SAMMPRIS (Stenting vs. Aggressive Medical Management for Preventing . . .

描述(由申请人提供)：主要颅内动脉的动脉粥样硬化性狭窄是中风的一个重要原因，在美国每年约有50,000例中风，第一年的成本为7.5亿美元，这些患者的一生成本为45亿美元。我们研究组先前进行的一项由美国国立卫生研究院资助的临床试验(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，而且尽管进行了抗血栓治疗和常规的血管危险因素处理，但70%-99%的颅内狭窄患者仍有较高的卒中风险。这些患者中风的高风险表明需要替代治疗，如强化血管危险因素的管理和颅内支架置入术。在本申请中，我们建议进行一项随机临床试验，以解决以下主要目标：在对有症状的颅内动脉狭窄的高危患者进行平均两年的随访期间，确定在预防主要终点(登记后30天内的任何中风或死亡或中风超过30天)方面，颅内支架置入术(使用翼展自膨式镍钛合金支架)和强化药物治疗是否优于单独的强化药物治疗。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，登记后90天内每天75毫克的氯吡格雷，以及主要针对血压和130/80毫米汞和低密度胆固醇&70毫克/dl的积极风险因素管理。基本假设是，与单纯强化药物治疗相比，在平均两年的随访中，颅内支架置入术结合强化药物治疗将使有症状的颅内大动脉狭窄的高危患者的主要终点风险降低35%。根据α为0.05，80%功率的logrank测试，并调整2%的随访率和5%的从医学到支架的交叉，每组382名患者，检测支架置入术的主要终点的比率降低35%所需的样本量。研究神经科医生将每4个月对患者进行评估，以确定终点的发生情况，研究内科医生将管理所有研究患者的血管风险因素。这项研究是第一次在研究设计中纳入对多种危险因素的强化管理的二级预防中风试验，也是第一次第三阶段颅内支架试验，预计这项研究的结果将导致对这种与预后不良相关的常见脑血管疾病进行更有效的治疗。

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.