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)

Overview

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.

Interventions

• Drug acetylsalicyclic acid (ASA)
  Daily dose 75 mg to 100 mg p.o.
• Drug Clopidogrel
  Daily dose 75 mg p.o.
• Drug Rosuvastatin
  Daily dose 20 mg p.o. (10 mg once daily for the first 4 weeks, then 20 mg once daily for the remainder of the study period if tolerated). If Rosuvastatin 20 mg is not tolerated, a dose reduction to 10 mg is allowed.
• Drug Atorvastatin
  Daily dose 40 mg p.o. If Atorvastatin 40 mg is not tolerated, a dose reduction to 20 mg is allowed.

Primary outcome measures

• Major Adverse Cardiac and Cerebral Events (MACCE) at 12 and 36 months [Time frame: 12 months and 36 months post-randomization.]
• Major and fatal bleeding at 12 and 36 months [Time frame: 12 months and 36 months post-randomization.]

Secondary outcome measures (11)

• All-cause dementia [Time frame: 12 months and 36 months post-randomization.]
• Cardiovascular-related mortality [Time frame: 12 months and 36 months post-randomization.]
• Cognitive decline [Time frame: After 12 months and a end of treatment at 36 months]
• Serious adverse event (SAE) [Time frame: From enrollment to the end of treatment at 36 months]
• Baseline MRI risk markers, quantified using the ordinal simplified SVD-score (small vessel disease) score [Time frame: After 12 months and at the end of treatment at 36 months]
• Physical activity levels [Time frame: At baseline]
• Modified Rankin Scale (mRS) score [Time frame: From baseline to 12 months and to the end of treatment at 36 months]
• Clinical Frailty Scale (CFS) score [Time frame: From baseline to 12 months and to the end of treatment at 36 months]
• Barthel Index (BI) for Activities of Daily Living (ADL) [Time frame: From enrollment to 12 months and to the end of treatment at 36 months]
• Quality of life (EQ-5D) [Time frame: From enrollment to 12 months and to the end of treatment at 36 months]
• CBI subtype [Time frame: At baseline]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Factorial

Masking

Single blind

Primary purpose

Treatment

Study locations

Denmark · 10 centers

• Aalborg Universitetshospital — Aalborg
• Aarhus Universitetshospital — Aarhus
• Aarhus University Hospital — Aarhus
• Rigshospitalet — Copenhagen
• Bispebjerg og Frederiksberg Hospital — Copenhagen
• Herlev Hospital — Herlev
• Regionshospitalet Gødstrup — Herning
• Kolding Hospital — Kolding
• … and 2 more centers

Germany · 1 center

• University Medical Center Hamburg-Eppendorf — Hamburg

Norway · 1 center

• Oslo University Hospital — Oslo

Sweden · 1 center

• Skånes Universitetssjukhus — Lund

Switzerland · 1 center

• Universitätsspital - Inselspital - University of Bern — Bern

Identifiers

NCT: NCT07012629 · 2025-521452-30-01 · 2025-521452-30-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗