Recovery Trajectories and Long-Term Outcomes in Traumatic Brain Injury: A Secondary Analysis of the Phase 3 Citicoline Brain Injury Treatment Clinical Trial.

Background: Prospects for recovery after traumatic brain injury (TBI) are often underestimated, potentially leading to withdrawal of care in the comatose TBI patient who may ultimately have a favorable outcome with aggressive care. Outcomes and trajectories of recovery in a large series of patients with TBI were evaluated at 30, 90, and 180 days postinjury.

Methods: A secondary analysis of the phase 3 Citicoline Brain Injury Treatment (COBRIT) trial was performed analyzing recovery trajectories and long-term outcomes at 30, 90, and 180 days postinjury. A Glasgow Outcome Scale-Extended (GOS-E) score of 5 or higher was considered favorable. Pearson χ analysis was used, and a P value of 0.05 was considered significant. A locally weighted, polynomial regression model was used to model recovery trajectories in a nonlinear fashion.

Results: Subjects with TBI in the COBRIT trial had high rates of favorable outcome (57% of severe TBI, 86% of moderate TBI, and 93% of complicated mild TBI) at 6-month follow-up. These favorable outcomes often converted from high rates of unfavorable outcome at initial 1-month follow-up (85% of severe TBI, 57% of moderate TBI, and 21% of complicated mild TBI). Recovery trajectories had not plateaued at 6 months, suggesting that further improvement occurs beyond 6 months postinjury.

Conclusions: In this secondary analysis of the COBRIT trial, most patients had favorable outcomes by the GOS-E at 6 months postinjury in all complicated mild and moderate TBI groups, with over half of patients with severe TBI achieving a favorable outcome as well. Of subjects in a vegetative state (GOS-E score 2) at 1 month postinjury, 18% improved to a favorable outcome by 6 months postinjury. There was substantial improvement in all groups from 1 to 6 months, and this improvement may continue beyond 6 months. Clinical trials in TBI should consider recovery curves with repeated measures to assess outcomes because arbitrary single-moment outcome determination likely underestimates treatment effect in TBI care.