Statistical Analysis Plan for L-oxiracetam Outcomes in Clinical Assessment of Traumatic Brain Injury Effects Trial (LOCATE trial): A Randomized Controlled Clinical Trial

Abstract

Background: The L-oxiracetam Outcomes in Clinical Assessment of Traumatic Brain Injury Effects (LOCATE) trial is a national, multicenter, randomized, parallel-group, phase III trial including 74 centers across 51 hospitals from 2019 to 2024. The objective is to evaluate the efficacy and safety of L-oxiracetam in improving memory and cognitive impairment in patients with acute traumatic brain injury (TBI). Methods: A total of 591 patients aged 18-75 years will be enrolled with mild acute TBI. The primary outcome is the change in scores on the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) at 90 days post-treatment compared to baseline. Secondary outcomes included change from baseline in LOTCA, Glasgow Coma Scale (GCS), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Glasgow Outcome Scale-Extended (GOS-E), and Barthel Index of Activities of Daily Living (ADL-BI) assessed at the end of treatment, 30 days, 60 days, and/or 90 days. A sample size of 591 allows 80% power (a=0.05) for the efficacy test in the primary outcome of LOTCA assessed at 90 days. Results: A detailed statistical analysis plan was developed for the LOCATE trial following international guidelines. The plan determined the statistical models for the primary and secondary outcomes and defined the covariates to be controlled and the content of the exploratory analyses. Conclusion: The application of this statistical analysis plan in the upcoming LOCATE trial will support an unbiased analysis of these important clinical data.