Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial - Hemodynamics (CREST-H)

无症状颈动脉狭窄试验的颈动脉血运重建和医疗管理 - 血流动力学 (CREST-H)

基本信息

批准号：
9923010
负责人：
EDWARD SANDER CONNOLLY
金额：
$ 61.77万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-05-15 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9923010
关键词：
Address Affect Age Algorithms Ancillary Study Blinded Carotid Artery Diseases Carotid Endarterectomy Carotid Stenosis Carotid stent Case Series Cerebral Infarction Cessation of life Circle of Willis Clinical Cognition Cognitive Core-Binding Factor Disease Embolism Enrollment Failure General Population Impaired cognition Impairment Individual Infarction Lead Magnetic Resonance Imaging Measures Medical Mental Depression National Institute of Neurological Disorders and Stroke Outcome Patients Pattern Perfusion Perfusion Weighted MRI Phase III Clinical Trials Physiological Population Prevalence Progressive Disease Public Health Randomized Randomized Clinical Trials Recurrence Risk Side Specificity Stenosis Stroke Stroke prevention Testing Therapeutic Embolization Thrombosis Time Vascular Cognitive Impairment arm cerebral blood volume cerebral hemodynamics cognitive performance cognitive testing hemodynamics imaging biomarker improved societal costs stroke risk

项目摘要

Cerebral hemodynamic impairment due to high-grade carotid artery stenosis can impair cognition even in the absence of stroke, contributing to cognitive decline either directly, or as a consequence of a higher occurrence of silent infarction. Although there is good preliminary evidence from case series and physiological studies that hemodynamic impairment affects cognition in patients with carotid occlusive disease, treatment of this condition has never been tested in a randomized clinical trial. We propose to conduct an ancillary study to the NINDS-sponsored CREST-2 trial, a pair of outcome-blinded, Phase 3 clinical trials for patients with asymptomatic high-grade carotid artery stenosis which will compare carotid endarterectomy plus optimal medical therapy (OMT) versus OMT alone (n=1,240), and carotid artery stenting plus OMT versus OMT alone (n=1,240) to prevent stroke and death. . Our application addresses the intriguing question of whether cognitive impairment can be reversed when it arises from abnormal cerebral hemodynamic perfusion in a hemodynamically impaired subset of the CREST-2 –randomized patients. We will enroll 500 patients from CREST-2, all of whom receive cognitive assessments at baseline and yearly thereafter. We will identify 100 patients with hemodynamic impairment as measured by an inter- hemispheral MRI perfusion “time to peak” (TTP) delay on the side of stenosis. Among those who are found to be hemodynamically impaired and have baseline cognitive impairment, the cognitive batteries at baseline and at 1 year will determine if those with flow failure who are assigned to revascularization arm in CREST-2 will have better cognitive outcomes than those in the medical- only arm compared with this treatment difference for those who have no flow failure. We hypothesize that hemodynamically significant “asymptomatic” carotid disease may represent one of the few examples of treatable causes of cognitive impairment. If cognitive decline can be reversed in these patients, then we will have established a new indication for carotid revascularization independent of the risk of recurrent stroke.

颈动脉高度狭窄导致的脑血流动力学损害会损害认知即使没有中风，也会直接或间接导致认知能力下降尽管有良好的初步证据表明无症状梗塞的发生率较高。系列和生理学研究表明血流动力学损伤影响患者的认知颈动脉闭塞性疾病，这种疾病的治疗从未在随机临床试验中进行过测试我们建议对 NINDS 赞助的 CREST-2 试验进行一项辅助研究。针对无症状高级别颈动脉患者的结果盲法 3 期临床试验狭窄，将比较颈动脉内膜切除术加最佳药物治疗 (OMT) 与单独使用 OMT（n=1,240），以及颈动脉支架置入术加 OMT 对比单独使用 OMT（n=1,240）以预防我们的应用程序解决了认知是否存在的有趣问题。当脑血流动力学灌注异常引起损伤时，损伤可以逆转。 CREST-2 中血流动力学受损的子集——随机分组的患者，我们将招募 500 名患者。来自 CREST-2 的患者，所有患者均在基线和每年接受认知评估此后，我们将确定 100 名患有血流动力学损伤的患者，并通过内部检查进行测量。狭窄一侧的半球 MRI 灌注“达到峰值时间”(TTP) 延迟。被发现存在血流动力学障碍并具有基线认知障碍，即认知障碍基线和 1 年时的电池将确定那些出现流动故障的人是否被分配到 CREST-2 中的血运重建臂将比医学上的血运重建臂具有更好的认知结果对于那些没有血流衰竭的人来说，这种治疗方法仅与手臂相比有差异。认为血流动力学显着的“无症状”颈动脉疾病可能代表其中一种如果认知能力下降可以逆转，那么可治疗的认知障碍的例子很少。在这些患者中，我们将确定颈动脉血运重建的新适应症与中风复发的风险无关。