Anticoagulation in ICH Survivors for Prevention and Recovery (ASPIRE)

ICH幸存者的抗凝治疗以预防和恢复（ASPIRE）

• 批准号: 10159987
• 负责人: Hooman Kamel
• 金额: $ 427.03万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10159987
• 关键词: Acute; Address; Adopted; Affect; Anticoagulant therapy; Anticoagulants; Anticoagulation; Aspirin; Atrial Fibrillation; Benefits and Risks; Blinded; Blood Platelets; Brain Injuries; Brain hemorrhage; Cerebral hemisphere hemorrhage; Cessation of life; Clinical; Clinical Trials; Confidence Intervals; Data; Disease; Double-Blind Method; Electrocardiogram; Event; Exclusion; Face; Fright; Future; General Population; Guidelines; Head; Hemorrhage; Hospitalization; Ischemia; Ischemic Stroke; Knowledge; Lobar; Magnetic Resonance Imaging; Measures; Mission; Multicenter Studies; National Institute of Neurological Disorders and Stroke; Observational Study; Oral; Outcome; Participant; Patient-Focused Outcomes; Patients; Phase; Physicians; Population; Prevention; Prevention trial; Quality of life; Randomized; Recommendation; Recording of previous events; Recovery; Recurrence; Risk; Safety; Severities; Site; Stroke; Stroke prevention; StrokeNet trials; Subarachnoid Hemorrhage; Survivors; Testing; Therapeutic Effect; United States National Institutes of Health; Warfarin; Work; antagonist; brain health; cerebrovascular; clinical care; clinical practice; cognitive function; comparative; disability; experience; functional improvement; functional outcomes; functional status; hazard; heart rhythm; high risk; improved; improved outcome; indexing; knowledge base; mortality; novel; patient oriented; patient population; post stroke; prevent; primary endpoint; primary outcome; public health relevance; randomized trial; randomized, clinical trials; recruit; secondary endpoint; stroke risk; thrombotic

Atrial fibrillation, the most common heart-rhythm disorder, increases the risk of ischemic stroke by 3- to 5-fold. Anticoagulant therapy has been proven to prevent 60-80% of ischemic strokes that would otherwise occur from atrial fibrillation. Patients with a history of intracerebral hemorrhage have been excluded from clinical trials of anticoagulation in patients with atrial fibrillation. Whether to use anticoagulation in these patients represents a major knowledge gap and clinical dilemma. Many clinicians fear that the proven benefit of anticoagulation in preventing ischemic stroke will be offset by an increase in hemorrhagic stroke. Preliminary data from multicenter studies indicate that, in patients with atrial fibrillation and recent intracerebral hemorrhage, anticoagulation is associated with a decreased risk of ischemic stroke and overall mortality with no offsetting increase in the burden of recurrent hemorrhagic stroke. These pilot data also suggest that anticoagulation is associated with better long-term functional outcomes. Although these data are compelling, they are observational findings and subject to confounding and bias. In clinical practice, about one-third of patients with intracerebral hemorrhage and atrial fibrillation receive anticoagulation and the remainder receive antiplatelet therapy such as aspirin. Current clinical guidelines call for randomized, blinded clinical trials to provide high-quality evidence to determine the best treatment. The argument for a clinical trial is made more compelling by the advent of apixaban, a relatively new oral anticoagulant drug, which was found to have similar bleeding risks as aspirin in a recent head-to-head trial. This application is for a multicenter, double-blinded, randomized clinical trial of apixaban versus aspirin in patients with atrial fibrillation and a recent intracerebral hemorrhage. Seven hundred patients will be recruited and followed for 1 to 3 years at 125 sites in NINDS StrokeNet. The aim of the study will be to test the hypothesis that apixaban improves outcomes compared to aspirin. The primary outcome will be any stroke (ischemic or hemorrhagic) or death. This composite outcome addresses both efficacy and safety, and represents a clinically meaningful endpoint often used in stroke prevention trials. The secondary endpoint will be functional status, as measured by the modified Rankin Scale score. This secondary endpoint will be used to test the hypothesis that apixaban not only reduces stroke recurrence but also the severity of any strokes that do occur. If confirmed, this novel finding would provide an important patient-centered context for the primary trial results. This proposal offers an opportunity to improve the outcomes of patients with intracerebral hemorrhage by focusing on their brain health both in the acute setting and over the long term. The impact of this study is that its successful completion, regardless of the direction of its results, would immediately guide clinical care and set the stage for future trials of antithrombotic therapy in patients with atrial fibrillation and other types of bleeding.

心房颤动是最常见的心脏节律障碍，将缺血性中风的风险增加3至 5倍。抗凝治疗已被证明可以预防60-80％的缺血性中风 从房颤发生。有脑内出血史的患者已被排除在外 心房颤动患者抗凝抗凝的临床试验。是否在这些中使用抗凝治疗 患者代表了主要的知识差距和临床困境。许多临床医生担心 止血性中风的增加将抵消预防缺血性中风的抗凝治疗。初步的 来自多中心研究的数据表明，在心房颤动和最近脑内的患者中 出血，抗凝症与缺血性中风的风险降低以及总体死亡率有关 反复出血性中风的负担没有抵消增加。这些试点数据还表明 抗凝治疗与更好的长期功能结果有关。尽管这些数据令人信服，但 它们是观察性的发现，并受到混淆和偏见的影响。在临床实践中，约有三分之一 脑内出血和房颤患者接受抗凝治疗，其余的患者接受 抗血小板疗法，例如阿司匹林。当前的临床准则要求对随机，盲目的临床试验进行 提供高质量的证据以确定最佳治疗方法。临床试验的论点更多 由阿皮克斯班（Apixaban 在最近的一项头对头试验中，将出血风险作为阿司匹林。此应用程序适用于多中心，双盲， 心房颤动患者和最近脑内的apixaban与阿司匹林的随机临床试验 出血。将在Ninds的125个地点招募700名患者，并在125个地点招募1至3年 Strokenet。该研究的目的是检验以下假设：apixaban与 阿司匹林。主要结果将是任何中风（缺血或出血）或死亡。这种综合结果 解决疗效和安全性，并代表经常在中风中使用的临床意义有意义的终点 预防试验。次要终点将是功能状态，如修改后的Rankin量表所测量 分数。该次要终点将用于测试apixaban不仅减少中风的假设 复发，但确实发生了任何中风的严重性。如果得到确认，这一小说发现将提供 主要试验结果的重要以患者为中心的环境。该建议提供了改进的机会 脑出血患者的结局，通过重点关注急性的大脑健康。 设置和长期。这项研究的影响是，无论是如何成功完成 其结果的方向将立即指导临床护理，并为抗血栓形成的未来试验奠定了基础 心房颤动和其他类型的出血患者的治疗。