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: 7696264
• 负责人: MARC IVOR CHIMOWITZ
• 金额: $ 397.83万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7696264
• 关键词: Accounting; Address; Alternative Therapies; Arteries; Asians; Aspirin; Blood Pressure; Blood Vessels; Bypass; Cerebrovascular Disorders; Cessation of life; Cholesterol; Clinical; Clinical Trials; Developed Countries; Developing Countries; Disease; Economics; End Point; Enrollment; Female; Funding; Gender; Hispanics; Internist; Ischemic Stroke; Lead; Life; Medical; Myocardial Infarction; Neurologist; Patients; Phase; Population; Process; Randomized; Randomized Clinical Trials; Rate; 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; Upper arm; Warfarin; base; basilar artery; blood pressure regulation; clopidogrel; cost; day; density; follow-up; intracranial artery; middle cerebral artery; nitinol; outcome forecast; prevent; racial and ethnic; 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.

颅内主要动脉的动脉粥样硬化性狭窄是中风的重要原因，占 在美国，每年大约有50,000次中风，第一年的成本为750,000,000美元，而 这些患者的生命周期。我们研究组之前由NIH资助的临床试验(WASID)显示 阿司匹林在预防颅内狭窄患者中风方面与华法林一样有效和安全， 尽管接受了抗血栓治疗，70%-99%的颅内狭窄患者仍有很高的中风风险 以及血管危险因素的常规管理。这些患者中风的高风险表明有必要 替代疗法，如血管危险因素的强化管理和颅内支架置入术。在这 应用我们提议进行一项随机临床试验，以解决以下主要目标：确定 颅内支架置入术(使用翼展自膨式镍钛合金支架)和强化内科治疗是否 在预防主要终点(30岁以内的任何中风或死亡)方面优于单独的强化药物治疗 登记后或在有症状的颅内动脉领域中风超过30天)期间 有症状性颅内动脉狭窄的高危患者的平均随访时间为两年。 这项研究的两个分支的强化药物治疗将包括整个随访期间每天325毫克的阿司匹林， 氯吡格雷75 mg/d，入选后90天，以积极的危险因素管理为主 目标血压和低密度胆固醇分别为130/80毫米汞柱和70毫克/分升。基本假设 与单纯的强化治疗相比，颅内支架置入术与强化治疗相结合 在高危人群平均两年的随访中，治疗将使主要终点的风险降低35% 有症状的颅内大动脉狭窄的患者。检测35%所需的样本大小 根据阿尔法为0.05-80%的LOGRANK测试，支架置入术降低了主要终点的发生率 功率，并调整2%的随访损失和5%的从医疗到支架臂的交叉是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的血管风险因素的研究内科医生。 预计这项研究的结果，这是第一个纳入中风二级预防试验的 在研究设计中集约化管理多个危险因素，也是首期颅内III期 支架植入试验，将导致对这种常见的脑血管疾病的更有效的治疗 预后不佳。