Transfusion of Red Blood Cells, Tranexamic Acid and Fibrinogen Concentrate for Severe Trauma Hemorrhage at Pre-hospital Phase of Care.

Study Overview
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Brief Summary
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This is a single-center, not-randomized, open-label, controlled pilot clinical trial. This study compares presence of Trauma Induced Coagulopathy (TIC) and acute traumatic hemorrhage treatment at pre-hospital phase of care with red blood cells (RBC), Tranexamic acid (TXA) and Fibrinogen Concentrate (FC) with the current treatment based on the administration of Crystalloids and TXA.

Detailed Description
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A pilot, non-randomized, open-label study of two intervention arms and controlled with the standard treatment in which 60 patients affected with acute hemorrhage due to severe trauma will enter the study with the main objective of evaluating the feasibility and the efficacy of early treatment during the pre-hospital care phase with packed red blood cells, fibrinogen concentrate and tranexamic acid (experimental arm) compared to the standard treatment based on crystalloids administration and tranexamic acid (control arm). The secondary objectives are to evaluate the safety and clinical evolution of the patients. Prior to the administration of the treatment, 2 blood samples will be extracted in both groups in order to compare the coagulation status and to be able to perform the pre-transfusion tests. On arrival at the hospital, another sample will be taken to compare changes in coagulation after the administration of the experimental or standard treatment and also between both groups. The assessment of the coagulation status will be made using the values provided by the viscoelastic test (TEG6s). The experimental and standard treatment will be administered endovenously. After treatment, patients will be evaluated up to 30 days.

Official Title
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Transfusion of Red Blood Cells (RBC), Tranexamic Acid (TXA) and Fibrinogen Concentrate (FC) for Severe Trauma Hemorrhage at Pre-hospital Phase of Care. A Pilot Trial.

Conditions
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Polytrauma, Traumatic Hemorrhage

Intervention / Treatment
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* Drug: Fibrinogen Concentrate (Human) 1 MG [RiaSTAP]
* Biological: Red blood cells concentrate
* Drug: Tranexamic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years AND Patients with severe trauma categorized as priority 0 or 1 according to the CatSalut Polytrauma Code (PPT) AND Evidence of bleeding or a high bleeding suspicion according to physician judgment OR Predicted to need transfusion according to TICCS score ≥10 Exclusion Criteria: Moribund patient with devastating injuries and expected to die within 1-hour OR Known objection to blood components transfusion OR Known acquired or congenital coagulopathies not related to the actual trauma OR Known anticoagulant treatment (vitamin K antagonist, dabigatran, rivaroxaban, apixaban) OR Known Pregnancy OR Severe isolated traumatic brain injury OR Hemorrhage not related to the actual trauma

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single-center, non-randomized, open-label, two-arms, controlled pilot clinical trial. The experimental and control arms will be determined according to the SEM units with RBC, TXA and FC administration capacity (i.e. helicopter unit, rapid intervention ambulance or advanced life support ambulance). The emergency SEM units are activated according current protocols based on distance, severity and weather conditions.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental treatment<br>The active treatment consists of intravenous injection of 2g of fibrinogen concentrate, 1g of tranexamic acid, 2 red bood cells concentrate O Rh(D) negative (Banc de Sang i Teixits, Barcelona, Spain), and crystalloids at pre-hospital phase of care. | Drug: Fibrinogen Concentrate (Human) 1 MG [RiaSTAP]<br>* Administration of 2 mg of FC together with RBC and TXA<br>Biological: Red blood cells concentrate<br>* Administration of 2 red blood cells concentrates together with FC and TXA<br>Drug: Tranexamic Acid<br>* Administration of 1g of TXA together with FC and RBC<br>|
| Active Comparator: Standard treatment<br>Patients in the control arm will be treated according the existing protocols based on crystalloids and tranexamic acid administration. | Drug: Tranexamic Acid<br>* Administration of 1g of TXA together with FC and RBC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TEG6s(R) parameters for Trauma Induced Coagulopathy (TIC) | TEG6s(R) parameters that define TIC | Basal (at the crash site) | 
| TEG6s(R) parameters for Trauma Induced Coagulopathy (TIC) | TEG6s(R) parameters that define TIC | Basal (at the hospital arrival) | 
| All-cause mortality | Mortality for any cause | 1 hour post hospital admission | 
| All-cause mortality | Mortality for any cause | 6 hours post hospital admission | 
| All-cause mortality | Mortality for any cause | 24 hours post hospital admission | 
| Accountability | Red bood cells concentrate accountability | 30 days | 
| Temperature storage conditions of the red blood cells concentrate | Red bood cells concentrate out of temperature range for storage | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality | Mortality for any cause | 48 hours post hospital admission | 
| All-cause mortality | Mortality for any cause | 30 days post hospital admission | 
| Adverse Events | Treatment emergent adverse events | 30 days post hospital admission (or previously at hospital discharge) | 
| Thromboembolism events | Thromboembolism events | 30 days | 
| Crystalloid fluid requirements | Volume of crystalloids required | 1 hour (from the crash site to the hospital admission) | 
| Crystalloid fluid requirements | Volume of crystalloids required | 30 days post hospital admission (or previously at hospital discharge) | 
| Transfusion requirements | Transfusion requirements of RBC, platelets and plasma | 24 hours (or previously at discharge of the emergency room) | 
| Transfusion requirements | Transfusion requirements of RBC, platelets and plasma | 30 days post hospital admission (or previously at hospital discharge) | 
| Water balance | Water balance at the Intensive Care Unit (ICU) | 24 hours of admission at the ICU | 
| Water balance | Water balance at the Intensive Care Unit (ICU) | 72 hours of admission at the ICU | 
| Ventilator-free days | Ventilator-free days at the ICU | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polytrauma, Red blood cells transfusion, Acute traumatic hemorrhage