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| Name | Class |
|---|---|
| United States Department of Defense | FED |
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The purpose of this study is to evaluate the effects of TXA on the immune system, its pharmacokinetics, as well as safety and efficacy in severely injured trauma patients.
Trauma is the leading cause of death in persons younger than 40 years. Hemorrhage is the etiology in 30% of these deaths, and remains the leading cause of potentially preventable mortality (66-80%) on the battlefield. Death secondary to hemorrhagic shock occurs from both surgical bleeding and coagulopathy. Due to the knowledge of increased fibrinolysis promoting a hypocoagulable state in severe trauma, trials have been performed to determine if antifibrinolytics such as tranexamic acid (TXA) could reduce morbidity and mortality by reducing death from hemorrhage. TXA is an antifibrinolytic that inhibits both plasminogen activation and plasmin activity, thus preventing clot break-down rather than promoting new clot formation. Despite the extensive use of TXA in many surgical populations and an increasing use in severe trauma patients, TXA does not have an FDA approved indication for patients with traumatic injuries. The effect of TXA on immune function has not been thoroughly examined, especially in patients with severe traumatic injury. The study of the effects of TXA use on endothelial activation and injury is also important due to the inter-relationship between coagulation and endothelial function. Endothelial injury secondary to local hypoperfusion causes acute traumatic coagulopathy with fibrinolysis. Therefore a thorough and comprehensive evaluation of the effects of TXA on immune, coagulation, and endothelial parameters is important to allow for a better understanding of the mechanisms of action of this agent.
This is a randomized placebo controlled trial to obtain mechanism of action data, pharmacokinetic information, and efficacy and safety data for the use of TXA in severely injured trauma patients. Participants will be randomized into 1 of 3 treatment arms (1:1:1): TXA 2 gram IV bolus, TXA 4 gram IV bolus, or placebo. The study period is from time of enrollment to hospital discharge or transfer. The study intervention will occur only once upon enrollment in the trial. Participants will receive study drug within two hours from their initial injury. Blood samples will be drawn at multiple time points for immune parameters, Pharmacodynamics, and repository samples.
Immune parameter samples will be drawn at at approximately 0, 6, 24 and 72 hours after study drug/placebo administration.
Pharmacokinetic and pharmacodynamic samples will be drawn according to two schedules. Even number sampling times, blood will be drawn at the approximate time points: 0, 20 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, and 12 hr. A patient sampled on odd number sampling times will have samples drawn at the approximate time points: 0, 10 min, 40 min, 1.5 hr, 3 hr, 6 hr, 10 hr and 24 hr.
Repository samples will be drawn at approximate time points: 0, 1, 6, 24, and 72 hours.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tranexamic Acid 2 Gram | Experimental | One time dose IV TXA 2 Grams given over 10 minutes within 2 hours of initial injury |
|
| Tranexamic Acid 4 Gram | Experimental | One time dose IV TXA 4 Grams given over 10 minutes within 2 hours of initial injury |
|
| Placebo | Placebo Comparator | Matching Volume Normal Saline Placebo given IV over 10 minutes within 2 hours of initial injury |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tranexamic Acid | Drug | Tranexamic acid is a man-made form of an amino acid (protein) called lysine. Tranexamic acid prevents enzymes in the body from breaking down blood clots. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in HLA-DR Expression on Monocytes 72 Hours After Drug or Placebo Administration in Patient Groups (0g TXA (Placebo); 2g TXA; 4g TXA)." | Blood was drawn from patients at baseline (0 h, just before placebo or drug administration) and at 72 hours post placebo or drug administration. Leukocytes in these blood samples were stained with fluroescent antibodies specific for CD45, CD14, and HLA-DR, analyzed by flow cytometry, and the median fluorescen intensity (MFI) of HLA-DR signal was recorded for monocytes (CD45+CD14+). The fold change in HLA-DR expression from prior to placebo/drug administration to 72 h after placebo/drug administration ("0 h : 72 h") was calculated as HLA-DR MFI72hours ÷ HLA-DR CD14 MFI0hours. Non-paramteric one-way ANOVA (Kruskal-Wallis test) was performed between each treatment group at the given time pont, and the p-value reported. | Samples Drawn through 72 hours after study initiation |
| Measure | Description | Time Frame |
|---|---|---|
| Differences in Cytokine Profiles Between the Three Study Groups | To evaluate the effects of TXA on immune function parameters we will, in a RCT, analyze samples from 150 patients (50 in each study group), at multiple time points. Parameters are: a. Cytokines measured from time 0 to 72 hours. | Samples Drawn through 72 hours after study initiation |
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Inclusion Criteria:
Exclusion Criteria:
Patients known to be < 18 years of age
Suspected Acute MI or stroke(thromboembolic and/or hemorrhagic) on admission
Known inherited coagulation disorders
Known history of thromboembolic events (DVT, PE, MI, Stroke)
• Please note that past medical history of hemorrhagic stroke is permitted, but not current admission with hemorrhagic stroke
Known history of seizures and/or seizure after injury/on admission related to this hospitalization
Suspected or known pregnancy
Known to be lactating
Suspected or known prisoners
Futile care
Known current state of immunosuppression (i.e. on high dose steroids, chemotherapeutics, etc.)
Unknown estimated time of injury 12). Patients wearing an "Opt Out" TAMPITI Study bracelet 13). Known presence of subarachnoid hemorrhage.
14.) Isolated injuries to hands and/or feet (distal) 15.) Administration of antifibrinolytics pre-hospital and/or during this ED admission prior to enrollment
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| Name | Affiliation | Role |
|---|---|---|
| Philip C Spinella, MD | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Barnes Jewish Hospital | St Louis | Missouri | 63110 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33013880 | Derived | Spinella PC, Thomas KA, Turnbull IR, Fuchs A, Bochicchio K, Schuerer D, Reese S, Coleoglou Centeno AA, Horn CB, Baty J, Shea SM, Meledeo MA, Pusateri AE, Levy JH, Cap AP, Bochicchio GV; TAMPITI Investigators. The Immunologic Effect of Early Intravenous Two and Four Gram Bolus Dosing of Tranexamic Acid Compared to Placebo in Patients With Severe Traumatic Bleeding (TAMPITI): A Randomized, Double-Blind, Placebo-Controlled, Single-Center Trial. Front Immunol. 2020 Sep 8;11:2085. doi: 10.3389/fimmu.2020.02085. eCollection 2020. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Tranexamic Acid 2 Gram | One time dose IV TXA 2 Grams given over 10 minutes within 2 hours of initial injury Tranexamic Acid: Tranexamic acid is a man-made form of an amino acid (protein) called lysine. Tranexamic acid prevents enzymes in the body from breaking down blood clots. |
| FG001 | Tranexamic Acid 4 Gram | One time dose IV TXA 4 Grams given over 10 minutes within 2 hours of initial injury Tranexamic Acid: Tranexamic acid is a man-made form of an amino acid (protein) called lysine. Tranexamic acid prevents enzymes in the body from breaking down blood clots. |
| FG002 | Placebo | Matching Volume Normal Saline Placebo given IV over 10 minutes within 2 hours of initial injury Placebo: Matching Volume Normal Saline Placebo given IV over 10 minutes within 2 hours of initial injury |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
All analysis is based on the number of participants per group.
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| ID | Title | Description |
|---|---|---|
| BG000 | Tranexamic Acid 2 Gram | One time dose IV TXA 2 Grams given over 10 minutes within 2 hours of initial injury Tranexamic Acid: Tranexamic acid is a man-made form of an amino acid (protein) called lysine. Tranexamic acid prevents enzymes in the body from breaking down blood clots. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in HLA-DR Expression on Monocytes 72 Hours After Drug or Placebo Administration in Patient Groups (0g TXA (Placebo); 2g TXA; 4g TXA)." | Blood was drawn from patients at baseline (0 h, just before placebo or drug administration) and at 72 hours post placebo or drug administration. Leukocytes in these blood samples were stained with fluroescent antibodies specific for CD45, CD14, and HLA-DR, analyzed by flow cytometry, and the median fluorescen intensity (MFI) of HLA-DR signal was recorded for monocytes (CD45+CD14+). The fold change in HLA-DR expression from prior to placebo/drug administration to 72 h after placebo/drug administration ("0 h : 72 h") was calculated as HLA-DR MFI72hours ÷ HLA-DR CD14 MFI0hours. Non-paramteric one-way ANOVA (Kruskal-Wallis test) was performed between each treatment group at the given time pont, and the p-value reported. | Change in HLA-DR Expression on Monocytes 72 hours after administration. Leukocytes stained with antibodies and analyzed by flow cytometry. The median fluorescen intensity of HLA-DR signal was measured for monocytes at 0 and 72 hours. Non-paramteric one-way ANOVA was performed and the p-value reported. | Posted | Median | Inter-Quartile Range | fold change | Samples Drawn through 72 hours after study initiation |
28 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tranexamic Acid 2 Gram | One time dose IV TXA 2 Grams given over 10 minutes within 2 hours of initial injury Tranexamic Acid: Tranexamic acid is a man-made form of an amino acid (protein) called lysine. Tranexamic acid prevents enzymes in the body from breaking down blood clots. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Deep Vein Thrombosis | Vascular disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pain | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Philip Spinella | Washington University School of Medicine | 314-286-0858 | pspinella@wustl.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 17, 2014 | Sep 6, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D006470 | Hemorrhage |
| D012769 | Shock |
| D014947 | Wounds and Injuries |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D014148 | Tranexamic Acid |
| ID | Term |
|---|---|
| D003509 | Cyclohexanecarboxylic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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|
| Placebo | Other | Matching Volume Normal Saline Placebo given IV over 10 minutes within 2 hours of initial injury |
|
| Differences in Leukocyte Function Parameters Between the Three Study Groups | To evaluate the effects of TXA on immune function parameters we will, in a RCT, analyze samples from 150 patients (50 in each study group), at multiple time points. Parameters are: a. Flow cytometric analyses on leukocytes measured from time 0 to 72 hours. | Samples Drawn through 72 hours after study initiation |
| Total Transfusion Volume CL | Pharmacokinetic data was analyzed with NONMEM, using both the first-order and conditional non-Laplacian (with centering) estimation techniques. We considered two- and three-compartment models, parameterized in terms of both compartment volumes and clearances (distribution and elimination). We compared a basic model (in which pharmacokinetic parameters were independent of weight) to a model in which the pharmacokinetic parameters were assumed to be proportional to weight. The optimal model was selected on the basis of the objective function logarithm of the likelihood of the results) using standard criteria (NONMEM guide). Equations from optimal model: CL=109*((WT/70)**0.75) * (SCRint^-0.084) * ((NIRSInt)/96)^ -0.27 ) * ((PLTint)/130)^0.45) V1=1,160*(WT/70) * (TxTot)^0.03) Q=174*((WT/70)**0.75) V2=1080 *(WT/70) "Total Transfusion Volume CL" equals clearance (CL) affected by the covariate of Total Transfusion Volume (TxTot). This value is unitless per NONMEM reporting. | 24 hours |
| Determine the Incidence of Thromboembolic Events (DVT, MI, PE, Stroke) in All Three Study Groups. | The number of events per group for the incidence of thromboembolic events (DVT, MI, PE, Stroke) in all three study groups. | Hospital Discharge (average 10 days) |
| Determine the Incidence of Seizures at 24 Hours in All Three Study Groups. | The incidence of seizures at 24 hours in all three study groups. Number of participants with seizures are reported | 24 hours following TXA |
| Determine the Incidence of All Adverse Events in All Three Study Groups | All adverse events were totaled for each of the three study groups based on the number of incidents. | Hospital Discharge (average 10 days) |
| Platelet Count CL | Pharmacokinetic data was analyzed with NONMEM, using both the first-order and conditional non-Laplacian (with centering) estimation techniques. We considered two- and three-compartment models, parameterized in terms of both compartment volumes and clearances (distribution and elimination). We compared a basic model (in which pharmacokinetic parameters were independent of weight) to a model in which the pharmacokinetic parameters were assumed to be proportional to weight. The optimal model was selected on the basis of the objective function logarithm of the likelihood of the results) using standard criteria (NONMEM guide). Equations from optimal model: CL=109*((WT/70)**0.75) * (SCRint^-0.084) * ((NIRSInt)/96)^ -0.27 ) * ((PLTint)/130)^0.45) V1=1,160*(WT/70) * (TxTot)^0.03) Q=174*((WT/70)**0.75) V2=1080 *(WT/70) "Platelet Count CL" equals clearance (CL) affected by the covariate of Platelet Count (PLTint). This value is unitless per NONMEM reporting. | 24 hours |
| Near Infrared Spectroscopy CL | Pharmacokinetic data was analyzed with NONMEM, using both the first-order and conditional non-Laplacian (with centering) estimation techniques. We considered two- and three-compartment models, parameterized in terms of both compartment volumes and clearances (distribution and elimination). We compared a basic model (in which pharmacokinetic parameters were independent of weight) to a model in which the pharmacokinetic parameters were assumed to be proportional to weight. The optimal model was selected on the basis of the objective function logarithm of the likelihood of the results) using standard criteria (NONMEM guide). Equations from optimal model: CL=109*((WT/70)**0.75) * (SCRint^-0.084) * ((NIRSInt)/96)^ -0.27 ) * ((PLTint)/130)^0.45) V1=1,160*(WT/70) * (TxTot)^0.03) Q=174*((WT/70)**0.75) V2=1080 *(WT/70) "Near Infrared Spectroscopy CL" equals clearance (CL) affected by the covariate of Near Infrared Spectroscopy (NIRSint). This value is unitless per NONMEM reporting. | 24 hours |
| Creatinine Count CL | Pharmacokinetic data was analyzed with NONMEM, using both the first-order and conditional non-Laplacian (with centering) estimation techniques. We considered two- and three-compartment models, parameterized in terms of both compartment volumes and clearances (distribution and elimination). We compared a basic model (in which pharmacokinetic parameters were independent of weight) to a model in which the pharmacokinetic parameters were assumed to be proportional to weight. The optimal model was selected on the basis of the objective function logarithm of the likelihood of the results) using standard criteria (NONMEM guide). Equations from optimal model: CL=109*((WT/70)**0.75) * (SCRint^-0.084) * ((NIRSInt)/96)^ -0.27 ) * ((PLTint)/130)^0.45) V1=1,160*(WT/70) * (TxTot)^0.03) Q=174*((WT/70)**0.75) V2=1080 *(WT/70) "Creatinine Count CL" equals clearance (CL) affected by the covariate of Creatinine levels (SCRint). This value is unitless per NONMEM reporting. | 24 hours |
| V2- Peripheral Volume (L/70kg) | Pharmacokinetic data was analyzed with NONMEM, using both the first-order and conditional non-Laplacian (with centering) estimation techniques. We considered two- and three-compartment models, parameterized in terms of both compartment volumes and clearances (distribution and elimination). We compared a basic model (in which pharmacokinetic parameters were independent of weight) to a model in which the pharmacokinetic parameters were assumed to be proportional to weight. The optimal model was selected on the basis of the objective function logarithm of the likelihood of the results) using standard criteria (NONMEM guide). Equations from optimal model: CL=109*((WT/70)**0.75) * (SCRint^-0.084) * ((NIRSInt)/96)^ -0.27 ) * ((PLTint)/130)^0.45) V1=1,160*(WT/70) * (TxTot)^0.03) Q=174*((WT/70)**0.75) V2=1080 *(WT/70) "V2" equals Peripheral Volume in L/70kg. | 24 hours |
| Q- Intercompartmental Clearance (L/70kg) | Pharmacokinetic data was analyzed with NONMEM, using both the first-order and conditional non-Laplacian (with centering) estimation techniques. We considered two- and three-compartment models, parameterized in terms of both compartment volumes and clearances (distribution and elimination). We compared a basic model (in which pharmacokinetic parameters were independent of weight) to a model in which the pharmacokinetic parameters were assumed to be proportional to weight. The optimal model was selected on the basis of the objective function logarithm of the likelihood of the results) using standard criteria (NONMEM guide). Equations from optimal model: CL=109*((WT/70)**0.75) * (SCRint^-0.084) * ((NIRSInt)/96)^ -0.27 ) * ((PLTint)/130)^0.45) V1=1,160*(WT/70) * (TxTot)^0.03) Q=174*((WT/70)**0.75) V2=1080 *(WT/70) "Q" equals intercompartmental clearance in L/70kg. | 24 hours |
| V1- Central Volume (L/70kg) | Pharmacokinetic data was analyzed with NONMEM, using both the first-order and conditional non-Laplacian (with centering) estimation techniques. We considered two- and three-compartment models, parameterized in terms of both compartment volumes and clearances (distribution and elimination). We compared a basic model (in which pharmacokinetic parameters were independent of weight) to a model in which the pharmacokinetic parameters were assumed to be proportional to weight. The optimal model was selected on the basis of the objective function logarithm of the likelihood of the results) using standard criteria (NONMEM guide). Equations from optimal model: CL=109*((WT/70)**0.75) * (SCRint^-0.084) * ((NIRSInt)/96)^ -0.27 ) * ((PLTint)/130)^0.45) V1=1,160*(WT/70) * (TxTot)^0.03) Q=174*((WT/70)**0.75) V2=1080 *(WT/70) "V1" equals central volume in L/70kg. | 24 hours |
| CL- Clearance of TXA (mL/(Min*70kg)) | Pharmacokinetic data was analyzed with NONMEM, using both the first-order and conditional non-Laplacian (with centering) estimation techniques. We considered two- and three-compartment models, parameterized in terms of both compartment volumes and clearances (distribution and elimination). We compared a basic model (in which pharmacokinetic parameters were independent of weight) to a model in which the pharmacokinetic parameters were assumed to be proportional to weight. The optimal model was selected on the basis of the objective function logarithm of the likelihood of the results) using standard criteria (NONMEM guide). Equations from optimal model: CL=109*((WT/70)**0.75) * (SCRint^-0.084) * ((NIRSInt)/96)^ -0.27 ) * ((PLTint)/130)^0.45) V1=1,160*(WT/70) * (TxTot)^0.03) Q=174*((WT/70)**0.75) V2=1080 *(WT/70) "CL" equals clearance of TXA in mL/(min*70kg). | 24 hours |
| Tranexamic Acid 4 Gram |
One time dose IV TXA 4 Grams given over 10 minutes within 2 hours of initial injury Tranexamic Acid: Tranexamic acid is a man-made form of an amino acid (protein) called lysine. Tranexamic acid prevents enzymes in the body from breaking down blood clots. |
| BG002 | Placebo | Matching Volume Normal Saline Placebo given IV over 10 minutes within 2 hours of initial injury Placebo: Matching Volume Normal Saline Placebo given IV over 10 minutes within 2 hours of initial injury |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Tranexamic Acid 2 Gram | One time dose IV TXA 2 Grams given over 10 minutes within 2 hours of initial injury Tranexamic Acid: Tranexamic acid is a man-made form of an amino acid (protein) called lysine. Tranexamic acid prevents enzymes in the body from breaking down blood clots. |
| OG001 | Tranexamic Acid 4 Gram | One time dose IV TXA 4 Grams given over 10 minutes within 2 hours of initial injury Tranexamic Acid: Tranexamic acid is a man-made form of an amino acid (protein) called lysine. Tranexamic acid prevents enzymes in the body from breaking down blood clots. |
| OG002 | Placebo | Matching Volume Normal Saline Placebo given IV over 10 minutes within 2 hours of initial injury Placebo: Matching Volume Normal Saline Placebo given IV over 10 minutes within 2 hours of initial injury |
|
|
| Secondary | Differences in Cytokine Profiles Between the Three Study Groups | To evaluate the effects of TXA on immune function parameters we will, in a RCT, analyze samples from 150 patients (50 in each study group), at multiple time points. Parameters are: a. Cytokines measured from time 0 to 72 hours. | Cytokine Levels at 0 and 72 hours after drug or placebo administration in patient groups. Blood was drawn, serum isolated, and frozen. Frozen sera were thawed and the listed cytokines measured uisng a multiplexed platform. Non-paramteric one-way ANOVA was performed between each treatment group, and the p- value reported. | Posted | Median | Inter-Quartile Range | pg/mL | Samples Drawn through 72 hours after study initiation |
|
|
|
| Secondary | Differences in Leukocyte Function Parameters Between the Three Study Groups | To evaluate the effects of TXA on immune function parameters we will, in a RCT, analyze samples from 150 patients (50 in each study group), at multiple time points. Parameters are: a. Flow cytometric analyses on leukocytes measured from time 0 to 72 hours. | Change in CD11b and CD16 Expression on neutrophils 72 hours after. Leukocytes stained with antibodies specific and analyzed by flow cytometry. The median fluorescen intensity of CD11b or CD16 signal was measured on neutrophils. The fold change was measured, MFI72hours/MFI0hours. Non-paramteric one-way ANOVA was performed and the p-value reported. | Posted | Median | Inter-Quartile Range | Fold Change | Samples Drawn through 72 hours after study initiation |
|
|
|
| Secondary | Total Transfusion Volume CL | Pharmacokinetic data was analyzed with NONMEM, using both the first-order and conditional non-Laplacian (with centering) estimation techniques. We considered two- and three-compartment models, parameterized in terms of both compartment volumes and clearances (distribution and elimination). We compared a basic model (in which pharmacokinetic parameters were independent of weight) to a model in which the pharmacokinetic parameters were assumed to be proportional to weight. The optimal model was selected on the basis of the objective function logarithm of the likelihood of the results) using standard criteria (NONMEM guide). Equations from optimal model: CL=109*((WT/70)**0.75) * (SCRint^-0.084) * ((NIRSInt)/96)^ -0.27 ) * ((PLTint)/130)^0.45) V1=1,160*(WT/70) * (TxTot)^0.03) Q=174*((WT/70)**0.75) V2=1080 *(WT/70) "Total Transfusion Volume CL" equals clearance (CL) affected by the covariate of Total Transfusion Volume (TxTot). This value is unitless per NONMEM reporting. | Of the 99 participants analyzed, 49 received the 2 gram dose and 50 received the 4 gram dose. | Posted | Mean | 95% Confidence Interval | unitless | 24 hours |
|
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| Secondary | Determine the Incidence of Thromboembolic Events (DVT, MI, PE, Stroke) in All Three Study Groups. | The number of events per group for the incidence of thromboembolic events (DVT, MI, PE, Stroke) in all three study groups. | The incidence of thromboembolic events (DVT, MI, PE, Stroke) in all three study groups are given based on events per group. | Posted | Number | events | Hospital Discharge (average 10 days) |
|
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| Secondary | Determine the Incidence of Seizures at 24 Hours in All Three Study Groups. | The incidence of seizures at 24 hours in all three study groups. Number of participants with seizures are reported | The incidence of seizures at 24 hours in all three study groups. This was done by totaling the number of participants with reported seizures. | Posted | Count of Participants | Participants | 24 hours following TXA |
|
|
|
| Secondary | Determine the Incidence of All Adverse Events in All Three Study Groups | All adverse events were totaled for each of the three study groups based on the number of incidents. | The number of incidents were totaled for the three study groups. | Posted | Number | events | Hospital Discharge (average 10 days) |
|
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| Secondary | Platelet Count CL | Pharmacokinetic data was analyzed with NONMEM, using both the first-order and conditional non-Laplacian (with centering) estimation techniques. We considered two- and three-compartment models, parameterized in terms of both compartment volumes and clearances (distribution and elimination). We compared a basic model (in which pharmacokinetic parameters were independent of weight) to a model in which the pharmacokinetic parameters were assumed to be proportional to weight. The optimal model was selected on the basis of the objective function logarithm of the likelihood of the results) using standard criteria (NONMEM guide). Equations from optimal model: CL=109*((WT/70)**0.75) * (SCRint^-0.084) * ((NIRSInt)/96)^ -0.27 ) * ((PLTint)/130)^0.45) V1=1,160*(WT/70) * (TxTot)^0.03) Q=174*((WT/70)**0.75) V2=1080 *(WT/70) "Platelet Count CL" equals clearance (CL) affected by the covariate of Platelet Count (PLTint). This value is unitless per NONMEM reporting. | Of the 99 participants analyzed, 49 received the 2 gram dose and 50 received the 4 gram dose. | Posted | Mean | 95% Confidence Interval | unitless | 24 hours |
|
|
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| Secondary | Near Infrared Spectroscopy CL | Pharmacokinetic data was analyzed with NONMEM, using both the first-order and conditional non-Laplacian (with centering) estimation techniques. We considered two- and three-compartment models, parameterized in terms of both compartment volumes and clearances (distribution and elimination). We compared a basic model (in which pharmacokinetic parameters were independent of weight) to a model in which the pharmacokinetic parameters were assumed to be proportional to weight. The optimal model was selected on the basis of the objective function logarithm of the likelihood of the results) using standard criteria (NONMEM guide). Equations from optimal model: CL=109*((WT/70)**0.75) * (SCRint^-0.084) * ((NIRSInt)/96)^ -0.27 ) * ((PLTint)/130)^0.45) V1=1,160*(WT/70) * (TxTot)^0.03) Q=174*((WT/70)**0.75) V2=1080 *(WT/70) "Near Infrared Spectroscopy CL" equals clearance (CL) affected by the covariate of Near Infrared Spectroscopy (NIRSint). This value is unitless per NONMEM reporting. | Of the 99 participants analyzed, 49 received the 2 gram dose and 50 received the 4 gram dose. | Posted | Mean | 95% Confidence Interval | unitless | 24 hours |
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| Secondary | Creatinine Count CL | Pharmacokinetic data was analyzed with NONMEM, using both the first-order and conditional non-Laplacian (with centering) estimation techniques. We considered two- and three-compartment models, parameterized in terms of both compartment volumes and clearances (distribution and elimination). We compared a basic model (in which pharmacokinetic parameters were independent of weight) to a model in which the pharmacokinetic parameters were assumed to be proportional to weight. The optimal model was selected on the basis of the objective function logarithm of the likelihood of the results) using standard criteria (NONMEM guide). Equations from optimal model: CL=109*((WT/70)**0.75) * (SCRint^-0.084) * ((NIRSInt)/96)^ -0.27 ) * ((PLTint)/130)^0.45) V1=1,160*(WT/70) * (TxTot)^0.03) Q=174*((WT/70)**0.75) V2=1080 *(WT/70) "Creatinine Count CL" equals clearance (CL) affected by the covariate of Creatinine levels (SCRint). This value is unitless per NONMEM reporting. | Of the 99 participants analyzed, 49 received the 2 gram dose and 50 received the 4 gram dose. | Posted | Mean | 95% Confidence Interval | unitless | 24 hours |
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| Secondary | V2- Peripheral Volume (L/70kg) | Pharmacokinetic data was analyzed with NONMEM, using both the first-order and conditional non-Laplacian (with centering) estimation techniques. We considered two- and three-compartment models, parameterized in terms of both compartment volumes and clearances (distribution and elimination). We compared a basic model (in which pharmacokinetic parameters were independent of weight) to a model in which the pharmacokinetic parameters were assumed to be proportional to weight. The optimal model was selected on the basis of the objective function logarithm of the likelihood of the results) using standard criteria (NONMEM guide). Equations from optimal model: CL=109*((WT/70)**0.75) * (SCRint^-0.084) * ((NIRSInt)/96)^ -0.27 ) * ((PLTint)/130)^0.45) V1=1,160*(WT/70) * (TxTot)^0.03) Q=174*((WT/70)**0.75) V2=1080 *(WT/70) "V2" equals Peripheral Volume in L/70kg. | Of the 99 participants analyzed 49 received the 2 gram dose and 50 received the 4 gram dose. | Posted | Mean | 95% Confidence Interval | L/70kg | 24 hours |
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| Secondary | Q- Intercompartmental Clearance (L/70kg) | Pharmacokinetic data was analyzed with NONMEM, using both the first-order and conditional non-Laplacian (with centering) estimation techniques. We considered two- and three-compartment models, parameterized in terms of both compartment volumes and clearances (distribution and elimination). We compared a basic model (in which pharmacokinetic parameters were independent of weight) to a model in which the pharmacokinetic parameters were assumed to be proportional to weight. The optimal model was selected on the basis of the objective function logarithm of the likelihood of the results) using standard criteria (NONMEM guide). Equations from optimal model: CL=109*((WT/70)**0.75) * (SCRint^-0.084) * ((NIRSInt)/96)^ -0.27 ) * ((PLTint)/130)^0.45) V1=1,160*(WT/70) * (TxTot)^0.03) Q=174*((WT/70)**0.75) V2=1080 *(WT/70) "Q" equals intercompartmental clearance in L/70kg. | Of the 99 participants analyzed, 49 received the 2 gram dose and 50 received the 4 gram dose. | Posted | Mean | 95% Confidence Interval | L/70kg | 24 hours |
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| Secondary | V1- Central Volume (L/70kg) | Pharmacokinetic data was analyzed with NONMEM, using both the first-order and conditional non-Laplacian (with centering) estimation techniques. We considered two- and three-compartment models, parameterized in terms of both compartment volumes and clearances (distribution and elimination). We compared a basic model (in which pharmacokinetic parameters were independent of weight) to a model in which the pharmacokinetic parameters were assumed to be proportional to weight. The optimal model was selected on the basis of the objective function logarithm of the likelihood of the results) using standard criteria (NONMEM guide). Equations from optimal model: CL=109*((WT/70)**0.75) * (SCRint^-0.084) * ((NIRSInt)/96)^ -0.27 ) * ((PLTint)/130)^0.45) V1=1,160*(WT/70) * (TxTot)^0.03) Q=174*((WT/70)**0.75) V2=1080 *(WT/70) "V1" equals central volume in L/70kg. | Of the 99 participants analyzed, 49 received the 2 gram dose and 50 received the 4 gram dose. | Posted | Mean | 95% Confidence Interval | L/70kg | 24 hours |
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| Secondary | CL- Clearance of TXA (mL/(Min*70kg)) | Pharmacokinetic data was analyzed with NONMEM, using both the first-order and conditional non-Laplacian (with centering) estimation techniques. We considered two- and three-compartment models, parameterized in terms of both compartment volumes and clearances (distribution and elimination). We compared a basic model (in which pharmacokinetic parameters were independent of weight) to a model in which the pharmacokinetic parameters were assumed to be proportional to weight. The optimal model was selected on the basis of the objective function logarithm of the likelihood of the results) using standard criteria (NONMEM guide). Equations from optimal model: CL=109*((WT/70)**0.75) * (SCRint^-0.084) * ((NIRSInt)/96)^ -0.27 ) * ((PLTint)/130)^0.45) V1=1,160*(WT/70) * (TxTot)^0.03) Q=174*((WT/70)**0.75) V2=1080 *(WT/70) "CL" equals clearance of TXA in mL/(min*70kg). | Of the 99 participants analyzed, 49 received the 2 gram dose and 50 received the 4 gram dose. | Posted | Mean | 95% Confidence Interval | mL/(min*70kg) | 24 hours |
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| 5 |
| 49 |
| 14 |
| 49 |
| 25 |
| 49 |
| EG001 | Tranexamic Acid 4 Gram | One time dose IV TXA 4 Grams given over 10 minutes within 2 hours of initial injury Tranexamic Acid: Tranexamic acid is a man-made form of an amino acid (protein) called lysine. Tranexamic acid prevents enzymes in the body from breaking down blood clots. | 4 | 50 | 18 | 50 | 39 | 50 |
| EG002 | Placebo | Matching Volume Normal Saline Placebo given IV over 10 minutes within 2 hours of initial injury Placebo: Matching Volume Normal Saline Placebo given IV over 10 minutes within 2 hours of initial injury | 9 | 50 | 13 | 50 | 26 | 50 |
| acute blood loss/anemia | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Acute desaturation | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Acute Kidney Injury | Renal and urinary disorders | Non-systematic Assessment |
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| Acute Respiratory Distress Syndrome | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Anastomatic Bleeding | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Arterial Bleeding | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Death | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
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| Sepsis | Infections and infestations | Non-systematic Assessment |
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| Hypotension | Cardiac disorders | Non-systematic Assessment |
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| Anemia | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Urinary tract infection | Infections and infestations | Non-systematic Assessment |
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| SVT | Cardiac disorders | Non-systematic Assessment |
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| Hyperphosphatemia | Blood and lymphatic system disorders | Non-systematic Assessment |
|
Not provided
Not provided
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| GM-CSF hour 0 |
|
| GM-CSF hour 72 |
|
| Factalkine hour 0 |
|
| Factalkine hour 72 |
|
| IFNgamma hour 0 |
|
| IFNgamma hour 72 |
|
| IL-10 hour 0 |
|
| IL-10 hour 72 |
|
| MIP-3a hour 0 |
|
| MIP-3a hour 72 |
|
| IL-12p70 hour 0 |
|
| IL-12p70 hour 72 |
|
| IL-13 hour 0 |
|
| IL-13 hour 72 |
|
| IL -17A hour 0 |
|
| IL-17A hour 72 |
|
| IL-1beta hour 0 |
|
| IL-1beta hour 72 |
|
| IL-2 hour 0 |
|
| IL-2 hour 72 |
|
| IL-21 hour 0 |
|
| IL-21 hour 72 |
|
| IL-4 hour 0 |
|
| IL-4 hour 72 |
|
| IL-23 hour 0 |
|
| IL-23 hour 72 |
|
| IL-5 hour 0 |
|
| IL-5 hour 72 |
|
| IL-6 hour 0 |
|
| IL-6 hour 72 |
|
| IL-7 hour 0 |
|
| IL-7 hour 72 |
|
| IL-8 hour 0 |
|
| IL-8 hour 72 |
|
| MIP-1alpha hour 0 |
|
| MIP-1alpha hour 72 |
|
| MIP-beta hour 0 |
|
| MIP-beta hour 72 |
|
| TNFa hour 0 |
|
| TNFa hour 72 |
|
|