Statistical and Data Coordinating Center for the ATACH - 2

描述(由申请人提供)：我们建议与明尼苏达大学(UMN)合作，进行一项为期五年的多中心随机第三阶段试验，以确定尼卡地平早期强化降压治疗幕上脑出血(ICH)患者的急性高血压的疗效。这项试验的基本假设是，在症状出现3小时内接受治疗的脑出血患者中，使用静脉注射尼卡地平进行24小时强化降压(SBP为140 mm Hg)的患者在3个月内的死亡和残疾比例比接受标准降压(SBP为180 mm Hg)的患者减少10%或更多。强化治疗预期有益效果的潜在机制是通过降低约38%的急性脑出血患者的血肿扩张速度和程度来实现的。该试验将招募最多1,280名符合资格标准的ICH受试者。主要结果是3个月时的死亡和残疾比例，由修正的Rankin量表(MRS)评分4到6。ATACH II试验的具体目标是：(1)明确在症状出现3个小时内接受治疗的脑出血患者3个月时强化治疗相对于标准治疗(MRS 4-6)的治疗益处；(2)评估强化治疗相对于标准治疗在3个月时的生活质量方面的疗效；(3)从血肿扩大的比例(定义为较基线血肿量增加33%)评估强化治疗相对于标准治疗的疗效；(4)根据72小时内出现治疗相关SAE的受试者的比例，评估强化治疗相对于标准治疗的安全性。随附的UMN拨款申请描述了ATACH II试验的临床背景和基本原理、资格标准、治疗和后续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、生物信息学和流行病学系(DB2E)的数据协调股(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的目标和专长/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.