Factor In the Initial Resuscitation of Severe Trauma 2 Patients
FiiRST-2
Prospective, Multi-center, Randomized, Parallel-control, Superiority Study Comparing Administration of Clotting Factor Concentrates With a Standard Massive Hemorrhage Protocol in Severely Bleeding Trauma Patients.
2 other identifiers
interventional
350
1 country
6
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Apr 2021
Typical duration for phase_4
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 27, 2020
CompletedFirst Posted
Study publicly available on registry
September 1, 2020
CompletedStudy Start
First participant enrolled
April 1, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
January 30, 2024
CompletedDecember 5, 2022
December 1, 2022
2.8 years
August 27, 2020
December 1, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Composite of total number of Allogeneic Blood Products (ABPs)
The primary endpoint is to demonstrate superiority with respect to the composite number of all ABP units (RBCs, FP and platelets) transfused
within 24 hours
Secondary Outcomes (3)
Total number of RBC units
Transfused within the 24 hours
Incidence of thromboembolic events
up to 28 days
Ventilator-free days
From arrival to day 28
Study Arms (2)
Intervention Group- Clotting Factor Concentrates
EXPERIMENTALFibryga + Octaplex (Fibrinogen + PCC) Fibrinogen Concentrate 4g (Fibryga) + Prothrombin Complex Concentrate 2000 IU (Octaplex) in the first and second massive hemorrhage protocol (MHP) packs.
Control Group: Standard FP transfusion
ACTIVE COMPARATORFrozen Plasma (FP)
Interventions
Patients randomized to the intervention group will receive 4g of Fibryga and 2000 IU Octaplex will be released as part of the first and second MHP packs, if requested. If a third MHP pack is required, and thereafter, FC will be administered if the fibrinogen level drops below 1.5-2.0 g/L at the discretion of the clinical team or based on conventional laboratory test results or viscoelastic methods. Patients in both groups will otherwise receive identical MHP treatment packs (4 units of red blood cells \[RBC\] in pack 1 and 4 units of RBC and 1 pool of platelets in pack 2 (equivalent to 4 units).
4U FP will be released as part of the first and second MHP packs. Patients in both groups will otherwise receive identical MHP treatment packs (4 units of red blood cells \[RBC\] in pack 1 and 4 units of RBC and 1 pool of platelets in pack 2 (equivalent to 4 units). Patients randomized to the control group may receive FC if the fibrinogen level drops below 1.5-2.0 g/L at the discretion of the clinical team or based on conventional laboratory test results or viscoelastic methods. FC dosing in MHP packs 3 and above will be site-specific and at the discretion of the treating clinician.
Eligibility Criteria
You may qualify if:
- Severely injured adult trauma patients who meet all following criteria:
- Estimated age greater than 16 years old
- Severely injured (penetrating or blunt) trauma patients
- Triggered MHP within first hour of hospital arrival at the trauma bay/ED
You may not qualify if:
- Patients who meet any of the following criteria are not eligible for the study:
- Have received more than 2 U RBCs during the pre-hospital phase of care
- Have received more than 2 U RBCs in the trauma bay/ED before activation of the MHP
- Have an elapsed time from injury of more than 3 hours
- Have a penetrating traumatic brain injury with Glasgow Coma Scale (GCS) of 3
- Are suspected or known to be on anticoagulants in the last 7 days
- Have known congenital or acquired bleeding disorders
- Have a known pregnancy
- Refuse blood transfusion due to religion or other reasons
- Previous history of heparin induced thrombocytopenia (HIT)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (6)
Vancouver General Hospital
Vancouver, British Columbia, V5Z 4E3, Canada
Hamilton Health Sciences and McMaster University
Hamitlon, Ontario, L8L 2X2, Canada
Kingston Health Sciences Centre
Kingston, Ontario, K7L 2V7, Canada
Victoria Hospital
London, Ontario, N6A 5W9, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5, Canada
St. Michael's Hospital
Toronto, Ontario, Canada
Related Publications (2)
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.
PMID: 40982282DERIVEDda 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.
PMID: 34479938DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Luis T Da Luz, MD
Sunnybrook Health Sciences Centre
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Given blood products in each randomized arm have different physical differences, it is not possible to blind the treating health care providers to group assignment. Clinicians not involved in the acute resuscitation period (MHP activations usually last under 4 hours) and outcome assessors will remain blinded by using a generic product label in the patient chart and/or the electronic product name (i.e., FiiRST-2 MHP pack 1 and pack 2, rather than specifying type of product used). The first pack will be sealed, and the treating health care providers will be instructed to refrain from opening the first pack until the decision is made to transfuse clotting factor replacement.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 27, 2020
First Posted
September 1, 2020
Study Start
April 1, 2021
Primary Completion
December 31, 2023
Study Completion
January 30, 2024
Last Updated
December 5, 2022
Record last verified: 2022-12
Data Sharing
- IPD Sharing
- Will not share
No current plan to make IPD available to other researchers.