SAMMPRIS (Stenting vs. Aggressive Medical Management for Preventing

SAMMPRIS（支架置入术与积极的医疗管理预防

• 批准号: 8064696
• 负责人: MARC IVOR CHIMOWITZ
• 金额: $ 420万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8064696
• 关键词: Accounting; Address; Alternative Therapies; Arteries; Asians; Aspirin; Blood Pressure; Blood Vessels; Bypass; Cerebrovascular Disorders; Cessation of life; Cholesterol; Clinical Trials; Developed Countries; Disease; Enrollment; Female; Funding; Gender; Hispanics; Internist; Ischemic Stroke; Lead; Life; Medical; Myocardial Infarction; National Institute of Neurological Disorders and Stroke; Neurologist; Patients; Phase; Population; Process; Randomized Clinical Trials; Recurrence; Research Design; Research Personnel; Risk; Risk Factors; Safety; Sample Size; Secondary Prevention; Stenosis; Stents; Stroke; Stroke prevention; Subgroup; Testing; Therapeutic; Time; United States National Institutes of Health; Warfarin; arm; base; basilar artery; blood pressure regulation; clinical practice; clopidogrel; cost; density; effective therapy; evidence base; follow-up; high risk; intracranial artery; middle cerebral artery; nitinol; outcome forecast; prevent; racial and ethnic; socioeconomics; spine bone structure; trial comparing; vertebral artery

Atherosclerotic stenosis of the major intracranial arteries is an important cause of stroke, accounting for approximately 50,000 strokes per year in the USA at a cost of $750,000,000 in year 1 and $4.5 billion over the life time of these patients. A previous NIH funded clinical trial (WASID) performed by our study group showed that aspirin was as effective and safer than warfarin for preventing stroke in patients with intracranial stenosis, and that patients with 70%-99% intracranial stenosis had a high risk of stroke despite antithrombotic therapy and usual management of vascular risk factors. The high risk of stroke in these patients suggests the need for alternative therapies such as intensive management of vascular risk factors and intracranial stenting. In this application we are proposing a randomized clinical trial to address the following primary aim: To determine whether intracranial stenting (using the Wingspan self-expanding nitinol stent) and intensive medical therapy is superior to intensive medical therapy alone for preventing the primary endpoint (any stroke or death within 30 days after enrollment or stroke in the territory of the symptomatic intracranial artery beyond 30 days) during a mean follow-up of two years in high-risk patients with symptomatic stenosis of a major intracranial artery. Intensive medical therapy in both arms of the study will consist of aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment, and aggressive risk factor management primarily targeting blood pressure < 130 / 80 mm Hg and low density cholesterol < 70 mg / dl. The Primary Hypothesis is that compared with intensive medical therapy alone, intracranial stenting combined with intensive medical therapy will decrease the risk of the primary endpoint by 35% over a mean follow-up of two years in high-risk patients with symptomatic stenosis of a major intracranial artery. The sample size required to detect a 35% reduction in the rate of the primary endpoint from stenting based on the logrank test with an alpha of 0.05, 80% power, and adjusting for a 2% loss to follow-up and a 5% crossover from the medical to the stenting arm is 382 patients per group. Patients will be evaluated by study neurologists every 4 months to determine the occurrence of endpoints and by study internists who will manage the vascular risk factors of all study patients. It is expected that the results of this study, which is the first secondary prevention stroke trial to incorporate intensive management of multiple risk factors in the study design, and is also the first Phase III intracranial stenting trial, will lead to more effective therapies for this common cerebrovascular disorder that is associated with a poor prognosis.

主要颅内动脉的动脉粥样硬化狭窄是中风的重要原因，考虑到 在美国，每年约50,000笔笔触，成本为750,000,000美元，超过45亿美元 这些患者的寿命。我们的研究组先前进行的NIH资助的临床试验（WASID）显示 阿司匹林比华法林与华法林一样有效，更安全，可预防颅内狭窄患者中风， 尽管抗血栓疗法 和平常管理血管危险因素。这些患者中风的高风险表明需要 替代疗法，例如对血管危险因素进行密集管理和颅内支架。在这个 应用我们正在提出一项随机临床试验以解决以下主要目的：确定 颅内支架（使用Wingspan自扩展硝基支架）和强化医疗疗法是否是 仅凭强化医疗疗法就可以防止主要终点（30岁以内任何中风或死亡 在有症状的颅内动脉征入或中风后的几天超过30天） 在主要颅内动脉症状狭窄的高危患者中的平均随访。 研究的两个臂中的强化药物疗法将包括阿司匹林325 mg / day，用于整个随访， 注册后90天，每天氯吡格雷每天75mg，主要是侵略性危险因素管理 靶向血压<130 /80 mm Hg，低密度胆固醇<70 mg / dL。主要假设 是与仅强化医疗疗法相比，颅内支架与密集型医疗相比 在高风险的平均随访中，治疗将使主要终点的风险降低35％ 主要颅内动脉有症状狭窄的患者。检测35％所需的样本量 基于logrank测试的支架降低了主要终点的速率，α为0.05，80％ 功率，调整2％的随访损失，从医疗到支架臂的5％的交叉为382 每组患者。研究神经科医生将每4个月对患者进行评估，以确定 终点的发生以及将管理所有研究患者血管风险因素的研究内科医生。 可以预期，这项研究的结果是第一次纳入二次预防中风试验 研究设计中多个风险因素的密集管理，也是颅内第一阶段 支架试验将导致对这种常见脑血管疾病的更有效疗法 预后不良。