The Restrictive Red Blood Cell Transfusion Strategy for Critically Injured Patients (RESTRIC) trial: a cluster-randomized, crossover, non-inferiority multicenter trial of restrictive transfusion in trauma

Abstract

Background: The efficacies of fresh frozen plasma and coagulation factor transfusion have been widely evaluated in trauma-induced coagulopathy management during the acute post-injury phase. However, the efficacy of red blood cell transfusion has not been adequately investigated in patients with severe trauma, and the optimal hemoglobin target level during the acute post-injury and resuscitation phases remains unclear. Therefore, this study aimed to examine whether a restrictive transfusion strategy was clinically non-inferior to a liberal transfusion strategy during the acute post-injury phase.

Methods: This cluster-randomized, crossover, non-inferiority multicenter trial was conducted at 22 tertiary emergency medical institutions in Japan and included adult patients with severe trauma at risk of major bleeding. The institutions were allocated a restrictive or liberal transfusion strategy (target hemoglobin levels: 7-9 or 10-12 g/dL, respectively). The strategies were applied to patients immediately after arrival at the emergency department. The primary outcome was 28-day survival after arrival at the emergency department. Secondary outcomes included transfusion volume, complication rates, and event-free days. The non-inferiority margin was set at 3%.

Results: The 28-day survival rates of patients in the restrictive (n = 216) and liberal (n = 195) strategy groups were 92.1% and 91.3%, respectively. The adjusted odds ratio for 28-day survival in the restrictive versus liberal strategy group was 1.02 (95% confidence interval: 0.49-2.13). Significant non-inferiority was not observed. Transfusion volumes and hemoglobin levels were lower in the restrictive strategy group than in the liberal strategy group. No between-group differences were noted in complication rates or event-free days.

Conclusions: Although non-inferiority of the restrictive versus liberal transfusion strategy for 28-day survival was not statistically significant, the mortality and complication rates were similar between the groups. The restrictive transfusion strategy results in a lower transfusion volume.

Trial registration number: umin.ac.jp/ctr: UMIN000034405, registration date: 8 October 2018.

Keywords: Hemoglobin; Red blood cell; Resuscitation; Transfusion; Trauma.

Fig. 1

Study design. A total of 22 emergency medical centers participated in the RESTRIC trial. The participating institutions were randomized to implement either the restrictive or liberal RBC transfusion strategy at a ratio of 1:1. Hb hemoglobin, RBC red blood cell, RESTRIC Restrictive Transfusion Strategy for Critically Injured Patients

Fig. 2

CONSORT diagram. ED emergency department

Fig. 3

Hemoglobin levels during the first 7 days after arrival at the ED. The restrictive RBC transfusion strategy (gray) was defined as RBC transfusion with a target hemoglobin level of 7–9 g/dL. The liberal RBC transfusion strategy (black) was defined as RBC transfusion with a target hemoglobin level of 10–12 g/dL. Data are expressed as medians (interquartile ranges). ED emergency department, RBC red blood cell

Fig. 4

Cumulative transfusion volume during the first 28 days after arrival at the ED. White, restrictive RBC transfusion strategy; gray, liberal RBC transfusion strategy. Data are expressed as medians (interquartile ranges). ED emergency department, FFP fresh frozen plasma, RBC red blood cell

Fig. 5

Proportion of patients without RBC transfusion. White, restrictive RBC transfusion strategy; gray, liberal RBC transfusion strategy. RBC red blood cell

Fig. 6

Twenty-eight-day survival Kaplan–Meier curves in the restrictive versus the liberal RBC transfusion strategy group. Gray, restrictive RBC transfusion strategy; black, liberal RBC transfusion strategy. HR hazard ratio, CI confidence interval, RBC red blood cell

Fig. 7

Adjusted odds ratio for the 28-day survival rate. Data are presented as unadjusted odds ratios and 95% CIs. Vertical dotted line = 0.680 (derived from a non-inferiority margin of 3% and an adjusted 28-day survival rate in the liberal RBC transfusion strategy group of 93.4%). AIS Abbreviated Injury Scale, CI confidence interval, ISS Injury Severity Score