Statistical and Data Coordinating Center for the ATACH - 2

描述（由申请人提供）：我们与明尼苏达大学（UMN）合作，提议开展一项为期五年的多中心随机III期试验，以确定尼卡地平早期强化降压治疗幕上脑出血（ICH）患者急性高血压的疗效。本试验的主要假设是，在症状出现3小时内接受强化降压（收缩压<140毫米汞柱）静脉滴注尼卡地平24小时治疗的脑出血患者中，与标准降压（收缩压<180毫米汞柱）治疗的患者相比，3个月时死亡和残疾的比例降低了10%或更高。强化治疗的这种预期有益效果的潜在机制是通过在大约38%的急性脑出血患者中观察到的血肿扩张率和程度的降低来介导的。该试验将招募最多1,280名符合资格标准的ICH受试者。主要终点是3个月时的死亡和残疾比例，由修改的Rankin量表（mRS）评分为4至6分确定。ATACH II试验的具体目的是：(1)明确确定强化治疗相对于标准治疗在3个月时在症状出现3小时内接受治疗的脑出血患者的死亡和残疾比例（mRS 4-6）的治疗益处；(2)评价强化治疗相对于标准治疗在受试者3个月时EuroQol测量的生活质量方面的治疗效益；(3)评价强化治疗相对于标准治疗在血肿扩大比例（定义为血肿体积较基线增加33%）方面的治疗效益；(4)相对于标准治疗，在72小时内发生与治疗相关的SAEs的受试者比例，评估强化治疗的安全性。随附的UMN资助申请描述了ATACH II试验的临床背景和基本原理、资格标准、治疗和随访程序以及组织结构的细节。南卡罗来纳医科大学（MUSC）生物统计学、生物信息学和流行病学（DB2E）系的数据协调单位（DCU）将作为ATACH II试验的统计和数据协调中心。在这个应用程序中，我们描述了数据处理组的目标和专业知识/资格，它在ATACH II试验中的作用，数据处理和管理的细节，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. PUBLIC HEALTH RELEVANCE: The proposed ATACH II Trial is a five-year multicenter randomized Phase III trial to determine the efficacy of early, intensive antihypertensive treatment for acute hypertension in subjects with supratentorial intracerebral hemorrhage (ICH). The primary hypothesis of this large, streamlined, and focused trial is that the group treated with intensive systolic blood pressure (SBP) reduction (<140 mm Hg) using intravenous nicardipine infusion for 24 hours reduces the proportion of death and disability (defined as the modified Rankin Scale score of 4-6) at 3 months from randomization by 10% or greater compared with the group treated with the standard SBP reduction (<180 mm Hg) among patients with ICH treated within 3 hours of symptom onset.