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| ID | Type | Description | Link |
|---|---|---|---|
| W81XWH1220028 | Other Grant/Funding Number | Department of Defense TATRC |
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Futility
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| Name | Class |
|---|---|
| U.S. Army Medical Research and Development Command | FED |
| University of Colorado, Denver | OTHER |
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Bleeding is the most avoidable cause of death in trauma patients. Up to one-third of severely injured trauma patients are found to be coagulopathic and forty percent of the mortality following severe injury is due to uncontrollable hemorrhage in the setting of coagulopathy. It has been established that early administration of fresh frozen plasma decreases mortality following severe injury, replacing lost coagulation factors, improving the coagulopathy and restoring blood volume. This study will determine if giving plasma to severely injured trauma patients during ambulance transport versus after arrival to the hospital will help reduce hemorrhage, thus decreasing both total blood product administration and mortality.
Study Design: Severely injured trauma patients with a systolic blood pressure (SBP) ≤ 70 or SBP ≤ 90 with a heart rate ≥ 108 bpm at the scene will be enrolled and randomized to receive either 2 units of frozen plasma thawed in the field or normal saline (the current standard of care), as the initial resuscitation fluid. After this initial resuscitation fluid, both groups will receive the same standard of care, including packed red blood cells, additional normal saline, or plasma as needed based on laboratory and clinical evidence of coagulopathy. Blood samples and clinical information will be collected throughout the hospital stay up to 28 days after injury.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Plasma | Experimental | If the patient is randomized to experimental arm, 2 units of frozen type AB plasma (FP24) will be thawed in the Plasmatherm Dry Thawing and Warming Device according to the operator manual as approved by the FDA in the ambulance and infusion will commence as soon as the type AB plasma is ready, and will continue during transport to the emergency department (ED). After infusion of 2 units of type AB plasma is completed, subsequent care will proceed per institutional, Advanced Trauma Life Support (ATLS) guided resuscitation with acute packed red blood cells (pRBC) administration determined by the hemodynamic response and additional blood component administration guided by rapid thrombelastography (rTEG) and coagulation panel assessment in conjunction with clinical scenario. |
|
| Standard | Active Comparator | If the patient is randomized to the standard arm, the patient will be given intravenous crystalloid fluid (normal saline) as the initial resuscitation fluid with 2 large bore IVs based on the current ATLS guidelines, the standard of care. Subsequent care will proceed per institutional, ATLS guided resuscitation with acute packed red blood cells pRBC administration determined by the hemodynamic response and additional blood component administration guided by rTEG and coagulation panel assessment in conjunction with clinical scenario. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Type AB plasma | Biological | The plasma is thawed and administered to subjects in the experimental (plasma) arm. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants That Died Within 28 Days Post Injury | death within 28 days post injury (death of any cause except for death due to a second, clearly unrelated traumatic injury suffered after discharge) | 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Composite Outcome of 28-day In-hospital Mortality and Postinjury Multiple Organ Failure (MOF) Incidence | The occurrence of in-hospital death or MOF within the first 28 days postinjury. MOF is defined using the validated Denver MOF score (Denver MOF score>3 of simultaneously obtained scores after 48 hours postinjury). | 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline (Field) Coagulation Factor Levels | defined as the first coagulation factor level obtained in the field prior to intervention Coagulation Factor Reference Ranges F2 F5 F7 F8 F9 F11
| after injury and prior to hospital arrival, at about 15 minutes after injury |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ernest E Moore, MD | Denver Health Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Denver Health Medical Center | Denver | Colorado | 80204 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40766812 | Derived | DeBot M, Erickson C, Schaid T, LaCroix I, Moore EE, Silliman C, Cohen MJ, D'Alessandro A, Hansen KC. Trauma-induced dysfibrinogenemia: the von Clauss assay does not accurately measure fibrinogen levels after injury. Blood Vessel Thromb Hemost. 2024 Jul 16;1(3):100017. doi: 10.1016/j.bvth.2024.100017. eCollection 2024 Sep. | |
| 31851290 |
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The enrollment and randomization occurred almost simultaneously. Once the paramedics determined the patient to be eligible, the cooler was opened and the randomization was done based on the cooler content: cooler with plasma randomized the patient to the experimental and cooler with frozen water randomized the patient to the control group.
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| ID | Title | Description |
|---|---|---|
| FG000 | Plasma | If the patient is randomized to experimental arm, 2 units of frozen Type AB plasma (FP24) will be thawed in the Plasmatherm Dry Thawing and Warming Device according to the operator manual as approved by the FDA in the ambulance and infusion will commence as soon as the Type AB plasma is ready, and will continue during transport to the ED. After infusion of 2 units of Type AB plasma is completed, subsequent care will proceed per institutional, Advanced Trauma Life Support (ATLS) guided resuscitation with acute packed red blood cells (pRBC) administration determined by hemodynamic response and additional blood component administration guided by rapid thrombelastography (rTEG) and coagulation panel assessment in conjunction with clinical scenario. Type AB plasma: The plasma is thawed and administered to subjects in the experimental (plasma) arm. |
| FG001 | Standard | If the patient is randomized to the standard arm, the patient will be given intravenous crystalloid fluid (normal saline) as the initial resuscitation fluid with 2 large bore IVs based on the current ATLS guidelines, the standard of care. Subsequent care will proceed per institutional, ATLS guided resuscitation with acute pRBC administration determined by hemodynamic response and additional blood component administration guided by rTEG and coagulation panel assessment in conjunction with clinical scenario. Crystalloid fluid (standard of care for resuscitation): Normal saline will be give to subjects in the standard arm as the current standard of care for an initial resuscitation fluid |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Plasma | If the patient is randomized to experimental arm, 2 units of frozen Type AB plasma (FP24) will be thawed in the Plasmatherm Dry Thawing and Warming Device according to the operator manual as approved by the FDA in the ambulance and infusion will commence as soon as the Type AB plasma is ready, and will continue during transport to the ED. After infusion of 2 units of Type AB plasma is completed, subsequent care will proceed per institutional, Advanced Trauma Life Support (ATLS) guided resuscitation with acute packed red blood cells (pRBC) administration determined by hemodynamic response and additional blood component administration guided by rapid thrombelastography (rTEG) and coagulation panel assessment in conjunction with clinical scenario. Type AB plasma: The plasma is thawed and administered to subjects in the experimental (plasma) arm. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | Number of Participants That Died Within 28 Days Post Injury | death within 28 days post injury (death of any cause except for death due to a second, clearly unrelated traumatic injury suffered after discharge) | Posted | Count of Participants | Participants | 28 days |
|
Hospital stay up to 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 | Plasma | If the patient is randomized to experimental arm, 2 units of frozen Type AB plasma (FP24) will be thawed in the Plasmatherm Dry Thawing and Warming Device according to the operator manual as approved by the FDA in the ambulance and infusion will commence as soon as the Type AB plasma is ready, and will continue during transport to the ED. After infusion of 2 units of Type AB plasma is completed, subsequent care will proceed per institutional, Advanced Trauma Life Support (ATLS) guided resuscitation with acute packed red blood cells (pRBC) administration determined by hemodynamic response and additional blood component administration guided by rapid thrombelastography (rTEG) and coagulation panel assessment in conjunction with clinical scenario. Type AB plasma: The plasma is thawed and administered to subjects in the experimental (plasma) arm. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infections | Infections and infestations | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Intensive Care Unit (ICU) delirium | Psychiatric disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ernest E. Moore | Denver Health Medical Center | 303.602.1820 | Ernest.Moore@dhha.org |
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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 | Dec 27, 2016 | Feb 27, 2018 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 7, 2017 | Feb 28, 2018 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D014947 | Wounds and Injuries |
| D012771 | Shock, Hemorrhagic |
| D020141 | Hemostatic Disorders |
| ID | Term |
|---|---|
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
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| ID | Term |
|---|---|
| D059039 | Standard of Care |
| D012151 | Resuscitation |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
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| Crystalloid fluid (standard of care for resuscitation) | Drug | Normal saline will be give to subjects in the standard arm as the current standard of care for an initial resuscitation fluid |
|
|
| Admission Coagulopathy |
Defined as the first international normalized ratio (INR) obtained upon ED arrival. The international normalized ratio (INR) is an international standard for the prothrombin time (PT). This measures the time it takes for blood to clot. The normal range for a healthy person is 0.83-1.19. Usually, a high INR indicates a higher risk of bleeding, while a low INR suggests a higher risk of developing a clot. |
| within 30 minutes of Emergency Department (ED) arrival |
| Number of Participants With Admission Severe Coagulopathy | Defined as international normalized ratio (INR) >1.3 obtained upon ED arrival. The international normalized ratio (INR) is an international standard for the prothrombin time (PT). This measures the time it takes for blood to clot. The normal range for a healthy person is 0.83-1.19. Usually, a high INR indicates a higher risk of bleeding, while a low INR suggests a higher risk of developing a clot. | within 30 minutes of Emergency Department (ED) arrival |
| Admission Clot Strength | Admission clot strength will be measured by thrombelastography G-value upon ED arrival. Clot strength measured in kilodynes per square centimetre (kdyn/cm^2). | within 30 minutes of ED arrival |
| Admission Acidosis | Admission acidosis measured by lactate upon ED arrival. | within 30 minutes of ED arrival |
| Number of Participants With Admission Severe Acidosis | Admission severe acidosis measured by lactate>5 upon ED arrival. | within 30 minutes of ED arrival |
| Admission Acidosis | Admission acidosis will be defined by base deficit (BD) upon ED arrival. | within 30 minutes of ED arrival |
| Number of Participants With Admission Severe Acidosis | Admission severe acidosis will be defined by base deficit (BD>10) upon ED arrival. | within 30 minutes of ED arrival |
| Number of Participants With Abnormal Baseline (Field) Coagulation Factor XIII Level | defined as abnormal coagulation factor XIII level obtained in the field prior to intervention | after injury prior to hospital arrival |
| Admission (First Arrival) Coagulation Factor Levels | defined as the first coagulation factor level obtained upon ED arrival Coagulation Factor Reference Ranges F2 F5 F7 F8 F9 F11
| after injury prior to hospital arrival |
| Number of Participants With Abnormal Admission Coagulation Factor XIII (Fibrin-stabilizing Factor) Level | defined as the first abnormal factor XIII (fibrin-stabilizing factor) level obtained upon ED arrival | within 30 minutes of Emergency Department (ED) arrival |
| Exploratory Analyses | Number of participants with 24-hour mortality, adverse outcome free days and transfusions | Hospital stay up to 28 days. |
| Exploratory Analyses. | Adverse outcome free days | Hospital stay up to 28 days. |
| Number of Participants With Mortality, Adverse Outcome-free Days and Transfusions in the Sub-group With Less Severe Hemorrhagic Shock | Mortality, adverse outcome-free days and transfusions in the patients with initial systolic blood pressure (SBP) 71-90 mmHg and heart rate (HR) of 108 or greater | Hospital stay up to 28 days. |
| Adverse Outcome-free Days in a Sub-group With Less Severe Hemorrhagic Shock | Adverse outcome-free days in the patients with initial systolic blood pressure (SBP) 71-90 mmHg and heart rate (HR) of 108 or greater | Hospital stay up to 28 days. |
| Level of Haemoglobin (Hb) in a Sub-group With Less Severe Hemorrhagic Shock | Level of Haemoglobin (Hb) in g/dL in the patients with initial systolic blood pressure (SBP) 71-90 mmHg and heart rate (HR) of 108 or greater | Hospital stay up to 28 days. |
| Blood Product Transfusion in a Sub-group With Less Severe Hemorrhagic Shock | Transfusions of blood products in units in the patients with initial systolic blood pressure (SBP) 71-90 mmHg and heart rate (HR) of 108 or greater | Hospital stay up to 28 days. |
| Time to Admission and First Blood Transfusion in a Sub-group With Less Severe Hemorrhagic Shock | Time to Admission and First Blood Transfusion in minutes in the patients with initial systolic blood pressure (SBP) 71-90 mmHg and heart rate (HR) of 108 or greater | Hospital stay up to 28 days. |
| Number of Participants With Mortality, Adverse Outcome-free Days and Transfusions in a Sub-group With Severe Hemorrhagic Shock | Mortality, adverse outcome-free days and transfusions in the patients with initial systolic blood pressure (SBP) <=70 mmHg | Hospital stay up to 28 days. |
| Number of Adverse Outcome Free Days in a Sub-group With Severe Hemorrhagic Shock | Adverse outcome-free days in the patients with initial systolic blood pressure (SBP) <=70 mmHg | Hospital stay up to 28 days. |
| Number of Participants in a Sub-group With no Severe Traumatic Brain Injury (TBI) | Number of participants with mortality, adverse outcome-free days and transfusions in the patients with no severe traumatic brain injury (TBI) is defined as Abbreviated Injury Score (AIS) for Head/Neck >=3. | Hospital stay up to 28 days. |
| Exploratory Analyses in a Sub-group With Severe Traumatic Brain Injury (TBI) | Number of participants with 28-day mortality. Traumatic brain injury (TBI) is defined as Abbreviated Injury Score (AIS) for Head/Neck >=3. | Hospital stay up to 28 days. |
| Severe Adverse Events (SAE) | Number of participants with severe adverse events (SAE) | Hospital stay up to day 28 |
| Haemoglobin (Hb) Level in a Sub-group With Severe Hemorrhagic Shock | Haemoglobin (Hb) level in the patients with initial systolic blood pressure (SBP) <=70 mmHg | Hospital stay up to 28 days. |
| Blood Product Transfusion in a Sub-group With Severe Hemorrhagic Shock | Number of blood products transfused in units in the patients with initial systolic blood pressure (SBP) <=70 mmHg | Hospital stay up to 28 days. |
| Time to Admission and First Blood Transfusion in a Sub-group With Severe Hemorrhagic Shock | Time to Admission and First Blood Transfusion in the patients with initial systolic blood pressure (SBP) <=70 mmHg | Hospital stay up to 28 days. |
| Haemoglobin (Hb) Level | Haemoglobin (Hb) level in g/dL units. | Hospital stay up to 28 days. |
| Number of Blood Products Transfused. | Number of blood products transfused in units. | Hospital stay up to 28 days. |
| Time to Admission and First Blood Transfusion | Time to admission and first blood product transfusion in minutes. | Hospital stay up to 28 days. |
| Pusateri AE, Moore EE, Moore HB, Le TD, Guyette FX, Chapman MP, Sauaia A, Ghasabyan A, Chandler J, McVaney K, Brown JB, Daley BJ, Miller RS, Harbrecht BG, Claridge JA, Phelan HA, Witham WR, Putnam AT, Sperry JL. Association of Prehospital Plasma Transfusion With Survival in Trauma Patients With Hemorrhagic Shock When Transport Times Are Longer Than 20 Minutes: A Post Hoc Analysis of the PAMPer and COMBAT Clinical Trials. JAMA Surg. 2020 Feb 1;155(2):e195085. doi: 10.1001/jamasurg.2019.5085. Epub 2020 Feb 19. |
| 30032977 | Derived | Moore HB, Moore EE, Chapman MP, McVaney K, Bryskiewicz G, Blechar R, Chin T, Burlew CC, Pieracci F, West FB, Fleming CD, Ghasabyan A, Chandler J, Silliman CC, Banerjee A, Sauaia A. Plasma-first resuscitation to treat haemorrhagic shock during emergency ground transportation in an urban area: a randomised trial. Lancet. 2018 Jul 28;392(10144):283-291. doi: 10.1016/S0140-6736(18)31553-8. Epub 2018 Jul 20. |
| 26220293 | Derived | Reynolds PS, Michael MJ, Cochran ED, Wegelin JA, Spiess BD. Prehospital use of plasma in traumatic hemorrhage (The PUPTH Trial): study protocol for a randomised controlled trial. Trials. 2015 Jul 30;16:321. doi: 10.1186/s13063-015-0844-5. |
| 25784527 | Derived | Chapman MP, Moore EE, Chin TL, Ghasabyan A, Chandler J, Stringham J, Gonzalez E, Moore HB, Banerjee A, Silliman CC, Sauaia A. Combat: Initial Experience with a Randomized Clinical Trial of Plasma-Based Resuscitation in the Field for Traumatic Hemorrhagic Shock. Shock. 2015 Aug;44 Suppl 1(0 1):63-70. doi: 10.1097/SHK.0000000000000376. |
| BG001 | Standard | If the patient is randomized to the standard arm, the patient will be given intravenous crystalloid fluid (normal saline) as the initial resuscitation fluid with 2 large bore IVs based on the current ATLS guidelines, the standard of care. Subsequent care will proceed per institutional, ATLS guided resuscitation with acute pRBC administration determined by hemodynamic response and additional blood component administration guided by rTEG and coagulation panel assessment in conjunction with clinical scenario. Crystalloid fluid (standard of care for resuscitation): Normal saline will be give to subjects in the standard arm as the current standard of care for an initial resuscitation fluid |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body Mass Index (BMI) | Median | Inter-Quartile Range | kg/m^2 |
|
| Comorbidities | Presence of one or more additional diseases or disorders co-occurring in trauma patient. | Count of Participants | Participants |
|
| Blunt injury mechanism | Blunt force trauma is an injury that occurs when an object hits or strikes a part of the body. | Count of Participants | Participants |
|
| New Injury Severity Scale (NISS) | The New Injury Severity Score (NISS) is an anatomical scoring system that provides an overall score for patients with multiple injuries. This is calculated as the sum of the squares of the top three Abbreviated Injury Scores (AIS) regardless of body region. AIS is an anatomical-based coding system on a scale of one to six, one being a minor injury and six being maximal. The NISS score takes values from 0 to 75. This score is virtually the only anatomical scoring system in use and correlates linearly with mortality, morbidity, hospital stay and other measures of severity. | Median | Inter-Quartile Range | units on a scale |
|
| Maximal Abbreviated Injury Score (AIS) for head and neck | Abbreviated Injury Score is an anatomical-based coding system on a scale of one to six, one being a minor injury and six being maximal. | Median | Inter-Quartile Range | units on a scale |
|
| Traumatic Brain Injury (TBI) defined as AIS head >=3 | Count of Participants | Participants |
|
| Maximal Abbreviated Injury Score (AIS) chest | Abbreviated Injury Score is an anatomical-based coding system on a scale of one to six, one being a minor injury and six being maximal. | Median | Inter-Quartile Range | units on a scale |
|
| Maximal Abbreviated Injury Score (AIS) abdomen and pelvis | Abbreviated Injury Score is an anatomical-based coding system on a scale of one to six, one being a minor injury and six being maximal. | Median | Inter-Quartile Range | units on a scale |
|
| Maximal Abbreviated Injury Score (AIS) extremities | Abbreviated Injury Score is an anatomical-based coding system on a scale of one to six, one being a minor injury and six being maximal. | Median | Inter-Quartile Range | units on a scale |
|
| Heart rate (HR) in the field | Median | Inter-Quartile Range | beats per minute (BPM) |
|
| Systolic blood pressure (SBP) in the field | Median | Inter-Quartile Range | mmHg |
|
| Severe shock defined as systolic blood pressure (SBP) in the field <=70mmHg | Count of Participants | Participants |
|
| Body temperature in the field | The body temperature was measured in the field with a temporal scanner infrared thermometer. Due to the specifics of the study (acute trauma setting), it was not always possible to obtain a body temperature reading in the field (accident scene). | Median | Inter-Quartile Range | degrees Celsius |
|
| Glasgow Coma Scale (GCS) in the field | Glasgow Coma Scale (GCS) is a neurological scale which aims to give a reliable and objective way of recording the conscious state of a person for initial as well as subsequent assessment. The GCS is the summation of scores for eye, verbal, and motor responses. The minimum score is a 3 which indicates deep coma or a brain-dead state. The maximum is 15 which indicates a fully awake patient. | Median | Inter-Quartile Range | units on a scale |
|
| Haemoglobin (Hb) in the field | Due to the specifics of the study (acute trauma setting) it was not always possible to obtain a blood sample in the field (accident scene). | Median | Inter-Quartile Range | g/dL |
|
| Platelet count in the field | Due to the specifics of the study (acute trauma setting) it was not always possible to obtain a blood sample in the field (accident scene). | Median | Inter-Quartile Range | 1000 cells/microL |
|
| Fibrinogen in the field | Due to the specifics of the study (acute trauma setting) it was not always possible to obtain a blood sample in the field (accident scene). | Median | Inter-Quartile Range | mg/dL |
|
| International normalized ratio (INR) in the field | Measure Analysis Population Description: Defined as the first international normalized ratio (INR) obtained upon ED arrival. The international normalized ratio (INR) is an international standard for the prothrombin time (PT). This measures the time it takes for blood to clot. The normal range for a healthy person is 0.83-1.19. | Median | Inter-Quartile Range | ratio |
|
| International normalized ratio (INR) in the field >=1.3 | Due to the specifics of the study (acute trauma setting) it was not always possible to obtain a blood sample in the field (accident scene). | Count of Participants | Participants |
|
| Partial thromboplastin time (PTT) in the field | Due to the specifics of the study (acute trauma setting) it was not always possible to obtain a blood sample in the field (accident scene). | Median | Inter-Quartile Range | seconds |
|
| OG001 | Standard | If the patient is randomized to the standard arm, the patient will be given intravenous crystalloid fluid (normal saline) as the initial resuscitation fluid with 2 large bore IVs based on the current ATLS guidelines, the standard of care. Subsequent care will proceed per institutional, ATLS guided resuscitation with acute pRBC administration determined by hemodynamic response and additional blood component administration guided by rTEG and coagulation panel assessment in conjunction with clinical scenario. Crystalloid fluid (standard of care for resuscitation): Normal saline will be give to subjects in the standard arm as the current standard of care for an initial resuscitation fluid |
|
|
| Secondary | Composite Outcome of 28-day In-hospital Mortality and Postinjury Multiple Organ Failure (MOF) Incidence | The occurrence of in-hospital death or MOF within the first 28 days postinjury. MOF is defined using the validated Denver MOF score (Denver MOF score>3 of simultaneously obtained scores after 48 hours postinjury). | Posted | Count of Participants | Participants | 28 days |
|
|
|
| Secondary | Admission Coagulopathy | Defined as the first international normalized ratio (INR) obtained upon ED arrival. The international normalized ratio (INR) is an international standard for the prothrombin time (PT). This measures the time it takes for blood to clot. The normal range for a healthy person is 0.83-1.19. Usually, a high INR indicates a higher risk of bleeding, while a low INR suggests a higher risk of developing a clot. | Posted | Median | Inter-Quartile Range | ratio | within 30 minutes of Emergency Department (ED) arrival |
|
|
|
| Secondary | Number of Participants With Admission Severe Coagulopathy | Defined as international normalized ratio (INR) >1.3 obtained upon ED arrival. The international normalized ratio (INR) is an international standard for the prothrombin time (PT). This measures the time it takes for blood to clot. The normal range for a healthy person is 0.83-1.19. Usually, a high INR indicates a higher risk of bleeding, while a low INR suggests a higher risk of developing a clot. | Posted | Count of Participants | Participants | within 30 minutes of Emergency Department (ED) arrival |
|
|
|
| Secondary | Admission Clot Strength | Admission clot strength will be measured by thrombelastography G-value upon ED arrival. Clot strength measured in kilodynes per square centimetre (kdyn/cm^2). | Posted | Median | Inter-Quartile Range | kdyne/cm^2 | within 30 minutes of ED arrival |
|
|
|
| Secondary | Admission Acidosis | Admission acidosis measured by lactate upon ED arrival. | Posted | Median | Inter-Quartile Range | mmol/L | within 30 minutes of ED arrival |
|
|
|
| Secondary | Number of Participants With Admission Severe Acidosis | Admission severe acidosis measured by lactate>5 upon ED arrival. | Posted | Count of Participants | Participants | within 30 minutes of ED arrival |
|
|
|
| Secondary | Admission Acidosis | Admission acidosis will be defined by base deficit (BD) upon ED arrival. | Posted | Median | Inter-Quartile Range | mEq/L | within 30 minutes of ED arrival |
|
|
|
| Secondary | Number of Participants With Admission Severe Acidosis | Admission severe acidosis will be defined by base deficit (BD>10) upon ED arrival. | Posted | Count of Participants | Participants | within 30 minutes of ED arrival |
|
|
|
| Other Pre-specified | Baseline (Field) Coagulation Factor Levels | defined as the first coagulation factor level obtained in the field prior to intervention Coagulation Factor Reference Ranges F2 F5 F7 F8 F9 F11
| Posted | Median | Inter-Quartile Range | percentage of activity | after injury and prior to hospital arrival, at about 15 minutes after injury |
|
|
|
| Other Pre-specified | Number of Participants With Abnormal Baseline (Field) Coagulation Factor XIII Level | defined as abnormal coagulation factor XIII level obtained in the field prior to intervention | Posted | Count of Participants | Participants | after injury prior to hospital arrival |
|
|
|
| Other Pre-specified | Admission (First Arrival) Coagulation Factor Levels | defined as the first coagulation factor level obtained upon ED arrival Coagulation Factor Reference Ranges F2 F5 F7 F8 F9 F11
| Not all the timepoints are available for all the patients. | Posted | Median | Inter-Quartile Range | percentage of activity | after injury prior to hospital arrival |
|
|
|
| Other Pre-specified | Number of Participants With Abnormal Admission Coagulation Factor XIII (Fibrin-stabilizing Factor) Level | defined as the first abnormal factor XIII (fibrin-stabilizing factor) level obtained upon ED arrival | Posted | Count of Participants | Participants | within 30 minutes of Emergency Department (ED) arrival |
|
|
|
| Other Pre-specified | Exploratory Analyses | Number of participants with 24-hour mortality, adverse outcome free days and transfusions | Posted | Count of Participants | Participants | Hospital stay up to 28 days. |
|
|
|
| Other Pre-specified | Exploratory Analyses. | Adverse outcome free days | Posted | Median | Inter-Quartile Range | days | Hospital stay up to 28 days. |
|
|
|
| Other Pre-specified | Number of Participants With Mortality, Adverse Outcome-free Days and Transfusions in the Sub-group With Less Severe Hemorrhagic Shock | Mortality, adverse outcome-free days and transfusions in the patients with initial systolic blood pressure (SBP) 71-90 mmHg and heart rate (HR) of 108 or greater | Posted | Count of Participants | Participants | Hospital stay up to 28 days. |
|
|
|
| Other Pre-specified | Adverse Outcome-free Days in a Sub-group With Less Severe Hemorrhagic Shock | Adverse outcome-free days in the patients with initial systolic blood pressure (SBP) 71-90 mmHg and heart rate (HR) of 108 or greater | Posted | Median | Inter-Quartile Range | days | Hospital stay up to 28 days. |
|
|
|
| Other Pre-specified | Level of Haemoglobin (Hb) in a Sub-group With Less Severe Hemorrhagic Shock | Level of Haemoglobin (Hb) in g/dL in the patients with initial systolic blood pressure (SBP) 71-90 mmHg and heart rate (HR) of 108 or greater | Posted | Median | Inter-Quartile Range | g/dL | Hospital stay up to 28 days. |
|
|
|
| Other Pre-specified | Blood Product Transfusion in a Sub-group With Less Severe Hemorrhagic Shock | Transfusions of blood products in units in the patients with initial systolic blood pressure (SBP) 71-90 mmHg and heart rate (HR) of 108 or greater | Posted | Median | Inter-Quartile Range | units | Hospital stay up to 28 days. |
|
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|
| Other Pre-specified | Time to Admission and First Blood Transfusion in a Sub-group With Less Severe Hemorrhagic Shock | Time to Admission and First Blood Transfusion in minutes in the patients with initial systolic blood pressure (SBP) 71-90 mmHg and heart rate (HR) of 108 or greater | Posted | Median | Inter-Quartile Range | minutes | Hospital stay up to 28 days. |
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| Other Pre-specified | Number of Participants With Mortality, Adverse Outcome-free Days and Transfusions in a Sub-group With Severe Hemorrhagic Shock | Mortality, adverse outcome-free days and transfusions in the patients with initial systolic blood pressure (SBP) <=70 mmHg | Posted | Count of Participants | Participants | Hospital stay up to 28 days. |
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| Other Pre-specified | Number of Adverse Outcome Free Days in a Sub-group With Severe Hemorrhagic Shock | Adverse outcome-free days in the patients with initial systolic blood pressure (SBP) <=70 mmHg | Not all the timepoints are available for all the patients. | Posted | Median | Inter-Quartile Range | days | Hospital stay up to 28 days. |
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| Other Pre-specified | Number of Participants in a Sub-group With no Severe Traumatic Brain Injury (TBI) | Number of participants with mortality, adverse outcome-free days and transfusions in the patients with no severe traumatic brain injury (TBI) is defined as Abbreviated Injury Score (AIS) for Head/Neck >=3. | Posted | Count of Participants | Participants | Hospital stay up to 28 days. |
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| Other Pre-specified | Exploratory Analyses in a Sub-group With Severe Traumatic Brain Injury (TBI) | Number of participants with 28-day mortality. Traumatic brain injury (TBI) is defined as Abbreviated Injury Score (AIS) for Head/Neck >=3. | Posted | Count of Participants | Participants | Hospital stay up to 28 days. |
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| Other Pre-specified | Severe Adverse Events (SAE) | Number of participants with severe adverse events (SAE) | Posted | Count of Participants | Participants | Hospital stay up to day 28 |
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| Other Pre-specified | Haemoglobin (Hb) Level in a Sub-group With Severe Hemorrhagic Shock | Haemoglobin (Hb) level in the patients with initial systolic blood pressure (SBP) <=70 mmHg | Not all the timepoints are available for all the patients. | Posted | Median | Inter-Quartile Range | g/dL | Hospital stay up to 28 days. |
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| Other Pre-specified | Blood Product Transfusion in a Sub-group With Severe Hemorrhagic Shock | Number of blood products transfused in units in the patients with initial systolic blood pressure (SBP) <=70 mmHg | Not all the timepoints are available for all the patients. | Posted | Median | Inter-Quartile Range | units | Hospital stay up to 28 days. |
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| Other Pre-specified | Time to Admission and First Blood Transfusion in a Sub-group With Severe Hemorrhagic Shock | Time to Admission and First Blood Transfusion in the patients with initial systolic blood pressure (SBP) <=70 mmHg | Not all the timepoints are available for all the patients. | Posted | Median | Inter-Quartile Range | minutes | Hospital stay up to 28 days. |
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| Other Pre-specified | Haemoglobin (Hb) Level | Haemoglobin (Hb) level in g/dL units. | Posted | Median | Inter-Quartile Range | g/dL | Hospital stay up to 28 days. |
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| Other Pre-specified | Number of Blood Products Transfused. | Number of blood products transfused in units. | Posted | Median | Inter-Quartile Range | units | Hospital stay up to 28 days. |
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| Other Pre-specified | Time to Admission and First Blood Transfusion | Time to admission and first blood product transfusion in minutes. | Posted | Median | Inter-Quartile Range | minutes | Hospital stay up to 28 days. |
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| Post-Hoc | Baseline (Field) Citrated Rapid Thrombelastography (CR-TEG) Parameters. | Baseline (field) sample drawn prior to intervention in the field and measured by citrated rapid thrombelastography (CR-TEG) activated clotting time (ACT). | Posted | Median | Inter-Quartile Range | second | after injury and prior to hospital arrival, at about 15 minutes after injury |
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| Post-Hoc | Admission (ED) Citrated Rapid Thrombelastography (CR-TEG) Parameters. | Admission (ED) sample drawn upon ED admission and measured by citrated rapid thrombelastography (CR-TEG) activated clotting time (ACT) in seconds. | Posted | Median | Inter-Quartile Range | second | post-intervention and upon ED arrival |
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| Post-Hoc | Baseline (Field) Citrated Rapid Thrombelastography (CR-TEG) Parameters. | Baseline (field) sample drawn prior to intervention in the field and measured by citrated rapid thrombelastography (CR-TEG) angle in degrees. | Posted | Median | Inter-Quartile Range | degrees | after injury and prior to hospital arrival, at about 15 minutes after injury |
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| Post-Hoc | Baseline (Field) Citrated Rapid Thrombelastography (CR-TEG) Parameters. | Baseline (field) sample drawn prior to intervention in the field and measured by citrated rapid thrombelastography (CR-TEG) maximum amplitude (MA). | Posted | Median | Inter-Quartile Range | millimeter (mm) | after injury and prior to hospital arrival, at about 15 minutes after injury |
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| Post-Hoc | Baseline (Field) Citrated Rapid Thrombelastography (CR-TEG) Parameters. | Baseline (field) sample drawn prior to intervention in the field and measured by citrated rapid thrombelastography (CR-TEG). Clot strength measured in kilodynes per square centimetre (kdyn/cm^2). | Posted | Median | Inter-Quartile Range | kdyn/cm^2 | after injury and prior to hospital arrival, at about 15 minutes after injury |
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| Post-Hoc | Baseline (Field) Citrated Rapid Thrombelastography (CR-TEG) Parameters. | Baseline (field) sample drawn prior to intervention in the field and measured by citrated rapid thrombelastography (CR-TEG). Percentage of clot lysis 30 minutes after maximal amplitude (MA) value is finalized. | Posted | Median | Inter-Quartile Range | percentage of clot lysed at 30 minutes | after injury and prior to hospital arrival, at about 15 minutes after injury |
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| Post-Hoc | Admission (ED) Citrated Rapid Thrombelastography (CR-TEG) Parameters. | Admission (ED) sample drawn upon ED admission and measured by citrated rapid thrombelastography (CR-TEG) angle measured in degrees. | Posted | Median | Inter-Quartile Range | degree | post-intervention and upon ED arrival |
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| Post-Hoc | Admission (ED) Citrated Rapid Thrombelastography (CR-TEG) Parameters. | Admission (ED) sample drawn upon ED admission and measured by citrated rapid thrombelastography (CR-TEG) maximal amplitude (MA). | Posted | Median | Inter-Quartile Range | millimeter (mm) | post-intervention and upon ED arrival |
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| Post-Hoc | Admission (ED) Citrated Rapid Thrombelastography (CR-TEG) Parameters. | Admission (ED) sample drawn upon ED admission and measured by citrated rapid thrombelastography (CR-TEG) clot strength measures by G value in kilodynes per square centimetre (kdyn/cm^2). | Posted | Median | Inter-Quartile Range | kdyn/cm^2 | post-intervention and upon ED arrival |
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| Post-Hoc | Admission (ED) Citrated Rapid Thrombelastography (CR-TEG) Parameters. | Admission (ED) sample drawn upon ED admission and measured by citrated rapid thrombelastography (CR-TEG) clot lysis 30 minutes after the maximal amplitude (MA) was finalized. | Posted | Median | Inter-Quartile Range | percentage of clot lysed at 30 minutes | post-intervention and upon ED arrival |
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| 12 |
| 75 |
| 34 |
| 75 |
| 5 |
| 75 |
| EG001 | Standard | If the patient is randomized to the standard arm, the patient will be given intravenous crystalloid fluid (normal saline) as the initial resuscitation fluid with 2 large bore IVs based on the current ATLS guidelines, the standard of care. Subsequent care will proceed per institutional, ATLS guided resuscitation with acute pRBC administration determined by hemodynamic response and additional blood component administration guided by rTEG and coagulation panel assessment in conjunction with clinical scenario. Crystalloid fluid (standard of care for resuscitation): Normal saline will be give to subjects in the standard arm as the current standard of care for an initial resuscitation fluid | 6 | 69 | 24 | 69 | 2 | 69 |
| DVTs and PEs | Vascular disorders | Systematic Assessment | Deep venous thrombosis (DVT), pulmonary embolism (PE) and pulmonary infarction (PI). |
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| Acute kidney injury (AKI) | Renal and urinary disorders | Systematic Assessment | Acute kidney injury (AKI), kidney failure and renal artery pseudoaneurysm. |
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| Acute respiratory distress syndrome (ARDS) | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Acute respiratory distress syndrome (ARDS) and lung failure |
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| Liver failure | Hepatobiliary disorders | Systematic Assessment | Liver failure and bile duct leak |
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| Cardiac | Cardiac disorders | Systematic Assessment | Organ failure, atrial fibrillation and ventricular tachycardia |
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| Adrenal insufficiency | Endocrine disorders | Systematic Assessment |
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| GI bleed | Gastrointestinal disorders | Systematic Assessment | Gastrointestinal bleeding and abdominal compartment syndrome |
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| Hematoma | Skin and subcutaneous tissue disorders | Systematic Assessment | Pre-sacral hematoma |
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| Hemorrhage | Surgical and medical procedures | Systematic Assessment | Delayed hemorrhage from surgical site and torn suture |
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| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Facial paralysis | Nervous system disorders | Systematic Assessment |
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Not provided
Not provided
| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006474 | Hemorrhagic Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D004638 | Emergency Treatment |
| D013812 | Therapeutics |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
| Unknown or Not Reported |
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| Coagulation factor VII (proconvertin) |
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| Coagulation factor VIII (antihemophilic factor) |
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| Coagulation factor IX (plasma thromboplastin comp) |
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| Coagulation factor XI (plasma thromboplastin ante) |
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| Coagulation factor II (prothrombin) |
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| Coagulation factor V (proaccelerin) |
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| Coagulation factor VII (proconvertin) |
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| Coagulation factor VIII (antihemophilic factor) |
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| Coagulation factor IX (plasma thromboplastin comp) |
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| Coagulation factor XI (plasma thromboplastin ante) |
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| Acute lung injury (ALI) within 6 hours post-transf |
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| MOF (Denver MOF score>3) |
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| Haemoglobin (Hb)<7g/dL within 6 hours |
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| Required red blood cell transf. within 24 hour |
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| Massive transf. (>=10 units of RBC or death/6 hrs |
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| Required plasma in first 24 h (not counting field) |
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| Required platelets in first 24 h |
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| Required cryoprecipitate in first 24 h |
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| Required tranexamic acid (TXA) in first 6 h |
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| Required factor VII infusion in first 24 h |
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| Acute lung injury (ALI) within 28 days |
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| Acute lung injury (ALI) within 6 h post-transfusio |
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| MOF (Denver MOF score>3) |
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| Haemoglobin (Hb)<7g/dL within 6 hours |
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| Required red blood cell transfusion within 24 h |
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| Massive transf. (>=10 units of RBC or death/6 hrs |
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| Required plasma in first 24 h (not counting field) |
|
| Required platelets in first 24 h |
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| Required cryoprecipitate in first 24 h |
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| Required tranexamic acid (TXA) in first 6 h |
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| Required factor VII infusion in first 24 h |
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| Platelets transfused in 24 h |
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| Cryoprecipitate transfused in 24 h |
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| 24-hour mortality |
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| Acute lung injury (ALI) within 28 days |
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| Acute lung injury (ALI) within 6 h post-transfusio |
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| MOF (Denver MOF score>3) |
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| Haemoglobin (Hb)<7g/dL within 6 hours |
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| Required red blood cell transfusion within 24 h |
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| Massive transf. (>=10 units of RBC or death/6 hrs |
|
| Required plasma in first 24 h (not counting field) |
|
| Required platelets in first 24 h |
|
| Required cryoprecipitate in first 24 h |
|
| Required tranexamic acid (TXA) in first 6 h |
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| Required factor VII infusion in first 24 h |
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| 24-hour mortality |
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| Acute lung injury (ALI) within 28 days |
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| Possible transfusion associated acute lung injury |
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| Required red blood cell transfusion within 72 h |
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| Massive transf. (>=10 units of RBC or death/6 hrs |
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| Required tranexamic acid (TXA) in first 6 h |
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| Required factor VII infusion in first 24 h |
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| Infections |
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| Thromboembolic events |
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| Non-infectious and non-thromboembolic events |
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| MOF (Denver MOF score>3) |
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| Organ failure (not MOF) |
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| Platelets transfused in 24 h |
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| Cryoprecipitate transfused in 24 h |
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| Platelets transfused in 24 h |
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| Cryoprecipitate transfused in 24 h |
|
| Time from ED admission to first unit of RBC |
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| Time to first plasma (including pre-admission) |
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| Time from admission to first platelet transfused |
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