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Comparative Effectiveness of INTERCEPT Fibrinogen Complex (IFC) and Cryoprecipitate-AHF (Cryo-AHF) for Treatment of Trauma Associated Hemorrhage

Not yet recruiting
Conditions
Hypofibrinogenemia
Hemorrhage
Interventions
Biological: Pathogen Reduced Cryoprecipitated Fibrinogen Complex
Biological: Cryoprecipitated-Antihemophilic Factor
Registration Number
NCT07218185
Lead Sponsor
Cerus Corporation
Brief Summary

The objective of this study is to determine the feasibility and effectiveness of early IFC administration in patients with functional hypofibrinogenemia associated with hemorrhagic shock (HS). This study will elucidate whether advancements in rapid testing for functional hypofibrinogenemia and provision of a shelf-stable fibrinogen complex (IFC) results in a shorter time to administration of fibrinogen replacement, thus overcoming the limitations encountered by prior trials.

This study aims to:

* Demonstrate the feasibility and response to early administration of pre-thawed IFC compared to CRYO-AHF when ordered during resuscitation of severely injured patients with HS and functional hypofibrinogenemia.

* Assess effectiveness of early administration of pre-thawed IFC vs CRYO-AHF in severely injured patients with HS and functional hypofibrinogenemia on proximate process measures of resuscitation.

* Assess clinical outcomes in severely injured patients with HS and functional hypofibrinogenemia receiving early administration of pre-thawed IFC vs CRYO-AHF product.

Detailed Description

This study is a multicenter, multi-period, by hospital cluster randomized, alternating treatment block crossover study comparing pre-thawed Pathogen Reduced Cryoprecipitated Fibrinogen Complex (INTERCEPT Fibrinogen Complex, IFC) to Cryoprecipitate-AHF (Cryo-AHF) in patients with hemorrhagic shock and functional hypofibrinogenemia.

This study will assess the feasibility and effectiveness of early IFC administration in trauma patients in hemorrhagic shock with functional hypofibrinogenemia. Specifically, it aims to determine whether IFC enables faster delivery of fibrinogen replacement compared to Cryo-AHF and equivalent correction of hypofibrinogenemia. Currently, the use of IFC vs Cryo-AHF varies by center and blood bank availability, and both are considered standard-of-care treatment options. This study evaluates their performance in routine clinical use.

The primary outcomes are the proportion of patients who receive fibrinogen replacement within 60 minutes of arrival; and the correction of functional hypofibrinogenemia. Secondary outcomes include proximate measures of resuscitation including time to hemostasis, estimated blood loss, blood transfusion burden, 3-hour, 6-hour, 24-hour and 30-day mortality and adverse event incidences including: adult respiratory distress syndrome, multiple organ dysfunction, venous thromboemboli, acute kidney injury, sepsis and transfusion related acute lung injury.

Patients ≥18 years old, or \>50 Kg if age unknown, arriving within one hour of estimated time of injury with signs of hemorrhagic shock, will be screened and arrival hypofibrinogenemia determined using the point-of care Quantra® Hemostasis Analyzer. Eligible patients will receive either IFC or Cryo-AHF, depending on site assignment, in alternating 6-month treatment clusters. A post-treatment assessment of fibrinogen will be performed to assess response to fibrinogen supplementation. All data will be collected through 30 days, discharge, or death, whichever occurs first. Four Level 1 trauma centers will enroll a total of 320 patients (estimated each center to enroll approximately 80 patients) over 24 months of the study. If a site under-recruits, other sites may increase recruitment with IRB approval.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
320
Inclusion Criteria
  • Traumatic injury

  • Age ≥18 years or estimated weight ≥ 50 kg, if age unknown

  • Presenting to participating trauma center ≤1 hour from estimated time of injury

  • Functional hypofibrinogenemia upon arrival to the trauma center as measured by POC testing (Quantra) with an FCS < 1.6 hPa

  • Hemorrhagic shock defined as:

    1. Initiation of transfusion of any uncross matched blood product AND
    2. Evidence of active hemorrhage as judged by the attending trauma surgeon AND
    3. Initiation of the participating trauma center's MTP
  • IFC or CRYO-AHF are available at the time of enrollment.

Exclusion Criteria
  • Suspected isolated severe brain or spinal cord injury
  • Isolated drowning or hanging
  • Burns > 20% total body surface area (TBSA)
  • Known pregnancy
  • Admitted from a correctional facility
  • Known do not resuscitate (DNR) order
  • Traumatic arrest >5 minutes
  • Isolated fall from standing
  • Emergency Department (ED) thoracotomy

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
IFC armPathogen Reduced Cryoprecipitated Fibrinogen ComplexSubjects will receive Pathogen Reduced Cryoprecipitated Fibrinogen Complex (IFC) for fibrinogen supplementation.
Cryo AHF armCryoprecipitated-Antihemophilic FactorSubjects will receive Cryoprecipitated-Antihemophilic Factor (Cryo-AHF) for fibrinogen supplementation.
Primary Outcome Measures
NameTimeMethod
Correction of functional fibrinogenFrom time of initiation of anesthesia until time of completion of resuscitation.

The correction of functional fibrinogen as measured by point-of-care testing (Quantra) after transfusion of IFC or CRYO-AHF, as measured at completion of resuscitation. The time to correction of functional fibrinogen is reported in hours and minutes.

The proportion (%) of patients who receive IFC or Cryo-AHF within 60 minutes of presentation to the participating trauma center.From time of admission to the hospital trauma service to initial transfusion of either IFC or Cryo-AHF, measured in hours and minutes.

The proportion (%) of patients with hemorrhagic shock who have functional hypofibrinogenemia and who receive IFC or Cryo-AHF within 60 minutes of presentation to the participating trauma center.

Secondary Outcome Measures
NameTimeMethod
Mortality ratesMeasured from the time of admission to the hospital trauma service until death. Measured at 3, 6, and 24 hours after admission and reported in hours. Beyond 24 hours and up to 30 days post-admission, mortality is measured and reported in days.

Mortality rates at 3, 6, 24 hours and 30 days.

Clinical complicationsWithin 24 hours of treatment.

Incidences of adverse events to include Acute blood loss anemia, Abdominal compartment syndrome, Acute Kidney Injury, Acute Renal Failure, Acute respiratory distress syndrome, Bleeding after hemostasis requires intervention, Coagulopathy, Febrile non-hemolytic transfusion reaction, Hospital Acquired Pneumonia, Intraabdominal infection, Liver Failure, multiple organ dysfunction (MOD), Multiple Organ Failure (MOF), Myocardial infarction, Sepsis, Stroke, Surgical Site infection, Symptomatic and asymptomatic deep vein thrombosis, Symptomatic and asymptomatic pulmonary embolism, Systemic Inflammatory Response Syndrome, Transfusion-associated circulatory overload (TACO), Transfusion-associated lung injury (TRALI), Transfusion-related allergic reactions, Transfusion-related hyperkalemia (in first 24hrs), Transfusion-related hypocalcemia (in first 24hrs, and Ventilator-associated pneumonia.

Trial Locations

Locations (4)

University of Colorado, Anschutz Medical Center

🇺🇸

Aurora, Colorado, United States

Jackson Memorial Hospital, University of Miami

🇺🇸

Miami, Florida, United States

University of Maryland School of Medicine

🇺🇸

Baltimore, Maryland, United States

Barnes-Jewish Hospital, Washington University of Saint Louis

🇺🇸

St Louis, Missouri, United States

University of Colorado, Anschutz Medical Center
🇺🇸Aurora, Colorado, United States
Mitchell Cohen, MD
Contact
303-602-1861
mitchell.cohen@cuanschutz.edu

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