A EUROpean Randomized Study on Blood-thinners and Cholesterol-lowering Treatments to Prevent Future Vascular Events in People With Covert Brain Infarcts (CBI) (EURO-CBI)

Aarhus University Hospital

Status and phase: Enrolling; Phase 3

Conditions: Covert Brain Infarction

Treatments: Drug: Atorvastatin; Drug: acetylsalicyclic acid (ASA); Drug: Rosuvastatin; Drug: Clopidogrel

Study type: Interventional

Funder types: Other

Identifiers

NCT07012629

2025-521452-30-01 (EU Trial (CTIS) Number)

Details and patient eligibility

About

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.

Enrollment: 1,652 estimated patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Single Blind

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1,652 participants in 4 patient groups

Group A: Platelet inhibitor - no Statin ("APT alone")

Experimental group

Description:

All patients will initiate treatment with Aspirin or Clopidogrel. The decision on which of the two drugs to initiate is at the discretion of the treating physician/center.

Treatment:

Drug: Clopidogrel

Drug: acetylsalicyclic acid (ASA)

Group B: Statins - no Platelet inhibitor ("Statin alone").

Experimental group

Description:

Patients will be treated with high-intensity statin therapy (Atorvastatin 40 mg once daily or Rosuvastatin 20 mg once daily)

Treatment:

Drug: Rosuvastatin

Drug: Atorvastatin

Group C: Statins - Platelet inhibitor ("APT AND statin")

Experimental group

Description:

Both types of medication are initiated as described in group A and B

Treatment:

Drug: Clopidogrel

Drug: Rosuvastatin

Drug: acetylsalicyclic acid (ASA)

Drug: Atorvastatin

Group D: No Statins - no Platelet inhibitor (current standard treatment)

No Intervention group

Description:

This group follows the current European recommendations of primary prevention which do not include statins and APT agents. If statins and/or platelet inhibitors are started during the study-period it should adhere to primary prevention guidelines. All four groups receive advice on lifestyle optimization and blood pressure management.