Statistical analysis plan for pooled individual patient data from two landmark randomized trials (INTERACT2 and ATACH-II) of intensive blood pressure lowering treatment in acute intracerebral hemorrhage

Background There is persistent uncertainty over the benefits of early intensive systolic blood pressure lowering in acute intracerebral hemorrhage. In particular, over the timing, target, and intensity of systolic blood pressure control for optimum balance of potential benefits (i.e. functional recovery) and risks (e.g. cerebral ischemia). Aims To determine associations of early systolic blood pressure lowering parameters and outcomes in patients with a hypertensive response in acute intracerebral hemorrhage. Secondary aims are to identify the modifying effects of patient characteristics and an optimal systolic blood pressure lowering profile. Methods Individual participant data pooled analyses of two large, multicenter, randomized controlled trials specifically undertaken to assess the effects of early intensive systolic blood pressure reduction on clinical outcomes in acute intracerebral hemorrhage: the Intensive Blood Pressure in Acute Intracerebral Hemorrhage Trial (INTERACT2) and the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II) trial. Combined data will include baseline characteristics; systolic blood pressure in the first 24 h; process of care measures; and key efficacy and safety outcomes. Outcomes The primary outcome is functional recovery, defined by an ordinal distribution of scores on the modified Rankin scale at 90 days post-randomization. Secondary outcomes include various standard binary cut-points for disability-free survival on the modified Rankin scale, and health-related quality of life at 90 days. Safety outcomes include symptomatic hypotension requiring corrective therapy and early neurologic deterioration within 24 h, and deaths, any serious adverse event, and cardiac and renal serious adverse events, within 90 days. Discussion A pre-determined protocol was developed to facilitate successful collaboration and reduce analysis bias arising from prior knowledge of the findings. Clinical trial registration URL: http://www.clinicaltrials.gov . Unique identifiers for INTERACT2 (NCT00716079) and ATACH-II (NCT01176565).