Coagulopathy, Hemorrhage, Trauma
Conditions
Keywords
Trauma, Hemostasis, Resuscitation, Coagulopathy, Transfusion
Brief summary
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
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.
Interventions
DEVICEVHA algorithm
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)
Sponsors
Oslo University Hospital
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Klinikum der Universität Köln
Rigshospitalet, Denmark
Oxford University Hospitals NHS Trust
Barts & The London NHS Trust
European Commission
Queen Mary University of London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects alive and free of massive transfusion | 24 hours | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 24hr Mortality | 24 hours | All-cause mortality at 24-hours post admission |
| 28d Mortality | 28-days | All-cause mortality at 28-days post admission |
| 90d Mortality | 90-days | All-cause mortality at 90-days post admission |
| Duration of coagulopathy | 28-days post admission | 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). |
| Severity of coagulopathy | 28-days post admission | 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). |
| Proportion of patients with corrected coagulopathy after first 8U RBC | 28-days post admission | Proportion of patients with corrected coagulopathy after first 8U RBC |
| Time to hemostasis | 28-days post admission | 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). |
| Time spent in coagulopathic condition until haemostasis | 28-days post admission | 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. |
| 6hr Blood products transfused | 6 hours | Total blood products (RBC, plasma, platelets alone and in total) transfused in first 6hours after admission |
| 6hr Mortality | 6 hours | All-cause mortality at 6-hours post admission |
| 28d Ventilator-free days | 28 days | Calculated by the subtracting the number of days spent on mechanical ventilation from 28. |
| 28d ICU-free days | 28 days | Calculated by the subtracting the number of days spent on intensive care unit from 28. |
| Length of stay | 28 days | 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. |
| Symptomatic thromboembolic events | 28 days | 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). |
| Transfusion-related complications | 28-days | Incidence, category and severity of acute transfusion reactions will be defined according to UK SHOT (United Kingdom Serious Hazards of Transfusion) |
| Organ dysfunction | 28-days | Organ dysfunction shall be measured as Sequential Organ Failure Assessment (SOFA) score from admission to day 28 or discharge |
| 28d/discharge QoL | 28 days | Health-Related Quality of Life (HRQoL) will be measured at 28 day post admission or upon discharge if sooner |
| 90d QoL | 90 days | Health-Related Quality of Life (HRQoL) will be measured at 90 day post admission |
| 24hr Blood products transfused | 24 hours | Total blood products (RBC, plasma, platelets alone and in total) transfused in first 24hours after admission |
Countries
Denmark, Germany, Netherlands, Norway, United Kingdom
Outcome results
None listed