Transfusion Strategy for Acute Brain Injury—Reply

In Reply We appreciated the opportunity to address the points raised in the thoughtful Letters regarding the TRAIN trial and its comparison with the HEMOTION trial. The difference in treatment duration between the 2 trials (ie, up to 28 days vs until ICU discharge, respectively) is indeed an important consideration. In a prior study, transfusion strategies were maintained for a maximum of 14 days, with hemoglobin values between groups tending to converge toward the end of the study period. The decision to extend the duration of transfusion thresholds in the TRAIN trial was based on the anticipated prolonged ICU stay in patients with brain injury and anemia and the hypothesis that prolonged exposure to distinct hemoglobin levels could yield a greater impact on outcomes. However, in the TRAIN study, monitoring of hemoglobin levels outside the ICU was limited to values requested by the treating physicians, potentially affecting the precision of between-group comparisons. Although the median ICU length of stay was longer in the TRAIN trial compared with the HEMOTION trial (21 vs 15 days, respectively), it remains challenging to attribute the observed differences in neurological outcomes between the 2 studies solely on this finding. Although further post hoc analyses of the TRAIN trial could help elucidate this issue, early deaths may serve as a competing risk and confound the validity of analyses related to treatment duration.