Denver Health has conducted the Control of Major Bleeding After Trauma (COMBAT) clinical research study, which aims to improve trauma care for all patients. The study began in April 2014 and concluded in March of 2017.
The COMBAT study conducted by Denver Health (DH), in collaboration with the University of Colorado Denver, was sponsored by the Department of Defense’s Telemedicine & Advanced Technology Research Center (TATRC). Dr. Ernest E Moore was the primary investigator (PI) of this trial.
Study Results
From April 1, 2014, to March 31, 2017, DH paramedics randomly assigned 144 patients to study groups. The as-treated analysis included 125 eligible patients, 65 received plasma and 60 received saline. Median age was 33 years (IQR 25–47) and median New Injury Severity Score was 27 (10–38). NISS ranges from 1 to 75 with higher score indicating more severe injury. 70 (56%) patients required blood transfusions within 6 h of injury. The study (who received plasma) and control (who received standard of care saline solution) groups were similar at baseline and had similar transport times (plasma group median 19 min [IQR 16–23] vs control 16 min [14–22]). The groups did not differ in mortality at 28 days (15% in the plasma group vs 10% in the control group, p=0∙37). In the intention-to-treat analysis, we saw no significant differences between the groups in safety outcomes and adverse events. Due to the consistent lack of differences in the analyses, the study was stopped for futility after 144 of 150 planned enrolments.
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Interpretation
The COMBAT study was a component of TATRC’s investigation to determine the effects of plasma first resuscitation in the prehospital phase of care for severely injured patients. DH represented the ground ambulance arm of the study, while the University of Pittsburgh conducted the air ambulance part (PAMPer study). The air ambulance (helicopter) trial demonstrated a survival benefit of prehospital plasma in fundamentally the same study population as COMBAT, but with longer transport times to the hospital. In fact, analyzing the combined COMBAT and PAMPer studies indicated a survival benefit for transport times > 20 min. However with transport times < 20 min, typical for the COMBAT study with rapid ground rescue to an urban level 1 trauma center, prehospital plasma did not improve survival. Thus, plasma administration may be beneficial in settings with longer transport times, but the financial burden and potential risks would not be justified in an urban environment with short distances to mature trauma centers.
Dr. Moore concluded “the COMBAT study was a remarkable achievement for DH, illustrated integrated team care with exceptional efforts by our EMS team in the field. While our patients did not benefit directly from this study, the critical information derived from this work will improve the outcome for future patients throughout the world”.
Background
Bleeding is the most avoidable cause of death in trauma patients. Up to one-third (1/3) of severely injured trauma patients lose the ability to form clots and as a result die from rapid and sudden blood loss. These patients need transfusion of red blood cells (RBC) and plasma which help the body to slow bleeding and restore blood volume. Plasma occurs naturally in whole blood and contains the proteins needed to form clots. When an individual experiences a severe injury, the plasma can become lost due to massive bleeding. This decreases the patient’s ability to form clots and ultimately stop their bleeding. Research suggests that administering plasma earlier to trauma patients who have serious and life-threatening bleeding improves their chances of survival. The plasma product being used in our study was AB-FP24, a universally compatible blood product. It is similar to fresh, frozen plasma but may have slightly lower levels of certain clotting proteins.
Study Design
Severely injured patients in presumed hemorrhagic (acute blood loss) shock were enrolled in the study at the scene of injury based on their vital signs (combination of blood pressure and heart rate). Once enrolled, patients were randomly chosen to receive either the control treatment, normal saline, which is the current standard of care, or the experimental treatment (AB-FP24 plasma) as the first treatment fluid. After the first treatment fluid, both groups were returned to the current standard of care. Blood samples and clinical information are collected throughout the hospital stay up to 28 days after injury.
The Objective
To determine if administering plasma to severely injured trauma patients during ambulance transport will reduce bleeding, and ultimately survival, versus plasma administered after arrival to the hospital. The AB-FP24 plasma contains special proteins and clotting factors. This helps slow bleeding and increase blood volume, which ultimately may improve patient survival.
The Current Standard of Care
Guidelines by the American College of Surgeons course of Advanced Trauma Life Support recommend giving sterile saline (salt water) first in the veins after injury in order to restore blood volume. If a patient continues to have signs of major blood loss after the saline is provided, transfusion of RBC and AB-FP24 plasma is started.
Study Location
Patients transported by Denver Health Paramedics to Denver Health were eligible to be a part of the study.
Emergency Research
This study is different from other research studies because it involves the enrollment of patients who cannot give consent to the treatment being given due to the nature of their injuries. Regulations created by the federal government (21 Code of Federal Regulations §50.24) state the conditions under which an exception from informed consent in emergency situations is allowed. This enables important research to be done when consent is not possible due to the nature and extent of a patient’s injuries.
In order to conduct this study without initial consent, Denver Health informed and consulted with the public through community outreach in the months leading up to the study’s approval and start date. The public was informed that unless they have visible OPT OUT items, which are provided by Denver Health at no cost, subjects/patients may be enrolled in the study without their consent.
These free OPT OUT items were Denver Health specific bracelets or dog tag necklaces that specify “NO COMBAT STUDY." The research team realized this OPT OUT method was not perfect, as the item worn by the patient may be lost as a result of the mechanism of their traumatic injury. Due to this risk, we recommended patients wear both items (the bracelet and the dog tag necklace) to maximize the ability for the research team to understand the patient’s wishes.
Once enrolled, researchers contacted the legally authorized representative (LAR) or proxy decision maker (PDM) to inform them of the research study and obtain consent for further blood samples and data collection. The LAR or PDM had the option to refuse further blood and data collection or withdraw from the research study in which case all the data for the patient will be destroyed.
Research in the emergent setting is very challenging due to the incomplete knowledge of the patients’ condition at the time of enrollment, particularly when the patient is in shock. Conducting these studies in the prehospital phase of care is further compounded by suboptimal conditions to evaluate the patient. The COMBAT study was a landmark achievement in illustrating that this research can be performed safely under these challenging circumstances.
About Denver Health
Denver Health is a comprehensive, integrated organization providing level one care for all, regardless of ability to pay. Denver Health provides medical care to nearly one-third of Denver’s population, proudly serving as the city’s safety-net hospital and providing preventative, primary and acute care services.
About Denver Health Foundation
The Denver Health Foundation has been the fundraising arm for Denver Health and Hospital Authority since 1998. We secure private funds to support the hospital, Denver’s only integrated health care system, in its mission to sustain and advance the health and well-being of Denver and the Rocky Mountain region.
About TATRC
The Telemedicine & Advanced Technology Research Center (TATRC) fosters research on health informatics, telemedicine/m-Health, medical training systems and computational biology to address gaps in DoD medical research programs and military healthcare. TATRC is engaged in essential medical research focused on advanced medical technologies and is dedicated to bringing innovative telehealth solutions to the Warfighter and the Military Health System.
