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.

Conditions

• Traumatic Hemorrhage
• Coagulopathy
• Massive Hemorrhage

Interventions

BIOLOGICAL

Fibrinogen + PCC

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).

BIOLOGICAL

Frozen Plasma

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.

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre

  collaborator OTHER

• Octapharma

  collaborator INDUSTRY

• Canadian Institutes of Health Research (CIHR)

  collaborator OTHER_GOV

• Canadian Institute for Military and Veteran Health Research Defense Research & Development Canada

  collaborator UNKNOWN

• University Health Network, Toronto

  lead OTHER

Principal Investigators

• Luis T Da Luz, MD · Sunnybrook Health Sciences Centre

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

16 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-04-01

Primary Completion

2023-12-31

Completion

2024-01-30

Countries

• Canada

Study Locations