Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion

• DOI: 10.1001/jama.2023.4080
• Publication Date: 2023-03-21T08:01:03Z
• Authors: Pierre Bouzat; Jonathan Charbit; Paer-Selim Abback; Delphine Huet-Gar...; Nathalie Delhaye; Marc Leone; Guillaume Marcotte; Jean-Stéphane David; Albrice Levrat; Karim Asehnoune; Julien Pottecher; Jacques Duranteau; Elie Courvalin; Anais Adolle; Dimitri Sourd; Jean-Luc Bosson; Bruno Riou; Tobias Gauss; Jean-François Payen; ; Jules Greze; Pierluigi Banco; Karine Berger; Stéphanie Druge; Martin Dupuis; Laure Janin; Caroline Machuron; Marine Thomas; Clotilde Schilte; Emmanuelle Hamad; Laurent Zieleskie...; Gary Duclos; Charlotte Arbelot; Karine Bezulier; Caroline Jeantrelle; Mathieu Raux; Pauline Glasman; Anatole Harrois; Virginie Tarazona; Aline Lambert; Olivia Vassal; Anne Li; Nicolas Grillot; Loïs Henry; Elise Blonde; Benjamin Bijok; Aurélien Rohn; Julie Bellet; Florence Lallemant; Nathalie Bruneau; Christine Ducam; Geoffrey Dagod; Pauline Deras; Xavier Capdevila; Magdalena Szczot; Alain Meyer; Stéphane Hecketsw...; Etienne Escudier; Michel Muller; Samuel Gray; Magalie Farines; Marie Lebouc; Sophie DEBORD-PEDET
• Keywords: Prothrombin complex concentrate; Blood product; Fresh frozen plasma; Recombinant Factor VIIa

Optimal transfusion strategies in traumatic hemorrhage are unknown. Reports suggest a beneficial effect of 4-factor prothrombin complex concentrate (4F-PCC) on blood product consumption.To investigate the efficacy and safety 4F-PCC administration patients at risk massive transfusion.Double-blind, randomized, placebo-controlled superiority trial 12 French designated level I trauma centers from December 29, 2017, to August 31, 2021, involving consecutive with transfusion. Follow-up was completed 2021.Intravenous 1 mL/kg (25 IU factor IX/kg) vs saline solution (placebo). Patients, investigators, data analysts were blinded treatment assignment. All received early ratio-based (packed red cells:fresh frozen plasma ratio 1:1 2:1) treated according European guidelines.The primary outcome 24-hour all consumption (efficacy); arterial or venous thromboembolic events secondary (safety).Of 4313 highest activation, 350 eligible for emergency inclusion, 327 324 analyzed (164 group 160 placebo group). The median (IQR) age participants 39 (27-56) years, Injury Severity Score 36 (26-50 [major trauma]), admission lactate 4.6 (2.8-7.4) mmol/L; prehospital systolic pressure less than 90 mm Hg 179 (59%), 233 (73%) men, 226 (69%) required expedient control. There no statistically clinically significant between-group difference total (12 [5-19] U 11 [6-19] group; absolute difference, 0.2 [95% CI, -2.99 3.33]; P = .72). In group, 56 (35%) presented least event 37 (24%) (absolute 11% 1%-21%]; relative risk, 1.48 1.04-2.10]; .03).Among transfusion, there reduction after 4F-PCC, but more common. These findings do not support systematic use transfusion.ClinicalTrials.gov Identifier: NCT03218722.