Clinical trial NCT07012629: A EUROpean Randomized Study on Blood-thinners and Cholesterol-lowering Treatments to Prevent Future Vascular Events in People With Covert Brain Infarcts (CBI)
Official title: A EUROpean Pragmatic Multicenter Randomized Trial on Platelet Inhibition and/or Lipid Lowering Treatment in Covert Brain Infarction (CBI)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Covert Brain Infarction
Keywords: CBI
Prevention
Asymptomatic brain infarction
Dementia
Lead sponsor: Aarhus University Hospital
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
name: Bispebjerg Hospital
name: Herlev Hospital
name: Zealand University Hospital
name: Odense University Hospital
name: Aalborg University Hospital
name: Gødstrup Hospital
name: Oslo University Hospital
name: University Medical Center Hamburg-Eppendorf (UKE)
name: Insel Gruppe AG, University Hospital Bern
name: Lund University Hospital
First posted: 2025-06-10
Enrollment: 1652
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: 2x2 factorial
Primary purpose: TREATMENT

Brief summary: Magnetic resonance imaging (MRI) is commonly used in healthcare, and sometimes it shows small areas of brain damage called Covert Brain Infarcts (CBIs). These are usually found by chance when people have scans for things like headaches or dizziness. Although CBIs don't cause symptoms at the time, they are linked to a higher risk of future stroke and death.

There is currently no standard treatment for CBIs, and doctors have different approaches-some give stroke-preventing medication (like antiplatelets or statins), while others don't treat at all. This is mostly because there isn't enough research yet.

This study will test whether stroke-preventing treatments help people with CBIs. It will also look at whether having a CBI increases the risk of dementia, and whether treatment might lower that risk.


Eligibility criteria: Inclusion Criteria:

* MRI demonstrating a lacunar infarct (acute/subacute/chronic) without prior stroke/TIA symptoms. (A round or ovoid, subcortical, fluid-filled cavity (signal similar to cerebrospinal fluid (CSF)) between 3 and 15 mm in diameter and demonstrating a peripheral T2/FLAIR hyperintense rim of marginal gliosis. For infratentorial lesions the hyperintense rim may be less marked and a complete ring is not required) OR
* MRI demonstrating a cortical infarct (acute/subacute/chronic) without prior stroke/TIA symptoms (A cortical infarct is defined as a fluid-filled cavity (signal similar to CSF) in the cortex, juxtacortical region or cerebellar cortex and with a ring of T2/FLAIR hyperintense lesions or as cortical T2/FLAIR lesions without a fluid-filled cavity with presumed vascular origin. Both supra- and infratentorial lesion will be included) AND Life expectancy \> 12 months AND Predominantly independent in actives of daily living (mRS score ≤ 3) AND Age ≥ 50 years

Exclusion Criteria:

* History of stroke/TIA
* High risk of bleeding (e.g., recent or recurrent gastrointestinal or genitourinary bleeding associated with a decrease in hemoglobin levels of at least 1 mmol/L, active peptic ulcer disease, MRI with cortical siderosis and/or prior lobar hemorrhage)
* Indication for long-term use of anticoagulants (e.g. deep vein thrombosis, pulmonary embolism, atrial fibrillation, and rarer indications; such as mechanical heart valve, antiphospholipid antibody syndrome etc.)
* Concurrent indication for lipid-lowering treatment and/or platelet-inhibitors for secondary cardiovascular prevention (ischemic heart disease, recent stenting, ischemic stroke, revascularization surgeries, lower-extremity atherosclerotic arterial disease etc.)
* Co-existing progressive neurodegenerative disease including dementia or Parkinson's disease.
* Neoplastic condition that is uncontrolled or associated with an increased risk of bleeding
* Patient already on antiplatelet or anticoagulation agent, regardless of indication
* Women with a history of menopause below 12 months are only included after negative pregnancy test

Primary outcomes:
measure: Major Adverse Cardiac and Cerebral Events (MACCE) at 12 and 36 months
timeFrame: 12 months and 36 months post-randomization.
measure: Major and fatal bleeding at 12 and 36 months
timeFrame: 12 months and 36 months post-randomization.
Secondary outcomes:
measure: All-cause dementia
timeFrame: 12 months and 36 months post-randomization.
measure: Cardiovascular-related mortality
timeFrame: 12 months and 36 months post-randomization.
measure: Cognitive decline
timeFrame: After 12 months and a end of treatment at 36 months
measure: Serious adverse event (SAE)
timeFrame: From enrollment to the end of treatment at 36 months
measure: Baseline MRI risk markers, quantified using the ordinal simplified SVD-score (small vessel disease) score
timeFrame: After 12 months and at the end of treatment at 36 months
measure: Physical activity levels
timeFrame: At baseline
measure: Modified Rankin Scale (mRS) score
timeFrame: From baseline to 12 months and to the end of treatment at 36 months
measure: Clinical Frailty Scale (CFS) score
timeFrame: From baseline to 12 months and to the end of treatment at 36 months
measure: Barthel Index (BI) for Activities of Daily Living (ADL)
timeFrame: From enrollment to 12 months and to the end of treatment at 36 months
measure: Quality of life (EQ-5D)
timeFrame: From enrollment to 12 months and to the end of treatment at 36 months
measure: CBI subtype
timeFrame: At baseline
Other outcomes:
measure: MRI-based assessment of small vessel disease progression (sub-study)
timeFrame: After 36 months (+/- 1 months)
measure: MRI-based assessment of white matter lesion (WML) volume growth
timeFrame: 36 months (+/- 1 month)
measure: Carotid plaque quantification on ultrasound
timeFrame: At baseline
measure: Pulsatility index on ultrasound
timeFrame: At baseline
Locations:
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Herning
country: Denmark
facility: Regionshospitalet Gødstrup
city: Kolding
country: Denmark
facility: Kolding Hospital
city: København
country: Denmark
facility: Rigshospitalet
city: København
country: Denmark
facility: Bispebjerg og Frederiksberg Hospital
city: Odense
country: Denmark
facility: Odense Universitetshospital
city: Roskilde
country: Denmark
facility: Roskilde Hospital
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Lund
country: Sweden
facility: Skånes Universitetssjukhus
city: Bern
country: Switzerland
facility: Universitätsspital - Inselspital - University of Bern
Study officials:
References: