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）

基本信息

批准号：
10170976
负责人：
Hooman Kamel
金额：
$ 50.28万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2021-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10170976
关键词：
2019-nCoV Acute Acute Brain Injuries Address Admission activity Affect Anticoagulant therapy Anticoagulants Anticoagulation Aspirin Atrial Fibrillation Blinded Blood Brain Injuries Brain hemorrhage C-reactive protein COVID-19 COVID-19 pandemic Cerebral Infarction Cerebral hemisphere hemorrhage Cessation of life Clinical Clinical Trials Collaborations Communities Complication Computer Interface Critical Care Critical Illness Data Data Set Decontamination Detection Devices Disease Double-Blind Method Electromagnetics Endothelium Enrollment Face Ferritin Fibrin fragment D Foundations Fright Functional disorder Future General Hospitals Guidelines Head Hemorrhage Image Infection Inflammatory Infrastructure Inpatients Intensive Care Units Intervention Studies Intracranial Hemorrhages Ischemic Stroke Knowledge Lead Link Liquid substance Magnetic Resonance Imaging Massachusetts Measures Medical Mission Multicenter Studies National Institute of Neurological Disorders and Stroke Nature Neuraxis Neurologic Neurological Models Oral Outcome Patient-Focused Outcomes Patients Phase Phenotype Physiological Prevention Prevention therapy Prevention trial Preventive Intervention Protocols documentation Public Health Randomized Randomized Clinical Trials Recording of previous events Recovery Recurrence Reporting Research Design Risk Risk Factors Safety Serological Severities Site Stroke Stroke prevention Survivors Symptoms Tablet Computer Testing Thrombophilia Thrombosis United States National Institutes of Health Ventilator Work Writing antimicrobial base body system brain health clinical care clinical practice clinical risk cohort comorbidity coronavirus disease cryogenics disability epidemiological model falls functional outcomes functional status heart rhythm high risk improved improved outcome instrument mortality neuroimaging novel patient oriented patient population portability predictive modeling prevent primary outcome public health relevance recruit secondary endpoint stroke risk

项目摘要

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，它会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，否则这些缺血性中风可能会因心房颤动而发生。有脑出血病史的患者已被排除在房颤患者抗凝临床试验之外。是否对这些患者使用抗凝治疗是一个重大的知识差距和临床困境。许多临床医生担心，抗凝治疗在预防缺血性中风方面已被证实的益处会被出血性中风的增加所抵消。多中心研究的初步数据表明，在房颤和近期脑出血患者中，抗凝治疗与缺血性中风风险降低和总体死亡率相关，但不会抵消复发性出血性中风负担的增加。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，但它们是观察结果，容易受到混杂因素和偏见的影响。在临床实践中，约三分之一的脑出血合并房颤患者接受抗凝治疗，其余患者接受阿司匹林等抗血小板治疗。目前的临床指南要求进行随机、盲法临床试验，以提供高质量的证据来确定最佳治疗方法。阿哌沙班是一种相对较新的口服抗凝药物，在最近的一项头对头试验中发现它具有与阿司匹林相似的出血风险，这使得临床试验的论点变得更加引人注目。该申请针对房颤和近期脑出血患者进行阿哌沙班与阿司匹林的多中心、双盲、随机临床试验。 NINDS StrokeNet 将在 125 个站点招募 700 名患者并进行为期 1 至 3 年的随访。该研究的目的是检验阿哌沙班与阿司匹林相比可改善预后的假设。主要结局是中风（缺血性或出血性）或死亡。这一综合结果解决了有效性和安全性问题，并代表了中风预防试验中经常使用的具有临床意义的终点。次要终点是功能状态，通过修改后的Rankin量表评分来衡量。该次要终点将用于检验以下假设：阿哌沙班不仅可以减少中风复发，还可以减少已发生中风的严重程度。如果得到证实，这一新发现将为初步试验结果提供重要的以患者为中心的背景。该提案提供了一个机会，通过关注急性期和长期的脑出血患者的大脑健康来改善脑出血患者的预后。这项研究的影响在于，无论结果如何，它的成功完成将立即指导临床护理，并为未来房颤和其他类型出血患者的抗血栓治疗试验奠定基础。

项目成果

期刊论文数量（42）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Anticoagulation after intracerebral hemorrhage: a perfect clinical scenario for genetics-based precision medicine.

脑出血后抗凝：基于遗传学的精准医学的完美临床方案。

DOI：
10.2217/pgs-2019-0181
发表时间：
2020
期刊：
Pharmacogenomics
影响因子：
2.1
作者：
Brown,StacyC;Sheth,KevinN;Falcone,GuidoJ
通讯作者：
Falcone,GuidoJ

Effect of Intensive Blood Pressure Control on Incident Stroke Risk in Patients With Mild Cognitive Impairment.

DOI：
10.1161/strokeaha.122.038818
发表时间：
2022-07
期刊：
STROKE
影响因子：
8.3
作者：
de Havenon, Adam;Sharma, Richa;Falcone, Guido J.;Prabhakaran, Shyam;Sheth, Kevin N.
通讯作者：
Sheth, Kevin N.

The Authors Reply.

DOI：
10.1038/ki.2015.131
发表时间：
2015-07
期刊：
Kidney international
影响因子：
19.6
作者：
Dong Z
通讯作者：
Dong Z

Disability Status and Secondary Prevention Among Survivors of Stroke: A Cross-Sectional Analysis of the 2011 to 2018 National Health and Nutrition Examination Survey.

DOI：
10.1161/jaha.123.030869
发表时间：
2023-12-05
期刊：
Journal of the American Heart Association
影响因子：
5.4
作者：
通讯作者：

Effect of Primary Prophylactic Antiseizure Medication for Seizure Prevention Following Intracerebral Hemorrhage in the ERICH Study.

DOI：
10.1016/j.jstrokecerebrovasdis.2021.106143
发表时间：
2022-01
期刊：
JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
影响因子：
2.5
作者：
Savalia, Krupa;Sekar, Padmini;Moomaw, Charles J.;Koch, Sebastian;Sheth, Kevin N.;Woo, Daniel;Mayson, Douglas
通讯作者：
Mayson, Douglas