Factor In the Initial Resuscitation of Severe Trauma 2 Patients

Summary

Injury is the leading cause of death for people between the ages of 1-44. This is especially true in trauma patients who have bleeding complications. Acute trauma coagulopathy (ATC) is associated with high transfusion requirements, longer ICU stays, and a greater incidence of multi-organ dysfunction. The cause of coagulopathy is multi-factorial. One major driver is acquired fibrinogen deficiency (hypofibrinogenemia). Fibrinogen is critical in clot formation and enhances platelet aggregation. Due to the body's limited reserve, it is the first clotting factor to fall to critical levels during life-threatening bleeding. This can impair coagulation and increases bleeding complications. There are two primary options available for fibrinogen supplementation: * Cryoprecipitate- North American standard * Fibrinogen Concentrate (FC)- European standard Consumption of coagulation factors, including fibrinogen, is another important component of ATC. To replenish these depleted coagulation factors and improve thrombin generation, two therapies are available: * Frozen Plasma (FP)- North American standard * Prothrombin Complex Concentrate (PCC)- European standard Strategies for hemorrhage and coagulopathy treatment have changed significantly over the last decade. Prompt hemorrhage control, along with targeted coagulation factor replacement, are emerging as key components of trauma care. Currently, the initiation of a massive hemorrhage protocol (MHP) results in red blood cells (RBCs) and FP transfusions in a 1:1 or 2:1 ratio. Clotting factors are replaced via FP administration. Fibrinogen supplementation is administration after lab verification or at the clinician's discretion. MHP continues until the rate of hemorrhage is under control. FC and PCC have several important advantages over cryoprecipitate and FP but there is a scarcity of data regarding their efficacy and safety of their use in hemorrhaging trauma patients. The FiiRST-2 study aims to understand if early use of FC and PCC in trauma patients at risk of massive hemorrhage will lead to superior patient outcomes. This trial will also provide safety data on early administration of FC and PCC as a first-line hemostatic therapy in trauma care, and its impact on hemostatic and other clinical endpoints.

Timeline

Start

2021-04-01

Primary completion

2023-12-31

Completion

2024-01-30

Publications

• da Luz LT, Karkouti K, Carroll J, Grewal D, Jones M, Altmann J, Lin Y, Gupta A, Nathens AB, Kron A, Notario L, Beckett A, Petrosoniak A, Pavenski K, Vogt K, Ball IM, Parry NG, Engels PT, Zeller MP, Arnold DM, Belley-Cote E, Evans C, Leitch J, Shih A, Dawe PJ, Gooch R, Callum J. Factors in the Initial Resuscitation of Patients With Severe Trauma: The FiiRST-2 Randomized Clinical Trial. JAMA Netw Open. 2025 Sep 2;8(9):e2532702. doi: 10.1001/jamanetworkopen.2025.32702.
• da Luz LT, Callum J, Beckett A, Hucke HP, Carroll J, Grewal D, Schwartz B, Peng H, Engels PT, Parry N, Petrosoniak A, Tien H, Nathens AB, Scales D, Karkouti K. Protocol for a multicentre, randomised, parallel-control, superiority trial comparing administration of clotting factor concentrates with a standard massive haemorrhage protocol in severely bleeding trauma patients: the FiiRST 2 trial (a 2020 EAST multicentre trial). BMJ Open. 2021 Sep 3;11(9):e051003. doi: 10.1136/bmjopen-2021-051003.

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Indications