Efficacy of prehospital administration of fibrinogen concentrate in trauma patients bleeding or presumed to bleed (FIinTIC): A multicentre, double-blind, placebo-controlled, randomised pilot study

Abstract

Background: Trauma-induced coagulopathy (TIC) substantially contributes to mortality in bleeding trauma patients.

Objective: The aim of the study was to administer fibrinogen concentrate in the prehospital setting to improve blood clot stability in trauma patients bleeding or presumed to bleed.

Design: A prospective, randomised, placebo-controlled, double-blinded, international clinical trial.

Setting: This emergency care trial was conducted in 12 Helicopter Emergency Medical Services (HEMS) and Emergency Doctors' vehicles (NEF or NAW) and four trauma centres in Austria, Germany and Czech Republic between 2011 and 2015.

Patients: A total of 53 evaluable trauma patients aged at least 18 years with major bleeding and in need of volume therapy were included, of whom 28 received fibrinogen concentrate and 25 received placebo.

Interventions: Patients were allocated to receive either fibrinogen concentrate or placebo prehospital at the scene or during transportation to the study centre.

Main outcome measures: Primary outcome was the assessment of clot stability as reflected by maximum clot firmness in the FIBTEM assay (FIBTEM MCF) before and after administration of the study drug.

Results: Median FIBTEM MCF decreased in the placebo group between baseline (before administration of study treatment) and admission to the Emergency Department, from a median of 12.5 [IQR 10.5 to 14] mm to 11 [9.5 to 13] mm (P = 0.0226), but increased in the FC Group from 13 [11 to 15] mm to 15 [13.5 to 17] mm (P = 0.0062). The median between-group difference in the change in FIBTEM MCF was 5 [3 to 7] mm (P < 0.0001). Median fibrinogen plasma concentrations in the fibrinogen concentrate Group were kept above the recommended critical threshold of 2.0 g l-1 throughout the observation period.

Conclusion: Early fibrinogen concentrate administration is feasible in the complex and time-sensitive environment of prehospital trauma care. It protects against early fibrinogen depletion, and promotes rapid blood clot initiation and clot stability.

Trial registry numbers: EudraCT: 2010-022923-31 and ClinicalTrials.gov: NCT01475344.

Fig. 1

Patient disposition

Fig. 2

Values at baseline (T1) and emergency room admission (T2), and the differences between these timepoints, in selected ROTEM parameters

Fig. 3

Changes in FIBTEM maximum clot firmness (FIBTEM MCF) between baseline (T1) and 7 days posttrauma (T7)