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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 : July 18, 2018
Sponsor:
Collaborators:
U.S. Army Medical Research and Materiel Command
University of Colorado, Denver
Information provided by (Responsible Party):
Ernest E. Moore, MD, Denver Health and Hospital Authority

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions: Trauma
Hemorrhagic Shock
Interventions: Biological: Type AB plasma
Drug: Crystalloid fluid (standard of care for resuscitation)

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
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.

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


Participant Flow:   Overall Study
    Plasma   Standard
STARTED   75   69 
COMPLETED   65   60 
NOT COMPLETED   10   9 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.

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

Total Total of all reporting groups

Baseline Measures
   Plasma   Standard   Total 
Overall Participants Analyzed 
[Units: Participants]
 65   60   125 
Age 
[Units: Years]
Median (Inter-Quartile Range)
     
Participants Analyzed   65   60   125 
   33 
 (25 to 51) 
 32.5 
 (25.8 to 42) 
 33 
 (25 to 47) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Participants Analyzed   65   60   125 
Female      13  20.0%      9  15.0%      22  17.6% 
Male      52  80.0%      51  85.0%      103  82.4% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
     
Participants Analyzed   65   60   125 
Hispanic or Latino      34  52.3%      39  65.0%      73  58.4% 
Not Hispanic or Latino      31  47.7%      21  35.0%      52  41.6% 
Unknown or Not Reported      0   0.0%      0   0.0%      0   0.0% 
Region of Enrollment 
[Units: Participants]
     
United States       
Participants Analyzed   65   60   125 
United States   65   60   125 
Body Mass Index (BMI) 
[Units: Kg/m^2]
Median (Inter-Quartile Range)
     
Participants Analyzed   65   60   125 
   27.1 
 (23.9 to 30.5) 
 26.1 
 (23.2 to 29.4) 
 26.7 
 (23.4 to 30.5) 
Comorbidities [1] 
[Units: Participants]
Count of Participants
     
Participants Analyzed   65   60   125 
   10   8   18 
[1] Presence of one or more additional diseases or disorders co-occurring in trauma patient.
Blunt injury mechanism [1] 
[Units: Participants]
Count of Participants
     
Participants Analyzed   65   60   125 
   30   32   62 
[1] Blunt force trauma is an injury that occurs when an object hits or strikes a part of the body.
New Injury Severity Scale (NISS) [1] 
[Units: Units on a scale]
Median (Inter-Quartile Range)
     
Participants Analyzed   65   60   125 
   27 
 (10 to 41) 
 27 
 (11.8 to 35) 
 27 
 (10 to 38) 
[1] 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.
Maximal Abbreviated Injury Score (AIS) for head and neck [1] 
[Units: Units on a scale]
Median (Inter-Quartile Range)
     
Participants Analyzed   65   60   125 
   0 
 (0 to 2) 
 0 
 (0 to 2.3) 
 0 
 (0 to 2) 
[1] 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.
Traumatic Brain Injury (TBI) defined as AIS head >=3 
[Units: Participants]
Count of Participants
     
Participants Analyzed   65   60   125 
   15   13   28 
Maximal Abbreviated Injury Score (AIS) chest [1] 
[Units: Units on a scale]
Median (Inter-Quartile Range)
     
Participants Analyzed   65   60   125 
   1 
 (0 to 3) 
 3 
 (0 to 3) 
 2 
 (0 to 3) 
[1] 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.
Maximal Abbreviated Injury Score (AIS) abdomen and pelvis [1] 
[Units: Units on a scale]
Median (Inter-Quartile Range)
     
Participants Analyzed   65   60   125 
   0 
 (0 to 3) 
 0 
 (0 to 3) 
 0 
 (0 to 3) 
[1] 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.
Maximal Abbreviated Injury Score (AIS) extremities [1] 
[Units: Units on a scale]
Median (Inter-Quartile Range)
     
Participants Analyzed   65   60   125 
   1 
 (0 to 3) 
 0 
 (0 to 2) 
 0 
 (0 to 2) 
[1] 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.
Heart rate (HR) in the field 
[Units: Beats per minute (BPM)]
Median (Inter-Quartile Range)
     
Participants Analyzed   65   60   125 
   110 
 (98 to 120) 
 112 
 (100 to 120) 
 110 
 (100 to 120) 
Systolic blood pressure (SBP) in the field 
[Units: mmHg]
Median (Inter-Quartile Range)
     
Participants Analyzed   65   60   125 
   64 
 (50 to 80) 
 70 
 (58 to 80) 
 68 
 (50 to 80) 
Severe shock defined as systolic blood pressure (SBP) in the field <=70mmHg 
[Units: Participants]
Count of Participants
     
Participants Analyzed   65   60   125 
   44   33   77 
Body temperature in the field [1] 
[Units: Degrees Celsius]
Median (Inter-Quartile Range)
     
Participants Analyzed   38   29   67 
   36 
 (34.8 to 36.6) 
 36 
 (35.1 to 37) 
 36 
 (34.9 to 36.9) 
[1] 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).
Glasgow Coma Scale (GCS) in the field [1] 
[Units: Units on a scale]
Median (Inter-Quartile Range)
     
Participants Analyzed   65   60   125 
   14 
 (7 to 15) 
 14 
 (8 to 15) 
 14 
 (8 to 15) 
[1] 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.
Haemoglobin (Hb) in the field [1] 
[Units: g/dL]
Median (Inter-Quartile Range)
     
Participants Analyzed   32   27   59 
   15.1 
 (13.6 to 15.7) 
 14.2 
 (13.2 to 15.9) 
 14.6 
 (13.2 to 15.7) 
[1] 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).
Platelet count in the field [1] 
[Units: 1000 cells/microL]
Median (Inter-Quartile Range)
     
Participants Analyzed   26   20   46 
   300.5 
 (251.8 to 353.2) 
 273.5 
 (219 to 331) 
 287.5 
 (245.5 to 345.8) 
[1] 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).
Fibrinogen in the field [1] 
[Units: mg/dL]
Median (Inter-Quartile Range)
     
Participants Analyzed   35   29   64 
   253 
 (226 to 308) 
 278 
 (250 to 331) 
 268 
 (228.5 to 322.5) 
[1] 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).
International normalized ratio (INR) in the field [1] 
[Units: Ratio]
Median (Inter-Quartile Range)
     
Participants Analyzed   36   29   65 
   1.1 
 (1 to 1.2) 
 1.1 
 (1 to 1.1) 
 1.1 
 (1 to 1.2) 
[1] 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.
International normalized ratio (INR) in the field >=1.3 [1] 
[Units: Participants]
Count of Participants
     
Participants Analyzed   36   29   65 
   2   2   4 
[1] 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).
Partial thromboplastin time (PTT) in the field [1] 
[Units: Seconds]
Median (Inter-Quartile Range)
     
Participants Analyzed   36   28   64 
   27.1 
 (25 to 30) 
 26.9 
 (24.6 to 30.4) 
 27.1 
 (24.7 to 30.4) 
[1] 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).


  Outcome Measures

1.  Primary:   Number of Participants That Died Within 28 Days Post Injury   [ Time Frame: 28 days ]

2.  Secondary:   Composite Outcome of 28-day In-hospital Mortality and Postinjury Multiple Organ Failure (MOF) Incidence   [ Time Frame: 28 days ]

3.  Secondary:   Admission Coagulopathy   [ Time Frame: within 30 minutes of Emergency Department (ED) arrival ]

4.  Secondary:   Number of Participants With Admission Severe Coagulopathy   [ Time Frame: within 30 minutes of Emergency Department (ED) arrival ]

5.  Secondary:   Admission Clot Strength   [ Time Frame: within 30 minutes of ED arrival ]

6.  Secondary:   Admission Acidosis   [ Time Frame: within 30 minutes of ED arrival ]

7.  Secondary:   Number of Participants With Admission Severe Acidosis   [ Time Frame: within 30 minutes of ED arrival ]

8.  Secondary:   Admission Acidosis   [ Time Frame: within 30 minutes of ED arrival ]

9.  Secondary:   Number of Participants With Admission Severe Acidosis   [ Time Frame: within 30 minutes of ED arrival ]

10.  Other Pre-specified:   Baseline (Field) Coagulation Factor Levels   [ Time Frame: after injury and prior to hospital arrival, at about 15 minutes after injury ]

11.  Other Pre-specified:   Number of Participants With Abnormal Baseline (Field) Coagulation Factor XIII Level   [ Time Frame: after injury prior to hospital arrival ]

12.  Other Pre-specified:   Admission (First Arrival) Coagulation Factor Levels   [ Time Frame: after injury prior to hospital arrival ]

13.  Other Pre-specified:   Number of Participants With Abnormal Admission Coagulation Factor XIII (Fibrin-stabilizing Factor) Level   [ Time Frame: within 30 minutes of Emergency Department (ED) arrival ]

14.  Other Pre-specified:   Exploratory Analyses   [ Time Frame: Hospital stay up to 28 days. ]

15.  Other Pre-specified:   Exploratory Analyses.   [ Time Frame: Hospital stay up to 28 days. ]

16.  Other Pre-specified:   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. ]

17.  Other Pre-specified:   Adverse Outcome-free Days in a Sub-group With Less Severe Hemorrhagic Shock   [ Time Frame: Hospital stay up to 28 days. ]

18.  Other Pre-specified:   Level of Haemoglobin (Hb) in a Sub-group With Less Severe Hemorrhagic Shock   [ Time Frame: Hospital stay up to 28 days. ]

19.  Other Pre-specified:   Blood Product Transfusion in a Sub-group With Less Severe Hemorrhagic Shock   [ Time Frame: Hospital stay up to 28 days. ]

20.  Other Pre-specified:   Time to Admission and First Blood Transfusion in a Sub-group With Less Severe Hemorrhagic Shock   [ Time Frame: Hospital stay up to 28 days. ]

21.  Other Pre-specified:   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. ]

22.  Other Pre-specified:   Number of Adverse Outcome Free Days in a Sub-group With Severe Hemorrhagic Shock   [ Time Frame: Hospital stay up to 28 days. ]

23.  Other Pre-specified:   Number of Participants in a Sub-group With no Severe Traumatic Brain Injury (TBI)   [ Time Frame: Hospital stay up to 28 days. ]

24.  Other Pre-specified:   Exploratory Analyses in a Sub-group With Severe Traumatic Brain Injury (TBI)   [ Time Frame: Hospital stay up to 28 days. ]

25.  Other Pre-specified:   Severe Adverse Events (SAE)   [ Time Frame: Hospital stay up to day 28 ]

26.  Other Pre-specified:   Haemoglobin (Hb) Level in a Sub-group With Severe Hemorrhagic Shock   [ Time Frame: Hospital stay up to 28 days. ]

27.  Other Pre-specified:   Blood Product Transfusion in a Sub-group With Severe Hemorrhagic Shock   [ Time Frame: Hospital stay up to 28 days. ]

28.  Other Pre-specified:   Time to Admission and First Blood Transfusion in a Sub-group With Severe Hemorrhagic Shock   [ Time Frame: Hospital stay up to 28 days. ]

29.  Other Pre-specified:   Haemoglobin (Hb) Level   [ Time Frame: Hospital stay up to 28 days. ]

30.  Other Pre-specified:   Number of Blood Products Transfused.   [ Time Frame: Hospital stay up to 28 days. ]

31.  Other Pre-specified:   Time to Admission and First Blood Transfusion   [ Time Frame: Hospital stay up to 28 days. ]

32.  Post-Hoc:   Baseline (Field) Citrated Rapid Thrombelastography (CR-TEG) Parameters.   [ Time Frame: after injury and prior to hospital arrival, at about 15 minutes after injury ]

33.  Post-Hoc:   Admission (ED) Citrated Rapid Thrombelastography (CR-TEG) Parameters.   [ Time Frame: post-intervention and upon ED arrival ]

34.  Post-Hoc:   Baseline (Field) Citrated Rapid Thrombelastography (CR-TEG) Parameters.   [ Time Frame: after injury and prior to hospital arrival, at about 15 minutes after injury ]

35.  Post-Hoc:   Baseline (Field) Citrated Rapid Thrombelastography (CR-TEG) Parameters.   [ Time Frame: after injury and prior to hospital arrival, at about 15 minutes after injury ]

36.  Post-Hoc:   Baseline (Field) Citrated Rapid Thrombelastography (CR-TEG) Parameters.   [ Time Frame: after injury and prior to hospital arrival, at about 15 minutes after injury ]

37.  Post-Hoc:   Baseline (Field) Citrated Rapid Thrombelastography (CR-TEG) Parameters.   [ Time Frame: after injury and prior to hospital arrival, at about 15 minutes after injury ]

38.  Post-Hoc:   Admission (ED) Citrated Rapid Thrombelastography (CR-TEG) Parameters.   [ Time Frame: post-intervention and upon ED arrival ]

39.  Post-Hoc:   Admission (ED) Citrated Rapid Thrombelastography (CR-TEG) Parameters.   [ Time Frame: post-intervention and upon ED arrival ]

40.  Post-Hoc:   Admission (ED) Citrated Rapid Thrombelastography (CR-TEG) Parameters.   [ Time Frame: post-intervention and upon ED arrival ]

41.  Post-Hoc:   Admission (ED) Citrated Rapid Thrombelastography (CR-TEG) Parameters.   [ Time Frame: post-intervention and upon ED arrival ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Dr. Ernest E. Moore
Organization: Denver Health Medical Center
phone: 303.602.1820
e-mail: Ernest.Moore@dhha.org


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Ernest E. Moore, MD, Denver Health and Hospital Authority
ClinicalTrials.gov Identifier: NCT01838863     History of Changes
Other Study ID Numbers: COMIRB# 12-1349
W81XWH1220028 ( Other Grant/Funding Number: Department of Defense TATRC )
First Submitted: April 22, 2013
First Posted: April 24, 2013
Results First Submitted: March 22, 2018
Results First Posted: July 18, 2018
Last Update Posted: July 18, 2018