Hemorrhage, Hemorrhagic Shock, Hypofibrinogenemia, Trauma Associated Hemorrhage
Conditions
Keywords
Fibrinogen, Hemorrhage, Trauma, Resuscitation, INTERCEPT Fibrinogen Complex, Pathogen Reduced Cryoprecipitated Fibrinogen Complex, Hemorrhagic Shock, Quantra
Brief summary
The objective of this multicenter, single-arm, observational study is to determine the feasibility and effectiveness of early administration of FDA-approved, pre-thawed Pathogen Reduced Cryoprecipitated Fibrinogen Complex (INTERCEPT Fibrinogen Complex, IFC) in trauma patients with hemorrhagic shock (HS) and functional hypofibrinogenemia. This study will determine whether rapid point-of-care testing for functional hypofibrinogenemia and availability of a shelf-stable fibrinogen complex (IFC) results in shorter time to administration of fibrinogen replacement and correction of functional hypofibrinogenemia, as compared with historical controls and published literature using conventional cryoprecipitate-AHF (CRYO-AHF). This study aims to: * Demonstrate the feasibility and response to early administration of pre-thawed IFC when ordered during initial resuscitation of severely injured patients with HS and functional hypofibrinogenemia. * Assess the effectiveness of early administration of pre-thawed IFC on correction of functional hypofibrinogenemia and on proximate process measures of resuscitation, including time to hemostasis, time to completion of resuscitation, and total volume of resuscitation. * Assess clinical outcomes in severely injured patients with HS and functional hypofibrinogenemia receiving early administration of pre-thawed IFC.
Detailed description
This is a multicenter, pragmatic, observational, single-arm study evaluating the feasibility and effectiveness of early administration of pre-thawed Pathogen Reduced Cryoprecipitated Fibrinogen Complex (INTERCEPT Fibrinogen Complex, IFC) in trauma patients with hemorrhagic shock and functional hypofibrinogenemia. Adult trauma patients age ≥18 years, or estimated weight ≥50 kg if age is unknown, who present to a participating trauma center within 1 hour of estimated time of injury and meet criteria for hemorrhagic shock will be screened using the point-of-care Quantra® Hemostasis Analyzer. Functional hypofibrinogenemia is defined as FCS \<1.6 hPa by Quantra® point-of-care testing. Patients are eligible only if cryoprecipitate administration is clinically indicated by the treating physician, IFC is available at the time of enrollment, and the patient will receive IFC per standard of care. Following administration of IFC, an additional Quantra® point-of-care test will be completed at completion of resuscitation (COR), defined as discontinuation of the massive transfusion protocol (MTP), to evaluate fibrinogen response. Additional IFC may be administered if additional hemostatic correction is determined to be needed by the treating clinician, repeat point-of-care testing, or clinical judgment. Primary outcomes are the proportion of patients with hemorrhagic shock and functional hypofibrinogenemia who receive IFC within 60 minutes of presentation to the participating trauma center and the proportion of patients with successful correction of functional hypofibrinogenemia at COR. Secondary outcomes include time to hemostasis, estimated blood loss, transfusion burden/total volume of resuscitation, mortality at 3 hours, 6 hours, 24 hours, and 30 days or in-hospital mortality, and adverse clinical outcomes through 30 days, hospital discharge, or death, whichever occurs first. Outcomes may be compared descriptively with historical controls, site medical databases, and published literature using CRYO-AHF. Four Level 1 trauma centers will enroll approximately 320 patients over approximately 24 months.
Interventions
BIOLOGICALPathogen Reduced Cryoprecipitated Fibrinogen Complex
Pre-thawed IFC will be administered per standard of care when cryoprecipitate administration is clinically indicated by the treating physician and IFC is available. Participants must have functional hypofibrinogenemia by Quantra® POC testing with FCS \<1.6 hPA. Additional IFC may be administered based on repeat POC testing or clinical judgment.
Sponsors
Cerus Corporation
Coalition for National Trauma Research
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Traumatic injury * Age ≥18 years or estimated weight ≥50 kg, if age unknown * Presenting to a participating trauma center ≤1 hour from estimated time of injury * Functional hypofibrinogenemia upon arrival to the trauma center as measured by point-of-care testing (Quantra®) with FCS \<1.6 hPa * Hemorrhagic shock, defined as: 1. Initiation of transfusion of any uncrossmatched blood product; 2. Evidence of active hemorrhage as judged by the attending trauma surgeon; and 3. Initiation of the participating trauma center's massive transfusion protocol (MTP) * IFC administration is clinically indicated per the treating physician * IFC is 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, defined as continuous CPR \>5 minutes at any time point prior to enrollment in the study * Isolated fall from standing * Emergency Department (ED) thoracotomy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| IFC administration within 60 minutes of presentation | From presentation/admission to the participating trauma center to initial IFC transfusion, assessed up to 60 minutes after presentation. | Proportion (%) of patients with hemorrhagic shock and functional hypofibrinogenemia who receive IFC within 60 minutes of presentation to the participating trauma center. |
| Correction of functional hypofibrinogenemia after IFC transfusion | At completion of resuscitation (COR), defined as discontinuation of the massive transfusion protocol (MTP), after IFC transfusion. | Proportion of patients with successful correction of functional fibrinogen, defined as FCS ≥1.6 hPa by Quantra® point-of-care testing after transfusion of IFC, measured at completion of resuscitation (COR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | 3, 6, and 24 hours after admission/enrollment; 30 days or in-hospital mortality. | Mortality incidence at 3 hours, 6 hours, 24 hours, and 30 days or in-hospital mortality. |
| Clinical complications/adverse clinical outcomes. | From enrollment through 30 days, hospital discharge, or death, whichever occurs first. | Incidences of acute blood loss anemia, abdominal compartment syndrome, acute kidney injury, acute renal failure, acute respiratory distress syndrome, bleeding after hemostasis requiring intervention, coagulopathy, febrile non-hemolytic transfusion reaction, hospital-acquired pneumonia, intraabdominal infection, liver failure, MOD, 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 the first 24 hours, transfusion-related hypocalcemia in the first 24 hours, and ventilator-associated pneumonia. |
Countries
United States
Contacts
CONTACTLaurence Corash, MD
Outcome results
None listed