Statistical and Data Coordinating Center for the ATACH - 2

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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.