Researchers in in JAMA have published their findings from the Transfusion Strategies in Acute Brain Injured Patients (TRAIN) randomized clinical trial examining whether a liberal versus restrictive transfusion strategy resulted in better neurological outcomes. They conducted the, “multicenter, phase III, parallel-group, investigator-initiated, pragmatic, open-label, outcome assessor–blinded, randomized clinical trial [in] 72 intensive care units (ICUs) across 22 countries.” Inclusion criteria for the trial required that patients have, “a Glasgow Coma Scale score of 13 or less on the day of randomization, an expected ICU stay of at least three days, and a hemoglobin level of 9 g/dL or less, measured using a valid point-of-care test (e.g., hospital laboratory or gas analyzer)” with enrollment taking place from September 2017 through December 2022.
The authors of the paper examining whether liberal transfusion strategy is better for acute brain injury patients explained that, “patients were randomly allocated in a 1:1 ratio to one of two thresholds to determine when red blood cell transfusion should be given, at a hemoglobin concentration of less than 7 g/dL (restrictive strategy group) or at that of less than 9 g/dL (liberal strategy group).” The trial’s transfusion thresholds were, “maintained for a maximum of 28 days after randomization or until hospital discharge or death, whichever event occurred first. Following randomization, all patients received one unit of packed red blood cells at a time when they met their allocated hemoglobin concentration threshold. In both treatment groups, there was no protocolization for the timing of transfusion once the trigger threshold was met, although it was recommended to administer the red blood cell transfusion within a few hours.”
The primary outcome measure for the trial examining whether liberal transfusion strategy is better for acute brain injury patients was, “the proportion of patients with unfavorable neurological outcome at 180 days after randomization. Neurological outcome was assessed using the Glasgow Outcome Scale Extended (GOS-E), which was dichotomized as unfavorable (GOS-E score of 1-5) or favorable (GOS-E score of 6-8); this scale ranges from 1 to 8, with death being included in the scale (GOS-E score of 1), and higher scores indicate better outcome [while] secondary outcome measures included 28-day survival; distribution of GOS-E scores in the two groups (i.e., ordinal outcome analysis) at 180 days; ICU and hospital lengths of stay.”
The researchers stated that the study population featured 820 individuals with, “397 in the liberal strategy group and 423 in the restrictive strategy group. The median time from ICU admission to randomization was 3 days (IQR, 2-5 days) in the liberal strategy group and 3 days (IQR, 2-6 days) in the restrictive strategy group.” They explained that a, “total of 910 blood transfusions were administered in the liberal strategy group during the study period and 373 transfusions in the restrictive strategy group (P < .001). The median cumulative count of blood transfusions after randomization was 2 (IQR, 1-3) units in the liberal strategy group and 0 (IQR, 0-1) units in the restrictive strategy group (absolute mean difference, 1.0 [95 percent CI, 0.87-1.12]; P < .001).”
The trial examining whether a liberal transfusion strategy is better for acute brain injury patients found that at, “180 days following randomization, 246 (62.6 percent) of 393 patients in the liberal strategy group and 300 (72.6 percent) of 413 patients in the restrictive strategy group had an unfavorable neurological outcome (absolute difference, −10.0 percent [95 percent CI, −16.5 percent to −3.6 percent]; unadjusted relative risk, 0.86 [95 percent CI, 0.78-0.95]; adjusted relative risk, 0.86 [95 percent CI, 0.79-0.94]; P = .002). The authors also explained that, “no evidence of a difference in 28-day survival between the liberal and restrictive strategy groups (82/397 [20.7 percent] vs 94/418 [22.5 percent]; relative risk, 0.95 [95 percent CI, 0.74-1.22]). [Additionally,] in the liberal strategy group, 35 (8.8 percent) of 397 patients had at least one cerebral ischemic event compared with 57 (13.5 percent) of 423 in the restrictive strategy group (relative risk, 0.65 [95 percent CI, 0.44-0.97]).”
The authors concluded that, “[p]atients with anemia and acute brain injury randomized to a liberal strategy of red blood cell transfusion at a hemoglobin threshold of 9 g/dL had a lower probability of unfavorable neurological outcome at 180 days than patients randomized to a restrictive strategy of transfusion at a hemoglobin threshold of 7 g/dL.”
The researchers explained that strengths of their trial included the, “concealed group assignment at randomization and blinding of outcome assessors to the assigned intervention. Recruitment of patients from various geographic regions enhances generalizability. The pragmatic trial protocol ensured that routine clinical practices were maintained, except for the specified hemoglobin thresholds for transfusion. “They acknowledged several limitations including, “the awareness of study group assignments by investigators and clinicians, coupled with an incomplete assessment of all concomitant interventions, could potentially introduce bias. [Some] patients may have received blood transfusions before randomization, which could have reduced the differences in hemoglobin values and transfusion exposure between the groups. [The] inclusion of patients with different types of brain injury raises the possibility that there may be varied susceptibility to cerebral ischemia from anemia, [and the] study may have had limited power to detect differences in some subgroup analyses.”
Citation: Taccone, F.S., Bittencourt, C.R., Møller, K.; et al. “Restrictive vs Liberal Transfusion Strategy in Patients With Acute Brain Injury.” JAMA. 2024.