Traumatic Hemorrhage
Conditions
Keywords
Tranexamic acid, randomized, hemorrhage, blinded
Brief summary
The purpose of this study is to determine if 1 gram of prehospital tranexamic acid given during emergency medical transport to a level 1 trauma center in patients at risk of hemorrhage is associated with lower 30 day mortality.
Detailed description
Background: Traumatically injured patients continue to be plagued with uncontrolled hemorrhage resulting in significant morbidity and early mortality. A primary driving force for this unbridled hemorrhage is known to be the early coagulopathy which complicates severe injury. Trauma induced coagulopathy has been postulated to be an equilibrium imbalance between pro and anticoagulant factors, platelets, endothelium and fibrinolysis soon after injury. Recent evidence demonstrates that the early use of the antifibrinolytic agent tranexamic acid (TXA) after trauma center arrival results in improved survival in patients at risk for bleeding. Bringing this proven treatment to the prehospital arena and intervening earlier in those patients who would otherwise not be candidates for treatment has the real potential to further reduce or prevent the vicious hemorrhagic cascade, improve clinical outcomes and provide insight into the underlying mechanisms responsible for and which maximize its benefit. Objective/Hypothesis: The primary hypothesis will be that prehospital infusion of tranexamic acid in patients at risk for bleeding will reduce the incidence of 30 day mortality. The secondary hypotheses include that prehospital tranexamic acid will reduce the incidence of hyperfibrinolysis, acute lung injury, multiple organ failure, nosocomial infection, mortality, early seizures, pulmonary embolism and early resuscitation needs, reduce or prevent the early coagulopathy as demonstrated by improving presenting INR and rapid thromboelastography parameters, reduce the early inflammatory response, plasmin levels, leukocyte, platelet and complement activation, and determine the optimal dosing of tranexamic acid post-injury.
Interventions
DRUGTranexamic Acid
1 gram of prehospital Tranexamic Acid
OTHERSaline control
Saline Control
Sponsors
University of Arizona
The University of Texas at San Antonio
University of Utah
Jason Sperry
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Blunt or penetrating injured patients at risk of bleeding being transported via air or ground medical services from the scene of injury or from referring hospital to a definitive trauma center that is participating in the trial AND 2. Within 2 hours of time of injury AND 3. Hypotension (Systolic Blood Pressure (SBP) \< 90mmHg) * At scene of injury or during air or ground medical transport * Documented at referring hospital prior to air or ground medical transport arrival OR 4. Tachycardia (heart rate \>110 beats per minute) * At scene of injury or during air or ground medical transport * Documented at referring hospital prior to air or ground medical transport arrival
Exclusion criteria
1. Age \> 90 or \< 18 years of age 2. Inability to obtain intravenous access or intraosseous 3. Documented (radiographic evidence) cervical cord injury with motor deficit 4. Known prisoner 5. Known pregnancy 6. Traumatic arrest with \> 5 minutes CPR without return of vital signs 7. Penetrating cranial injury 8. Traumatic brain injury with brain matter exposed 9. Isolated drowning or hanging victims 10. Wearing an opt out bracelet. 11. Isolated fall from standing 12. Patient or Family Objection at scene
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 30 Day Mortality | 30 Day | Because not all patients had available data regarding 30-day mortality (patients were discharged and there 30-day outcome was unable to be determined) there may be differences between the 30Day mortality relative to the other outcomes. There were 5 and 4 patients from each arm that did not have 30-day outcome and thus are different. |
Secondary
| Measure | Time frame |
|---|---|
| Acute Lung Injury | 7 days |
| Multiple Organ Failure | 30 days |
| 24 Hour Mortality | 24 Hours |
| 24 Hour Total Blood Transfusion | 24 hours |
| Hyperfinbrinolysis | 24 hours |
| Nosocomial Infection | 30 days |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prehospital Tranexamic Acid 1 gram of Tranexamic Acid will be given during emergency medical transport
Tranexamic Acid: 1 gram of prehospital Tranexamic Acid | 447 |
| Control Identical volume of saline during emergency medical transport
Saline control: Saline Control | 456 |
| Total | 903 |
Baseline characteristics
| Characteristic | Control | Total | Prehospital Tranexamic Acid |
|---|---|---|---|
| Age, Continuous | 39 years | 39 years | 39 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 40 Participants | 89 Participants | 49 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 49 Participants | 90 Participants | 41 Participants |
| Race (NIH/OMB) White | 361 Participants | 714 Participants | 353 Participants |
| Sex: Female, Male Female | 115 Participants | 235 Participants | 120 Participants |
| Sex: Female, Male Male | 341 Participants | 668 Participants | 327 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 36 / 447 | 45 / 456 |
| other Total, other adverse events | 4 / 447 | 14 / 456 |
| serious Total, serious adverse events | 4 / 447 | 7 / 456 |
Outcome results
Primary
30 Day Mortality
Because not all patients had available data regarding 30-day mortality (patients were discharged and there 30-day outcome was unable to be determined) there may be differences between the 30Day mortality relative to the other outcomes. There were 5 and 4 patients from each arm that did not have 30-day outcome and thus are different.
Time frame: 30 Day
Population: Because not all patients had available data regarding 30-day mortality (patients were discharged and there 30-day outcome was unable to be determined) there may be differences between the 30Day mortality relative to the other outcomes. There were 5 and 4 patients from each arm that did not have 30-day outcome and thus are different.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prehospital Tranexamic Acid | 30 Day Mortality | 36 Participants |
| Control | 30 Day Mortality | 45 Participants |
Secondary
24 Hour Mortality
Time frame: 24 Hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prehospital Tranexamic Acid | 24 Hour Mortality | 16 Participants |
| Control | 24 Hour Mortality | 17 Participants |
Secondary
24 Hour Total Blood Transfusion
Time frame: 24 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prehospital Tranexamic Acid | 24 Hour Total Blood Transfusion | 0 units of blood transfusion |
| Control | 24 Hour Total Blood Transfusion | 0 units of blood transfusion |
Secondary
Acute Lung Injury
Time frame: 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prehospital Tranexamic Acid | Acute Lung Injury | 42 Participants |
| Control | Acute Lung Injury | 39 Participants |
Secondary
Hyperfinbrinolysis
Time frame: 24 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prehospital Tranexamic Acid | Hyperfinbrinolysis | 145 Participants |
| Control | Hyperfinbrinolysis | 144 Participants |
Secondary
Multiple Organ Failure
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prehospital Tranexamic Acid | Multiple Organ Failure | 33 Participants |
| Control | Multiple Organ Failure | 39 Participants |
Secondary
Nosocomial Infection
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prehospital Tranexamic Acid | Nosocomial Infection | 88 Participants |
| Control | Nosocomial Infection | 66 Participants |