Implementing Treatment Algorithms for the Correction of Trauma Induced Coagulopathy

Study Overview
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Brief Summary
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This trial compares the haemostatic effect of viscoelastic haemostatic assay (VHA)-guided transfusion strategy versus non-VHA guided transfusion strategy in haemorrhaging trauma patients. Half of the randomised patients will receive VHA-led management of bleeding, whilst the other half will receive massive transfusion protocol resuscitation using conventional coagulation tests.

Detailed Description
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Trauma is the most frequent cause of death in persons aged under 40, with half of these deaths resulting from uncontrolled bleeding. 1 in 4 of all severely injured and shocked patients develop a clotting abnormality termed Trauma Induced Coagulopathy (TIC) within minutes of injury, which causes blood to continue being lost from the body faster than it can be stemmed. Many more injured patients will go on to develop different types of coagulopathy at different times during the course of their treatment, either as a result of their body's ongoing response to trauma or as a consequence of their clinical care. Ultimately coagulopathic patients have increased blood transfusion requirements and suffer more adverse outcomes (e.g. multi organ failure). Current management of coagulopathic, haemorrhaging trauma patients comprises the unguided transfusion of large volumes of red blood cells and clotting product supplements. Without rapidly available and validated diagnostics, products are delivered empirically to patients blind to the type and severity of TIC they may have or indeed even if they do not have TIC. This study will compare outcomes of viscoelastic haemostatic assay (VHA)-guided resuscitation versus conventional management of critically bleeding trauma patients. The hypothesis is that goal-directed haemostatic resuscitation of coagulopathic bleeding trauma patients will yield improved outcomes and reduced blood product demand, compared to empiric massive transfusion therapy.

Official Title
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A Multi-centre, Prospective, Randomized Controlled Study to Compare Outcomes of Viscoelastic Haemostatic Assay (VHA)-Guided Resuscitation Versus Conventional Resuscitation Support in Haemorrhaging Trauma Patients

Conditions
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Hemorrhage, Coagulopathy, Trauma

Intervention / Treatment
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* Device: VHA algorithm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult trauma patients (according to local definitions) will be enrolled if they: Present with hemorrhagic shock at any time from the time of injury until admission to the emergency department (where shock is defined by HR>100 b/min and/or systolic BP<90 mmHg) AND activate the local massive transfusion protocol Randomized within 3 hours of injury and 1 hour of admission to the emergency department Agreement is provided on behalf of incapacitated patients by Personal Consultee or Nominated Consultee (e.g.trauma team leader) Exclusion Criteria: Any inclusion criteria are not met

Ages Eligible for Study
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Minimum Age: 16 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: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VHA algorithm<br>Massive transfusion protocol resuscitation aiming at ratio 1:1:1 of blood components (RBC 1: plasma 1: platelets 1) and VHA-guiding further resuscitation with blood products and procoagulant factors | Device: VHA algorithm<br>* Analysis of more than 2,200 trauma subjects has enabled the definition of clinically-relevant VHA thresholds (i.e. ROTEM® and TEG® parameters) and patterns by which it is possible to rapidly identify coagulopathic patients and anticipate the need for massive transfusion. These threshold parameters have been defined and applied to the generation of an evidence-based targeted treatment algorithm (i.e. the Intervention)<br>|
| No Intervention: Control<br>Massive transfusion protocol resuscitation aiming at ratio 1:1:1 of blood components (RBC 1: plasma 1: platelets 1) and conventional coagulation tests guiding further resuscitation with blood products and procoagulant factors | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects alive and free of massive transfusion | Proportion of subjects at 24 hours post-admission who are alive and free of massive transfusion (i.e. received 10 or more units of red blood cells within 24 hours) | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6hr Mortality | All-cause mortality at 6-hours post admission | 6 hours | 
| 24hr Mortality | All-cause mortality at 24-hours post admission | 24 hours | 
| 28d Mortality | All-cause mortality at 28-days post admission | 28-days | 
| 90d Mortality | All-cause mortality at 90-days post admission | 90-days | 
| Duration of coagulopathy | The time spent in coagulopathic state, as defined by Prothrombin Time / International Ratio (PTr) PTr >1.2) from Admission until the point of hemostasis (itself defined as having occurred at the end of the first hour free of red cell transfusions and the treating clinicians believe primary hemostasis has been achieved). | 28-days post admission | 
| Severity of coagulopathy | Defined by the area under the Prothrombin Time / International Ratio (PTr) curve from Admission to the point of haemostasis (where time of hemostasis is defined as having occurred at the end of the first hour free of red cell transfusions and the treating clinicians believe primary hemostasis has been achieved). | 28-days post admission | 
| Proportion of patients with corrected coagulopathy after first 8U RBC | Proportion of patients with corrected coagulopathy after first 8U RBC | 28-days post admission | 
| Time to hemostasis | Time from Admission to the point of hemostasis (where time of hemostasis is defined as having occurred at the end of the first hour free of red cell transfusions and the treating clinicians believe primary hemostasis has been achieved). | 28-days post admission | 
| Time spent in coagulopathic condition until haemostasis | Time of haemostasis is defined the period from Admission to the point as having occurred at the end of the first hour free of red cell transfusions and the treating clinicians believe primary hemostasis has been achieved. Coagulopathy defined as PTr >1.2. | 28-days post admission | 
| 6hr Blood products transfused | Total blood products (RBC, plasma, platelets alone and in total) transfused in first 6hours after admission | 6 hours | 
| 24hr Blood products transfused | Total blood products (RBC, plasma, platelets alone and in total) transfused in first 24hours after admission | 24 hours | 
| 28d Ventilator-free days | Calculated by the subtracting the number of days spent on mechanical ventilation from 28. | 28 days | 
| 28d ICU-free days | Calculated by the subtracting the number of days spent on intensive care unit from 28. | 28 days | 
| Length of stay | Length of stay will be recorded in days, for the total number spent in ICU and in Hospital. If the patient is in the hospital at any time point during a day, this day will be considered a hospital day. | 28 days | 
| Symptomatic thromboembolic events | Symptomatic venous thromboembolic events shall be recorded, as confirmed by radiology. Other thromboembolic events such as myocardial infarction and/or stroke shall be identified by standard clinical diagnostic investigation(s). | 28 days | 
| Transfusion-related complications | Incidence, category and severity of acute transfusion reactions will be defined according to UK SHOT (United Kingdom Serious Hazards of Transfusion) | 28-days | 
| Organ dysfunction | Organ dysfunction shall be measured as Sequential Organ Failure Assessment (SOFA) score from admission to day 28 or discharge | 28-days | 
| 28d/discharge QoL | Health-Related Quality of Life (HRQoL) will be measured at 28 day post admission or upon discharge if sooner | 28 days | 
| 90d QoL | Health-Related Quality of Life (HRQoL) will be measured at 90 day post admission | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Trauma, Hemostasis, Resuscitation, Coagulopathy, Transfusion