: November 23, 2017
• First Submitted That Met QC Criteria: November 30, 2017
• First Posted (Actual): December 6, 2017

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 16, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Acute stroke, Biomarkers
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infarction; Brain Infarction; Stroke; Brain Ischemia; Ischemia; Cerebral Infarction
• Other Study ID Numbers: PHRCI 2016/FLAG1 - RICHARD /MS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No