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律失常，可使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，否则可能会导致缺血性中风。 由心房颤动引起。有脑出血病史的患者已被排除在外 房颤患者抗凝治疗的临床试验。这些情况是否要使用抗凝药物 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，已证实的益处 预防缺血性中风的抗凝治疗将被出血性中风的增加所抵消。初步的 多中心研究的数据表明，在患有心房颤动和近期脑内出血的患者中， 出血、抗凝治疗与缺血性中风和总体死亡率降低的风险相关 复发性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相关。尽管这些数据令人信服， 它们是观察结果，容易受到混杂和偏见的影响。在临床实践中，大约有三分之一 脑出血和房颤患者接受抗凝治疗，其余患者接受抗凝治疗 抗血小板治疗，如阿司匹林。目前的临床指南要求进行随机、盲法临床试验 提供高质量的证据以确定最佳治疗方案。临床试验的论点更加充分 阿哌沙班（一种相对较新的口服抗凝药物）的出现引人注目，人们发现它具有类似的作用 在最近的一项头对头试验中，其出血风险与阿司匹林相同。该申请适用于多中心、双盲、 阿哌沙班与阿司匹林在心房颤动和近期脑内出血患者中的随机临床试验 出血。 NINDS 将在 125 个地点招募 700 名患者并进行为期 1 至 3 年的随访 中风网。该研究的目的是检验以下假设：与阿哌沙班相比，阿哌沙班可以改善结果 阿司匹林。主要结局是中风（缺血性或出血性）或死亡。这个综合结果 解决了有效性和安全性的问题，并代表了经常用于中风的具有临床意义的终点 预防试验。次要终点是功能状态，通过修改后的Rankin量表测量 分数。该次要终点将用于检验阿哌沙班不仅可以减少中风的假设 复发以及任何确实发生的中风的严重程度。如果得到证实，这一新颖的发现将提供 初步试验结果以患者为中心的重要背景。该提案提供了一个改进的机会 通过关注急性期脑出血患者的大脑健康来评估脑出血患者的结局 设置和长期。这项研究的影响在于它的成功完成，无论 其结果的方向，将立即指导临床护理，并为未来的抗血栓试验奠定基础 房颤和其他类型出血患者的治疗。