Control of Major Bleeding After Trauma Study (COMBAT)
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ClinicalTrials.gov Identifier: NCT01838863 |
Recruitment Status :
Terminated
(Futility)
First Posted : April 24, 2013
Results First Posted : July 18, 2018
Last Update Posted : January 8, 2019
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Condition or disease | Intervention/treatment | Phase |
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Trauma Hemorrhagic Shock | Biological: Type AB plasma Drug: Crystalloid fluid (standard of care for resuscitation) | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 144 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Prospective, Randomized Comparison of Fresh Frozen Plasma Versus Standard Crystalloid Intravenous Fluid as Initial Resuscitation Fluid |
Actual Study Start Date : | April 7, 2014 |
Actual Primary Completion Date : | April 3, 2017 |
Actual Study Completion Date : | April 3, 2017 |

Arm | Intervention/treatment |
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Experimental: 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 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.
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Biological: Type AB plasma
The plasma is thawed and administered to subjects in the experimental (plasma) arm.
Other Name: Plasma frozen within 24 hours (FP24, PF24) |
Active Comparator: 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 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.
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Drug: 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
Other Name: Normal saline |
- Number of Participants That Died Within 28 Days Post Injury [ Time Frame: 28 days ]death within 28 days post injury (death of any cause except for death due to a second, clearly unrelated traumatic injury suffered after discharge)
- Composite Outcome of 28-day In-hospital Mortality and Postinjury Multiple Organ Failure (MOF) Incidence [ Time Frame: 28 days ]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).
- Admission Coagulopathy [ Time Frame: within 30 minutes of Emergency Department (ED) arrival ]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.
- Number of Participants With Admission Severe Coagulopathy [ Time Frame: within 30 minutes of Emergency Department (ED) arrival ]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.
- Admission Clot Strength [ Time Frame: within 30 minutes of ED arrival ]Admission clot strength will be measured by thrombelastography G-value upon ED arrival. Clot strength measured in kilodynes per square centimetre (kdyn/cm^2).
- Admission Acidosis [ Time Frame: within 30 minutes of ED arrival ]Admission acidosis measured by lactate upon ED arrival.
- Number of Participants With Admission Severe Acidosis [ Time Frame: within 30 minutes of ED arrival ]Admission severe acidosis measured by lactate>5 upon ED arrival.
- Admission Acidosis [ Time Frame: within 30 minutes of ED arrival ]Admission acidosis will be defined by base deficit (BD) upon ED arrival.
- Number of Participants With Admission Severe Acidosis [ Time Frame: within 30 minutes of ED arrival ]Admission severe acidosis will be defined by base deficit (BD>10) upon ED arrival.
- Baseline (Field) Coagulation Factor Levels [ Time Frame: after injury and prior to hospital arrival, at about 15 minutes after injury ]
defined as the first coagulation factor level obtained in the field prior to intervention
Coagulation Factor Reference Ranges
F2 F5 F7 F8 F9 F11
- % % % % % % 67.0 - 107.0 63.0 - 116.0 52.0 - 120.0 58.0 - 132.0 47.0 - 122.0 52.0 - 120.0
- Number of Participants With Abnormal Baseline (Field) Coagulation Factor XIII Level [ Time Frame: after injury prior to hospital arrival ]defined as abnormal coagulation factor XIII level obtained in the field prior to intervention
- Admission (First Arrival) Coagulation Factor Levels [ Time Frame: after injury prior to hospital arrival ]
defined as the first coagulation factor level obtained upon ED arrival
Coagulation Factor Reference Ranges
F2 F5 F7 F8 F9 F11
- % % % % % % 67.0 - 107.0 63.0 - 116.0 52.0 - 120.0 58.0 - 132.0 47.0 - 122.0 52.0 - 120.0
- Number of Participants With Abnormal Admission Coagulation Factor XIII (Fibrin-stabilizing Factor) Level [ Time Frame: within 30 minutes of Emergency Department (ED) arrival ]defined as the first abnormal factor XIII (fibrin-stabilizing factor) level obtained upon ED arrival
- Exploratory Analyses [ Time Frame: Hospital stay up to 28 days. ]Number of participants with 24-hour mortality, adverse outcome free days and transfusions
- Exploratory Analyses. [ Time Frame: Hospital stay up to 28 days. ]Adverse outcome free days
- Number of Participants With Mortality, Adverse Outcome-free Days and Transfusions in the Sub-group With Less Severe Hemorrhagic Shock [ Time Frame: Hospital stay up to 28 days. ]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
- Adverse Outcome-free Days in a Sub-group With Less Severe Hemorrhagic Shock [ Time Frame: Hospital stay up to 28 days. ]Adverse outcome-free days in the patients with initial systolic blood pressure (SBP) 71-90 mmHg and heart rate (HR) of 108 or greater
- Level of Haemoglobin (Hb) in a Sub-group With Less Severe Hemorrhagic Shock [ Time Frame: Hospital stay up to 28 days. ]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
- Blood Product Transfusion in a Sub-group With Less Severe Hemorrhagic Shock [ Time Frame: Hospital stay up to 28 days. ]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
- Time to Admission and First Blood Transfusion in a Sub-group With Less Severe Hemorrhagic Shock [ Time Frame: Hospital stay up to 28 days. ]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
- Number of Participants With Mortality, Adverse Outcome-free Days and Transfusions in a Sub-group With Severe Hemorrhagic Shock [ Time Frame: Hospital stay up to 28 days. ]Mortality, adverse outcome-free days and transfusions in the patients with initial systolic blood pressure (SBP) <=70 mmHg
- Number of Adverse Outcome Free Days in a Sub-group With Severe Hemorrhagic Shock [ Time Frame: Hospital stay up to 28 days. ]Adverse outcome-free days in the patients with initial systolic blood pressure (SBP) <=70 mmHg
- Number of Participants in a Sub-group With no Severe Traumatic Brain Injury (TBI) [ Time Frame: Hospital stay up to 28 days. ]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.
- Exploratory Analyses in a Sub-group With Severe Traumatic Brain Injury (TBI) [ Time Frame: Hospital stay up to 28 days. ]Number of participants with 28-day mortality. Traumatic brain injury (TBI) is defined as Abbreviated Injury Score (AIS) for Head/Neck >=3.
- Severe Adverse Events (SAE) [ Time Frame: Hospital stay up to day 28 ]Number of participants with severe adverse events (SAE)
- Haemoglobin (Hb) Level in a Sub-group With Severe Hemorrhagic Shock [ Time Frame: Hospital stay up to 28 days. ]Haemoglobin (Hb) level in the patients with initial systolic blood pressure (SBP) <=70 mmHg
- Blood Product Transfusion in a Sub-group With Severe Hemorrhagic Shock [ Time Frame: Hospital stay up to 28 days. ]Number of blood products transfused in units in the patients with initial systolic blood pressure (SBP) <=70 mmHg
- Time to Admission and First Blood Transfusion in a Sub-group With Severe Hemorrhagic Shock [ Time Frame: Hospital stay up to 28 days. ]Time to Admission and First Blood Transfusion in the patients with initial systolic blood pressure (SBP) <=70 mmHg
- Haemoglobin (Hb) Level [ Time Frame: Hospital stay up to 28 days. ]Haemoglobin (Hb) level in g/dL units.
- Number of Blood Products Transfused. [ Time Frame: Hospital stay up to 28 days. ]Number of blood products transfused in units.
- Time to Admission and First Blood Transfusion [ Time Frame: Hospital stay up to 28 days. ]Time to admission and first blood product transfusion in minutes.

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age>=18 years
- Acutely injured
- SBP<70 mmHg or SBP 71-90 mmHg with heart rate (HR)>108 beats per minute.
Exclusion Criteria:
- Visibly or verbally reported pregnant women
- known prisoners
- unsalvageable injuries (defined as asystolic or cardiopulmonary resuscitation prior to randomization)
- known objection to blood products
- the patient has an opt-out bracelet or, necklace or wallet card
- a family member present at the scene objects to the patient's enrollment in research.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01838863
United States, Colorado | |
Denver Health Medical Center | |
Denver, Colorado, United States, 80204 |
Principal Investigator: | Ernest E Moore, MD | Denver Health Medical Center |
Documents provided by Ernest E. Moore, MD, Denver Health and Hospital Authority:
Responsible Party: | Ernest E. Moore, MD, Professor and Vice Chair, Department of Surgery, Denver Health and Hospital Authority |
ClinicalTrials.gov Identifier: | NCT01838863 |
Other Study ID Numbers: |
COMIRB# 12-1349 W81XWH1220028 ( Other Grant/Funding Number: Department of Defense TATRC ) |
First Posted: | April 24, 2013 Key Record Dates |
Results First Posted: | July 18, 2018 |
Last Update Posted: | January 8, 2019 |
Last Verified: | December 2018 |
coagulopathy hemorrhagic shock plasma blood product transfusion |
Shock, Hemorrhagic Shock Pathologic Processes Hemorrhage |