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: 7858317
• 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
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7858317
• 关键词: SAMMPRIS; Stenting; vs.; Aggressive; Medical

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：颅内主要动脉粥样硬化性狭窄是卒中的重要原因，在美国每年约有50，000例卒中，第1年的成本为7.5亿美元，这些患者的终生成本为45亿美元。我们的研究小组先前进行的一项由NIH资助的临床试验（WASID）显示，阿司匹林在预防颅内狭窄患者卒中方面与华法林一样有效和安全，并且颅内狭窄70%-99%的患者尽管接受抗血栓治疗和血管风险因素的常规管理，但卒中风险较高。这些患者卒中的高风险表明需要替代治疗，如血管危险因素的强化管理和颅内支架植入术。在本申请中，我们提出了一项随机临床试验，以解决以下主要目的：为了确定颅内支架植入术（使用Wingspan自膨式镍钛合金支架）和强化药物治疗在预防主要终点方面上级单独强化药物治疗（入组后30天内的任何卒中或死亡或30天后症状性颅内动脉区域内的卒中）对于颅内主要动脉有症状性狭窄的高危患者，最长可达两年。研究两组的强化药物治疗将包括阿司匹林325 mg /天（整个随访期），氯吡格雷75 mg/天（入组后90天）和积极的风险因素管理（主要针对血压< 130 / 80 mm Hg和低密度胆固醇< 70 mg / dl）。主要假设是，与单独强化药物治疗相比，颅内支架植入术联合强化药物治疗在平均随访2年的颅内主要动脉症状性狭窄高危患者中将主要终点风险降低35%。基于对数秩检验（α = 0.05，80%把握度），检测支架植入术的主要终点发生率降低35%所需的样本量为每组382例患者，并调整了2%的失访和5%的从医疗组到支架植入组的交叉。研究神经科医生将每4个月对患者进行一次评价，以确定终点的发生率，研究内科医生将管理所有研究患者的血管风险因素。这项研究是首个在研究设计中纳入多种风险因素强化管理的二级预防卒中试验，也是首个III期颅内支架植入试验，预计其结果将为这种预后不良的常见脑血管疾病提供更有效的治疗方法。