Traumatic HemorrhagePhase 4FiiRST-2NCT04534751
Factor In the Initial Resuscitation of Severe Trauma 2 Patients
A Phase 4 study testing Fibrinogen + PCC and Frozen Plasma in people with Traumatic Hemorrhage and Coagulopathy, run by University Health Network, Toronto at 6 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Traumatic Hemorrhage, Coagulopathy, Massive Hemorrhage
- What is being tested?
- Fibrinogen + PCC and Frozen Plasma
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 142 participants
- Where
- 6 sitesCanada
- Study dates
- 1 Apr 2021to 31 Jul 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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)
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Canada6 sites
Hamilton Health Sciences and McMaster University
Hamitlon, Ontario, L8L 2X2
Kingston Health Sciences Centre
Kingston, Ontario, K7L 2V7
Victoria Hospital
London, Ontario, N6A 5W9
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
St. Michael's Hospital
Toronto, Ontario
Vancouver General Hospital
Vancouver, British Columbia, V5Z 4E3
About this study
Official title: 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.
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:
Read more
- 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.
Read the detailed description
Study Design and Duration FiiRST-2 is a multicenter, randomized, parallel-control, superiority trial, utilizing a conventional two-armed, two-stage design, with an adaptive interim analysis, performed at Level 1 Trauma Centers in Canada. The study is designed to examine the effect of replacing fibrinogen and clotting factors via FC and PCC following activation of the massive hemorrhage protocol (MHP) on the number of ABP units transfused in trauma patients with severe hemorrhage versus the current standard of care (ratio-based plasma resuscitation).
Test Products, Dose, and Mode of Administration:
Patients will be randomized if the MHP is activated according to the MHP activation criteria at each study site. Once eligibility is confirmed, the blood bank medical laboratory technologist will randomize the patient to one of two groups: the intervention group or the control group.
- Intervention group: 4 g Fibryga and 2000 IU Octaplex will be released as part of the first and second MHP packs.
- Control group: 4 U FP will be released as part of the first and second MHP packs.
- Concomitant therapy: In both groups, 4 U RBC will be included as part of the first and second MHP packs, and 1 dose of platelets (4 U of pooled random donor or single donor apheresis) will also be included as part of the second MHP pack. Both RBCs and platelets will be administered according to the clinical situation and/or lab results as per the discretion of the clinical team. The second MHP pack will be released at the request of the clinical team, but clinicians will be instructed to administer all of the investigational product (Fibryga/Octaplex or FP) in the first pack before moving onto the second pack. Similarly, if the second pack is opened, clinicians will be instructed to administer all of the investigational products contained within, before moving to the third pack. Not administering all of the investigational products in the first pack, once started, will be a protocol deviation.
Administration of all non-investigational products will be at the discretion of the clinical team according to the hemodynamic status of the patient and/or laboratory results (standard and/or point-of-care as per institutional practice). While platelets will be routinely included in the second pack, clinicians can request platelets outside of the packs (e.g., for patients on antiplatelet therapy or with marked thrombocytopenia). In the control group, FC may be administered if hypofibrinogenemia (fibrinogen level below 1.5-2.0 g/L or FIBTEM A10 below 8-12 mm) is identified as part of routine testing, at the discretion of the clinical team. Patients in the intervention group can receive additional FC if hypofibrinogenemia (as per above criteria) is identified after the full dose (4g) in the first pack is administered (if the second pack is not opened). If the second pack is opened, additional doses of FC will be permitted after the full dose (4g) in the second pack is administered..
Patients in the control group will not be permitted to receive PCC during the study. Patients in the intervention group may receive FP in the third and subsequent MHP packs. If a third MHP pack is required, and thereafter, MHP packs will contain ABPs (RBCs, platelets and plasma) according to guidelines at each participating site or revert to laboratory-guided transfusion as per the local guidelines once bleeding is controlled. The MHP should be terminated once bleeding is controlled and the MHP criteria are no longer met. Termination of the MHP may occur at any time based on the discretion of the clinical team.
The maximum time frame for administration of the second MHP pack (if required) for both groups is 24 hours from arrival to the trauma bay/ED or termination of the MHP (whichever comes first).
We anticipate for the trial to begin in June 2020 and be completed over a 3 year period.
Sample Size The study will enroll up to 350 trauma patients with approximately 175 assigned to each of the two treatment groups.
Due to the inherent variability in the primary endpoint and a yet substantial uncertainty about the effect size, an adaptive design approach will be used. For this, a planned interim analysis will be performed after 120 patients have completed the study at up to four hospital sites. Primary aim of this interim analysis is to calculate the p-value and conditional power of the test statistic and perform a sample size re-assessment. This will be done in an unblinded interim analysis performed by an independent statistician who will report the results only to the independent data safety monitoring committee (IDSMC) which will make recommendations to the sponsor without revealing the treatment groups. Hence, the final number of enrolled patients will depend on the sample size re-calculation.
- Conditions
- Traumatic Hemorrhage, Coagulopathy, Massive Hemorrhage
- Being tested
- Fibrinogen + PCC, Frozen Plasma
- Keywords
- Trauma, Injury, Acute trauma coagulopathy, Traumatic bleeding, Clotting factors, Fibrinogen, Fibrinogen concentrate, Prothrombin complex concentrate, Massive Hemorrhage Protocol, Frozen Plasma
- Medical subject headings
- Hemostatic Disorders, Wounds and Injuries, Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fibrinogen + PCCBiological
Also called Fibryga + Octaplex
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).
Frozen PlasmaBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Intervention Group- Clotting Factor Concentrates | Experimental | Fibryga + Octaplex (Fibrinogen + PCC)
Fibrinogen Concentrate 4g (Fibryga) + Prothrombin Complex Concentrate 2000 IU (Octaplex) in the first and second massive hemorrhage protocol (MHP) packs. Receives: Biological: Fibrinogen + PCC |
| Control Group: Standard FP transfusion | Active comparator | Frozen Plasma (FP) Receives: Biological: Frozen Plasma |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: within 24 hours
Secondary outcomes (3)
Total number of RBC units
RBC - Red Blood Cells
Measured: Transfused within the 24 hours
Incidence of thromboembolic events
Defined by evidence of any of the following:
- Deep vein thrombosis (DVT)
- Pulmonary embolism (PE)
- Myocardial infarction (MI)
- Ischemic stroke o. Arterial or venous thrombosis at other sites
Measured: up to 28 days
Ventilator-free days
defined as the number of days up to Day 28 following arrival at the trauma bay/ED on which a patient breathed without assistance (if period of unassisted breathing lasted at least 48 consecutive hours). Patients who die during study follow-up or require 28 or more days of mechanical ventilation will be assigned zero ventilator-free days
Measured: From arrival to day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2020
- Study start1 Apr 2021
- Primary completion15 Mar 2023
- Study completion31 Jul 2026
Why it stopped: Upon IDSMC's review of interim data, they recommended the trial be stopped based on futility.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Traumatic HemorrhageStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 142 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Sunnybrook Health Sciences Centre, Octapharma, Canadian Institutes of Health Research (CIHR), Canadian Institute for Military and Veteran Health Research Defense Research & Development Canada
- Responsible party
- Sponsor
- Investigators
- Luis T Da Luz, MD, Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04534751
- Sponsor's protocol ID
- 20-5828
- Other IDs
- 2031 (CTO ID)
- Acronym
- FiiRST-2
- Status last verified
- Oct 2026
- First submitted
- 27 Aug 2020
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No current plan to make IPD available to other researchers.
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.
PubMed 40982282da 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.
PubMed 34479938
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT04534751
- Acronym / sponsor ID
- FiiRST-2 / 20-5828
- Conditions
- Traumatic Hemorrhage, Coagulopathy, Massive Hemorrhage
- Keywords
- Trauma, Injury, Acute trauma coagulopathy, Traumatic bleeding, Clotting factors, Fibrinogen, Fibrinogen concentrate, Prothrombin complex concentrate
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Upon IDSMC's review of interim data, they recommended the trial be stopped based on futility.
- Enrolment
- 142 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Sunnybrook Health Sciences Centre, Octapharma, Canadian Institutes of Health Research (CIHR), Canadian Institute for Military and Veteran Health Research Defense Research & Development Canada
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- 15 Mar 2023 (actual)
- Study completion
- 31 Jul 2026 (actual)
- First posted
- 1 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Study Design and Duration FiiRST-2 is a multicenter, randomized, parallel-control, superiority trial, utilizing a conventional two-armed, two-stage design, with an adaptive interim analysis, performed at Level 1 Trauma Centers in Canada. The study is designed to examine the effect of replacing fibrinogen and clotting factors via FC and PCC following activation of the massive hemorrhage protocol (MHP) on the number of ABP units transfused in trauma patients with severe hemorrhage versus the current standard of care (ratio-based plasma resuscitation).
Test Products, Dose, and Mode of Administration:
Patients will be randomized if the MHP is activated according to the MHP activation criteria at each study site. Once eligibility is confirmed, the blood bank medical laboratory technologist will randomize the patient to one of two groups: the intervention group or the control group.
- Intervention group: 4 g Fibryga and 2000 IU Octaplex will be released as part of the first and second MHP packs.
- Control group: 4 U FP will be released as part of the first and second MHP packs.
- Concomitant therapy: In both groups, 4 U RBC will be included as part of the first and second MHP packs, and 1 dose of platelets (4 U of pooled random donor or single donor apheresis) will also be included as part of the second MHP pack. Both RBCs and platelets will be administered according to the clinical situation and/or lab results as per the discretion of the clinical team. The second MHP pack will be released at the request of the clinical team, but clinicians will be instructed to administer all of the investigational product (Fibryga/Octaplex or FP) in the first pack before moving onto the second pack. Similarly, if the second pack is opened, clinicians will be instructed to administer all of the investigational products contained within, before moving to the third pack. Not administering all of the investigational products in the first pack, once started, will be a protocol deviation.
Administration of all non-investigational products will be at the discretion of the clinical team according to the hemodynamic status of the patient and/or laboratory results (standard and/or point-of-care as per institutional practice). While platelets will be routinely included in the second pack, clinicians can request platelets outside of the packs (e.g., for patients on antiplatelet therapy or with marked thrombocytopenia). In the control group, FC may be administered if hypofibrinogenemia (fibrinogen level below 1.5-2.0 g/L or FIBTEM A10 below 8-12 mm) is identified as part of routine testing, at the discretion of the clinical team. Patients in the intervention group can receive additional FC if hypofibrinogenemia (as per above criteria) is identified after the full dose (4g) in the first pack is administered (if the second pack is not opened). If the second pack is opened, additional doses of FC will be permitted after the full dose (4g) in the second pack is administered..
Patients in the control group will not be permitted to receive PCC during the study. Patients in the intervention group may receive FP in the third and subsequent MHP packs. If a third MHP pack is required, and thereafter, MHP packs will contain ABPs (RBCs, platelets and plasma) according to guidelines at each participating site or revert to laboratory-guided transfusion as per the local guidelines once bleeding is controlled. The MHP should be terminated once bleeding is controlled and the MHP criteria are no longer met. Termination of the MHP may occur at any time based on the discretion of the clinical team.
The maximum time frame for administration of the second MHP pack (if required) for both groups is 24 hours from arrival to the trauma bay/ED or termination of the MHP (whichever comes first).
We anticipate for the trial to begin in June 2020 and be completed over a 3 year period.
Sample Size The study will enroll up to 350 trauma patients with approximately 175 assigned to each of the two treatment groups.
Due to the inherent variability in the primary endpoint and a yet substantial uncertainty about the effect size, an adaptive design approach will be used. For this, a planned interim analysis will be performed after 120 patients have completed the study at up to four hospital sites. Primary aim of this interim analysis is to calculate the p-value and conditional power of the test statistic and perform a sample size re-assessment. This will be done in an unblinded interim analysis performed by an independent statistician who will report the results only to the independent data safety monitoring committee (IDSMC) which will make recommendations to the sponsor without revealing the treatment groups. Hence, the final number of enrolled patients will depend on the sample size re-calculation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Intervention Group- Clotting Factor Concentrates | Experimental | Biological: Fibrinogen + PCCFibryga + 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 comparator | Biological: Frozen PlasmaFrozen Plasma (FP) |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fibrinogen + PCCAlso: Fibryga + OctaplexPatients 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). | Biological | Intervention Group- Clotting Factor Concentrates |
| Frozen Plasma4U 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. | Biological | Control Group: Standard FP transfusion |
Primary outcome
Composite of total number of Allogeneic Blood Products (ABPs)
Time frame: within 24 hours
The primary endpoint is to demonstrate superiority with respect to the composite number of all ABP units (RBCs, FP and platelets) transfused
3 secondary outcomes
Total number of RBC units
Time frame: Transfused within the 24 hours
Incidence of thromboembolic events
Time frame: up to 28 days
Ventilator-free days
Time frame: From arrival to day 28
Results and safety
The study was stopped early (reason given: Upon IDSMC's review of interim data, they recommended the trial be stopped based on futility.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2026.
- Derived from this study: PubMed 40982282da 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.
- Derived from this study: PubMed 34479938da 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.
- Individual participant dataSharing planned: No. No current plan to make IPD available to other researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luis T Da Luz, MD principal investigator
Sunnybrook Health Sciences Centre
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fibrinogen + PCC and Frozen Plasma in people with Traumatic Hemorrhage and Coagulopathy, run by University Health Network, Toronto at 6 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Upon IDSMC's review of interim data, they recommended the trial be stopped based on futility.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite of total number of Allogeneic Blood Products (ABPs) (time frame: within 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04534751, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2026.