Restrictive vs Liberal Transfusion Strategy in Patients with Acute Brain Injury: The TRAIN Randomized Clinical Trial

Fabio Silvio Taccone*, Carla Rynkowski Bittencourt, Kirsten Møller, Piet Lormans, Manuel Quintana-Díaz, Anselmo Caricato, Marco Antonio Cardoso Ferreira, Rafael Badenes, Pedro Kurtz, Christian Baastrup Søndergaard, Kirsten Colpaert, Leticia Petterson, Herve Quintard, Raphael Cinotti, Elisa Gouvêa Bogossian, Cassia Righy, Serena Silva, Erik Roman-Pognuz, Catherine Vandewaeter, Daniel LemkeOlivier Huet, Ata Mahmoodpoor, Aaron Blandino Ortiz, Mathieu Van Der Jagt, Russell Chabanne, Walter Videtta, Pierre Bouzat, Jean Louis Vincent

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

46 Citations (Scopus)
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Abstract

Importance: 

Blood transfusions are commonly administered to patients with acute brain injury. The optimal hemoglobin transfusion threshold is uncertain in this patient population. 

Objective: 

To assess the impact on neurological outcome of 2 different hemoglobin thresholds to guide red blood cell transfusions in patients with acute brain injury. 

Design, Setting, and Participants: 

Multicenter, phase 3, parallel-group, investigator-initiated, pragmatic, open-label randomized clinical trial conducted in 72 intensive care units across 22 countries. Eligible patients had traumatic brain injury, aneurysmal subarachnoid hemorrhage, or intracerebral hemorrhage; hemoglobin values below 9 g/dL within the first 10 days after injury; and an expected intensive care unit stay of at least 72 hours. Enrollment occurred between September 1, 2017, and December 31, 2022. The last day of follow-up was June 30, 2023. 

Interventions: 

Eight hundred fifty patients were randomly assigned to undergo a liberal (transfusion triggered by hemoglobin <9 g/dL; n = 408) or a restrictive (transfusion triggered by hemoglobin <7 g/dL; n = 442) transfusion strategy over a 28-day period. 

Main Outcomes and Measures: 

The primary outcome was occurrence of an unfavorable neurological outcome, defined as a Glasgow Outcome Scale Extended score between 1 and 5, at 180 days following randomization. There were 14 prespecified serious adverse events, including occurrence of cerebral ischemia after randomization. 

Results: 

Among 820 patients who completed the trial (mean age, 51 years; 376 [45.9%] women), 806 had available data on the primary outcome, 393 in the liberal strategy group and 413 in the restrictive strategy group. The liberal strategy group received a median of 2 (IQR, 1-3) units of blood, and the restrictive strategy group received a median of 0 (IQR, 0-1) units of blood, with an absolute mean difference of 1.0 unit (95% CI, 0.87-1.12 units). At 180 days after randomization, 246 patients (62.6%) in the liberal strategy group had an unfavorable neurological outcome compared with 300 patients (72.6%) in the restrictive strategy group (absolute difference, -10.0% [95% CI, -16.5% to -3.6%]; adjusted relative risk, 0.86 [95% CI, 0.79-0.94]; P =.002). The effect of the transfusion thresholds on neurological outcome at 180 days was consistent across prespecified subgroups. In the liberal strategy group, 35 (8.8%) of 397 patients had at least 1 cerebral ischemic event compared with 57 (13.5%) of 423 in the restrictive strategy group (relative risk, 0.65 [95% CI, 0.44-0.97]). 

Conclusions and Relevance: 

Patients with acute brain injury and anemia randomized to a liberal transfusion strategy were less likely to have an unfavorable neurological outcome than those randomized to a restrictive strategy.

Original languageEnglish
JournalJAMA
Volume332
Issue number19
DOIs
Publication statusPublished - 9 Oct 2024

Bibliographical note

Publisher Copyright:
Copyright © 2024 American Medical Association.

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