StAtins Use in intRacereberal hemorrhage patieNts MRI (SATURN MRI) Ancillary Study

他汀类药物在脑出血患者中的使用 MRI (SATURN MRI) 辅助研究

• 批准号: 10179775
• 负责人: Magdy H Selim
• 金额: $ 270.54万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10179775
• 关键词: Address; American; Ancillary Study; Area; Benefits and Risks; Biological Markers; Blinded; Boston; Brain; Brain hemorrhage; Brain imaging; Cardiovascular system; Cerebral Amyloid Angiopathy; Cerebral hemisphere hemorrhage; Cerebral small vessel disease; Cerebrum; Cholesterol; Cognitive; Complement; Data; Decision Making; Deterioration; Elderly; Enrollment; Event; Funding; Hemorrhage; Hospitalization; Impaired cognition; Incidence; Infarction; Injury; Knowledge; Lead; Lesion; Link; Lobar; Location; Long-Term Effects; Magnetic Resonance Imaging; Monitor; National Institute of Neurological Disorders and Stroke; Outcome; Participant; Pathogenesis; Patients; Pharmaceutical Preparations; Phase III Clinical Trials; Predisposition; Prevention; Protocols documentation; Public Health Practice; Quality of life; Randomized; Recurrence; Reporting; Research; Risk; Safety; Screening procedure; Secondary to; Siderosis; Standardization; Study of magnetics; Telephone; Uncertainty; United States National Institutes of Health; Validation; White Matter Hyperintensity; cerebral microbleeds; cognitive testing; disability; follow-up; functional decline; functional outcomes; high risk; imaging biomarker; imaging study; improved; insight; neuroimaging; new therapeutic target; novel; open label; personalized decision; primary outcome; progression marker; prospective; risk stratification; stroke patient; tool; welfare

There is a knowledge gap as to whether statins should be used in patients with intracerebral hemorrhage (ICH), in particular patients with lobar ICH who are at high-risk for recurrent ICH. There are no prospective or randomized data on the effects of continuation vs. discontinuation of statins after ICH regarding the risks of ICH recurrence, incidence of cardiovascular events, or long-term functional or cognitive outcomes and quality of life. The SATURN trial (a multi-center, pragmatic, prospective, randomized, open-label, Phase III clinical trial with blinded end-point assessment in patients with lobar ICH taking statins) was recently funded within the NIH/NINDS StrokeNet to address the above uncertainties. We propose an ancillary MRI study (SATURN MRI) which builds on SATURN’s framework. Participants in SATURN will undergo a standardized brain MRI at baseline and at 24 months in order to assess for the presence and burden of markers of cerebral small vessel disease (CSVD) and their progression. The main objective is to determine the effects of continued long-term statin therapy compared to statin discontinuation on the incidence of new hemorrhagic MRI markers of CSVD, namely cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS) on end-study MRI. Secondary objectives are: 1) to assess whether the presence and burden of CMBs and cSS on baseline MRI can be used as an imaging marker to stratify the risk/benefit of statin therapy in patients with lobar ICH; and 2) to evaluate the effects of statin continuation vs. discontinuation on the incidence of new ischemic MRI markers (white matter hyperintensities and covert infarcts) on end-study MRI. This information will be invaluable to complement the interpretation of SATURN’s results. It will provide unique insights on the effect of statins on progression of markers of CSVD, and could lead to validation of MRI imaging markers as tools to assist with individualized decision-making regarding the safety of statins use/continuation in ICH patients and the mitigation of late life cognitive and functional decline. SATURN and SATURN MRI will provide a unique opportunity to simultaneously address important areas in ICH research identified by the NINDS PRG and StrokeNet: 1) prevention of ICH recurrence; and 2) biomarkers that may modify treatment decisions in stroke patients. Furthermore, observations from SATURN MRI could lead to novel hypotheses for further research elucidating the pathogenesis of CSVD implicated in lobar ICH and ultimately lead to novel therapeutic targets aimed at mitigating the progression of microvascular cerebral injury and ensuing disability. These studies have important potential public health and practice implications.

对于脑出血（ICH），特别是患有高风险经常性ICH的LOBAR ICH患者，是否应使用他汀类药物的知识差距。关于ICH之后的持续性与汀类药物的造成影响的前瞻性或随机数据，关于ICH复发的风险，心血管事件的发生率或长期功能或认知结果以及生活质量的影响。土星试验（一项多中心，务实，前瞻性，随机，开放标签，III期临床试验，对LOBAR ICH统计的患者进行了盲目的终点评估）最近在NIH/NIHNS Strokenet中资助，以解决上述不确定性。我们提出了一项辅助MRI研究（土星MRI），该研究基于土星的框架。土星的参与者将在基线和24个月时接受标准化的大脑MRI，以评估脑小血管疾病（CSVD）的标记物及其进展。主要目的是确定与他汀类药物中断对CSVD的新出血MRI标记的事件相比，持续长期他汀类药物治疗的影响，即脑微粒（CMBS）和皮质浅表表层（CMBS）对终结MRI的影响。次要目标是：1）评估CMB和CSS在基线MRI上的存在和伯恩是否可以用作成像标记，以分层LOBAR ICH患者他汀类药物治疗的风险/益处； 2）评估他汀类药物持续性与停用对新缺血性MRI标记（白质超强度和秘密梗塞）事件的影响。这些信息将是无价的，可以完成对土星结果的解释。它将提供有关他汀类药物对CSVD标记进展的影响的独特见解，并可能导致对MRI成像标记的验证，作为有关ICH患者的统计使用/持续性的个性化决策以及缓解后期生活认知和功能下降和功能下降和功能性下降的工具。土星和土星MRI将提供一个独特的机会，可以简单地解决Ninds PRG和Strokenet确定的ICH研究中的重要领域：1）预防ICH复发； 2）可能会改变中风患者治疗决策的生物标志物。此外，土星MRI的观察结果可能导致新的假设，以进一步研究阐明Lobar ICH中实施的CSVD的发病机理，并最终导致旨在减轻微血管大脑损伤进展并确保残疾的新型治疗靶标。这些研究具有重要的潜在公共卫生和实践意义。

项目成果

Use of Lipid-Lowering Drugs After Intracerebral Hemorrhage.

• DOI: 10.1161/strokeaha.122.036889
• 发表时间: 2022-07
• 期刊: Stroke
• 影响因子: 8.3

Etiology of Primary Cerebellar Intracerebral Hemorrhage Based on Topographic Localization.

基于地形定位的原发性小脑脑出血的病因学。

• DOI: 10.1161/strokeaha.123.044271
• 发表时间: 2023
• 期刊: Stroke
• 影响因子: 8.3
• 作者: Incontri,Diego;Marchina,Sarah;Andreev,Alexander;Wilson,Mitchell;Wang,Jia-Yi;Lin,David;Heistand,ElizabethC;Carvalho,Filipa;Selim,Magdy;Lioutas,Vasileios-Arsenios
• 通讯作者: Lioutas,Vasileios-Arsenios

Effect of Deferoxamine on Trajectory of Recovery After Intracerebral Hemorrhage: A Post Hoc Analysis of the i-DEF Trial.

• DOI: 10.1161/strokeaha.121.037298
• 发表时间: 2022-07
• 期刊: Stroke
• 影响因子: 8.3