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）：颅内大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，第一年的成本为7.5亿美元，这些患者的整个生命周期的成本为45亿美元。先前由我们的研究组进行的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，并且尽管抗血栓治疗和血管危险因素的常规管理，70%-99%颅内狭窄的患者仍有较高的卒中风险。这些患者中风的高风险提示需要替代疗法，如强化血管危险因素管理和颅内支架置入术。在此申请中，我们建议进行随机临床试验，以解决以下主要目标：为了确定颅内支架植入（使用翼展自扩式镍钛诺支架）和强化药物治疗是否优于单独强化药物治疗，以预防主要终点（入组后30天内的任何卒中或死亡，或30天以上症状性颅内动脉狭窄的高危患者），平均随访2年。在整个随访期间，两组患者的强化药物治疗包括阿司匹林325 mg /天，入组后90天氯吡格雷75mg /天，积极的危险因素管理，主要目标是血压< 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，颅内支架植入联合强化药物治疗在颅内大动脉症状性狭窄的高危患者中，平均随访2年，主要终点风险降低35%。根据logrank检验（alpha值为0.05，功率为80%），检测支架术主要终点发生率降低35%所需的样本量为每组382例患者，并对随访损失2%和从医学组到支架术组交叉5%进行调整。研究神经学家将每4个月对患者进行评估，以确定终点的发生，并由研究内科医生对所有研究患者的血管危险因素进行管理。该研究是首个在研究设计中纳入多危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，预计该研究结果将为这种常见的预后较差的脑血管疾病提供更有效的治疗方法。