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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
1,652
Daily dose 75 mg to 100 mg p.o.
Daily dose 75 mg p.o.
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.
Daily dose 40 mg p.o. If Atorvastatin 40 mg is not tolerated, a dose reduction to 20 mg is allowed.
Aalborg Universitetshospital
Aalborg, Denmark
NOT_YET_RECRUITINGAarhus Universitetshospital
Aarhus, Denmark
NOT_YET_RECRUITINGAarhus University Hospital
Aarhus, Denmark
RECRUITINGRigshospitalet
Copenhagen, Denmark
NOT_YET_RECRUITINGBispebjerg og Frederiksberg Hospital
Copenhagen, Denmark
NOT_YET_RECRUITINGHerlev Hospital
Herlev, Denmark
NOT_YET_RECRUITINGRegionshospitalet Gødstrup
Herning, Denmark
NOT_YET_RECRUITINGKolding Hospital
Kolding, Denmark
NOT_YET_RECRUITINGOdense Universitetshospital
Odense, Denmark
NOT_YET_RECRUITINGRoskilde Hospital
Roskilde, Denmark
NOT_YET_RECRUITING...and 4 more locations
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
Time frame: 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.
Time frame: 12 months and 36 months post-randomization.
All-cause dementia
Dementia is identified through phone contact and review of the patient's electronic health record, based on national diagnostic standards. Accepted diagnoses align with ICD-10 and ICD-11. ICD-10 codes include: dementia in Alzheimer's disease (F00.0-F00.9, DG30.0-DG30.9), vascular dementia (F01.0-F01.9, F00.2), dementia in other diseases classified elsewhere (F02.0-F02.8), unspecified dementia (F03.9), Lewy body dementia (DG31.8E), progressive isolated aphasia (DG31.0A), Pick disease (DG31.0B), and unspecified degenerative disease of the nervous system (DG31.9). ICD-11 codes include: dementia due to Alzheimer's disease (6D80), cerebrovascular disease (6D81), Lewy body disease (6D82), frontotemporal dementia (6D83), other specified diseases (6D85.Y), and dementia of unknown or unspecified cause (6D8Z). The accepted time window for evaluation is ±30 days.
Time frame: 12 months and 36 months post-randomization.
Cardiovascular-related mortality
Information about cardiovascular mortality is collected from telephone contacts and from the patient's electronic health record. See the table below for the definition of cardiovascular mortality. Cardiovascular Mortality are defined as: * Acute MI * Sudden cardiac death * Heart failure * Stroke: death as a direct consequence or complication of stroke * Cardiovascular procedure * Cardiovascular-related haemorrhage: non-stroke intracranial haemorrhage (subdural hematoma), non-procedural or non-traumatic vascular rupture (e.g. aortic aneurysm), or haemorrhage causing cardiac tamponade * Death due to other cardiovascular causes: a cardiovascular death not included in the above categories but with a specific, known cause (e.g., pulmonary embolism or peripheral arterial disease) Accepted time for evaluation is +/- 30 days
Time frame: 12 months and 36 months post-randomization.
Cognitive decline
A significant cognitive decline, defined as a ≥2-point reduction in Montreal Cognitive Assessment (MoCA) scores at 36 months. The participant's score on the full 12 item in-person MoCA (30 points) at the initial visit is compared to the scores on the telephone administrated Tele-MoCA (items from MoCA not requiring the use of a pencil and paper or visual stimulus, maximum of 22 points) after 12 and 36 months. Accepted time for evaluation is +/- 30 days
Time frame: After 12 months and a end of treatment at 36 months
Serious adverse event (SAE)
Information on SAEs will be reported by the investigators and recorded in the eCRF.
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
Simple SVD defined as score: Microbleeds: 0 microbleeds = 0 point; ≥ 1 microbleed = 1 point White matter hyperintensities (Fazekas): Fazekas 0-1 = 0 point; Fazekas 2-3 = 1 point. Lacunes: 0-2 lacunes = 0 point; \>2 lacunes = 1 point. Total SVD score (range): 0-3.
Time frame: After 12 months and at the end of treatment at 36 months
Physical activity levels
Baseline physical activity levels are measured by the International Physical Activity Questionnaire (IPAQ).It yields a categorical score: low, moderate, or high level of physical activity. The follow-up assessment will be performed by staff from the enrolling site. Accepted time for evaluation is +/- 30 days
Time frame: At baseline
Modified Rankin Scale (mRS) score
The change in mRS score will be assessed to evaluate shifts in functional independence and disability over time. The mRS ranges from 0 to 6, with higher scores indicating worse outcomes. The follow-up assessment at 12 and 36 months will be performed by staff from the enrolling site. Accepted time for evaluation is +/- 30 days
Time frame: From baseline to 12 months and to the end of treatment at 36 months
Clinical Frailty Scale (CFS) score
The change in CFS score will be assessed from baseline to 12 and 36 months to evaluate the progression of frailty and its impact on functional status and overall health over time. It ranges from 1 to 9, with 1 indicating "very fit" and 9 indicating "terminally ill." The follow-up assessments at 12 and 36 months will be performed by staff from the enrolling site Accepted time for evaluation is +/- 30 days
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)
The Barthel Index is a score that describes the degree of independence in relation to assistance from another person. It ranges from 0 to 100, with higher scores indicating greater independence. A score close to 100 reflects that the individual is self-sufficient, whereas lower scores indicate increasing dependence on others in daily activities. A score near 0 typically suggests that the individual is bedridden and requires help with all tasks. The follow-up assessments at 12 and 36 months will be performed by staff from the enrolling site. Accepted time for evaluation is +/- 30 days
Time frame: From enrollment to 12 months and to the end of treatment at 36 months
Quality of life (EQ-5D)
The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The follow-up assessments at 12 and 36 months will be performed by staff from the enrolling site. Accepted time for evaluation is +/- 30 days
Time frame: From enrollment to 12 months and to the end of treatment at 36 months
CBI subtype
The CBI subtype and infarct appearance will be described by the enrolling physician, who has been trained to identify these findings on MRI. The baseline MRI will be visually graded by the investigators and the total SVD score calculated. The DICOM (Digital Imaging and Communications in Medicine) file containing the MRI will be downloaded and uploaded to the electronic case report form (eCRF) at redcap.au.dk, for later assessment by an imaging core lab.
Time frame: At baseline
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