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

Cerus

Status: Begins enrollment in 2 months

Conditions: Hemorrhage; Hypofibrinogenemia

Treatments: Biological: Pathogen Reduced Cryoprecipitated Fibrinogen Complex; Biological: Cryoprecipitated-Antihemophilic Factor

Study type: Observational

Funder types: Other; Industry

Identifiers

NCT07218185

CLI 00193

Details and patient eligibility

About

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.

Full 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.

Enrollment: 320 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

320 participants in 2 patient groups

IFC arm

Description:

Subjects will receive Pathogen Reduced Cryoprecipitated Fibrinogen Complex (IFC) for fibrinogen supplementation.

Treatment:

Biological: Pathogen Reduced Cryoprecipitated Fibrinogen Complex

Cryo AHF arm

Description:

Subjects will receive Cryoprecipitated-Antihemophilic Factor (Cryo-AHF) for fibrinogen supplementation.

Treatment:

Biological: Cryoprecipitated-Antihemophilic Factor