Biomarker Signature of Stroke Aetiology Study: The BIOSIGNAL-Study

NCT ID: NCT02274727

Last Updated: 2021-11-11

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 1800 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2021-12-31

Brief Summary

The three-year cumulative risk of a recurrent stroke, dependent on aetiology, is up to 25 per cent. At present, preventing recurrence relies on a broad approach to reduce risk factors associated with atherosclerosis, heart disease and metabolic disorders. However, more specific interventions, such as anticoagulation and surgery or stenting, need aetiologic information. BIOSIGNAL aims to determine where the most promising candidate biomarkers can help identify stroke aetiology and also predict overall MACE, including specifically recurrent stroke. In addition, the insights gained into the processes underlying different stroke subtypes may lead to more targeted diagnostic tools.

Detailed Description

Objectives and specific aims:

The investigators propose to prospectively evaluate the predictive value of the most promising blood bio-markers to identify treatable stroke etiologies on admission and risk of MACE and its components in consecutive ischemic stroke patients enrolled by several centers in Europe.

The clinical endpoints of the study are 1) recurrent cerebrovascular events (ischemic stroke and / or transient ischemic attack (TIA)) and major cardiac events (MACE) within one year after the index stroke and after 3-5 years of follow up (2021) 2) all types of atrial fibrillation (AF) detected on admission or by prolonged ambulatory cardiac rhythm monitors during the follow up period 3) presence of cerebrovascular atherosclerosis detected by ultrasound investigations and 4) overall mortality, functional outcome, cognitive impairment, occurrence of epilepsy, and newly diagnosed cancer, according to data collected in telephonic interviews in 2021 (only in Zurich and Basel) with the patients enrolled between 2014-2017.

Aim 1: To determine whether the proposed and novel biomarkers independently predict recurrent stroke and a composite outcome consisting of recurrent cerebrovascular event (ischemic stroke (AIS), intracranial hemorrhage (ICH) or transient ischemic attack (TIA), as well as myocardial infarction (MI), cardiovascular death (CVD)). i.e. major adverse cardiac events (MACE) among all patients. Hypothesis 1: Elevated levels of one or more of the proposed and novel biomarkers will independently predict MACE and its components during trial follow-up, assessed by structured interviews, as well as chart reviews 90 days, 1 year after the index stroke as well as in 2021 (only in Zurich and Basel).

Aim 2: To determine whether CE biomarkers are associated with atrial fibrillation among all patients. Hypothesis 2: Baseline values of one or more of the CE biomarkers will be independently associated with AF, including history of AF, AF detection at baseline, or AF detected during the follow up period by prolonged (at least 7-day) ambulatory cardiac rhythm monitors and structured interviews as well as chart reviews 90 days, 1 year after the index stroke as well as in 2021 (only in Zurich and Basel).

Aim 3: To determine whether LAA biomarkers are associated with a) the presence of cerebrovascular atherosclerosis among all patients. Hypothesis 3: Baseline values of one or more of LAA biomarkers will be independently associated with the presence of extra and intracranial atherosclerosis among patients with ischemic stroke.

Exploratory Aim 4: To determine whether the proposed and novel biomarkers will predict a) occurrence of epileptic seizures and diagnosis of epilepsy b) newly diagnosed cancer, c) functional outcome and cognitive impairment. Hypothesis 4: Baseline values of one or more of the proposed and potentially novel biomarkers will independently predict a) occurrence of epileptic seizures and the diagnosis of epilepsy b)occurrence of newly diagnosed cancer c) functional outcome and cognitive impairment assessed by a follow up structured telephone interview performed in 2021 with the patients enrolled between 2014-2017 (only in Zurich and Basel).

This study will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, and Good Clinical Practice (GCP) guidelines as well as all national legal and regulatory requirements.

Conditions

Stroke, Acute

Keywords

Biomarker; Stroke; Etiology; Outcome

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

All consecutive patients (above the age of 18) who are admitted with a suspected ischemic stroke within 24 hours of symptom onset are eligible.

Ischemic stroke is defined as an acute localized ischemic lesion in the brain not attributable to central nervous system infection, tumor, demyelinating, or degenerative neurologic diseases due to an occlusive vascular disorder.

1. Rapid onset of a focal neurologic deficit, with signs or symptoms persisting beyond 24 hours & NOT associated with:

• infection
• trauma
• tumor of the brain
• severe metabolic disorders
• chronic degenerative neurologic disease

2. The development of an acute focal neurologic deficit persisting >24 hours in conjunction with brain imaging consistent with acute ischemic stroke.

The CT or MRI may either show a new infarct or no change from the study performed at entry, i.e. the diagnosis is clinical and does not require CT/MRI confirmation. Secondary hemorrhagic infarction is permissible.

Exclusion Criteria

1. Hemorrhagic stroke

2. All patients discharged from the hospital with a diagnosis different from ischemic stroke (i.e. stroke mimics)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss National Science Foundation

OTHER

Sponsor Role: collaborator

University of Zurich

OTHER

Sponsor Role: lead

Responsible Party

Mira Katan

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mira Katan, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Name: Mira Katan, MD, Msc

Locations

University Hospital of Frankfurt

Frankfurt am Main, , Germany

Larissa University Hospital of Thessaly

Larissa, , Greece

Universitiy Hospital Vall d'Hebron

Barcelona, , Spain

Kantonsspital Aarau, Department of Neurology

Aarau, Canton of Aargau, Switzerland

University Hospital of Basel

Basel, , Switzerland

University Hospital of Bern/Inselspital

Bern, , Switzerland

Stroke Center ; Neurocentro(EOC) della Svizzera Italiana

Lugano, , Switzerland

Stroke Center, Kantonsspital St.Gallen

Sankt Gallen, , Switzerland

University Hospital of Zurich, Department of Neurology

Zurich, , Switzerland

Countries

United States; Germany; Greece; Spain; Switzerland

References

Cameron AC, Arnold M, Katsas G, Yang J, Quinn TJ, Abdul-Rahim AH, Campbell R, Docherty K, De Marchis GM, Arnold M, Kahles T, Nedeltchev K, Cereda CW, Kagi G, Bustamante A, Montaner J, Ntaios G, Foerch C, Spanaus K, Eckardstein AV, Dawson J, Katan M. Natriuretic Peptides to Classify Risk of Atrial Fibrillation Detection After Stroke: Analysis of the BIOSIGNAL and PRECISE Cohort Studies. Neurology. 2024 Aug 13;103(3):e209625. doi: 10.1212/WNL.0000000000209625. Epub 2024 Jul 1.

Reference Type: DERIVED

PMID: 38950311 (View on PubMed)

Schweizer J, Arnold M, Konig IR, Bicvic A, Westphal LP, Schutz V, Inauen C, Scherrer N, Luft A, Galovic M, Ferreira Atuesta C, Pokorny T, Arnold M, Fischer U, Bonati LH, De Marchis GM, Kahles T, Nedeltchev K, Cereda CW, Kagi G, Bustamante A, Montaner J, Ntaios G, Sagris D, Foerch C, Spanaus K, von Eckardstein A, Katan M. Measurement of Midregional Pro-Atrial Natriuretic Peptide to Discover Atrial Fibrillation in Patients With Ischemic Stroke. J Am Coll Cardiol. 2022 Apr 12;79(14):1369-1381. doi: 10.1016/j.jacc.2022.01.042.

Reference Type: DERIVED

PMID: 35393018 (View on PubMed)

Other Identifiers

2014-001

Identifier Type: -

Identifier Source: org_study_id