Comparison of Rapid Thrombelastography and Conventional Coagulation Testing for Haemostatic Resuscitation in Trauma

Study Overview
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Brief Summary
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The purpose of this study is to compare rapid thrombelastography (r-TEG) with conventional coagulation testing for diagnosing and treating coagulation abnormalities in severely injured patients who are likely to require transfusion therapy.

Detailed Description
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This is a prospective, randomized study comparing rapid thrombelastography (r-TEG) with conventional coagulation testing for diagnosing post-injury coagulopathy and guiding haemostatic resuscitation strategy in severely injured patients arriving at the trauma center who are likely to require transfusion therapy. Our global hypothesis is that: r-TEG is an effective tool for early identification of specific coagulation abnormalities via real time analysis, providing rapid results at the point of care (POC), r-TEG can be used to guide resuscitation strategy by permitting transfusion based upon individual patient deficits, r-TEG will result in appropriate transfusion of plasma, cryoprecipitate, and platelets in the individual trauma patient, r-TEG will result in reduced transfusion requirements in patients with post-injury coagulopathy. Our specific study aims are: To compare r-TEG parameters [TEG-ACT, alpha angle, K value, MA (maximum amplitude), G value (clot strength), and fibrinolysis (EPL=estimated percent lysis)] with conventional coagulation testing [aPTT, INR, platelet count, fibrinogen level, D-dimer] in their ability to diagnose and monitor coagulation abnormalities in the trauma patient specifically. To compare blood product administration (packed red blood cells, fresh frozen plasma, cryoprecipitate and apheresis platelets) in the first 24 hours post-injury when transfusion is guided by r-TEG versus conventional coagulation tests. To determine whether normalization of r-TEG values predicts cessation of coagulopathic bleeding better than normalization of conventional clinical coagulation tests based upon clinical impressions of the treating surgeons and review of operative records and outcome. To determine and compare patterns of transfusion ratios of packed red blood cells: fresh frozen plasma: platelets for resuscitation of patients with post-injury coagulopathy in the r-TEG versus conventional coagulation test guided groups for the first 24 hours post-injury. To determine and compare the timeframes of blood product administration throughout the first 24 hours post-injury when transfusion is guided by r-TEG versus conventional coagulation testing. To compare the incidence of hemorrhage-related deaths as: very early mortality (<2 hours post-injury), early (2<6 hours post-injury) and delayed (6-24 post-injury) based upon review of death/autopsy records for date, time and cause of death in patients whose resuscitation is guided by r-TEG versus conventional coagulation testing. To compare a) the incidence of transfusion associated lung injury (TRALI), transfusion associated circulatory overload (TACO), acute respiratory distress syndrome (ARDS), and multiple organ failure (MOF); b) the length of stay in the surgical intensive care unit (SICU) and the number of ventilator free days in the SICU; and c) late mortality (>24 hour to Day 30), including day number and cause of death, in patients whose resuscitation is guided by r-TEG versus conventional coagulation testing.

Official Title
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A Prospective, Randomized Comparison Of Rapid Thrombelastography (r-TEG) And Conventional Coagulation Testing For Guiding The Diagnosis And Haemostatic Resuscitation Of Trauma Patients At Risk For Post-Injury Coagulopathy

Conditions
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Acute Coagulopathy

Intervention / Treatment
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* Biological: Blood product transfusion based on conventional coagulation tests.
* Biological: Blood product transfusion based on rapid thrombelastography (r-TEG) results.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age >18 years admitted to Denver Health Medical Center. Blunt or penetrating trauma sustained < 6 hours before admission, with Injury Severity Score > 15 (ISS>15), likely to require transfusion of RBC within 6 hours from admission as indicated by clinical assessment. Exclusion Criteria: Age < 18 years. Documented chronic liver disease (total bilirubin >2.0 mg/dL). Advanced cirrhosis discovered on laparotomy will be a criterion for study withdrawal and exclusion of conventional coagulation or r-TEG/TEG data from the analysis). Known inherited defects of coagulation function (e.g. hemophilia, Von Willebrand's disease). Prisoner. Pregnancy.

Ages Eligible for Study
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Minimum Age: 18 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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control (INR, PTT, fibrinogen, D-dimer)<br>Patients randomized to the Control Group will receive blood component therapy guided by conventional coagulation tests per usual clinical practice. The control arm involves the use of conventional coagulation tests (aPTT, INR, fibrinogen level, D-dimer) to diagnose and describe post-injury coagulopathy and to guide blood product replacement. In the Control Group, blood will be drawn for conventional coagulation testing (aPTT, INR, platelet count, fibrinogen level, D-dimer) at Baseline (as defined above), then twice more during the first six hours at the discretion of the treating team, then again at 12 hours and at 24 hours post-injury. The current institutional massive transfusion protocol will be followed. Only the results pertinent to the group to which randomized will be released to the treating team, unless otherwise requested. | Biological: Blood product transfusion based on conventional coagulation tests.<br>* Transfusion of blood products.<br>|
| Active Comparator: Test (r-TEG)<br>Patients randomized to the r-TEG guided haemostatic resuscitation group (Test Group) will receive blood component therapy per usual clinical practice. The test arm involves the use of rapid-TEG to diagnose and describe post-injury coagulopathy and to guide blood product replacement per institutional algorithm. In the Test Group, blood for r-TEG will be collected on admission, or upon entering the operating room, depending on the acuity of the injury (Baseline), and this will be followed by two additional r-TEG analyses during the first six hours at the discretion of the treating team (attending surgeon, anesthesiologist) and then two further r-TEG analyses at 12 hours and at 24 hours post-injury respectively. The current institutional massive transfusion protocol will be followed. Only the results pertinent to the group to which randomized will be released to the treating team, unless otherwise requested. | Biological: Blood product transfusion based on rapid thrombelastography (r-TEG) results.<br>* Transfusion of blood products.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28 Day In-hospital Mortality |  | 28 days in hospital | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Deaths Specified as Early Mortality (<6 Hours Post-injury) and Delayed Mortality (6-24 Hours Post-injury). |  | Within 24 hours post-injury. | 
| Deaths Related to Coagulopathic Bleeding Based Upon Clinical Impressions of the Treating Surgeons and Review of Operative Records and Outcome (Hours Since Injury). |  | Up to 28 days post-injury. | 
| Time to Death From Injury in Hours. |  | From time of injury to 28th day of hospitalization. | 
| Change in INR Test Results. | A high International Normalized Ratio (INR) indicates a higher risk of bleeding, while a low INR suggests a higher risk of developing a clot. | Within first 6 hours post-injury, 12 and 24 hours post-injury. | 
| Change in Fibrinogen Test Results. |  | Within first 6 hours post-injury, 12 and 24 hours post-injury. | 
| Change in Platelet Count Test Results. |  | Within first 6 hours post-injury, 12 and 24 hours post-injury. | 
| Change in D-dimer Test Results. |  | Within first 6 hours post-injury, 12 and 24 hours post-injury. | 
| Change in r-TEG ACT (Activated Clotting Time) Test Results. |  | Within first 6 hours post-injury, 12 and 24 hours post-injury. | 
| Change in r-TEG Angle Test Results. |  | Within first 6 hours post-injury, 12 and 24 hours post-injury. | 
| Change in r-TEG Maximal Amplitude (MA) Test Results. |  | Within first 6 hours post-injury, 12 and 24 hours post-injury. | 
| Change in r-TEG LY30 Test Results. |  | Within first 6 hours post-injury, 12 and 24 hours post-injury. | 
| Composition and Quantity of Blood Products Transfused at 24 Hours Post-injury | Amount of blood product (red blood cells, plasma, cryoprecipitate and platelets) in units. | 24 hours post-injury | 
| Length of Stay (Days) in the Surgical Intensive Care Unit (SICU) Reported as ICU-free Days and Number of Days on the Ventialator Reported as Ventilator Free Days. |  | 28 days. | 
| Number of Participants With Multiple Organ Failure (MOF) During This Hospitalization. | Multiple Organ Failure (MOF) score (Denver method) was calculated for the participants. This score rates the dysfunction of four organ systems (pulmonary, renal, hepatic, and cardiac), which are evaluated daily throughout the patient's intensive care unit stay and graded on a scale from 0 to 3, with the total score ranging from 0-12. Higher values on the score represent worse outcome. Participants with score above 3 were considered to have MOF. | Up to 30 days post-injury. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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transfusion, coagulopathy, trauma, hemorrhagic shock, thrombelastography, resuscitation