Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion: The PROCOAG Randomized Clinical Trial

Université Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institute Neurosciences, Grenoble, France. Trauma Critical Care Unit, Montpellier University Hospital, F-34295 Montpellier Cedex 5, France. Department of Anesthesiology and Critical Care, Beaujon Hospital, DMU Parabol, AP-HP. Nord, Clichy, France. Department of Anesthesiology and Critical Care, Centre Hospitalier Universitaire Lille, Surgical Critical Care, Lille, France. AP-HP, Groupe Hospitalier Universitaire APHP-Sorbonne Université, site Pitié-Salpêtrière, Département d'Anesthésie Réanimation, Paris, France. Aix Marseille University, Assistance Publique Hôpitaux Universitaires de Marseille, Department of Anesthesiology and Intensive Care Unit, North Hospital, and Centre for CardioVascular and Nutrition Research (C2VN), Inserm 1263, Inrae 1260, Marseille, France. Hospices Civils de Lyon, Hopital Edouard Herriot, Department of Anesthesia and Intensive Care, Lyon, France. University Claude Bernard Lyon 1, INSERM U1290, Research on Healthcare Performance (RESHAPE), and Hospices Civils de Lyon, Groupement Hospitalier Sud, Department of Anesthesia and Intensive Care, Pierre Benite, France. Intensive care unit, Annecy Hospital, Annecy, France. Université de Nantes, CHU Nantes, Pôle anesthésie réanimations, Service d'Anesthésie Réanimation chirurgicale, Hôtel Dieu, Nantes, France. Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, Service d'Anesthésie-Réanimation & Médecine Péri-Opératoire - Université de Strasbourg, Faculté de Médecine, FMTS, ER3072, Strasbourg, France. Département d'Anesthésie-Réanimation, Hôpitaux Universitaires Paris Sud, Université Paris XI, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France. Pôle d'Anesthésie-Réanimation, CHU Grenoble Alpes, Grenoble, France. Univ. Grenoble Alpes, CNRS, Public Health department CHU Grenoble Alpes, TIMC-IMAG, Grenoble, France. Sorbonne Université, UMR-S INSERM 1166, IHU ICAN, and Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Department of Emergency medicine and Surgery, Paris, France.

Jama. 2023
PICO Summary

Population

Patients with trauma at risk of massive transfusion enrolled in the PROCOAG trial, in 12 level I trauma centers in France (n= 327).

Intervention

Intravenous administration of 4-factor prothrombin complex concentrate (4F-PCC group, n= 164).

Comparison

Saline solution (placebo group, n= 160).

Outcome

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