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)

• 批准号: 9311842
• 负责人: EDWARD SANDER CONNOLLY
• 金额: $ 71.45万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 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/9311842
• 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; cost; hemodynamics; imaging biomarker; improved

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.

高级颈动作狭窄引起的脑血流动力学损害会损害认知 即使在没有中风的情况下，也直接导致认知能力下降，或结果 较高的沉默梗塞发生。虽然有案件的良好初步证据 血液动力学障碍会影响患者认知的系列和物理研究 颈动脉闭塞性疾病，这种疾病的治疗从未在随机临床上进行测试 审判。我们建议对Ninds赞助的CREST-2试验进行辅助研究，一对 结果盲，第3阶段的临床试验，针对无症状高级颈动脉的患者 狭窄将比较颈动脉内膜切除术以及最佳药物疗法（OMT）与 仅OMT（n = 1,240），颈动脉支架支架加上OMT对OMT（n = 1,240），以防止 中风和死亡。 。我们的申请解决了是否认知的有趣问题 当损伤因脑部异常血液动力学灌注而造成损害 CREST-2-2型患者的血液动力学受损子集。我们将注册500 Crest-2的患者，所有人都在基线和年度接受认知评估 此后。我们将确定100例由Inter-Inter-inter-inter-into-Inter-in- 半球MRI灌注“达到峰值的时间”（TTP）狭窄侧的延迟。在那些人中 被认为是血液动力学障碍，并且具有基线认知障碍，认知能力 基线和1年时的电池将确定分配给流量故障的人是否被分配给 Crest-2中的血运臂比医学中的认知结果更好 与没有流量故障的人相比，只有手臂与这种治疗差异相比。我们 假设血液动力学意义上的“无症状”颈动脉疾病可能代表 可治疗原因障碍原因的几个例子。如果认知能力下降可以逆转 在这些患者中，我们将建立一个新的颈动脉血运重建指标 独立于复发性中风的风险。