Statistical and Data Coordinating Center for the ATACH - 2

描述（由申请人提供）：与明尼苏达大学（UMN）合作，我们计划进行一项为期5年的多中心、随机III期试验，以确定早期、强化尼卡地平降压治疗幕上脑出血（ICH）受试者急性高血压的疗效。本试验的主要假设是，与标准降压治疗组相比，静脉输注尼卡地平24小时（SBP <140 mm Hg）可使3个月时的死亡和残疾比例降低10%或更多（SBP <180 mm Hg）。强化治疗的这种预期有益作用的潜在机制是通过降低在约38%的急性ICH患者中观察到的血肿扩张的速率和幅度介导的。本试验将招募最多1，280例符合合格性标准的ICH受试者。主要结局是3个月时的死亡和残疾比例，定义为改良兰金量表（mRS）评分4 - 6分。 ATACH II试验的具体目的是：（1）在症状发作3小时内接受治疗的ICH受试者中，在3个月时死亡和残疾（mRS 4-6）比例方面，确定强化治疗相对于标准治疗的治疗获益;（2）评价强化治疗相对于标准治疗在3个月时通过EuroQol测量的受试者生活质量方面的治疗益处;（3）在血肿扩大（定义为血肿体积较基线增加>33%）的比例方面，评价强化治疗相对于标准治疗的治疗获益;（4）在72小时内发生治疗相关SAE的受试者比例方面，评价强化治疗相对于标准治疗的安全性。 随附的UMN资助申请描述了ATACH II试验的临床背景和原理、合格标准、治疗和随访程序以及组织结构的详细信息。南卡罗来纳州医科大学（MUSC）生物统计学、生物信息学和流行病学系（DB2 E）的数据协调单位（DCU）将作为ATACH II试验的统计和数据协调中心。在本申请中，我们描述了DCU的目标和专业知识/资质、其在ATACH II试验中的作用、数据处理和管理的详细信息以及统计设计、问题和分析计划。

DESCRIPTION (provided by applicant): In collaboration with the University of Minnesota (UMN), we propose to conduct a five-year multicenter, randomized Phase III trial to determine the efficacy of early, intensive antihypertensive treatment with nicardipine for acute hypertension in subjects with supratentorial intracerebral hemorrhage (ICH). The primary hypothesis of this trial is that the group treated with intensive blood pressure reduction (SBP of <140 mm Hg) using intravenous nicardipine infusion for 24 hours reduces the proportion of death and disability at 3 months by 10% or greater compared with the group treated with the standard blood pressure reduction (SBP of <180 mm Hg) among patients with ICH treated within 3 hours of symptom onset. The underlying mechanism for this expected beneficial effect of intensive treatment is mediated through reduction of the rate and magnitude of hematoma expansion observed in approximately 38% of patients with acute ICH. The trial will recruit a maximum of 1,280 subjects with ICH who meet the eligibility criteria. The primary outcome is the proportion of death and disability at 3 months defined by modified Rankin scale (mRS) score of 4 to 6. The specific aims of the ATACH II Trial are to: (1) Definitively determine the therapeutic benefit of the intensive treatment relative to the standard treatment in the proportion of death and disability (mRS 4-6) at 3 months among subjects with ICH who are treated within 3 hours of symptom onset; (2) Evaluate the therapeutic benefit of the intensive treatment relative to the standard treatment in the subjects' quality of life as measured by EuroQol at 3 months; (3) Evaluate the therapeutic benefit of the intensive treatment relative to the standard treatment in the proportion of hematoma expansion (defined as increase from baseline hematoma volume of >33%); and (4) Assess the safety of the intensive treatment relative to the standard treatment in the proportion of subjects with treatment-related SAEs within 72 hours. The accompanying grant application of the UMN describes the details of the clinical background and rationale, eligibility criteria, treatment and follow-up procedures, and the organizational structure of the ATACH II Trial. The Data Coordination Unit (DCU) in the Department of Biostatistics, Bioinformatics an Epidemiology (DB2E) at the Medical University of South Carolina (MUSC) will serve as the statistical and data coordination center for the ATACH II Trial. In this application, we describe the aims and the expertise/qualifications of the DCU, its role in the ATACH II Trial, and the details of data processing and management, and the statistical design, issues and analysis plan.