Cryo-FIRST: Effectiveness of INTERCEPT Fibrinogen Complex (IFC) for Trauma-Associated Hemorrhage

Official title

Cryo-FIRST: Cryoprecipitate For Immediate Resuscitation in Severe Trauma: Effectiveness of Pathogen Reduced Cryoprecipitated Fibrinogen Complex (INTERCEPT Fibrinogen Complex, IFC) for Treatment of Trauma Associated Hemorrhage

Overview

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

• Biological Pathogen 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.

Primary outcome measures

• IFC administration within 60 minutes of presentation [Time frame: From presentation/admission to the participating trauma center to initial IFC transfusion, assessed up to 60 minutes after presentation.]
• Correction of functional hypofibrinogenemia after IFC transfusion [Time frame: At completion of resuscitation (COR), defined as discontinuation of the massive transfusion protocol (MTP), after IFC transfusion.]

Secondary outcome measures (2)

• Mortality [Time frame: 3, 6, and 24 hours after admission/enrollment; 30 days or in-hospital mortality.]
• Clinical complications/adverse clinical outcomes. [Time frame: From enrollment through 30 days, hospital discharge, or death, whichever occurs first.]

Eligibility criteria

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:

• Initiation of transfusion of any uncrossmatched blood product;
• Evidence of active hemorrhage as judged by the attending trauma surgeon; and
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 4 centers

• Anschutz Medical Center, University of Colorado — Aurora
• Ryder Trauma Center/Jackson Memorial Hospital, University of Miami — Miami
• R Adams Cowley Shock Trauma Center, University of Maryland — Baltimore
• Barnes Jewish Hospital, Washington University of Saint Louis — St Louis

Publications

• Rossetto A, Wohlgemut JM, Brohi K, Davenport R. Sonorheometry versus rotational thromboelastometry in trauma: a comparison of diagnostic and prognostic performance. J Thromb Haemost. 2023 Aug;21(8):2114-2125. doi: 10.1016/j.jtha.2023.04.031. Epub 2023 May 8. PMID 37164268
• Huffman G, Wilken N, Loh JH, Fazal M, Lei I, Myers A, et al. Analysis of Wastage, Savings, and Maternal and Pediatric Outcomes for Pooled Pathogen Reduced Cryoprecipitate versus Conventional Cryoprecipitate. Baylor College of Medicine; Abstract AABB Annual Meeting. 2024.
• Holcomb JB, Tilley BC, Baraniuk S, Fox EE, Wade CE, Podbielski JM, del Junco DJ, Brasel KJ, Bulger EM, Callcut RA, Cohen MJ, Cotton BA, Fabian TC, Inaba K, Kerby JD, Muskat P, O'Keeffe T, Rizoli S, Robinson BR, Scalea TM, Schreiber MA, Stein DM, Weinberg JA, Callum JL, Hess JR, Matijevic N, Miller CN, Pittet JF, Hoyt DB, Pearson GD, Leroux B, van Belle G; PROPPR Study Group. Transfusion of plasma, PMID 25647203
• Davenport R, Curry N, Fox EE, Thomas H, Lucas J, Evans A, Shanmugaranjan S, Sharma R, Deary A, Edwards A, Green L, Wade CE, Benger JR, Cotton BA, Stanworth SJ, Brohi K; CRYOSTAT-2 Principal Investigators. Early and Empirical High-Dose Cryoprecipitate for Hemorrhage After Traumatic Injury: The CRYOSTAT-2 Randomized Clinical Trial. JAMA. 2023 Nov 21;330(19):1882-1891. doi: 10.1001/jama.2023.21019. PMID 37824155
• Curry N, Rourke C, Davenport R, Beer S, Pankhurst L, Deary A, Thomas H, Llewelyn C, Green L, Doughty H, Nordmann G, Brohi K, Stanworth S. Early cryoprecipitate for major haemorrhage in trauma: a randomised controlled feasibility trial. Br J Anaesth. 2015 Jul;115(1):76-83. doi: 10.1093/bja/aev134. Epub 2015 May 19. PMID 25991760
• McQuilten ZK, Bailey M, Cameron PA, Stanworth SJ, Venardos K, Wood EM, Cooper DJ. Fibrinogen concentration and use of fibrinogen supplementation with cryoprecipitate in patients with critical bleeding receiving massive transfusion: a bi-national cohort study. Br J Haematol. 2017 Oct;179(1):131-141. doi: 10.1111/bjh.14804. Epub 2017 Jun 27. PMID 28653339
• Holcomb JB, del Junco DJ, Fox EE, Wade CE, Cohen MJ, Schreiber MA, Alarcon LH, Bai Y, Brasel KJ, Bulger EM, Cotton BA, Matijevic N, Muskat P, Myers JG, Phelan HA, White CE, Zhang J, Rahbar MH; PROMMTT Study Group. The prospective, observational, multicenter, major trauma transfusion (PROMMTT) study: comparative effectiveness of a time-varying treatment with competing risks. JAMA Surg. 2013 Feb;148 PMID 23560283

Identifiers

NCT: NCT07218185 · CLI 00193

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗