Clinical trial NCT05685069: Prevalence of Attributable Etiology and Modifiable Stroke Risk Factors in Patients With Covert Brain Infarctions
Official title: Prevalence of Attributable Etiology and Modifiable Stroke Risk Factors in Patients With Covert Brain Infarctions (CBI-registry)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Silent Stroke
Silent Cerebral Infarct
Covert Brain Infarct
Covert Brain Infarction
Lacune
Silent Brain Infarction
Keywords: Covert brain infarction
Covert cerebrovascular disease
Ischemic stroke
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2023-01-13
Enrollment: 230
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients will be recruited by the Neuroradiology Department of Inselspital Bern. All patients undergoing a brain MRI showing a presumably silent brain lesion and fulfilling the inclusion/exclusion criteria will be eligible for the study. Inpatients will be contacted while on a ward and outpatients by telephone calls.

Brief summary: The CBI registry is a prospective, interdisciplinary, multimodal observational registry of patients with covert brain infarction. Methods: A standardized workup in analogy to manifest ischemic stroke including cerebral MRI, long-term rhythm monitoring (3 x 7 days ECG), echocardiography, laboratory work-up and risk factor assessment as well as noninvasive angiography of the cervical and intracranial arteries will be performed.

Detailed description: Background: Covert brain infarction (CBI) are incidental lesions of presumably vascular etiology, detected on cerebral imaging and without attributable event of an acute ischemic stroke (AIS). Formerly thought to be completely "silent", CBI do have consequences: patients with CBI have a two-fold increased risk of severe stroke in the future, more often covert neurological deficits, and a steeper decline in cognitive function with increased risk of dementia. Important associations of CBI are described with hypertension, carotid stenosis, chronic kidney disease and metabolic syndrome, heart failure, coronary artery disease, hyperhomocysteinemia and obstructive sleep apnea. No trustworthy guidelines exist how to approach a patient with CBI.

Aim and hypothesis: The investigators want to provide a reliable estimate on the yield and relevance of a complete stroke workup to identify modifiable vascular risk factors in patients with CBI searching for an easily treatable cause of the event like a carotid stenosis, atrial fibrillation, hypertension or diabetes. The investigators' hypothesis is that a complete workup in patients with CBI has a similar yield of underlying pathological findings as compared to workup recommended for AIS.

Design: The SILENT registry is a prospective, interdisciplinary, multimodal observational registry of 230 patients with CBI. Methods: A standardized workup procedures including cerebral MRI, long-term rhythm monitoring (3 x 7 days ECG), echocardiography and noninvasive angiography of the cervical and intracranial arteries will be performed.

Statistics: A sample size calculation estimated a sample size of 230 patients. A prespecified analysis protocol will be used.

Significance: This study has the potential to extend the work-up of stroke to patients with CBI. Since CBI are up to three times more frequent than manifest ischemic stroke, this would have huge implications for primary stroke prevention.

Eligibility criteria: Inclusion Criteria:

* Any clinically silent ischemic lesions of the brain parenchyma detected on neuroimaging defined according to established criteria as either:

  * DWI positive lesions: Focus of restricted diffusion (high DWI signal and low ADC value) occurring in either white or gray matter, located in the cerebrum, cerebellum, or brain stem AND not satisfying the diagnostic criteria for MS OR
  * Cavitatory Lesions: ≥ 3 mm in size that follow CSF on all sequences that are slit or wedge shaped with an irregular margin AND NOT longitudinally aligned with perforating vessels or with a multiple, bilateral symmetrical distribution OR
  * T2W hyperintense/T1W hypointense lesions: Focal lesion with high T2W signal and low T1W signal that have prior evidence of restricted diffusion; OR present within cortical gray matter or deep gray matter nuclei OR a lesion that is new, compared with an MRI performed within 3 months OR T2W hyper/T1W hypointense lesions in the white matter, which are discontinuous but associated with the classic confluent periventricular T2 intense change of leukoaraiosis (Fazekas ≥2) AND NOT satisfying the diagnostic criteria for MS or with a significant patient history of severe trauma, radiation, drug toxicity, or carbon monoxide poisoning
* Informed Consent as documented by signature by patient or legally authorized representative

Exclusion Criteria:

* Projected life expectancy of less than 2 years,
* Contraindication to MRI,
* Patients with a history of symptoms compatible with an AIS/TIA attributable to the lesion observed, covert neurological deficits are allowed,
* Patient is already included in another clinical trial that will affect the objectives of this study,
* Patient's lack of accountability, inability to appreciate the nature, meaning and consequences of the study and to formulate his/her own wishes correspondingly,
* Women who are pregnant or breast feeding or intention to become pregnant during the course of the study,
* Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
* Contraindications to any of the routine procedures, e.g. inability to obtain neurovascular ultrasound examination,
* Known or suspected non-compliance, drug or alcohol abuse

Primary outcomes:
measure: Percentage of Modified Trial of Org 10172 in Acute Stroke Treatment etiology
timeFrame: After baseline work-up, expected to be at least 3 months after brain imaging
Secondary outcomes:
measure: Percentage of Modified Trial of Org 10172 in Acute Stroke Treatment etiology
timeFrame: At the end of follow-up (2 years)
measure: Median of National Institute of Health Stroke score (NIHSS)
timeFrame: At baseline visit, expected to be at least 3 months after brain imaging
measure: Percentage of Presence of covert neurological deficits corresponding to the CBI
timeFrame: At baseline visit, expected to be at least 3 months after brain imaging
measure: Median of Modified Rankin Scale functional status (mRS)
timeFrame: At baseline visit, expected to be at least 3 months after brain imaging
measure: Median of Montreal Cognitive Assessment (MOCA)
timeFrame: At baseline visit, expected to be at least 3 months after brain imaging
measure: Median of Becks-Depression-Inventar-II
timeFrame: At baseline visit, expected to be at least 3 months after brain imaging
measure: Median of EuroQol-5d
timeFrame: At baseline visit, expected to be at least 3 months after brain imaging
measure: Number of Participants with Dyslipidemia
timeFrame: After baseline work-up, expected to be at least 3 months after brain imaging
measure: Number of Participants with New diagnosis of diabetes mellitus type 2
timeFrame: After baseline work-up, expected to be at least 3 months after brain imaging
measure: Number of Participants with Hematological abnormality
timeFrame: After baseline work-up, expected to be at least 3 months after brain imaging
measure: Number of Participants with Abnormality in renal function or electrolytes
timeFrame: After baseline work-up, expected to be at least 3 months after brain imaging
measure: Number of Participants with Ischemic stroke
timeFrame: At the end of follow-up (2 years)
measure: Number of Participants with TIA
timeFrame: At the end of follow-up (2 years)
measure: Number of Participants with Myocardial infarction
timeFrame: At the end of follow-up (2 years)
measure: Number of Participants with relevant symptomatic intracranial hemorrhage
timeFrame: At the end of follow-up (2 years)
measure: Number of Participants with Major cardiovascular events
timeFrame: At the end of follow-up (2 years)
measure: Number of Participants with Systemic embolism
timeFrame: At the end of follow-up (2 years)
measure: Number of Participants with Vascular death
timeFrame: At the end of follow-up (2 years)
measure: Number of Participants with All-cause mortality
timeFrame: At the end of follow-up (2 years)
Other outcomes:
Locations:
city: Tours
country: France
facility: Centre Hospitalier Universitaire de Tours
city: Bern
country: Switzerland
facility: Inselspital Bern
Study officials:
affiliation: Insel Gruppe AG, University Hospital Bern
name: Urs Fischer, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Meinel TR, Kaesmacher J, Roten L, Fischer U. Covert Brain Infarction: Towards Precision Medicine in Research, Diagnosis, and Therapy for a Silent Pandemic. Stroke. 2020 Aug;51(8):2597-2606. doi: 10.1161/STROKEAHA.120.030686. Epub 2020 Jul 10. No abstract available.