Traumatic Brain Injury
Conditions
Keywords
tranexamic acid, traumatic brain injury, intracranial hemorrhage, prehospital, neurologic outcome, glasgow outcome scale extended, disability rating scale
Brief summary
Primary aim: To determine the efficacy of two dosing regimens of TXA initiated in the prehospital setting in patients with moderate to severe TBI (GCS score ≤12). Primary hypothesis: The null hypothesis is that random assignment to prehospital administration of TXA in patients with moderate to severe TBI will not change the proportion of patients with a favorable long-term neurologic outcome compared to random assignment to placebo, based on the GOS-E at 6 months. Secondary aims: To determine differences between TXA and placebo in the following outcomes for patients with moderate to severe TBI treated in the prehospital setting with 2 dosing regimens of TXA: * Clinical outcomes: ICH progression, Marshall and Rotterdam CT classification scores, DRS at discharge and 6 months, GOS-E at discharge, 28-day survival, frequency of neurosurgical interventions, and ventilator-free, ICU-free, and hospital-free days. * Safety outcomes: Development of seizures, cerebral ischemic events, myocardial infarction, deep venous thrombosis, and pulmonary thromboembolism. * Mechanistic outcomes: Alterations in fibrinolysis based on fibrinolytic pathway mediators and degree of clot lysis based on TEG. Inclusion: Blunt and penetrating traumatic mechanism consistent with TBI with prehospital GCS ≤ 12 prior to administration of sedative and/or paralytic agents, prehospital SBP ≥ 90 mmHg, prehospital intravenous (IV) access, age ≥ 15yrs (or weight ≥ 50kg if age is unknown), EMS transport destination based on standard local practices determined to be a participating trauma center. Exclusion: Prehospital GCS=3 with no reactive pupil, estimated time from injury to start of study drug bolus dose \>2 hours, unknown time of injury, clinical suspicion by EMS of seizure activity, acute MI or stroke or known history, to the extent possible, of seizures, thromboembolic disorders or renal dialysis, CPR by EMS prior to randomization, burns \> 20% TBSA, suspected or known prisoners, suspected or known pregnancy, prehospital TXA or other pro-coagulant drug given prior to randomization, subjects who have activated the opt-out process when required by the local regulatory board. A multi-center double-blind randomized controlled trial with 3 treatment arms: * Bolus/maintenance: 1 gram IV TXA bolus in the prehospital setting followed by a 1 gram IV maintenance infusion initiated on hospital arrival and infused over 8 hours. * Bolus only: 2 grams IV TXA bolus in the prehospital setting followed by a placebo maintenance infusion initiated on hospital arrival and infused over 8 hours. * Placebo: Placebo IV bolus in the prehospital setting followed by a placebo maintenance infusion initiated on hospital arrival and infused over 8 hours.
Detailed description
1. Overview This multi-center, Phase II trial is designed to determine if Tranexamic Acid (TXA) initiated in the prehospital setting improves long-term neurologic outcome compared to placebo in patients with moderate to severe TBI who are not in shock. This study protocol will be conducted as part of the Resuscitation Outcomes Consortium (ROC) at trauma centers in the United States and Canada. ROC is funded by the National Heart Lung and Blood Institute (NHLBI) in partnership with the US Army Medical Research and Materiel Command (USAMRMC), Canadian Institutes of Health Research, the Heart & Stroke Foundation of Canada, the American Heart Association (AHA), and the Defense Research and Development Canada. ROC is a clinical trials network focusing on research primarily in the area of prehospital cardiopulmonary arrest and severe traumatic injury. The mission of ROC is to provide infrastructure and project support for clinical trials and other outcome-oriented research in the areas of cardiopulmonary arrest and severe traumatic injury that lead to evidence-based change in clinical practice. 2. Specific Aims/Hypothesis Statement 2.1 Clinical Hypotheses and Aims Specific aim 1: To compare 6-month neurologic outcome between subjects who are randomly assigned to TXA to subjects who are randomly assigned to placebo by evaluating the Glasgow Outcome Scale Extended score (GOS-E) at 6 months post-injury. Primary Hypotheses: We will perform a one-sided test of the following null hypothesis: The proportion of subjects who have a favorable neurologic outcome (GOS-E \> 4) at six months post injury who are randomly assigned to TXA is not different from the proportion of subjects who have a favorable neurologic outcome (GOS-E \> 4) who are randomly assigned to placebo. This hypothesis will be tested versus the alternative that the proportion of subjects with a favorable neurologic outcome who are randomly assigned to TXA is higher than in subjects who are randomly assigned to placebo at the .1 level and versus the alternative that the proportion of subjects with a favorable neurologic outcome who are randomly assigned to TXA is lower than it is in the placebo group at the .025 level Specific aim 2: To assess differences in morbidity and mortality measured from randomization through 28 days or initial hospital discharge and differences in neurologic outcomes at 6 months between subjects in the bolus/maintenance arm, bolus only arm, and placebo arm. Secondary Hypotheses: The null hypotheses are that there will be no difference between subjects who are randomly assigned to TXA and subjects who are randomly assigned to placebo in the following: both absolute and relative volume of intracranial hemorrhage (ICH) progression, proportion of subjects with ICH progression, frequency of neurosurgical interventions, GOS-E measured at discharge and 6 months, Disability Rating Scale score (DRS) measured at discharge and 6 months, 28-day survival, and ventilator-free, intensive care unit (ICU)-free, and hospital-free days. Specific aim 3: To assess differences in adverse events measured from randomization to initial hospital discharge between subjects in the bolus/maintenance arm, bolus only arm, and placebo arm. Tertiary Hypotheses: The null hypotheses are that there will be no difference between subjects who are randomly assigned to TXA and subjects who are randomly assigned to placebo in the following: proportion of subjects experiencing seizures, cerebral ischemic events, myocardial infarction (MI), deep venous thrombosis (DVT), or pulmonary thromboembolism (PE) post randomization through 28 days or discharge, whichever occurs first. 2.2 Laboratory Hypotheses and Aims Specific aim 1: To compare coagulation profiles over time using kaolin activated thrombelastography (TEG) results between subjects who are randomly assigned to TXA and subjects who are randomly assigned to placebo. Primary hypothesis: The null hypothesis is that there will be no difference in the degree of fibrinolysis as assessed by percentage of clot lysis determined 30 minutes after the maximum amplitude is reached (LY30) between subjects who are randomly assigned to TXA and subjects who are randomly assigned to placebo. Specific aim 2: To explore the underlying mechanism of TXA by comparing fibrinolytic pathway mediator activity between subjects who are randomly assigned to TXA and subjects who are randomly assigned to placebo. Secondary hypothesis: The null hypothesis is that there will be no change in fibrinolytic pathway mediators between subjects who are randomly assigned to TXA and subjects who are randomly assigned to placebo. Specific aim 3: To estimate the association between the degree of fibrinolysis based on kaolin activated TEG results and fibrinolytic pathway mediators on primary and secondary clinical outcomes. Tertiary hypothesis: The null hypothesis is that no association will exist between the degree of fibrinolysis and fibrinolytic pathway mediators and primary and secondary clinical outcomes. 3. Study Enrollment EMS agencies will carry blinded sealed study drug kits. Once the seal is broken in the presence of the patient, the patient is randomized. The EMS study drug kit will contain a vial of either 1 gram TXA, 2 grams TXA, or placebo. EMS will mix the study drug in a 250 mL bag of 0.9% sodium chloride and administer the bolus infusion as soon as life-saving interventions are performed. After randomization, EMS will provide the study drug kit ID# to the receiving pharmacy. The hospital pharmacist will obtain the randomization assignment from the coordinating center and prepare the appropriate drug to be administered in the hospital. 4. Sample Size and Statistical Analysis The total sample size is 963 (321 per group) starting treatment, which will allow for 80% power to detect a 7.1% absolute difference in favorable long-term neurological outcome as determined by the GOS-E 6 months after injury comparing the combined TXA treatment groups to placebo, using a one-sided, level 0.1 test. Statistical analysis of primary hypothesis: Modified intention-to-treat analysis using logistic regression to test for association and estimate the strength of the association of treatment group with a favorable 6-month outcome (defined as a GOS-E \> 4), after adjustment for study site. 5. Human subjects protection This study qualifies for the exception from informed consent (EFIC) required for emergency research outlined in FDA regulation 21CFR50.24. EFIC applies because of life-threatening situation, intervention must be administered before consent is feasible, no reasonable way to identify prospectively individuals at risk, patients have the prospect of benefit from the treatment, and the research could not practically be carried out without the waiver of consent.
Interventions
DRUG1 gram Tranexamic Acid (TXA)
TXA produces an antifibrinolytic effect by competitively inhibiting the activation of plasminogen to plasmin.
DRUG2 grams TXA
TXA produces an antifibrinolytic effect by competitively inhibiting the activation of plasminogen to plasmin.
DRUG0.9% Sodium Chloride injectable
Loading dose of 0.9% Sodium Chloride solution given prior to hospital arrival followed by a placebo of 0.9% Sodium Chloride solution infusion over 8 hours after hospital arrival. No active drug is added to the solution.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
U.S. Army Medical Research and Development Command
Canadian Institutes of Health Research (CIHR)
Heart and Stroke Foundation of Canada
American Heart Association
Defence Research and Development Canada
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Blunt or penetrating traumatic mechanism consistent with traumatic brain injury 2. Prehospital Glasgow Coma Score (GCS) score ≤ 12 at any time prior to randomization and administration of sedative and/or paralytic agents 3. Prehospital systolic blood pressure (SBP) ≥ 90 mmHg prior to randomization 4. Prehospital intravenous (IV) or intraosseous (IO) access 5. Estimated Age ≥ 15 (or estimated weight \> 50 kg if age is unknown) 6. Emergency Medicine System (EMS) transport to a participating trauma center
Exclusion criteria
1. Prehospital GCS=3 with no reactive pupil 2. Estimated time from injury to hospital arrival \> 2 hours 3. Unknown time of injury - no known reference times to support estimation 4. Clinical suspicion by EMS of seizure activity or known history of seizures, acute myocardial infarction (MI) or stroke 5. Cardio-pulmonary resuscitation (CPR) by EMS prior to randomization 6. Burns \> 20% total body surface area (TBSA) 7. Suspected or known prisoners 8. Suspected or known pregnancy 9. Prehospital TXA given prior to randomization 10. Subjects who have activated the opt-out process when required by the local regulatory board
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dichotomized Glasgow Outcome Scale Extended (GOS-E) at 6 Months | 6 months post-injury | GOS-E subdivides the categories of severe and moderate disability and good recovery using a scale of 1 to 8 where 1 = death, 2 = vegetative state, 3 = lower severe disability, 4 = upper severe disability, 5 = lower moderate disability, 6 = upper moderate disability, 7 = lower good recovery, and 8 = upper good recovery. Structured telephone interviews have been developed and validated for the GOS-E and these questions were incorporated into the follow-up survey. GOS-E was dichotomized into unfavorable (1 to 4) and favorable (5 to 8) outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disability Rating Scale (DRS) at 6 Months | 6 months post-injury | The DRS is designed to classify patients based on their degree of function after brain injury. The DRS consists of 8 items that fall into 4 categories: (a) arousability, awareness and responsivity, (b) cognitive ability for self-care activities, (c) dependence on others, and (d) psychosocial adaptability. The score ranges from 0 (no disability) to 30 (death). |
| Number of Participants With Unfavorable Outcome on Dichotomized Glasgow Outcome Scale Extended (GOS-E) at Discharge | At the end of the hospital stay (average of 9 days post injury) | GOS-E subdivides the categories of severe and moderate disability and good recovery using a scale of 1 to 8 where 1 = death, 2 = vegetative state, 3 = lower severe disability, 4 = upper severe disability, 5 = lower moderate disability, 6 = upper moderate disability, 7 = lower good recovery, and 8 = upper good recovery. Structured telephone interviews have been developed and validated for the GOS-E and these questions were incorporated into the follow-up survey. GOS-E was dichotomized into unfavorable (1 to 4) and favorable (5 to 8) outcomes. The number of subjects with unfavorable outcome is reported. |
| Disability Rating Scale (DRS) at Discharge | At the end of the hospital stay (average of 9 days post injury) | The DRS is designed to classify patients based on their degree of function after brain injury. The DRS consists of 8 items that fall into 4 categories: (a) arousability, awareness and responsivity, (b) cognitive ability for self-care activities, (c) dependence on others, and (d) psychosocial adaptability. The score ranges from 0 (no disability) to 30 (death). |
| Number of Participants With Intracranial Hemorrhage (ICH) Progression | From hospital admission through 28 days or the end of the hospital stay if sooner (average of 13 days among patients with multiple scans) | All clinically indicated head computed tomography (CT) scans obtained during the initial hospitalization or within the first 28 days were assessed for ICH. Parenchymal (IPH), subdural (SDH) and epidural (EDH) hemorrhage volumes were measured and quantified using volumetric software and verified by manual calculations based on the previously validated ABC/2 technique. The sum of the IPH, SDH, and EDH volumes were compared across scans. A relative increase of 33% (and at least a 1 ml increase) on any subsequent scan compared to the initial scan was defined as a progression. |
| Number of Participants With Myocardial Infarction (MI) | From hospital admission through 28 days or the end of the hospital stay if sooner (average of 9 days) | Diagnosis of an acute myocardial infarction |
| Marshall Computed Tomography (CT) Score on Initial Head CT | Initial head CT (average of 1.9 hours post-injury) | The Marshall classification categorizes patients into one of six categories (I to VI) of increasing severity on the basis of findings on non-contrast CT scan of the brain. Higher categories have worse prognosis and survival. |
| Rotterdam Computed Tomography (CT) Score Among Subjects With Intracranial Hemorrhage (ICH) on Initial Head CT | Initial head CT (average of 1.9 hours post-injury) | The Rotterdam classification includes four independently scored elements: degree of basal cistern compression, degree of midline shift, presence of epidural hematomas, and presence of intraventricular or subarachnoid blood. The elements are combined to form an overall score from 1 to 6 with higher scores having worse prognosis and survival. |
| Number of Participants With One or More Neurosurgical Interventions | From hospital admission through 28 days or the end of the hospital stay if sooner (average of 9 days) | Neurosurgical interventions include craniotomy, craniectomy, and placement of a neuromonitoring or drainage device. Counts are of subjects with one or more neurosurgical interventions. |
| Hospital-free Days | From hospital admission through day 28 | Hospital-free days count any day from hospital admission through day 28 that the patient is alive and out of the hospital. |
| Intensive Care Unit (ICU)-Free Days | From hospital admission through day 28 | ICU-free days count any day from hospital admission through day 28 that the patient is alive and not in the ICU. Subjects who die prior to discharge (even if after 28 days) are assigned a value of 0. |
| Ventilator-free Days | From hospital admission through day 28 | Ventilator-free days count any day from hospital admission through day 28 that the patient is alive and does not require mechanical ventilatory support. Subjects who die prior to discharge (even if after 28 days) are assigned a value of 0. |
| Number of Participants With Seizure | From start of study drug infusion through 28 days or the end of the hospital stay if sooner (average of 9 days) | Seizures may cause involuntary changes in body movement or function, sensation, awareness, or behavior. Seizures are often associated with a sudden and involuntary contraction of a group of muscles and loss of consciousness. Seizures or episodes of seizure-like activity were reported by medics in the field following the start of study drug infusion through hand-off to the trauma center and by trauma center staff through discharge. Reported events were included if providers gave anti-seizure medication and/or the event was confirmed by EEG. |
| Number of Participants With Cerebral Ischemic Event | From hospital admission through 28 days or the end of the hospital stay if sooner (average of 9 days) | Diagnosis of cerebral ischemic event |
| Number of Participants With Deep Vein Thrombosis (DVT) | From hospital admission through 28 days or the end of the hospital stay if sooner (average of 9 days) | Diagnosis of DVT |
| Number of Participants With Pulmonary Embolus (PE) | From hospital admission through 28 days or the end of the hospital stay if sooner (average of 9 days) | Diagnosis of PE |
| Number of Participants With Any Thromboembolic Event | From hospital admission through 28 days or the end of the hospital stay if sooner (average of 9 days) | Diagnosis of one or more of the following: cerebral ischemic event, myocardial infarction (MI), deep vein thrombosis (DVT), pulmonary embolism (PE), or any other thromboembolic event |
| Number of Participants Who Died Within 28 Days | 28 days after hospital arrival | The counts of patients who died on or before day 28 are reported. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Fibrinolysis at Hospital Admission | First blood draw (average of 1.6 hours post-injury) | Alterations in fibrinolysis based on fibrinolytic pathway mediators and degree of clot lysis based on kaolin-activated thromboelastography (TEG) and defined as LY30 or the per cent lysis that occurs 30 minutes after maximum amplitude (MA) is achieved. LY30 is categorized as \<0.8% (fibrinolysis shutdown), 0.8-3% (normal), and \>3% (hyperfibrinolysis). |
Countries
Canada, United States
Participant flow
Recruitment details
Between May 2015 and March 2017, participants were enrolled by 39 emergency management service (EMS) agencies and transported to 20 trauma centers within 12 regional sites in North America.
Pre-assignment details
Some persons for whom the blinded study kit was opened did not actually receive any of the study drug. These persons are not included in the enrollment numbers. However, they are enumerated in the first section of the patient flow tables.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo IV bolus in the prehospital setting followed by a placebo maintenance infusion initiated on hospital arrival and infused over 8 hours. | 309 |
| Bolus-Maintenance 1 gram IV TXA bolus in the prehospital setting followed by a 1 gram IV maintenance infusion initiated on hospital arrival and infused over 8 hours. | 312 |
| Bolus Only 2 grams IV TXA bolus in the prehospital setting followed by a placebo maintenance infusion initiated on hospital arrival and infused over 8 hours. | 345 |
| Total | 966 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| 6-Month Follow-up | Calls unreturned or refused contact | 4 | 15 | 20 |
| 6-Month Follow-up | Homeless | 4 | 3 | 6 |
| 6-Month Follow-up | No contact information | 5 | 6 | 5 |
| 6-Month Follow-up | Patient at psychiatric hospital | 1 | 0 | 0 |
| 6-Month Follow-up | Prisoner at time of enrollment | 0 | 0 | 1 |
| 6-Month Follow-up | Prisoner at time of follow-up | 0 | 2 | 0 |
| 6-Month Follow-up | Withdrawal by Subject | 25 | 25 | 26 |
| In-Hospital Study Drug Infusion | CVA/thrombotic event or concern for one | 5 | 5 | 4 |
| In-Hospital Study Drug Infusion | Death or comfort care | 12 | 11 | 6 |
| In-Hospital Study Drug Infusion | Discharged | 19 | 18 | 13 |
| In-Hospital Study Drug Infusion | Emergency unblinding | 11 | 4 | 7 |
| In-Hospital Study Drug Infusion | Found not to be injured | 1 | 1 | 1 |
| In-Hospital Study Drug Infusion | Other procoagulant administered | 0 | 1 | 2 |
| In-Hospital Study Drug Infusion | Other safety concern | 4 | 2 | 3 |
| In-Hospital Study Drug Infusion | Protocol non-compliance | 14 | 17 | 10 |
| In-Hospital Study Drug Infusion | Required CPR | 3 | 7 | 1 |
| In-Hospital Study Drug Infusion | Seizure or concern for seizure | 8 | 9 | 17 |
| In-Hospital Study Drug Infusion | Taken into police custody | 4 | 0 | 3 |
| In-Hospital Study Drug Infusion | Transfer to non-participating facility | 1 | 1 | 0 |
| In-Hospital Study Drug Infusion | Unknown if completed | 0 | 0 | 1 |
| In-Hospital Study Drug Infusion | Withdrawal by Subject | 13 | 7 | 12 |
| Intervention Started | Discovered to be pregnant | 0 | 1 | 0 |
| Intervention Started | Found to be ineligible | 14 | 13 | 11 |
| Intervention Started | IV lost | 2 | 2 | 2 |
| Intervention Started | Not enough time for EMS to enroll | 4 | 3 | 0 |
| Intervention Started | Patient became ineligible due to vitals | 5 | 5 | 2 |
| Intervention Started | Patient care priority | 1 | 2 | 3 |
| Intervention Started | Required CPR | 1 | 1 | 0 |
| Intervention Started | Seizure or hx of seizure | 0 | 0 | 2 |
| Intervention Started | Study drug issue or kit malfunction | 9 | 6 | 7 |
| Prehospital Study Drug Infusion | Death | 3 | 1 | 1 |
| Prehospital Study Drug Infusion | Discharged | 2 | 1 | 0 |
| Prehospital Study Drug Infusion | Emergency unblinding | 0 | 0 | 1 |
| Prehospital Study Drug Infusion | Other safety concern | 2 | 1 | 1 |
| Prehospital Study Drug Infusion | Protocol non-compliance | 4 | 11 | 10 |
| Prehospital Study Drug Infusion | Required CPR | 2 | 6 | 0 |
| Prehospital Study Drug Infusion | Seizure or concern for seizure | 4 | 3 | 4 |
| Prehospital Study Drug Infusion | Unknown if completed | 1 | 4 | 2 |
| Prehospital Study Drug Infusion | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Bolus Only | Bolus-Maintenance |
|---|---|---|---|---|
| Age, Continuous | 36 years | 38 years | 40 years | 39 years |
| Cause of injury Assault | 24 Participants | 69 Participants | 25 Participants | 20 Participants |
| Cause of injury Fall at ground level | 37 Participants | 126 Participants | 45 Participants | 44 Participants |
| Cause of injury Fall at more than 1 meter | 32 Participants | 110 Participants | 38 Participants | 40 Participants |
| Cause of injury Motor vehicle bicycle/pedestrian | 56 Participants | 179 Participants | 62 Participants | 61 Participants |
| Cause of injury Motor vehicle motorcycle | 33 Participants | 109 Participants | 44 Participants | 32 Participants |
| Cause of injury Motor vehicle occupant | 113 Participants | 331 Participants | 115 Participants | 103 Participants |
| Cause of injury Other | 4 Participants | 14 Participants | 6 Participants | 4 Participants |
| Cause of injury Suicide | 9 Participants | 22 Participants | 5 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 40 Participants | 123 Participants | 43 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 225 Participants | 700 Participants | 251 Participants | 224 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 44 Participants | 143 Participants | 51 Participants | 48 Participants |
| Head Abbreviated Injury Score (AIS) 0-1 | 76 Participants | 265 Participants | 103 Participants | 86 Participants |
| Head Abbreviated Injury Score (AIS) 2 | 46 Participants | 142 Participants | 48 Participants | 48 Participants |
| Head Abbreviated Injury Score (AIS) 3 | 61 Participants | 191 Participants | 66 Participants | 64 Participants |
| Head Abbreviated Injury Score (AIS) 4 | 67 Participants | 194 Participants | 71 Participants | 56 Participants |
| Head Abbreviated Injury Score (AIS) 5-6 | 51 Participants | 159 Participants | 56 Participants | 52 Participants |
| Injury Severity Score (ISS) | 17 score on a scale | 17 score on a scale | 17 score on a scale | 17 score on a scale |
| Penetrating injury | 16 Participants | 33 Participants | 5 Participants | 12 Participants |
| Prehospital Glasgow Coma Scale 13-15 | 8 Participants | 31 Participants | 9 Participants | 14 Participants |
| Prehospital Glasgow Coma Scale 3-8 | 186 Participants | 532 Participants | 177 Participants | 169 Participants |
| Prehospital Glasgow Coma Scale 9-12 | 115 Participants | 403 Participants | 159 Participants | 129 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 10 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 30 Participants | 10 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 46 Participants | 149 Participants | 53 Participants | 50 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 5 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 38 Participants | 127 Participants | 50 Participants | 39 Participants |
| Race (NIH/OMB) White | 213 Participants | 642 Participants | 227 Participants | 202 Participants |
| Region of Enrollment Canada | 24 participants | 88 participants | 36 participants | 28 participants |
| Region of Enrollment United States | 285 participants | 878 participants | 309 participants | 284 participants |
| Sex: Female, Male Female | 76 Participants | 251 Participants | 90 Participants | 85 Participants |
| Sex: Female, Male Male | 233 Participants | 715 Participants | 255 Participants | 227 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 50 / 309 | 53 / 312 | 40 / 345 |
| other Total, other adverse events | 81 / 309 | 74 / 312 | 92 / 345 |
| serious Total, serious adverse events | 25 / 309 | 13 / 312 | 24 / 345 |
Outcome results
Primary
Dichotomized Glasgow Outcome Scale Extended (GOS-E) at 6 Months
GOS-E subdivides the categories of severe and moderate disability and good recovery using a scale of 1 to 8 where 1 = death, 2 = vegetative state, 3 = lower severe disability, 4 = upper severe disability, 5 = lower moderate disability, 6 = upper moderate disability, 7 = lower good recovery, and 8 = upper good recovery. Structured telephone interviews have been developed and validated for the GOS-E and these questions were incorporated into the follow-up survey. GOS-E was dichotomized into unfavorable (1 to 4) and favorable (5 to 8) outcomes.
Time frame: 6 months post-injury
Population: Subjects for whom study drug administration was started minus one Bolus Only arm subject who was mistakenly enrolled while in police custody.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Dichotomized Glasgow Outcome Scale Extended (GOS-E) at 6 Months | Unfavorable GOS-E (<=4) | 107 Participants |
| Placebo | Dichotomized Glasgow Outcome Scale Extended (GOS-E) at 6 Months | Missing GOS-E | 39 Participants |
| Placebo | Dichotomized Glasgow Outcome Scale Extended (GOS-E) at 6 Months | Favorable GOS-E (>4) | 163 Participants |
| Bolus-Maintenance | Dichotomized Glasgow Outcome Scale Extended (GOS-E) at 6 Months | Unfavorable GOS-E (<=4) | 108 Participants |
| Bolus-Maintenance | Dichotomized Glasgow Outcome Scale Extended (GOS-E) at 6 Months | Missing GOS-E | 51 Participants |
| Bolus-Maintenance | Dichotomized Glasgow Outcome Scale Extended (GOS-E) at 6 Months | Favorable GOS-E (>4) | 153 Participants |
| Bolus Only | Dichotomized Glasgow Outcome Scale Extended (GOS-E) at 6 Months | Favorable GOS-E (>4) | 178 Participants |
| Bolus Only | Dichotomized Glasgow Outcome Scale Extended (GOS-E) at 6 Months | Unfavorable GOS-E (<=4) | 110 Participants |
| Bolus Only | Dichotomized Glasgow Outcome Scale Extended (GOS-E) at 6 Months | Missing GOS-E | 57 Participants |
| Combined TXA Arms | Dichotomized Glasgow Outcome Scale Extended (GOS-E) at 6 Months | Unfavorable GOS-E (<=4) | 218 Participants |
| Combined TXA Arms | Dichotomized Glasgow Outcome Scale Extended (GOS-E) at 6 Months | Missing GOS-E | 108 Participants |
| Combined TXA Arms | Dichotomized Glasgow Outcome Scale Extended (GOS-E) at 6 Months | Favorable GOS-E (>4) | 331 Participants |
Comparison: This study was designed with an asymmetric boundary for tests for treatment harm and benefit. The conventional 0.025 level was used to test for harm while a 0.1 level was used to determine benefit for this Phase II trial. Statistical significance for the primary analysis was conducted under a group-sequential design that included a single, interim futility analysis using a Wang-Tsiatis boundary with parameter 0.8 based on outcome data from the first 200 subjects.p-value: 0.1809Regression, Logistic
Secondary
Disability Rating Scale (DRS) at 6 Months
The DRS is designed to classify patients based on their degree of function after brain injury. The DRS consists of 8 items that fall into 4 categories: (a) arousability, awareness and responsivity, (b) cognitive ability for self-care activities, (c) dependence on others, and (d) psychosocial adaptability. The score ranges from 0 (no disability) to 30 (death).
Time frame: 6 months post-injury
Population: Subjects for whom study drug administration was started and DRS questions were obtained at 6 months. Excluded subjects include those who withdrew prior to 6 months after injury and those lost to follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Disability Rating Scale (DRS) at 6 Months | 8.0 score on a scale | Standard Deviation 11.8 |
| Bolus-Maintenance | Disability Rating Scale (DRS) at 6 Months | 8.1 score on a scale | Standard Deviation 11.9 |
| Bolus Only | Disability Rating Scale (DRS) at 6 Months | 6.6 score on a scale | Standard Deviation 10.8 |
Secondary
Disability Rating Scale (DRS) at Discharge
The DRS is designed to classify patients based on their degree of function after brain injury. The DRS consists of 8 items that fall into 4 categories: (a) arousability, awareness and responsivity, (b) cognitive ability for self-care activities, (c) dependence on others, and (d) psychosocial adaptability. The score ranges from 0 (no disability) to 30 (death).
Time frame: At the end of the hospital stay (average of 9 days post injury)
Population: Subjects for whom study drug administration was started and for whom discharge Disability Rating Scale was obtained. Subjects who withdrew prior to discharge make up most of the subjects who were excluded from this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Disability Rating Scale (DRS) at Discharge | 9.0 score on a scale | Standard Deviation 11.1 |
| Bolus-Maintenance | Disability Rating Scale (DRS) at Discharge | 9.4 score on a scale | Standard Deviation 11 |
| Bolus Only | Disability Rating Scale (DRS) at Discharge | 8.1 score on a scale | Standard Deviation 9.8 |
Secondary
Hospital-free Days
Hospital-free days count any day from hospital admission through day 28 that the patient is alive and out of the hospital.
Time frame: From hospital admission through day 28
Population: Subjects for whom study drug administration was started and for whom discharge status was known. Subjects who withdrew prior to discharge make up most of the subjects who were excluded from this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Hospital-free Days | 13.6 days | Standard Deviation 10.7 |
| Bolus-Maintenance | Hospital-free Days | 13.6 days | Standard Deviation 10.7 |
| Bolus Only | Hospital-free Days | 14.1 days | Standard Deviation 10.4 |
Secondary
Intensive Care Unit (ICU)-Free Days
ICU-free days count any day from hospital admission through day 28 that the patient is alive and not in the ICU. Subjects who die prior to discharge (even if after 28 days) are assigned a value of 0.
Time frame: From hospital admission through day 28
Population: Subjects for whom study drug administration was started and for whom number of ICU days through 28 days was known. Subjects who withdrew prior to discharge make up most of the subjects who were excluded from this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Intensive Care Unit (ICU)-Free Days | 18.5 days | Standard Deviation 10.6 |
| Bolus-Maintenance | Intensive Care Unit (ICU)-Free Days | 18.1 days | Standard Deviation 10.8 |
| Bolus Only | Intensive Care Unit (ICU)-Free Days | 19.1 days | Standard Deviation 9.7 |
Secondary
Marshall Computed Tomography (CT) Score on Initial Head CT
The Marshall classification categorizes patients into one of six categories (I to VI) of increasing severity on the basis of findings on non-contrast CT scan of the brain. Higher categories have worse prognosis and survival.
Time frame: Initial head CT (average of 1.9 hours post-injury)
Population: Subjects who received an initial head computed tomography scan with sufficient information to be scored.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Marshall Computed Tomography (CT) Score on Initial Head CT | Diffuse injury IV | 7 Participants |
| Placebo | Marshall Computed Tomography (CT) Score on Initial Head CT | Diffuse injury III | 12 Participants |
| Placebo | Marshall Computed Tomography (CT) Score on Initial Head CT | Diffuse injury I | 120 Participants |
| Placebo | Marshall Computed Tomography (CT) Score on Initial Head CT | Diffuse injury II | 106 Participants |
| Placebo | Marshall Computed Tomography (CT) Score on Initial Head CT | Mass lesion V/VI | 46 Participants |
| Bolus-Maintenance | Marshall Computed Tomography (CT) Score on Initial Head CT | Diffuse injury III | 12 Participants |
| Bolus-Maintenance | Marshall Computed Tomography (CT) Score on Initial Head CT | Diffuse injury I | 115 Participants |
| Bolus-Maintenance | Marshall Computed Tomography (CT) Score on Initial Head CT | Diffuse injury II | 117 Participants |
| Bolus-Maintenance | Marshall Computed Tomography (CT) Score on Initial Head CT | Diffuse injury IV | 4 Participants |
| Bolus-Maintenance | Marshall Computed Tomography (CT) Score on Initial Head CT | Mass lesion V/VI | 42 Participants |
| Bolus Only | Marshall Computed Tomography (CT) Score on Initial Head CT | Mass lesion V/VI | 46 Participants |
| Bolus Only | Marshall Computed Tomography (CT) Score on Initial Head CT | Diffuse injury IV | 5 Participants |
| Bolus Only | Marshall Computed Tomography (CT) Score on Initial Head CT | Diffuse injury I | 134 Participants |
| Bolus Only | Marshall Computed Tomography (CT) Score on Initial Head CT | Diffuse injury III | 12 Participants |
| Bolus Only | Marshall Computed Tomography (CT) Score on Initial Head CT | Diffuse injury II | 135 Participants |
Secondary
Number of Participants Who Died Within 28 Days
The counts of patients who died on or before day 28 are reported.
Time frame: 28 days after hospital arrival
Population: Subjects for whom study drug administration was started and 28-day vital status was definitively obtained. Patients excluded from the counts include subjects who withdrew from the study prior to day 28 and subjects who were lost to follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Died Within 28 Days | 50 Participants |
| Bolus-Maintenance | Number of Participants Who Died Within 28 Days | 53 Participants |
| Bolus Only | Number of Participants Who Died Within 28 Days | 40 Participants |
Secondary
Number of Participants With Any Thromboembolic Event
Diagnosis of one or more of the following: cerebral ischemic event, myocardial infarction (MI), deep vein thrombosis (DVT), pulmonary embolism (PE), or any other thromboembolic event
Time frame: From hospital admission through 28 days or the end of the hospital stay if sooner (average of 9 days)
Population: Subjects for whom study drug administration was started minus one Bolus Only arm subject who was mistakenly enrolled while in police custody.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Any Thromboembolic Event | 30 Participants |
| Bolus-Maintenance | Number of Participants With Any Thromboembolic Event | 13 Participants |
| Bolus Only | Number of Participants With Any Thromboembolic Event | 31 Participants |
Secondary
Number of Participants With Cerebral Ischemic Event
Diagnosis of cerebral ischemic event
Time frame: From hospital admission through 28 days or the end of the hospital stay if sooner (average of 9 days)
Population: Subjects for whom study drug administration was started minus one Bolus Only arm subject who was mistakenly enrolled while in police custody.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Cerebral Ischemic Event | 10 Participants |
| Bolus-Maintenance | Number of Participants With Cerebral Ischemic Event | 3 Participants |
| Bolus Only | Number of Participants With Cerebral Ischemic Event | 13 Participants |
Secondary
Number of Participants With Deep Vein Thrombosis (DVT)
Diagnosis of DVT
Time frame: From hospital admission through 28 days or the end of the hospital stay if sooner (average of 9 days)
Population: Subjects for whom study drug administration was started minus one Bolus Only arm subject who was mistakenly enrolled while in police custody.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Deep Vein Thrombosis (DVT) | 9 Participants |
| Bolus-Maintenance | Number of Participants With Deep Vein Thrombosis (DVT) | 3 Participants |
| Bolus Only | Number of Participants With Deep Vein Thrombosis (DVT) | 10 Participants |
Secondary
Number of Participants With Intracranial Hemorrhage (ICH) Progression
All clinically indicated head computed tomography (CT) scans obtained during the initial hospitalization or within the first 28 days were assessed for ICH. Parenchymal (IPH), subdural (SDH) and epidural (EDH) hemorrhage volumes were measured and quantified using volumetric software and verified by manual calculations based on the previously validated ABC/2 technique. The sum of the IPH, SDH, and EDH volumes were compared across scans. A relative increase of 33% (and at least a 1 ml increase) on any subsequent scan compared to the initial scan was defined as a progression.
Time frame: From hospital admission through 28 days or the end of the hospital stay if sooner (average of 13 days among patients with multiple scans)
Population: Subjects for whom study drug administration was started and for whom two or more analyzable head CT scans were obtained prior to a hematoma evacuation. Excluded subjects primarily include those who died or withdrew before an initial or second CT scan was taken, who had a hematoma evacuation prior to a second scan, or who had only one negative CT.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Intracranial Hemorrhage (ICH) Progression | 30 Participants |
| Bolus-Maintenance | Number of Participants With Intracranial Hemorrhage (ICH) Progression | 26 Participants |
| Bolus Only | Number of Participants With Intracranial Hemorrhage (ICH) Progression | 27 Participants |
Secondary
Number of Participants With Myocardial Infarction (MI)
Diagnosis of an acute myocardial infarction
Time frame: From hospital admission through 28 days or the end of the hospital stay if sooner (average of 9 days)
Population: Subjects for whom study drug administration was started minus one Bolus Only arm subject who was mistakenly enrolled while in police custody.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Myocardial Infarction (MI) | 1 Participants |
| Bolus-Maintenance | Number of Participants With Myocardial Infarction (MI) | 3 Participants |
| Bolus Only | Number of Participants With Myocardial Infarction (MI) | 2 Participants |
Secondary
Number of Participants With One or More Neurosurgical Interventions
Neurosurgical interventions include craniotomy, craniectomy, and placement of a neuromonitoring or drainage device. Counts are of subjects with one or more neurosurgical interventions.
Time frame: From hospital admission through 28 days or the end of the hospital stay if sooner (average of 9 days)
Population: Subjects for whom study drug administration was started minus one Bolus Only arm subject who was mistakenly enrolled while in police custody.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With One or More Neurosurgical Interventions | 54 Participants |
| Bolus-Maintenance | Number of Participants With One or More Neurosurgical Interventions | 62 Participants |
| Bolus Only | Number of Participants With One or More Neurosurgical Interventions | 75 Participants |
Secondary
Number of Participants With Pulmonary Embolus (PE)
Diagnosis of PE
Time frame: From hospital admission through 28 days or the end of the hospital stay if sooner (average of 9 days)
Population: Subjects for whom study drug administration was started minus one Bolus Only arm subject who was mistakenly enrolled while in police custody.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Pulmonary Embolus (PE) | 5 Participants |
| Bolus-Maintenance | Number of Participants With Pulmonary Embolus (PE) | 3 Participants |
| Bolus Only | Number of Participants With Pulmonary Embolus (PE) | 6 Participants |
Secondary
Number of Participants With Seizure
Seizures may cause involuntary changes in body movement or function, sensation, awareness, or behavior. Seizures are often associated with a sudden and involuntary contraction of a group of muscles and loss of consciousness. Seizures or episodes of seizure-like activity were reported by medics in the field following the start of study drug infusion through hand-off to the trauma center and by trauma center staff through discharge. Reported events were included if providers gave anti-seizure medication and/or the event was confirmed by EEG.
Time frame: From start of study drug infusion through 28 days or the end of the hospital stay if sooner (average of 9 days)
Population: Subjects for whom study drug administration was started minus one Bolus Only arm subject who was mistakenly enrolled while in police custody.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Seizure | 7 Participants |
| Bolus-Maintenance | Number of Participants With Seizure | 5 Participants |
| Bolus Only | Number of Participants With Seizure | 17 Participants |
Secondary
Number of Participants With Unfavorable Outcome on Dichotomized Glasgow Outcome Scale Extended (GOS-E) at Discharge
GOS-E subdivides the categories of severe and moderate disability and good recovery using a scale of 1 to 8 where 1 = death, 2 = vegetative state, 3 = lower severe disability, 4 = upper severe disability, 5 = lower moderate disability, 6 = upper moderate disability, 7 = lower good recovery, and 8 = upper good recovery. Structured telephone interviews have been developed and validated for the GOS-E and these questions were incorporated into the follow-up survey. GOS-E was dichotomized into unfavorable (1 to 4) and favorable (5 to 8) outcomes. The number of subjects with unfavorable outcome is reported.
Time frame: At the end of the hospital stay (average of 9 days post injury)
Population: Subjects for whom study drug administration was started and for whom Glasgow Outcome Score Extended was obtained at discharge. Subjects who withdrew prior to discharge make up most of the subjects who were excluded from this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Unfavorable Outcome on Dichotomized Glasgow Outcome Scale Extended (GOS-E) at Discharge | 196 Participants |
| Bolus-Maintenance | Number of Participants With Unfavorable Outcome on Dichotomized Glasgow Outcome Scale Extended (GOS-E) at Discharge | 193 Participants |
| Bolus Only | Number of Participants With Unfavorable Outcome on Dichotomized Glasgow Outcome Scale Extended (GOS-E) at Discharge | 228 Participants |
Secondary
Rotterdam Computed Tomography (CT) Score Among Subjects With Intracranial Hemorrhage (ICH) on Initial Head CT
The Rotterdam classification includes four independently scored elements: degree of basal cistern compression, degree of midline shift, presence of epidural hematomas, and presence of intraventricular or subarachnoid blood. The elements are combined to form an overall score from 1 to 6 with higher scores having worse prognosis and survival.
Time frame: Initial head CT (average of 1.9 hours post-injury)
Population: Subjects determined by the central image reviewer to have an intracranial hemorrhage (ICH) on the initial head computed tomography (CT) scan and sufficient information to assign the Rotterdam score.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Rotterdam Computed Tomography (CT) Score Among Subjects With Intracranial Hemorrhage (ICH) on Initial Head CT | 1 | 2 Participants |
| Placebo | Rotterdam Computed Tomography (CT) Score Among Subjects With Intracranial Hemorrhage (ICH) on Initial Head CT | 2 | 32 Participants |
| Placebo | Rotterdam Computed Tomography (CT) Score Among Subjects With Intracranial Hemorrhage (ICH) on Initial Head CT | 3 | 81 Participants |
| Placebo | Rotterdam Computed Tomography (CT) Score Among Subjects With Intracranial Hemorrhage (ICH) on Initial Head CT | 4 | 17 Participants |
| Placebo | Rotterdam Computed Tomography (CT) Score Among Subjects With Intracranial Hemorrhage (ICH) on Initial Head CT | 5 | 21 Participants |
| Placebo | Rotterdam Computed Tomography (CT) Score Among Subjects With Intracranial Hemorrhage (ICH) on Initial Head CT | 6 | 5 Participants |
| Bolus-Maintenance | Rotterdam Computed Tomography (CT) Score Among Subjects With Intracranial Hemorrhage (ICH) on Initial Head CT | 6 | 5 Participants |
| Bolus-Maintenance | Rotterdam Computed Tomography (CT) Score Among Subjects With Intracranial Hemorrhage (ICH) on Initial Head CT | 1 | 1 Participants |
| Bolus-Maintenance | Rotterdam Computed Tomography (CT) Score Among Subjects With Intracranial Hemorrhage (ICH) on Initial Head CT | 4 | 24 Participants |
| Bolus-Maintenance | Rotterdam Computed Tomography (CT) Score Among Subjects With Intracranial Hemorrhage (ICH) on Initial Head CT | 5 | 12 Participants |
| Bolus-Maintenance | Rotterdam Computed Tomography (CT) Score Among Subjects With Intracranial Hemorrhage (ICH) on Initial Head CT | 2 | 28 Participants |
| Bolus-Maintenance | Rotterdam Computed Tomography (CT) Score Among Subjects With Intracranial Hemorrhage (ICH) on Initial Head CT | 3 | 91 Participants |
| Bolus Only | Rotterdam Computed Tomography (CT) Score Among Subjects With Intracranial Hemorrhage (ICH) on Initial Head CT | 2 | 36 Participants |
| Bolus Only | Rotterdam Computed Tomography (CT) Score Among Subjects With Intracranial Hemorrhage (ICH) on Initial Head CT | 3 | 98 Participants |
| Bolus Only | Rotterdam Computed Tomography (CT) Score Among Subjects With Intracranial Hemorrhage (ICH) on Initial Head CT | 6 | 3 Participants |
| Bolus Only | Rotterdam Computed Tomography (CT) Score Among Subjects With Intracranial Hemorrhage (ICH) on Initial Head CT | 4 | 28 Participants |
| Bolus Only | Rotterdam Computed Tomography (CT) Score Among Subjects With Intracranial Hemorrhage (ICH) on Initial Head CT | 1 | 5 Participants |
| Bolus Only | Rotterdam Computed Tomography (CT) Score Among Subjects With Intracranial Hemorrhage (ICH) on Initial Head CT | 5 | 17 Participants |
Secondary
Ventilator-free Days
Ventilator-free days count any day from hospital admission through day 28 that the patient is alive and does not require mechanical ventilatory support. Subjects who die prior to discharge (even if after 28 days) are assigned a value of 0.
Time frame: From hospital admission through day 28
Population: Subjects for whom study drug administration was started and for whom number of ventilator days through 28 days was known. Subjects who withdrew prior to discharge make up most of the subjects who were excluded from this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Ventilator-free Days | 20.2 days | Standard Deviation 10.5 |
| Bolus-Maintenance | Ventilator-free Days | 19.9 days | Standard Deviation 10.8 |
| Bolus Only | Ventilator-free Days | 20.9 days | Standard Deviation 9.7 |
Other Pre-specified
Fibrinolysis at Hospital Admission
Alterations in fibrinolysis based on fibrinolytic pathway mediators and degree of clot lysis based on kaolin-activated thromboelastography (TEG) and defined as LY30 or the per cent lysis that occurs 30 minutes after maximum amplitude (MA) is achieved. LY30 is categorized as \<0.8% (fibrinolysis shutdown), 0.8-3% (normal), and \>3% (hyperfibrinolysis).
Time frame: First blood draw (average of 1.6 hours post-injury)
Population: Subjects with an LY30 measurement at hospital admission are included. Subjects who were transported to trauma centers without a TEG machine, who died prior to the initial blood draw, or who withdrew or refused a blood draw were excluded. Additional exclusions included blood draw missed by study staff and technical difficulties with processing.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Fibrinolysis at Hospital Admission | 0.8-3% (normal) | 56 Participants |
| Placebo | Fibrinolysis at Hospital Admission | <0.8 (fibrinolysis shutdown) | 148 Participants |
| Placebo | Fibrinolysis at Hospital Admission | >3% (hyperfibrinolysis) | 36 Participants |
| Bolus-Maintenance | Fibrinolysis at Hospital Admission | 0.8-3% (normal) | 61 Participants |
| Bolus-Maintenance | Fibrinolysis at Hospital Admission | <0.8 (fibrinolysis shutdown) | 157 Participants |
| Bolus-Maintenance | Fibrinolysis at Hospital Admission | >3% (hyperfibrinolysis) | 28 Participants |
| Bolus Only | Fibrinolysis at Hospital Admission | <0.8 (fibrinolysis shutdown) | 165 Participants |
| Bolus Only | Fibrinolysis at Hospital Admission | >3% (hyperfibrinolysis) | 31 Participants |
| Bolus Only | Fibrinolysis at Hospital Admission | 0.8-3% (normal) | 65 Participants |