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Factor In the Initial Resuscitation of Severe Trauma 2 Patients (FiiRST-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04534751
Recruitment Status : Recruiting
First Posted : September 1, 2020
Last Update Posted : October 11, 2021
Sponsor:
Collaborators:
Sunnybrook Health Sciences Centre
Octapharma
Canadian Institutes of Health Research (CIHR)
Canadian Institute for Military and Veteran Health Research Defense Research & Development Canada
Information provided by (Responsible Party):
University Health Network, Toronto

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.


Condition or disease Intervention/treatment Phase
Traumatic Hemorrhage Coagulopathy Massive Hemorrhage Biological: Fibrinogen + PCC Biological: Frozen Plasma Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 350 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Investigator, Outcomes Assessor)
Masking Description:

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.

Primary Purpose: Treatment
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.
Actual Study Start Date : April 1, 2021
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : January 30, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Intervention Group- Clotting Factor Concentrates

Fibryga + Octaplex (Fibrinogen + PCC)

Fibrinogen Concentrate 4g (Fibryga) + Prothrombin Complex Concentrate 2000 IU (Octaplex) in the first and second massive hemorrhage protocol (MHP) packs.

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).

Other Name: Fibryga + Octaplex

Active Comparator: Control Group: Standard FP transfusion
Frozen Plasma (FP)
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.





Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Total number of RBC units [ Time Frame: Transfused within the 24 hours ]
    RBC - Red Blood Cells

  2. Incidence of thromboembolic events [ Time Frame: up to 28 days ]

    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

  3. Ventilator-free days [ Time Frame: From arrival to day 28 ]
    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



Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Severely injured adult trauma patients who meet all following criteria:

  1. Estimated age greater than 16 years old
  2. Severely injured (penetrating or blunt) trauma patients
  3. Triggered MHP within first hour of hospital arrival at the trauma bay/ED

Exclusion Criteria:

Patients who meet any of the following criteria are not eligible for the study:

  1. Have received more than 2 U RBCs during the pre-hospital phase of care
  2. Have received more than 2 U RBCs in the trauma bay/ED before activation of the MHP
  3. Have an elapsed time from injury of more than 3 hours
  4. Have a penetrating traumatic brain injury with Glasgow Coma Scale (GCS) of 3
  5. Are suspected or known to be on anticoagulants in the last 7 days
  6. Have known congenital or acquired bleeding disorders
  7. Have a known pregnancy
  8. Refuse blood transfusion due to religion or other reasons
  9. Previous history of heparin induced thrombocytopenia (HIT)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04534751


Contacts
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Contact: Jo Carroll, RN 416-340-4800 ext 3243 Jo.Carroll@uhn.ca
Contact: Deep K Grewal, MD 416-340-4800 ext 4221 Deep.Grewal@uhn.ca

Locations
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Canada, Ontario
Hamilton Health Sciences and McMaster University Not yet recruiting
Hamitlon, Ontario, Canada, L8L 2X2
Contact: Paul Engels, MD         
London Health Sciences Centre & St. Joseph's Health Care London Not yet recruiting
London, Ontario, Canada
Contact: Ziad Solh, MD         
Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Luis T Da Luz, MD         
St. Michael's Hospital Not yet recruiting
Toronto, Ontario, Canada
Contact: Katerina Pavenski, MD         
Sponsors and Collaborators
University Health Network, Toronto
Sunnybrook Health Sciences Centre
Octapharma
Canadian Institutes of Health Research (CIHR)
Canadian Institute for Military and Veteran Health Research Defense Research & Development Canada
Investigators
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Principal Investigator: Luis T Da Luz, MD Sunnybrook Health Sciences Centre
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT04534751    
Other Study ID Numbers: 2031 (CTO ID)
First Posted: September 1, 2020    Key Record Dates
Last Update Posted: October 11, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No current plan to make IPD available to other researchers.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Health Network, Toronto:
Trauma
Injury
Acute trauma coagulopathy
Traumatic bleeding
Clotting factors
Fibrinogen
Fibrinogen concentrate
Prothrombin complex concentrate
Massive Hemorrhage Protocol
Frozen Plasma
Additional relevant MeSH terms:
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Hemostatic Disorders
Blood Coagulation Disorders
Hemorrhage
Pathologic Processes
Hematologic Diseases
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders