Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2025 Sep 2;8(9):e2532702.
doi: 10.1001/jamanetworkopen.2025.32702.

Factors in the Initial Resuscitation of Patients With Severe Trauma: The FiiRST-2 Randomized Clinical Trial

Luis T da Luz  1   2 , Keyvan Karkouti  2   3 , Jo Carroll  4 , Deep Grewal  4 , Marti Jones  5 , Jennifer Altmann  6 , Yulia Lin  2   7 , Akash Gupta  2   7 , Avery B Nathens  1   2 , Amie Kron  7 , Lowyl Notario  2   8 , Andrew Beckett  2   9 , Andrew Petrosoniak  2   10 , Katerina Pavenski  2   11 , Kelly Vogt  12   13 , Ian M Ball  13   14 , Neil G Parry  13   15 , Paul T Engels  16   17 , Michelle P Zeller  17   18 , Donald M Arnold  17   18 , Emilie Belley-Côté  17   19 , Chris Evans  20   21 , Jordan Leitch  21   22 , Andrew Shih  23   24 , Philip Jean Dawe  24   25 , Robert Gooch  24   26 , Jeannie Callum  21   27
Affiliations
Multicenter Study

Factors in the Initial Resuscitation of Patients With Severe Trauma: The FiiRST-2 Randomized Clinical Trial

Luis T da Luz et al. JAMA Netw Open. .

Abstract

Importance: Patients with bleeding and coagulopathic trauma often require more transfusions and have higher mortality rates, motivating research on improving hemostatic strategies.

Objective: To evaluate the replacement of clotting factors with frozen plasma (FP) or factor concentrates (fibrinogen concentrate [FC] and prothrombin complex concentrate [PCC]) in the initial resuscitation of patients with trauma.

Design, setting, and participants: This multicenter, parallel-control, superiority randomized clinical trial was conducted at 6 level I trauma centers in Canada, between April 2021 and February 2023. Eligible patients were those with massive hemorrhage protocol (MHP) activation on admission and aged 16 years or older. Patients were excluded if they received more than 2 red blood cell (RBC) units either before hospital admission or in the hospital prior to randomization or if they had a catastrophic head injury. Follow-up was completed on March 25, 2023. The primary analysis was based on the modified intention-to-treat approach.

Interventions: The intervention group received FC 4 g and PCC 2000 IU in MHP packs 1 and 2. The control group received 4 FP units. Concurrently, patients received 4 RBC units (both packs) and 1 dose of platelets (pack 2). After pack 2, FP was administered at clinician discretion.

Main outcomes and measures: Primary outcome was the number of allogeneic blood product (RBC, FP, and platelet) units administered within 24 hours. Secondary outcomes included incidence of thromboembolic events, duration of intensive care unit stay, and mortality.

Results: Of the 217 patients enrolled, 107 were randomly assigned to the FC-PCC group and 110 to the FP group; 137 patients were included in the primary analysis (66 in the FC-PCC group and 71 in the FP group). Baseline characteristics were similar between groups (median [IQR] age, 38 [29-55] years; 111 males [81.0%]). Among these patients, 95 (69.3%) had blunt mechanisms of injury, and the median (IQR) Injury Severity Score was 29 (19-43). Mean 24-hour transfusions were 20.8 (95% CI, 16.7-25.9) units in the FC-PCC group and 23.8 (95% CI, 19.2-29.4) units in the FP group. The mean ratio was 0.87 (1-sided 97.5% CI, 0.00-1.19; P = .20 for superiority). No significant differences were found in thromboembolic complications or 24-hour and 28-day mortality. The trial was terminated after the interim analysis showed conditional power of less than 25%, requiring an impractically large sample to show superiority.

Conclusions and relevance: In this randomized clinical trial, clotting factor concentrates were not superior to FP for initial resuscitation of patients with trauma. Efficacy and safety outcomes were similar across the treatment groups.

Trial registration: ClinicalTrials.gov Identifier: NCT04534751.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr da Luz reported receiving grants and personal fees from Octapharma AG during the conduct of the study. Dr Karkouti reported receiving grants from Octapharma during the conduct of the study and personal fees from Octapharma and Werfen Consulting outside the submitted work. Ms Carroll reported receiving grants from Octapharma AG, grants from Canadian Institutes of Health Research (CIHR), and the Defense Research and Development Canada (DRDC) during the conduct of the study and grants from Octapharma AG outside the submitted work. Dr Grewal reported receiving grants from CIHR, Octapharma AG, and DRDC during the conduct of the study and grants from Octapharma AG outside the submitted work. Dr Jones reported receiving funding for her employer from Octapharma during the conduct of the study. Ms Altmann reported receiving funding for her employer from Octapharma during the conduct of the study. Dr Lin reported receiving grants from CIHR during the conduct of the study; grants from Octapharma and Canadian Blood Services outside the submitted work; and personal fees from Choosing Wisely Canada and Pfizer outside the submitted work. Dr Petrosoniak reported receiving personal fees from Astra Zeneca and Octapharma outside the submitted work. Dr Pavenski reported receiving nonfinancial support from Octapharma outside the submitted work. Dr Zeller reported receiving grants from CIHR during the conduct of the study; personal fees from Canadian Blood Services, Pfizer, Octapharma, and American Society of Hematology outside the submitted work; grants from Pfizer, CIHR, and (Mid Career Research Award) Department of Medicine McMaster University outside the submitted work. Dr Arnold reported receiving a grant from Canadian Blood Services outside the submitted work. Dr Belley-Côté reported receiving grants from Abbott Laboratories, Bayer, and Roche Diagnostics outside the submitted work. Dr Shih reported receiving personal fees from Octapharma Canada, CSL Behring Canada, and Takeda Canada during the conduct of the study and grants from Canadian Blood Services outside the submitted work. Dr Callum reported receiving grants from Canadian Blood Services, grants from Octapharma, and personal fees from Octapharma during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flow Diagram of FiiRST-2 Trial Participants
FC-PCC indicates fibrinogen concentrate and prothrombin complex concentrate; FP, frozen plasma; GCS, Glasgow Coma Scale (score range: 3-15, with higher scores indicating greater disability); MHP, massive hemorrhage protocol; RBCs, red blood cells.
Figure 2.
Figure 2.. Allogeneic Blood Products (ABPs) Administered in the First 24 h After Admission to the Trauma Bay
Error bars represent 95% CIs. FC-PCC indicates fibrinogen concentrate and prothrombin complex concentrate; FP, frozen plasma; RBC, red blood cell.
Figure 3.
Figure 3.. Time to Death Within 28 d After Admission and Time to First Thromboembolic Event (TEE)
Squares represent censored time (last visit date or death date; limited to 28 days). FC-PCC indicates fibrinogen concentrate and prothrombin complex concentrate; FP, frozen plasma.
See this image and copyright information in PMC

Comment in

  • doi: 10.1001/jamanetworkopen.2025.32717

References

    1. Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma. 2003;54(6):1127-1130. doi: 10.1097/01.TA.0000069184.82147.06 - DOI - PubMed
    1. Duque P, Calvo A, Lockie C, Schöchl H. Pathophysiology of trauma-induced coagulopathy. Transfus Med Rev. 2021;35(4):80-86. doi: 10.1016/j.tmrv.2021.07.004 - DOI - PubMed
    1. Callum JL, Yeh CH, Petrosoniak A, et al. A regional massive hemorrhage protocol developed through a modified Delphi technique. CMAJ Open. 2019;7(3):E546-E561. doi: 10.9778/cmajo.20190042 - DOI - PMC - PubMed
    1. Baksaas-Aasen K, Gall LS, Stensballe J, et al. Viscoelastic haemostatic assay augmented protocols for major trauma haemorrhage (ITACTIC): a randomized, controlled trial. Intensive Care Med. 2021;47(1):49-59. doi: 10.1007/s00134-020-06266-1 - DOI - PMC - PubMed
    1. Rossaint R, Afshari A, Bouillon B, et al. The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition. Crit Care. 2023;27(1):80. doi: 10.1186/s13054-023-04327-7 - DOI - PMC - PubMed

Associated data