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

NCT07012629 | Recruiting Phase 3 DMC

• 1 other identifier: 2025-521452-30-01
• Study Type: interventional
• Target: 1,652
• Locations: 5 countries
• Sites: 14

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.

Conditions

Covert Brain Infarction

Keywords

CBI; Prevention; Asymptomatic brain infarction; Dementia

Outcome Measures

Primary Outcomes (2)

• Major Adverse Cardiac and Cerebral Events (MACCE) at 12 and 36 months

  MACCE are defined as the occurrence of any of the following events * All cause death: Death from any cause * Acute myocardial infarction: Admission with a discharge diagnosis of ST-elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI) and * Stroke: AIS\* or Intracerebral hemorrhage (non-traumatic) \*Including Transient Ischemic Attack (TIA) with evidence of brain tissue infarction i.e. remission of symptoms within 24 hours but who have an acute ischemic lesion on diffusion weighted imaging MRI. All events qualifying for a MACCE event will be adjudicated by the Clinical event committee. Accepted timeframe for evaluation is +/- 30 days

  12 months and 36 months post-randomization.

• Major and fatal bleeding at 12 and 36 months

  Major and fatal bleeding events are defined according to criteria established by the International Society on Thrombosis and Haemostasis (ISTH): * Fatal bleeding, and/or * Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome, and/or * Bleeding leading to a drop in hemoglobin of ≥20 g/L (1.24 mmol/L), or requiring transfusion of two or more units of whole blood or red cells. All qualifying events will be adjudicated by an independent Clinical Event Committee (CEC). The accepted time window for assessment is ±30 days.

  12 months and 36 months post-randomization.

Secondary Outcomes (11)

• All-cause dementia

  12 months and 36 months post-randomization.

• Cardiovascular-related mortality

  12 months and 36 months post-randomization.

• Cognitive decline

  After 12 months and a end of treatment at 36 months

• Serious adverse event (SAE)

  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

  After 12 months and at the end of treatment at 36 months

Other Outcomes (4)

• MRI-based assessment of small vessel disease progression (sub-study)

  After 36 months (+/- 1 months)

• MRI-based assessment of white matter lesion (WML) volume growth

  36 months (+/- 1 month)

• Carotid plaque quantification on ultrasound

  At baseline

Study Arms (4)

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

EXPERIMENTAL

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.

Drug: acetylsalicyclic acid (ASA); Drug: Clopidogrel

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

EXPERIMENTAL

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

Drug: Rosuvastatin; Drug: Atorvastatin

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

EXPERIMENTAL

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

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

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

NO INTERVENTION

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.

Interventions

Clopidogrel DRUG

Daily dose 75 mg p.o.

Group A: Platelet inhibitor - no Statin ("APT alone"); Group C: Statins - Platelet inhibitor ("APT AND statin")

Rosuvastatin DRUG

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.

Group B: Statins - no Platelet inhibitor ("Statin alone").; Group C: Statins - Platelet inhibitor ("APT AND statin")

Atorvastatin DRUG

Daily dose 40 mg p.o. If Atorvastatin 40 mg is not tolerated, a dose reduction to 20 mg is allowed.

Group B: Statins - no Platelet inhibitor ("Statin alone").; Group C: Statins - Platelet inhibitor ("APT AND statin")

acetylsalicyclic acid (ASA) DRUG

Daily dose 75 mg to 100 mg p.o.

Also known as: Aspirin

Group A: Platelet inhibitor - no Statin ("APT alone"); Group C: Statins - Platelet inhibitor ("APT AND statin")

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Aarhus University Hospital: lead
• Rigshospitalet, Denmark: collaborator
• Bispebjerg Hospital: collaborator
• Herlev Hospital: collaborator
• Zealand University Hospital: collaborator
• Odense University Hospital: collaborator
• Aalborg University Hospital: collaborator
• Gødstrup Hospital: collaborator
• Oslo University Hospital: collaborator
• University Medical Center Hamburg-Eppendorf (UKE): collaborator
• Insel Gruppe AG, University Hospital Bern: collaborator
• Lund University Hospital: collaborator

Study Sites (14)

Aalborg Universitetshospital

Aalborg, 9000, Denmark

NOT YET RECRUITING

Aarhus Universitetshospital

Aarhus, 8200, Denmark

NOT YET RECRUITING

Aarhus University Hospital

Aarhus, 8200, Denmark

RECRUITING

Rigshospitalet

Copenhagen, 2100, Denmark

NOT YET RECRUITING

Bispebjerg og Frederiksberg Hospital

Copenhagen, 2400, Denmark

NOT YET RECRUITING

Herlev Hospital

Herlev, 2730, Denmark

NOT YET RECRUITING

Regionshospitalet Gødstrup

Herning, 7400, Denmark

NOT YET RECRUITING

Kolding Hospital

Kolding, 6000, Denmark

NOT YET RECRUITING

Odense Universitetshospital

Odense, 5000, Denmark

NOT YET RECRUITING

Roskilde Hospital

Roskilde, 4000, Denmark

NOT YET RECRUITING

University Medical Center Hamburg-Eppendorf

Hamburg, 20246, Germany

NOT YET RECRUITING

Oslo University Hospital

Oslo, 0450, Norway

NOT YET RECRUITING

Skånes Universitetssjukhus

Lund, 22242, Sweden

NOT YET RECRUITING

Universitätsspital - Inselspital - University of Bern

Bern, 3010, Switzerland

NOT YET RECRUITING

MeSH Terms

Conditions

Dementia

Interventions

Aspirin; Clopidogrel; Rosuvastatin Calcium; Atorvastatin

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Sulfones; Pyrimidines; Pyrroles; Azoles; Heptanoic Acids; Fatty Acids; Lipids

Central Study Contacts

Rolf Blauenfeldt

CONTACT

+4529318244; rolfblau@rm.dk

Ida Thingholm Norup

CONTACT

+4520848978; idnoru@rm.dk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Associate professor of Neurology.

Model Details: 2x2 factorial

Study Record Dates

• First Submitted: June 1, 2025
• First Posted: June 10, 2025
• Study Start: November 26, 2025
• Primary Completion (Estimated): September 30, 2031
• Study Completion (Estimated): January 1, 2040
• Last Updated: December 4, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: After publication of the primary endpoint (estimated Sept 30, 2032)
• Access Criteria: To gain access to these data, data requestors will need to sign a data processing agreement.

Locations

NO (1); SE (1); CH (1); DK (10); DE (1)