Biomarker Signature of Stroke Aetiology Study: The BIOSIGNAL-Study

Stroke, Acute Clinical Trial

Official title:

Biomarker Signature of Stroke Aetiology Study: The BIOSIGNAL-Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02274727
• Other study ID #: 2014-001
• Status: Active, not recruiting
• Start date: September 2014
• Est. completion date: December 2021

Study information

• Verified date: November 2021
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1800
• Est. completion date: December 2021
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Detailed Inclusion Criteria:

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)

Related Conditions & MeSH terms

• Stroke
• Stroke, Acute

Locations

Country	Name	City	State
Germany	University Hospital of Frankfurt	Frankfurt am Main
Greece	Larissa University Hospital of Thessaly	Larissa
Spain	Universitiy Hospital Vall d'Hebron	Barcelona
Switzerland	Kantonsspital Aarau, Department of Neurology	Aarau	Argau
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	St.Gallen
Switzerland	University Hospital of Zurich, Department of Neurology	Zurich

Sponsors (2)

Lead Sponsor	Collaborator
University of Zurich	Swiss National Science Foundation

Countries where clinical trial is conducted

Germany,  Greece,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Functional outcome	Assessed by the modified Rankin scale (mRS)	Within 3 month after the index stroke and at one year. In Zurich and Basel also in 2021
Other	Occurrence of epileptic seizures and the diagnosis of epilepsy	According to the medical history reported by patient and a questionnaire	During 2021 (only in Zurich and Basel)
Other	Ooccurrence of newly diagnosed cancer	According to the medical history reported by patient	During 2021 (only in Zurich and Basel)
Other	Cognitive impairment	Assessed by the Telephone Interview for Cognitive Status (TICS) Questionnaire	During 2021 (only in Zurich and Basel)
Other	Mortality	All-cause death	Within 1 year after the index event. In Zurich and Basel also in 2021
Primary	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)	Within 1 year after the index event. In Zurich and Basel also in 2021
Secondary	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)	Within one year after the index stroke
Secondary	Stroke aetiology	According to TOAST and SS TOAST criteria	During first hospitalisation (cross-sectional analysis, up to 14 days)
Secondary	History of AF	Assessed by chart review and taking the patients history	Diagnosed befor the stroke
Secondary	Newly Atrial Fibrillation (AF)	Newly diagnosed atrial fibrillation in patients with no history of AF	On admission and during a one year of follow-up by PCM. In Zurich and Basel also in 2021
Secondary	The presence of cerebrovascular atherosclerosis among all patients.	Assessed by duplex sonography.	During first hospitalisation (cross-sectional analysis, up to 14 days)