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）：颅内主要动脉的粥样硬化性狭窄是中风的重要原因，在美国每年约导致 50,000 例中风，第一年的费用为 750,000,000 美元，这些患者一生的费用为 45 亿美元。我们的研究小组之前进行的一项NIH资助的临床试验（WASID）表明，阿司匹林对于预防颅内狭窄患者的卒中与华法林一样有效且安全，并且颅内狭窄70%-99%的患者尽管进行了抗血栓治疗和常规的血管危险因素管理，但卒中的风险较高。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。在本申请中，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 Wingspan 自膨式镍钛合金支架）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 天内的任何中风或死亡，或超过 30 天的有症状颅内动脉区域的中风），对患有以下疾病的高危患者进行平均随访两年： 颅内主要动脉有症状的狭窄。该研究的两个分支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 90 天每天服用氯吡格雷 75 毫克，以及主要针对血压 < 130 / 80 毫米汞柱和低密度胆固醇 < 70 毫克/分升的积极危险因素管理。主要假设是，与单独强化药物治疗相比，对于有症状的颅内主要动脉狭窄的高危患者，颅内支架置入术联合强化药物治疗将在平均两年随访中将主要终点风险降低 35%。基于对数秩检验（α 为 0.05，功效为 80%），并针对 2% 的随访损失和从医疗到支架置入组的 5% 交叉进行调整，检测支架置入术主要终点率降低 35% 所需的样本量为每组 382 名患者。研究神经科医生将每 4 个月对患者进行一次评估，以确定终点的发生情况，研究内科医生将管理所有研究患者的血管危险因素。这项研究是第一个将多种危险因素的强化管理纳入研究设计的二级预防卒中试验，也是第一个III期颅内支架置入试验，预计该研究的结果将为这种与预后不良相关的常见脑血管疾病带来更有效的治疗方法。