Stroke, AcuteNCT02274727
Biomarker Signature of Stroke Aetiology Study: The BIOSIGNAL-Study
An observational study of Stroke, Acute, run by University of Zurich at 9 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke, Acute
- How many people
- 1,800 participants
- Where
- 9 sitesin 4 countries
- Study dates
- Sep 2014to Dec 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The BIOSIGNAL study will be a prospective observational multicenter cohort study to evaluate selected CE and LAA blood biomarkers in patients with incident ischemic stroke. We will consecutively recruit patients over a planned time period of two years. All participants will be followed for 1 year.
Who may be able to join
- 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.
- Detailed Inclusion Criteria:
- Rapid onset of a focal neurologic deficit, with signs or symptoms persisting beyond 24 hours \& NOT associated with:
- infection
- trauma
Show all 11Show fewer
- tumor of the brain
- severe metabolic disorders
- chronic degenerative neurologic disease
- 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.
Who cannot join
- Hemorrhagic stroke
- All patients discharged from the hospital with a diagnosis different from ischemic stroke (i.e. stroke mimics)
Trial locations and contacts
9 sites in 4 countries.
9 sites in 4 countries
Switzerland6 sites
Kantonsspital Aarau, Department of Neurology
Aarau, Canton of Aargau, 5001
University Hospital of Basel
Basel, 4031
University Hospital of Bern/Inselspital
Bern, 3010
Stroke Center ; Neurocentro(EOC) della Svizzera Italiana
Lugano, 6900
Stroke Center, Kantonsspital St.Gallen
Sankt Gallen, 9007
University Hospital of Zurich, Department of Neurology
Zurich, 8091
About this study
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.
Read the 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
- Medical subject headings
- Stroke
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite of Major adverse cardiac events (MACE)
Recurrent cerebrovascular events (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)
Measured: Within 1 year after the index event. In Zurich and Basel also in 2021
Secondary outcomes (5)
Single components and combinations of MACE
Recurrent cerebrovascular events (ischemic stroke (AIS), intracranial hemorrhage (ICH) or transient ischemic attack (TIA)), myocardial infarction (MI) or cardiovascular death (CVD)
Measured: Within one year after the index stroke
Stroke aetiology
According to TOAST and SS TOAST criteria
Measured: During first hospitalisation (cross-sectional analysis, up to 14 days)
History of AF
Assessed by chart review and taking the patients history
Measured: Diagnosed befor the stroke
Newly Atrial Fibrillation (AF)
Newly diagnosed atrial fibrillation in patients with no history of AF
Measured: On admission and during a one year of follow-up by PCM. In Zurich and Basel also in 2021
The presence of cerebrovascular atherosclerosis among all patients.
Assessed by duplex sonography.
Measured: During first hospitalisation (cross-sectional analysis, up to 14 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2014 (estimated)
- Study startSep 2014
- Primary completionDec 2021 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Stroke, AcuteStudies of the same condition, open and under way.
- More trials run by University of ZurichThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,800 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Collaborators
- Swiss National Science Foundation
- Responsible party
- Principal investigator, Mira Katan, University of Zurich
- Investigators
- Mira Katan, MD, MS, Principal investigator, Name: Mira Katan, MD, Msc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02274727
- Sponsor's protocol ID
- 2014-001
- Status last verified
- Nov 2021
- First submitted
- 17 Oct 2014
- Last updated
- 11 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Dittrich TD, Zietz AV, Arnold M, Gross F, Kriemler L, Inauen C, Westphal L, Pokorny T, Arnold M, Kahles T, Cereda CW, Kagi G, Bustamante A, Montaner J, Ntaios G, Foerch C, Spanaus K, Gawinecka J, von Eckardstein A, De Marchis GM, Katan M; BIOSIGNAL investigators. Association between aldehyde dehydrogenase 4 family member A1 plasma concentrations and atherosclerotic disease in patients with ischemic stroke: Results from the prospective multicenter BIOSIGNAL study. Clin Chim Acta. 2026 Aug 15;590:121089. doi: 10.1016/j.cca.2026.121089. Epub 2026 May 15.
PubMed 42142696Cameron 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.
PubMed 38950311Schweizer 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.
PubMed 35393018
Study at a glance
From the registry record, last updated by the sponsor on 11 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarker Signature of Stroke Aetiology Study: The BIOSIGNAL-Study
- ClinicalTrials.gov ID
- NCT02274727
- Acronym / sponsor ID
- 2014-001
- Conditions
- Stroke, Acute
- Keywords
- Biomarker, Stroke, Etiology, Outcome
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1,800 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Collaborators
- Swiss National Science Foundation
- Study start
- Sep 2014
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 24 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The BIOSIGNAL study will be a prospective observational multicenter cohort study to evaluate selected CE and LAA blood biomarkers in patients with incident ischemic stroke. We will consecutively recruit patients over a planned time period of two years. All participants will be followed for 1 year.
Key inclusion criteria (11 listed)
- 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.
- Rapid onset of a focal neurologic deficit, with signs or symptoms persisting beyond 24 hours \& NOT associated with:
- 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.
Key exclusion criteria (2 listed)
- Hemorrhagic stroke
- All patients discharged from the hospital with a diagnosis different from ischemic stroke (i.e. stroke mimics)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Composite of Major adverse cardiac events (MACE)
Time frame: Within 1 year after the index event. In Zurich and Basel also in 2021
Recurrent cerebrovascular events (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)
5 secondary outcomes
Single components and combinations of MACE
Time frame: Within one year after the index stroke
Stroke aetiology
Time frame: During first hospitalisation (cross-sectional analysis, up to 14 days)
History of AF
Time frame: Diagnosed befor the stroke
Newly Atrial Fibrillation (AF)
Time frame: On admission and during a one year of follow-up by PCM. In Zurich and Basel also in 2021
The presence of cerebrovascular atherosclerosis among all patients.
Time frame: During first hospitalisation (cross-sectional analysis, up to 14 days)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2021.
- Derived from this study: PubMed 42142696Dittrich TD, Zietz AV, Arnold M, Gross F, Kriemler L, Inauen C, Westphal L, Pokorny T, Arnold M, Kahles T, Cereda CW, Kagi G, Bustamante A, Montaner J, Ntaios G, Foerch C, Spanaus K, Gawinecka J, von Eckardstein A, De Marchis GM, Katan M; BIOSIGNAL investigators. Association between aldehyde dehydrogenase 4 family member A1 plasma concentrations and atherosclerotic disease in patients with ischemic stroke: Results from the prospective multicenter BIOSIGNAL study. Clin Chim Acta. 2026 Aug 15;590:121089. doi: 10.1016/j.cca.2026.121089. Epub 2026 May 15.
- Derived from this study: PubMed 38950311Cameron 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.
- Derived from this study: PubMed 35393018Schweizer 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mira Katan, MD, MS principal investigator
Name: Mira Katan, MD, Msc
9 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Stroke, Acute, run by University of Zurich at 9 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Switzerland, Germany, Greece, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite of Major adverse cardiac events (MACE) (time frame: Within 1 year after the index event. In Zurich and Basel also in 2021). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02274727, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Nov 2021.