TraumaPhase 2COMBATNCT01838863
Control of Major Bleeding After Trauma Study
A Phase 2 study testing Type AB plasma in people with Trauma and Hemorrhagic Shock, run by Denver Health and Hospital Authority at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Trauma, Hemorrhagic Shock
- What is being tested?
- Type AB plasma
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 144 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Apr 2014to 3 Apr 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age>=18 years
- Acutely injured
- SBP<70 mmHg or SBP 71-90 mmHg with heart rate (HR)>108 beats per minute.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Denver Health Medical Center
Denver, Colorado, 80204
About this study
Official title: A Prospective, Randomized Comparison of Fresh Frozen Plasma Versus Standard Crystalloid Intravenous Fluid as Initial Resuscitation Fluid
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.
Read the detailed description
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.
- Conditions
- Trauma, Hemorrhagic Shock
- Being tested
- Type AB plasma, Crystalloid fluid (standard of care for resuscitation)
- Keywords
- coagulopathy, hemorrhagic shock, plasma, blood product transfusion
- Medical subject headings
- Wounds and Injuries, Shock, Hemorrhagic, Hemostatic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Type AB plasmaBiological
Also called Plasma frozen within 24 hours (FP24, PF24)
The plasma is thawed and administered to subjects in the experimental (plasma) arm.
Crystalloid fluid (standard of care for resuscitation)Drug
Also called Normal saline
Normal saline will be give to subjects in the standard arm as the current standard of care for an initial resuscitation fluid
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Type AB plasma |
| 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. Receives: Drug: Crystalloid fluid (standard of care for resuscitation) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 28 days
Secondary outcomes (8)
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).
Measured: 28 days
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.
Measured: 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.
Measured: 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).
Measured: within 30 minutes of ED arrival
Admission Acidosis
Admission acidosis measured by lactate upon ED arrival.
Measured: within 30 minutes of ED arrival
Number of Participants With Admission Severe Acidosis
Admission severe acidosis measured by lactate>5 upon ED arrival.
Measured: within 30 minutes of ED arrival
Admission Acidosis
Admission acidosis will be defined by base deficit (BD) upon ED arrival.
Measured: 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.
Measured: within 30 minutes of ED arrival
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2013 (estimated)
- Study start7 Apr 2014
- Primary completion3 Apr 2017
- Study completion3 Apr 2017
Why it stopped: Futility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for TraumaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 144 participants (actual)
Sponsor and investigators
- Lead sponsor
- Denver Health and Hospital Authority
- Sponsor type
- University, hospital or other
- Collaborators
- U.S. Army Medical Research and Development Command, University of Colorado, Denver
- Responsible party
- Principal investigator, Ernest E. Moore, MD, Denver Health and Hospital Authority
- Investigators
- Ernest E Moore, MD, Principal investigator, Denver Health Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01838863
- Sponsor's protocol ID
- COMIRB# 12-1349
- Other IDs
- W81XWH1220028
- Acronym
- COMBAT
- Status last verified
- Dec 2018
- First submitted
- 22 Apr 2013
- Last updated
- 8 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Boateng NKK, Wimberley R, Rose J, D'Alessandro A, Cohen M, Moore E, Schmitt L, Poole L, Luyendyk J, Hansen K. Tissue transglutaminase drives fibrin beta-chain cross-linking: a novel fibrin modification observed in patients with trauma. Blood. 2026 Jan 1;147(1):87-92. doi: 10.1182/blood.2025029458.
PubMed 40983029DeBot 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.
PubMed 40766812Pusateri 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.
PubMed 31851290Moore 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.
PubMed 30032977Reynolds 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.
PubMed 26220293Chapman 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.
PubMed 25784527
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized Comparison of Fresh Frozen Plasma Versus Standard Crystalloid Intravenous Fluid as Initial Resuscitation Fluid
- ClinicalTrials.gov ID
- NCT01838863
- Acronym / sponsor ID
- COMBAT / COMIRB# 12-1349
- Conditions
- Trauma, Hemorrhagic Shock
- Keywords
- coagulopathy, hemorrhagic shock, plasma, blood product transfusion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Futility
- Enrolment
- 144 participants (actual)
- Lead sponsor
- Denver Health and Hospital AuthorityUniversity, hospital or other
- Collaborators
- U.S. Army Medical Research and Development Command, University of Colorado, Denver
- Study start
- 7 Apr 2014 (actual)
- Primary completion
- 3 Apr 2017 (actual)
- Study completion
- 3 Apr 2017 (actual)
- First posted
- 24 Apr 2013 (estimated)
- Results
- Posted 18 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Plasma | Experimental | Biological: Type AB plasmaIf 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 | Drug: Crystalloid fluid (standard of care for resuscitation)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age>=18 years
- Acutely injured
- SBP<70 mmHg or SBP 71-90 mmHg with heart rate (HR)>108 beats per minute.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Type AB plasmaAlso: Plasma frozen within 24 hours (FP24, PF24)The plasma is thawed and administered to subjects in the experimental (plasma) arm. | Biological | Plasma |
| Crystalloid fluid (standard of care for resuscitation)Also: Normal salineNormal saline will be give to subjects in the standard arm as the current standard of care for an initial resuscitation fluid | Drug | Standard |
Primary outcome
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)
8 secondary outcomes
Composite Outcome of 28-day In-hospital Mortality and Postinjury Multiple Organ Failure (MOF) Incidence
Time frame: 28 days
Admission Coagulopathy
Time frame: within 30 minutes of Emergency Department (ED) arrival
Number of Participants With Admission Severe Coagulopathy
Time frame: within 30 minutes of Emergency Department (ED) arrival
Admission Clot Strength
Time frame: within 30 minutes of ED arrival
Admission Acidosis
Time frame: within 30 minutes of ED arrival
Number of Participants With Admission Severe Acidosis
Time frame: within 30 minutes of ED arrival
Admission Acidosis
Time frame: within 30 minutes of ED arrival
Number of Participants With Admission Severe Acidosis
Time frame: within 30 minutes of ED arrival
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40983029Boateng NKK, Wimberley R, Rose J, D'Alessandro A, Cohen M, Moore E, Schmitt L, Poole L, Luyendyk J, Hansen K. Tissue transglutaminase drives fibrin beta-chain cross-linking: a novel fibrin modification observed in patients with trauma. Blood. 2026 Jan 1;147(1):87-92. doi: 10.1182/blood.2025029458.
- Derived from this study: PubMed 40766812DeBot 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.
- Derived from this study: PubMed 31851290Pusateri 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.
- Derived from this study: PubMed 30032977Moore 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.
- Derived from this study: PubMed 26220293Reynolds 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.
- Derived from this study: PubMed 25784527Chapman 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ernest E Moore, MD principal investigator
Denver Health Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Type AB plasma in people with Trauma and Hemorrhagic Shock, run by Denver Health and Hospital Authority at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants That Died Within 28 Days Post Injury (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01838863, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2019.