A EUROpean Pragmatic Multicenter Randomized Trial on Platelet Inhibition and/or Lipid Lowering Treatment in Covert Brain Infarction (CBI)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 1,652
- 试验地点
- 14
- 主要终点
- Major Adverse Cardiac and Cerebral Events (MACCE) at 12 and 36 months
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Group A: Platelet inhibitor - no Statin ("APT alone")
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.
干预措施: acetylsalicyclic acid (ASA) (Drug)
Group A: Platelet inhibitor - no Statin ("APT alone")
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.
干预措施: Clopidogrel (Drug)
Group B: Statins - no Platelet inhibitor ("Statin alone").
Patients will be treated with high-intensity statin therapy (Atorvastatin 40 mg once daily or Rosuvastatin 20 mg once daily)
干预措施: Rosuvastatin (Drug)
Group B: Statins - no Platelet inhibitor ("Statin alone").
Patients will be treated with high-intensity statin therapy (Atorvastatin 40 mg once daily or Rosuvastatin 20 mg once daily)
干预措施: Atorvastatin (Drug)
Group C: Statins - Platelet inhibitor ("APT AND statin")
Both types of medication are initiated as described in group A and B
干预措施: acetylsalicyclic acid (ASA) (Drug)
Group C: Statins - Platelet inhibitor ("APT AND statin")
Both types of medication are initiated as described in group A and B
干预措施: Clopidogrel (Drug)
Group C: Statins - Platelet inhibitor ("APT AND statin")
Both types of medication are initiated as described in group A and B
干预措施: Rosuvastatin (Drug)
Group C: Statins - Platelet inhibitor ("APT AND statin")
Both types of medication are initiated as described in group A and B
干预措施: Atorvastatin (Drug)
结局指标
主要结局
Major Adverse Cardiac and Cerebral Events (MACCE) at 12 and 36 months
时间窗: 12 months and 36 months post-randomization.
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
Major and fatal bleeding at 12 and 36 months
时间窗: 12 months and 36 months post-randomization.
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.
次要结局
- 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)
- Physical activity levels(At baseline)
- Modified Rankin Scale (mRS) score(From baseline to 12 months and to the end of treatment at 36 months)
- Clinical Frailty Scale (CFS) score(From baseline to 12 months and to the end of treatment at 36 months)
- Barthel Index (BI) for Activities of Daily Living (ADL)(From enrollment to 12 months and to the end of treatment at 36 months)
- Quality of life (EQ-5D)(From enrollment to 12 months and to the end of treatment at 36 months)
- CBI subtype(At baseline)
研究者
Rolf Blauenfeldt
MD, PhD, Associate professor of Neurology.
Aarhus University Hospital