Hemostasis, Hematoma Expansion, and Outcomes After Intracerebral Hemorrhage

脑出血后的止血、血肿扩张和结果

• 批准号: 10388105
• 负责人: ANDREW M NAIDECH
• 金额: $ 60.76万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10388105
• 关键词: Acute; Affect; Age; American; Aminocaproic Acids; Antifibrinolytic Agents; Aspirin; Blood Coagulation Factor VII; Blood Platelets; Brain Injuries; Cerebral hemisphere hemorrhage; Cessation of life; Chicago; Clinical Trials; Coagulation Process; Data; Dependence; Desmopressin; Development; Diagnostic; Doctor of Philosophy; Enrollment; Factor VIIa; Fibrinolysis; Future; Growth; Hematoma; Hemorrhage; Hemostatic Agents; Hemostatic function; Hypomagnesemia; Image; Information Systems; Intervention; Intuition; Lead; Machine Learning; Measurement; Measures; Medicine; Myocardial Ischemia; Nervous System Trauma; Outcome; Outcome Measure; Pathway interactions; Patient Outcomes Assessments; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Platelet Transfusion; Population; Quality of life; Recording of previous events; Reporting; Risk; Scanning; Stroke; Survivors; System; Texas; Thrombelastography; Tranexamic Acid; United States Food and Drug Administration; United States National Institutes of Health; Universities; Vascular Diseases; X-Ray Computed Tomography; brain tissue; clopidogrel; disability; effective therapy; follow-up; health related quality of life; improved; improved outcome; machine learning algorithm; metropolitan; point of care; prevent; prospective; stroke trials; treatment strategy

PROJECT SUMMARY Intracerebral hemorrhage (ICH) is the most morbid form of stroke and has no treatment approved by the US Food and Drug Administration. Hematoma expansion (HE), interval growth of the hematoma, is a proximate cause of worse patient outcomes and death as larger hematomas displace brain tissue; hematomas > 60 mL reliably lead to disability or death at follow-up. Preventing HE is a promising strategy to improve outcomes for patients with ICH. Our relative inability to predict HE, however, has impeded the development of effective treatment strategies for ICH, and several clinical trials have been unsuccessful. Even when HE has been reduced, our ability to detect a benefit is hampered by relatively insensitive patient outcomes. This proposal will resolve two roadblocks that prevent the development of effective treatments for ICH, the most morbid form of stroke. Three comprehensive stroke centers (two from the Northwestern Medicine system in metropolitan Chicago, IL, and the University of Texas at Houston) will partner to prospectively enroll patients with ICH, measure hemostasis, measure HE, and record patient outcomes with state of the art assessments, including the NIH Patient Reported Outcomes Measurement Information System (PROMIS) and NIH Toolbox. First, we will determine the mechanisms that lead to HE in acute ICH, broadly grouped into platelet activity, activation of coagulation, and fibrinolysis. Each can be specifically measured and has specific treatments to improve it. For example, reduced platelet activity due to aspirin can be reliably improved with desmopressin, delayed activation of coagulation may be related to hypomagnesemia, and accelerated fibrinolysis may be reduced with tranexamic acid or aminocaproic acid. Each will be examined for predicting HE; if multiple pathways are found, we will determine which are most important with machine learning. Once the most important mechanisms of hemostasis for HE are determined, we will explore if specific therapies improve platelet activity. It is possible that specific treatments for specific deficits in hemostasis will be more likely to reduce HE than single therapies applied to ICH patients generally (e.g., Factor VII). Once hemostatic mechanisms of HE are determine, we will determine the effect of HE on patient outcomes such as the modified Rankin Scale (mRS, a global ordinal scale), PROMIS, and NIH Toolbox. This will be crucial to plan for future clinical trials intended to improve patient outcomes through correcting abnormal hemostasis in acute ICH. Results will apply broadly to other bleeding conditions (e.g., neurotrauma).

项目概要 脑出血 (ICH) 是最常见的中风形式，美国尚无批准的治疗方法 食品和药物管理局。血肿扩张（HE），即血肿的间隔增长，是一种近似的 由于较大的血肿取代了脑组织，导致患者预后更差和死亡；血肿 > 60 mL 随访时可靠地导致残疾或死亡。预防 HE 是改善预后的一项有前景的策略 脑出血患者。然而，我们相对无法预测 HE，这阻碍了有效方法的开发。 ICH 的治疗策略和一些临床试验均未成功。即使他已经 减少，我们发现益处的能力受到相对不敏感的患者结果的阻碍。该提案将 解决阻碍 ICH 有效治疗方法开发的两个障碍，ICH 是最常见的疾病形式 中风。 三个综合性中风中心（其中两个来自伊利诺伊州芝加哥大都市的西北医学系统， 和德克萨斯大学休斯敦分校）将合作前瞻性地招募 ICH 患者，测量 通过最先进的评估（包括 NIH）来止血、测量 HE 并记录患者结果 患者报告结果测量信息系统 (PROMIS) 和 NIH 工具箱。 首先，我们将确定导致急性脑出血中 HE 的机制，大致分为血小板活性、 激活凝血和纤维蛋白溶解。每一个都可以专门测量并有特定的治疗方法 改进它。例如，使用去氨加压素可以可靠地改善阿司匹林导致的血小板活性降低， 凝血激活延迟可能与低镁血症有关，而纤维蛋白溶解加速可能与低镁血症有关。 用氨甲环酸或氨基己酸还原。每一项都将接受检查以预测 HE；如果有多个 找到路径后，我们将确定哪些对机器学习最重要。曾经最 HE 止血的重要机制已确定，我们将探讨具体疗法是否有所改善 血小板活性。针对特定止血缺陷的特定治疗可能更有可能 与一般应用于 ICH 患者的单一疗法（例如因子 VII）相比，可减少 HE。 一旦确定了 HE 的止血机制，我们将确定 HE 对患者预后的影响 例如修改后的Rankin量表（mRS，全球序数量表）、PROMIS和NIH Toolbox。这将是 对于计划未来旨在通过纠正异常来改善患者结果的临床试验至关重要 急性脑出血的止血。结果将广泛适用于其他出血情况（例如神经外伤）。