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.

颅内大动脉粥样硬化性狭窄是中风的重要原因， 美国每年约有 50,000 例中风，第一年的成本为 7.5 亿美元，之后的成本为 45 亿美元 这些患者的生命周期。我们的研究小组之前进行的一项 NIH 资助的临床试验 (WASID) 显示 阿司匹林对于预防颅内狭窄患者中风与华法林一样有效且安全， 颅内狭窄 70%-99% 的患者尽管接受抗血栓治疗，仍有较高的中风风险 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需要 替代疗法，例如血管危险因素的强化管理和颅内支架置入术。在这个 我们正在提议一项随机临床试验来解决以下主要目标： 颅内支架置入术（使用 Wingspan 自膨式镍钛合金支架）和强化药物治疗是否有效 在预防主要终点（30 天内任何中风或死亡）优于单独强化药物治疗 入组后的天数或有症状的颅内动脉区域中风超过 30 天） 对有症状的颅内主要动脉狭窄的高危患者进行平均两年的随访。 研究两组的强化药物治疗将包括在整个随访期间每天服用 325 毫克阿司匹林， 入组后每天服用氯吡格雷 75 毫克，持续 90 天，并主要进行积极的危险因素管理 目标血压 < 130 / 80 mm Hg 和低密度胆固醇 < 70 mg/dl。主要假设 与单纯强化药物治疗相比，颅内支架置入术联合强化药物治疗 在高风险患者的平均随访两年内，该治疗将使主要终点的风险降低 35% 有症状的颅内主要动脉狭窄的患者。检测35%所需的样本量 基于对数秩检验，α 为 0.05，支架置入术主要终点率降低 80% 第 382 章 每组患者。研究神经科医生将每 4 个月对患者进行一次评估，以确定 终点的发生以及由研究内科医生管理所有研究患者的血管危险因素。 预计这项研究的结果将纳入第一个二级预防中风试验 研究设计中对多个危险因素进行强化管理，也是首个颅内III期研究 支架置入试验将为这种与相关的常见脑血管疾病提供更有效的治疗方法 预后不良。