Shock, Whole Blood, and Assessment of TBI S.W.A.T. (LITES TO 2)

Background

The LITES Network is an operational trauma center consortium which has the expertise, track
record and confirmed capabilities to conduct prospective, multicenter, injury care and
outcomes research of relevance to the Department of Defense (DoD). Clinical trials from the
point of injury in the prehospital arena through the trauma bay and operating theatre, thru
ICU and beyond discharge are feasible and critical to the overall goals of the network. Novel
capabilities include prehospital point of care testing for shock severity and sequential
coagulopathy measurements. The network and leadership have a track record of Exception From
Informed Consent (EFIC) trials and expertise with those injury subtypes including traumatic
brain injury, hemorrhagic shock and coagulopathy of trauma, poly-trauma and severe extremity
trauma. In addition to the track record and proven capabilities, the LITES Network uses a
central IRB and efficient methods to minimize time, resources, cost and regulatory burdens
and improve recruitment, consent rates and ease of data acquisition to promote successful
execution of those task orders provided to the network from the DoD.

Traumatic injury represents an incredible health care burden in the United States and
worldwide.1 Hemorrhage and Traumatic Brain Injury (TBI) are responsible for the largest
proportion of all trauma-related deaths. Despite advances in trauma resuscitation and brain
injury management, few therapeutic interventions are available to reduce the downstream
morbidity and mortality attributable to these injury patterns. It is the poly-trauma patient
who suffers both hemorrhagic shock and traumatic brain injury where a paucity of evidence
exists to direct treatment, limiting the development of beneficial trauma practice
guidelines.

Ongoing traumatic blood loss is complicated by trauma induced coagulopathy which results in
further unbridled hemorrhage and resultant shock and organ dysfunction. Secondary to
increasing evidence and knowledge, in-hospital resuscitation of traumatic hemorrhage has
changed over the past decade to reduce the coagulopathic response to ischemia and tissue
injury. The underlying principle of current resuscitation practice focuses on preventing or
reversing the effects of coagulopathy with the early use of a balanced component transfusion
strategy (1:1:1 - plasma: packed red blood cells: platelets). This reconstituted strategy has
also been coined 'whole blood-like' resuscitation despite being inferior from a compositional
standpoint relative to Whole Blood (WB). The use of WB was historically the gold standard for
treating hemorrhagic shock during World War I and II, prior to sweeping changes in blood
banking practice. The use of WB for early trauma resuscitation is making a resurgence,
primarily based upon the military experience and has been touted as the 'essential next step'
in the evolution of trauma resuscitation. Despite its historical and more recent use, little
is known regarding WB's benefit relative to the 'current practice' ratio based blood
component therapy in the acutely injured patients and even less is known regarding its
effects in patients with TBI.

Permissive hypotension has been thought to improve outcome in injured patients with
hemorrhagic shock in the prehospital and acute resuscitation phase of treatment allowing for
the ability to obtain surgical control of bleeding while minimizing ongoing hemorrhage.
Despite this benefit for hemorrhagic shock patients, hypotension has been consistently shown
to be associated with worse outcomes in patients with TBI. Interestingly, newer animal data
suggests permissive hypotension may be beneficial in a swine TBI model.The majority of prior,
high level TBI trials have excluded patients with concomitant hemorrhagic shock. Prospective
evidence and long term TBI outcome data are lacking for these complex poly-trauma patients
and the most appropriate blood pressure and most efficacious resuscitation target for
patients with TBI and acute hemorrhage remain poorly characterized.

Hypothesis #1A: Whole blood resuscitation will be associated with a lower 4 hour mortality in
poly-trauma patients as compared to those resuscitated with component therapy.

Hypothesis #1B: Whole blood resuscitation will be associated with a lower incidence of 12
hour and 24 hour mortality, a lower incidence of death from exsanguination, incidence of MOF,
nosocomial infection, improved transfusion ratios, lower overall blood transfusion
requirements and shorter time to hemostasis as compared to those resuscitated with component
therapy.

Hypothesis #1C: Whole blood resuscitation will be associated with an improved Glasgow Outcome
Score-Extended at 6 months post injury as compared to those resuscitated with component
therapy in patients with traumatic brain injury.

Hypothesis #2A: A nadir prehospital and acute phase resuscitation systolic blood pressure
greater than or equal to 120 mmHg will be associated with improved traumatic brain injury
outcomes at discharge and at 6 months.

Hypothesis #2B: The magnitude of the dose depth curve of systolic blood pressure during the
prehospital and acute phase resuscitation will be associated with neurological outcome
differences at discharge and at 6 months following traumatic brain injury.

Research Design and Methods

Study Design: The LITES Network will perform a multicenter, prospective, observational cohort
study over a 4 year period to determine the impact of whole blood resuscitation in trauma
patients with hemorrhagic shock at risk of large volume resuscitation with and without TBI.
Early whole blood resuscitation will be compared to standard component resuscitation. The
study will also further characterize blood pressure and resuscitation endpoints in
poly-trauma patients with traumatic brain injury. Six trauma sites with appropriate
characteristics will be selected from 12 network sites across the country.

Study Setting: The study will be performed utilizing busy level I trauma centers from within
the LITES Network located across the country, at sites where either whole blood has currently
been incorporated into standard of care or where component blood transfusion is being
utilized for patients in hemorrhagic shock at risk for large volume resuscitation. Due to the
paucity of trauma centers who are currently utilizing whole blood for trauma patients as
standard of care, the potential to incorporate sites outside of the current LITES Network may
be required over time.

Inclusion Criteria:

Patients with blunt or penetrating injury who meet the following criteria: 1, 2, and 3

1. Has 2 or more of any of the following:

1. Hypotension (systolic blood pressure ≤ 90 mmHg) in the prehospital or emergency
department setting,

2. Penetrating mechanism,

3. Positive FAST abdominal ultrasound,

4. Heart Rate ≥ 120 in the prehospital or emergency department setting.

AND

2. Taken to the Operating Room (laparotomy, thoracotomy or vascular exploration) or
Interventional Radiology within 60 minutes of arrival.

AND

3. Need of blood/blood component transfusion in prehospital setting, ED or OR within 60
minutes of arrival.

Exclusion Criteria:

1. Age ≤ 14

2. CPR > 5 consecutive minutes without ROSC

3. Penetrating brain injury with brain matter exposed

4. ED death