Trauma Induced Coagulopathy and Inflammation
Conditions: Trauma Injury, Trauma, Coagulopathy
Sponsor: University of Pennsylvania

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Clinical trials identifier:   NCT03128658 
 
Principal Investigator:      SIMS, CARRIE 
 
Protocol Title:                  Trauma Induced Coagulopathy and Inflammation 
 
Date:  
 
  August 2, 2018 
 
Protocol Description:       This  is  a  prospective  observational  trial  designed  to  evaluate  the  factors  that  contribute  
to  the development of trauma induced coagulopathy, post injury inflammation and the 
development of organ dysfunction in adult trauma patients. Demographic data, physiologic 
data, blood samples and clinical variables will be collected over the 5 days following traumatic 
injury. 
 
 
 
 

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Protocol 
 
Abstract 
While  a  number  of  factors  are  known  to  be  associated  with  the  development  of  trauma  induced 
coagulopathy (TIC), inflammation, and multi-organ failure, we currently cannot predict which patients 
are  at  risk  for  developing  these  life-threatening  conditions  with  any  certainty.  In  this  prospective 
observational study, we will investigate the many factors that contribute to the development of trauma 
induced coagulopathy, post injury inflammation and the development of organ dysfunction in order to 
develop  a  multi  scale  computational  algorhythm  and  ex  vivo  models  capable  of  clinical  prediction. 
Using a convenience sample technique, demographic data, physiologic data, fresh and residual blood 
samples, urine samples, and clinical variables will be collected over 5 days following traumatic injury. In 
addition to a computational model, ex vivo models using microfluidic devices and high resolution cellular  
respirometry,  and  nucleic  acid  analysis  will  be  used  to  predict  the  development  of  TIC  and multi-
organ failure. 
 
Objectives 
 
Overall objectives 
1)  Develop  a  computational  algorithm  to  predict  the  development  of  trauma  induced  coaguloapthy 
(TIC)     2)  Validate  ex-vivo  microfluidic  TIC  models  3)  Develop  ex-vivo  assays  to  predict  the 
development of trauma-induced inflammation and the development of multi-organ failure 
 
Primary outcome variable(s) 
Coagulation parameters including thromboelastrography and mirocofluidic assessment on admission, 3 
hours, 6 hours, 12 hours, 24 hours, 48 hours, and 5 days post admission. 
 
Secondary outcome variable(s) 
Respirometry of platelets, peripheral blood mononuclear cells, and neutrophils on admission, 3 hours, 6 
hours,  12  hours,  24  hours,  48  hours,  and  5  days  post  admission;  Development  of  multiorgan  
failure within  30  days  of  admission;  Level  of  free  serum  free  nucleic  acids;  Expression  of  pro  
and  anti- inflammatory proteins and genes and genetic variants in serum, platelets, and white blood cells. 
 
Background 
Traumatic injury results in 5-6 million deaths per year worldwide with $518 billion global cost with about 
half of trauma deaths due to acute blood loss. Acute blood loss and standard resuscitation with crystalloids  
and  stored  blood  products  causes  hypothermia,  acidosis,  tissue  hypoxia,  hypotension, inflammation, 
the activation and consumption of coagulation factors including platelets, the release of free  nucleic  
acids,  the  development  of  mitochondrial  dysfunction  and  eventually  organ  failure. Importantly, 
about a quarter of trauma patients display a coagulopathy, (trauma induced coagulopathy, TIC)  which  
greatly  increases  the  risk  of  death  and/or  the  development  of  multigrain  failure.  We currently, 
however, cannot predict who will develop TIC or its associated complications. In fact, two patients who 
have the same clinical presentation may have very different outcomes. Developing a multi scale 
computational model and ex-vivo point of care assays would allow us to efficiently identify and 
effectively treat at risk patients and potentially improve outcomes. 
 
Study Design 
 
Phase* 
Not applicable 
 
Design 
Prospective, observational, convenience sampling of trauma patients 18 yrs old or older who present to 
the trauma bay will be included. Minimally injured patients will be compared to those with a systolic 
blood pressure of 90 mmHg or less, the need for blood product transfusion within 1 hour of admission, 
and/or  an  ISS  of  greater  than  or  equal  to  15.  Demographic  data  including  past  medical/medication 
history as well as clinical data including continuous vital signs (when available) will be recorded. Blood 
samples (approximately 15 ml) and urine samples (approximately 10 ml) will be taken on admission, 
3hr,  6hrs,  12hrs,  24  hrs,  48  hrs,  and  5  days  post  admission.  Residual  blood  samples  (which  
would otherwise  be  discarded)  will  be  obtained  from  the  PPMC  clinical  laboratory  on  0  and  2  
days  post admission. Blood samples may be analyzed for coagulation parameters included ex vivo 
microfluidic

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assays,  blood  gas  analysis,  cellular  respirometry,  inflammatory  mediators,  free  nucleic  acids,  DNA 
polymorphisms,  and  pro/anti-inflammatory  protein  and  gene  expression.  Residual  samples  will  be 
collected for protein biomarker measurements and DNA analyses. Urine samples will be analyzed for 
biomarkers of organ injury and dysfunction. When the patient is capable of consenting, or the patient's 
power of attorney is identified, they will be approached for consent and for continued participation. If 
consent is denied, all collected data/samples will be discarded and the subject will not be enrolled. 
 
Study duration 
We anticipate enrolling and completing this study within 3 years. Each subject's maximum participation 
will be 30 days. Blood and urine samples will be taken over 5 days and clinical data will be collected until 
the subject is discharged. Residual samples will be collected on day 0 and day 2. If patients are discharged 
from the hospital before 30 days, the study will end on the date of discharge. We anticipate starting this 
study February 1, 2017 and ending February 28, 2022. 
 
Resources necessary for human research protection 
Describe research staff and justify that the staff are adequate in number and qualifications to conduct the  
research.  Describe  how  you  will  ensure  that  all  staff  assisting  with  the  research  are  adequately 
informed  about  the  protocol  and  their  research  related  duties.  Please  allow  adequate  time  for  the 
researchers to conduct and complete the research. Please confirm that there are adequate facilities for the 
research. 
In addition to the PI's (Sims and Diamond), this research will be conducted by the Penn Acute Research 
Collaboration  (PARC)  research  coordinators  and  assistants.  PARC  provides  24  hour  translational 
research services to the Penn Presbyterian community. All PARC research staff are CITI trained and will 
be familiar with the study protocol and execution prior to its initiation. The PI is a qualified trauma surgeon  
with  clinical  trial  experience  and  training.  The  PARC  research  coordinators  have  clinical research 
experience and will directly oversee the training of research assistants in order to coordinate the study and 
ensure compliance. After each enrollment, the study coordinator will evaluate for study compliance.  The  
entire  research  staff  will  conduct  monthly  meetings  and  the  PI  and  research coordinator will meet 
at least every 2 weeks.  All patients, including enrolled subjects, will be admitted to the trauma and 
surgical critical care service. They will be managed according to generally accepted medical   standards   
for   traumatic   injury,   which   includes   surgical   interventions,   damage   control maneuvers,  and  
sub-specialty  consultation  as  needed  and  at  the  discretion  of  the  treating  trauma surgeon/surgical 
intensivist. Blood and urine samples will be processed and analyzed in the trauma at PPMC as well as at 
the PARC facility on 3 Mutch, PPMC. Blood and urine samples and case report forms will be stored at 
the PARC facility on 3 Mutch, PPMC. 
 
 
 
 
Characteristics of the Study Population 
 
Target population 
trauma patients 18 years or older who present to the trauma bay 
 
Subjects enrolled by Penn Researchers 
300 
 
Subjects enrolled by Collaborating Researchers 
0 
 
Accrual 
This  will  be  prospective  observational  study  using  convenience  enrollment.  Injured  patients  who 
present  to  the  trauma  bay  will  be  evaluated  by  the  on  call  trauma  surgeon  and  as  well  as  the  
PARC research assistant . If eligibility criteria are met, the research blood samples will be drawn at the 
same time  as  routine  clinical  samples.  Depending  on  the  research  expertise  available  (e.g.  
microfluidic assessments  or  cellular  respiration  experiments),  eligible  patients  may  not  have  all  the  
research variables  investigated  at  each  time  point.  Given  that  we  will  be  recruiting  a  number  of  
minimally injured patients, as well as injured patients with significant variability (eg severity of injury, 
age, gender, race, and past medical history), a large accrual number is required in order to develop a 
computational model that can accurately determine which factors predict the development of TIC, 
inflammation and

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multiorgan failure. 
 
Key inclusion criteria 
In  order  to  develop  a  robust  predictive  model,  we  will  need  to  include  a  variety  of  injured  
patients ranging  from  minimally  injured  to  severely  injured.  Inclusion  criteria,  therefore,  will  
include  any trauma  alert  activation.  This  highest  level  of  activation  is  reserved  for  patients  who  
meet  either physiologic  parameters  (e.g.  hypotension)  or  who  have  a  mechanism  of  injury  that  
would  suggest significant injury ( e.g. high speed motor vehicle crash). that being said roughly 30% of 
trauma alerts are not found to have significant injury. Only patient's whose age is equal to or greater than 
18 years old will be included. 
 
Key exclusion criteria 
Transfer  to  trauma  service  of  greater  than  6  hours  Known  pregnancy  -  these  patients  are  excluded 
because drawing multiple blood samples has an unknown risk to the fetus. Women of child bearing age, 
however, will be eligible. If they are found to be pregnant before enrollment, they will be excluded (eg. 
obvious gravid uterus, + fetus seen on trauma ultrasound, or + pregnancy test, which is routinely done on 
all female trauma patients) . If they are found to be pregnant after the initial blood draw, this sample will  
be  processed,  but  no  additional  blood  samples  will  be  taken.  The  patient,  or  next  of  kin  if 
appropriate, will be asked to consent for analysis of the processed sample and for continued clinical data 
collection. 
 
Vulnerable 
Populations 
 
Children Form 
x  Pregnant  women  (if  the  study  procedures  may  affect  the  condition  of  the  pregnant  woman  
or fetus) Form 
Fetuses and/or Neonates Form 
Prisoners Form 
Other 
x  None of the above populations are included in the research study 
 
 
The following documents are currently attached to this item: 
 
There are no documents attached for this 
item. 
 
Populations vulnerable to undue influence or coercion 
Given the nature of trauma and the physiologic consequences associated with hemorrhagic shock, many 
of the eligible trauma patients in this study would be considered cognitively or decisionally impaired. 
Obtaining informed consent from the patient or their surrogate at the time of the initial blood draw may 
not  be  practicable  in  many  circumstances. As  such,  we  will  be  seeking  delay  in  obtaining  informed 
consent under these circumstances. HIPAA authorization and consent to continued participation will be 
obtained from the patient's next of kin or surrogate when available. If and when the subject becomes 
capable of consenting during their hospitalization, he/she will informed of the study including the risks 
and benefits and HIPAA authorization/consent will be obtained from the patient. If he/she declines, he/ 
she will be de-enrolled. All data and blood samples will be purged.  On occasion, enrolled patients may 
become arrested while in hospital. If consent for enrollment has been obtained prior to the arrest, the IRB 
will be consulted to determine if subjects can continue in the study. If the arrest (and not merely 
detainment or police presence) occurs prior to obtaining consent, the patient will be de-enrolled given the  
risk  of  undue  influence  or  coercion.  On  occasion,  people  who  work  at  or  attend  school  at  the 
University of Pennsylvania will be trauma victims and therefore eligible for enrollment. These patients 
and/or  their  next  of  kin  will  be  consented  as  in  private  and  data  will  be  de-identified  as  previously 
described.  Subjects  will  be  informed  in  person  and  in  the  consent  form  that  their  standing  with  
the University will not in any way be affected by their decision to participate. 
 
Subject recruitment 
Given  the  unexpected  nature  of  trauma,  subjects  will  not  be  recruited  for  this  study  a  priori  of  
their injury.

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Will the recruitment plan propose to use any Penn media services (communications, marketing, etc.) for 
outreach via social media avenues (examples include: Facebook, Twitter, blogging, texting, etc.) or does 
the study team plan to directly use social media to recruit for the research? 
No 
 
The following documents are currently attached to this item: 
 
There are no documents attached for this 
item. 
 
Subject compensation* 
Will subjects be financially compensated for their participation? 
No 
 
The following documents are currently attached to this item: 
 
There are no documents attached for this 
item. 
 
If there is subject compensation, provide the schedule for compensation per study visit or session 
and total amount for entire participation, either as text or separate document 
 
 
 
 
 
Study Procedures 
 
Suicidal Ideation and Behavior 
Does this research qualify as a clinical investigation that will utilize a test article (ie- drug or biological) 
which may carry a potential for central nervous system (CNS) effect(s)? 
No 
 
Procedures 
During the initial trauma evaluation, 15 ml of blood will be collected for research purposes during the 
routine trauma blood draw. Additionally, 10 ml of urine will be collected directly from a Foley catheter, 
or  if  a  catheter  is  not  in  place  as  part  of  standard  care,  from  a  spontaneous  void. Additional  
15ml samples of blood and 10 ml samples of urine will be collected at 3 hours, 6 hours, 12 hours, 24 
hours, 
48  hours  and  5  days  post  admission.  Blood  and  urine  sample  collection  in  unstable  patients  will  
be deferred or delayed if it is determined by the clinical team that taking the sample would interfere with 
clinical care. Smaller blood and urine volume samples maybe taken at each time point (eg 10 ml rather 
than 15 ml of blood) if research expertise is not available for sample analysis (e.g microfluidic or high 
resolution respirometry) at that time point. Residual plasma and whole blood samples will be collected 
from the PPMC clinical laboratory on day 0 and day 2 from trauma bay admission. Blood samples will 
be analyzed for coagulation and microfluidic flow parameters, proteins involved in inflammation and 
coagulation, mitochondrial function and respiration of white blood cells and platelets, DNA sequencing 
of specific genes involved in organ failure, and gene expression of proteins of interest. Residual samples 
will be further studied for protein biomarker measurements and DNA analyses. Urine samples will be 
analyzed  for  biomarkers  of  organ  injury  and  dysfunction. Vital  signs,  number  of  blood  transfusions, 
volume  of  crystalloid,  administration  of  medications,  and  the  values  of  routine  laboratories  will  
be monitored continuously for 24 hours, and then cumulatively for up to 5 days. This data will be collected 
by  reviewing  the  electronic  medical  record  via  EPIC.  Discrete  data  will  be  recorded  on  case  
report forms and then entered into REDCap - an institutionally approved and managed secure network 
that is also  password  protected.  Continuous  data  will  be  deidentified  and  maintained  on  REDCap.  
The development of multiorgan failure will be monitored for up to 30 days post enrollment. If patients 
are discharged  or  die  prior  to  completing  the  5  days  of  blood  samples,  additional  samples  and/or  
clinic appointments  for  the  purpose  of  research  will  not  be  obtained. After  the  last  blood  draw,  
we  will  be following  the  patient's  outcome  until  discharge.  This  data  is  routinely  extracted  as  part  
of  the Pennsylvania  Trauma  Outcomes  Study  -  a  state  trauma  center  requirement  -  and  will  not  
require additional contact with the patient. We will not personally follow up patients if they are discharged 
prior to 30 days. 

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The following documents are currently attached to this item: 
 
There are no documents attached for this 
item. 
 
Deception 
Does your project use deception? 
No 
 
Analysis Plan 
Patients who develop coagulopathy, altered cellular respiration, or multi-organ failure will be compared 
using T-tests or Mann-Whitney tests for continuous variables and Chi-squared or Fischers exact tests for 
dichotomous  variables.  Spearmans  rank  correlation  will  be  used  to  assess  associations  between 
continuous  variables.  Logistic  regression  analysis  will  be  used  to  identify  risk  factors  for  the 
development of trauma induced coagulopathy or multiorgan failure.. Receiver operating characteristic 
curves will be used to assess accuracy of microfluidic measurements compared to standard measures of 
coagulation  .   Continuous  deidentified  data  including  vital  signs,  laboratory  values,  and  medications 
will be shared with collaborators at Princeton University in order to create a mathematical model. The 
computational  whole-patient  systems  model  is  a  multiscale,  multi-compartment  model  whose  state- 
space is defined by a very large and heterogeneous set of variables as well as a large number of input 
parameters. It is straightforward to make direct contact with the clinical trauma blood profiles because the 
measured variables in these profiles are also included in the model state space. This comparison first will 
be used to establish the validity of the model. Here, the model will simply be integrated in time for various  
initial  trauma  conditions  in  an  attempt  to  determine  whether  the  model  can  be  predictive.  In 
particular, we will determine whether it is possible to reproduce the variation between the various time 
states at admission,3, 6, 12, 24, 48 hours and 5 days post admission. A more challenging data mining 
application  is  to  discover  new  variables  that  are  more  predictive  of  clinical  outcomes  than  those 
employed  in  current  clinical  protocols.  The  workhorse  data  mining  technique  we  plan  to  explore, 
extend, and use to establish links between our multiscale model and clinical data is known as Diffusion 
Maps.   This   is   a   framework   based   upon   diffusion   processes   for   finding   meaningful   geometric 
descriptions  of  data  sets,  even  when  the  underlying  geometry  of  the  data  is  complex,  nonlinear  
and corrupted by noise. The method is based on the construction of a Markov transition probability matrix 
corresponding  to  a  random  walk  on  a  graph  whose  vertices  are  the  data  points  with  transition 
probabilities being the local similarities between pairs of data points. The framework relates the spectral 
properties of Markov processes to their geometric counterparts and it unifies ideas arising in a variety of 
contexts such as nonlinear dimensionality reduction methods, machine learning, and harmonic analysis. 
The first few eigenvectors of the sparse Markov matrix are then used to generate a new set of intelligent 
coordinates that embody the intrinsic geometry of the data set. These are the diffusion map coordinates. 
Most  importantly,  these  eigenvectors  integrate  the  local  similarities  into  a  globally  efficient  low- 
dimensional representation of the complex geometric structure. The usage of eigenvectors of similarity 
matrices for dimensionality reduction is not new. In fact, the classical method of principal component 
analysis (PCA) computes principal components as eigenvectors of the covariance matrix of the data set 
and find a low dimensional representation of the data by projecting it onto the subspace spanned by the 
first few principal components that capture the most variability (or energy) of the data. Diffusion Maps is  
a  successful  generalization  of  PCA  to  complex  nonlinear  data  sets  whose  structure  is  unknown  in 
advance: unlike PCA, the diffusion map coordinates are nonlinear projections of the data; moreover, the 
nonlinear embedding is based only upon local similarities of neighboring data points. Diffusion Maps first 
will be used on the multiscale simulation data sets. This will establish macroscopic observables that define  
the  trajectory  of  the  overall  patient-scale  model. This  is  crucial  because  it  is  much  simpler  to 
establish a connection to patient outcome when only a few variables are being tracked (instead of the large 
variable space that defines the full multiscale model). However, these variables are generally not 
obviously connected to clinical variables and we will use the simulation data to establish relationships 
between the Diffusion Maps variables and actual measureable quantities. The result of this work will be 
to  isolate  variables  that  are  highly  predictive  of  patient  outcome  and  allow  assessment  of  different 
interventions. 
 
The following documents are currently attached to this item: 
 
There are no documents attached for this 
item.

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Are you conducting research outside of the United States? 
No 
 
Data 
confidentiality 
 
x  Paper-based records will be kept in a secure location and only be accessible to personnel involved 
in the study. 
x  Computer-based files will only be made available to personnel involved in the study through the 
use of access privileges and passwords. 
x  Prior  to  access  to  any  study-related  information,  personnel  will  be  required  to  sign  
statements agreeing to protect the security and confidentiality of identifiable information. 
x  Wherever feasible, identifiers will be removed from study-related information. 
A Certificate of Confidentiality will be obtained, because the research could place the subject at risk   
of   criminal   or   civil   liability   or   cause   damage   to   the   subject's   financial   standing, 
employability, or liability. 
A  waiver  of  documentation  of  consent  is  being  requested,  because  the  only  link  between  the 
subject  and  the  study  would  be  the  consent  document  and  the  primary  risk  is  a  breach  of 
confidentiality. (This is not an option for FDA-regulated research.) 
Precautions are in place to ensure the data is secure by using passwords and encryption, because 
the research involves web-based surveys. 
Audio  and/or  video  recordings  will  be  transcribed  and  then  destroyed  to  eliminate  audible 
identification of subjects. 
 
 
Subject Confidentiality 
Each  patient  will  be  assigned  a  study  number.  A  protected  REDCap  database,an  institutionally 
maintained and protected data network, will be used to link each patient to their assigned study number. 
Only the assigned study number will be directly connected to patient data and only Dr. Sims will have 
access to this link. The database linking each patient to their assigned study number will be destroyed five 
years after the conclusion of the study. The data collected will only be used for the proposed IRB study. 
Only de-identified patient data will be shared with Dr. Diamond and our Princeton collaborators using  
DataLocker,  an  encrypted  portable  data  device.   Samples  (without  patient  identifiers)  will  be labeled  
with  the  study  number.  Samples  will  be  stored  in  a  locked  laboratory  facility  on  Mutch  3. Samples 
will be stored for 5 years and then will be destroyed. Laboratory reports, medication reports, and vital 
signs will be downloaded via EPIC. Each continuous file will be de-identified and labeled only with the 
study number, these will then be stored on a password protected REDCap database. This de- identified  
file  will  be  given  to  Dr.  Diamond  and  Dr.  Sinno  for  mathematical  modeling.  Laboratory results, 
specific medications, fluid balance and vital signs will be recorded at specific time points on a case  report  
form  with  only  the  study  ID  number  and  recorded  into  a  secure,  password  protected REDCap 
database. Consent, patient data and case report forms will be collected and stored in a locked cabinet on 
Mutch 3. As mentioned data will be entered and stored using REDCap. Only Dr. Sims, Dr. Diamond and 
PARC research team will have access to the RedCAP file. Only Dr. Sims will have access to both the 
patients name and their research number.   The PARC office and lab space on Mutch 3 are locked with 
front door security code. Computers and REDCap files are password protected. 
 
Sensitive Research Information* 
Does this research involve collection of sensitive information about the subjects that should be excluded 
from the electronic medical record? 
No 
 
Subject Privacy 
Privacy refers to the person's desire to control access of others to themselves. Privacy concerns people, 
whereas confidentiality concerns data. Describe the strategies to protect privacy giving consideration to 
the following: The degree to which privacy can be expected in the proposed research and the safeguards 
that  will  be  put  into  place  to  respect  those  boundaries.  The  methods  used  to  identify  and  contact 
potential participants. The settings in which an individual will be interacting with an investigator. The 
privacy   guidelines   developed   by   relevant   professions,   professional   associations   and   scholarly

Page 8 of 11 
 
disciplines (e.g., psychiatry, genetic counseling, oral history, anthropology, psychology). 
Consent  will  only  be  obtained  in  a  private  setting  (private  family  or  consultation  room,  private  
ICU room, etc. Consent will only be obtained with the next of kin or patient. Additional family members/ 
friends  will  not  be  part  of  the  discussion.   Consents,  patient  notes,  CRF's  will  be  stored  in  a  
locked facility immediately accessible only to the research staff (PARC research space, Mutch 3). Each 
patient will be assigned a study number. A REDCap database will be used to link each patient to their 
assigned study number. Only the assigned study number will be directly connected to patient data and 
only Dr. Sims will have access to this link. The database linking each patient to their assigned study 
number will be destroyed at the conclusion of the study. Only de-identified and encrypted data will be 
shared with Dr.  Diamond  and  our  Princeton  collaborators.    Data  will  be  entered  and  stored  using  
a  password- protected RedCAP file. Only Dr. Sims, Dr. Diamond and the PARC research team will have 
access to this RedCAP file. 
 
Data Disclosure 
Will the data be disclosed to anyone who is not listed under Personnel? 
Data will disclosed to members of the research team, Office of Regulatory Affairs, Office of Human 
Research, the FDA and NIH as needed. 
 
Data 
Protection* 
 
x  Name 
Street address, city, county, precinct, zip code, and equivalent geocodes 
x  All elements of dates (except year) for dates directly related to an individual and all ages over 89 
Telephone and fax number 
Electronic mail addresses 
Social security numbers 
x  Medical record numbers 
Health plan ID numbers 
Account numbers 
Certificate/license numbers 
Vehicle identifiers and serial numbers, including license plate numbers 
Device identifiers/serial numbers 
Web addresses (URLs) 
Internet IP addresses 
Biometric identifiers, incl. finger and voice prints 
Full face photographic images and any comparable images 
Any other unique identifying number, characteristic, or code 
None 
 
 
Does your research request both a waiver of HIPAA authorization for collection of patient information 
and  involve  providing  Protected  Health  Information  ("PHI")  that  is  classified  as  a  "limited  data  
set" (city/town/state/zip  code,  dates  except  year,  ages  less  than  90  or  aggregate  report  for  over  
90)  to  a recipient outside of the University of Pennsylvania covered entity? 
No 
 
Tissue Specimens Obtained as Part of Research* 
Are Tissue Specimens being obtained for research? 
Yes 
 
Tissue Specimens - Collected during regular care* 
Will tissue specimens be collected during regulator clinical care (for treatment or diagnosis)? 
Yes

Page 9 of 11 
 
Tissue Specimens - otherwise discarded* 
Would specimens otherwise be discarded? 
No 
 
Tissue Specimens - publicly available* 
Will tissue specimens be publicly available? 
No 
 
Tissue Specimens - Collected as part of research protocol* 
Will tissue specimens be collected as part of the research protocol? 
Yes 
 
Tissue Specimens - Banking of blood, tissue etc. for future use* 
Does research involve banking of blood, tissue, etc. for future use? 
Yes 
 
Genetic testing 
If genetic testing is involved, describe the nature of the tests, including if the testing is predicative or 
exploratory in nature. If predictive, please describe plan for disclosing results to subjects and provision of 
genetic counseling. Describe how subject confidentiality will be protected Note: If no genetic testing is 
to be obtained, write: "Not applicable." 
The concentration of free nucleic acids in the serum will be measured. We will measure the expression of 
pro- and anti-inflammatory genes by extracting RNA from white blood cell populations and platelets and 
creating a cDNA library for the gene expression of proteins of interest that will be studied. Further, the 
DNA sequences of these proteins will be analyzed to look for polymorphisms associated with organ 
failure. The results of these investigations will only be linked to the patient's study number and not their 
name. 
 
 
 
 
Consent 
 
1. Consent Process 
 
Overview 
Given the unpredictability and emergent nature of trauma, we will not be able to identify potentially 
eligible  patients  until  they  arrive  to  the  trauma  bay.  All  patients  will  have  suffered  an  unexpected 
traumatic event, they will be in pain, and the trauma service will be assessing them rapidly in order to 
identify potentially life-threatening injuries. In the majority of these cases, the patients will be severely 
injured,  hemodynamically  unstable  and  unable  to  consent  for  themselves.  Given  the  urgent  and 
timesensitive nature of the proposed research, we will be seeking a delay in obtaining informed consent. 
Specifically, we will be requesting that the initial 15 ml of blood sample for research be collected at the 
same time that other blood samples for clinical care are drawn on admission to the trauma bay. Patients 
who have a Glasgow Coma Score of 15 and do not appear to be clinically intoxicated will be considered 
able to consent and approached after the initial trauma evaluation. In circumstances where the patient is 
unable to consent, we will approach the patient's next of kin or power of attorney after the trauma team 
has had the opportunity to update them regarding the patient's clinical condition. The next of kin will be 
informed that the initial blood sample has been drawn. After explaining the study, including its risks and 
benefits, we will ask for HIPAA authorization and consent. The next of kin will be able to withhold 
consent, in which case we will cease collecting data and samples. They may also consent to the initial 
blood draw and data collection, but decline further sample and data collection, or they may consent to full 
enrollment. When the patient is consentable, and after the trauma team has had the opportunity to inform 
the patient of his/her clinical situation, the research team will inform the patient of any blood draws that 
have occurred. At this time, the patient can consent to enrollment (and any further sample collection) or 
withhold consent (even if the next of kin had already authorized). If HIPAA authorization or consent is 
withheld, all data and samples will be destroyed. The discussion of the study as well as the consent will 
be conducted at the level of a 5th or 6th grade reading comprehension. Consent will only be obtained in a 
private setting with the patient and/or his/her next of kin. Additionally, in the event that the patient expires 
prior to consent, we will approach the family only after the clinicians have explained

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to the family the clinical course and outcome. We will explain the purpose of the study and explain that 
samples  were  collected.  We  will  then  attempt  to  consent  the  family.  If  the  family  is  in  distress  
and cannot be consented prior to leaving the hospital, we will obtain the family's contact information. The 
PI will then contact the family member at least two weeks after the patients passing to discuss the study 
and attempt verbal consent in the presence of a witness. If the family member does not consent to the 
patient  participating  in  the  study,  all  samples  and  clinical  data  will  then  be  destroyed. Theoretically, 
enrolled  subjects  could  represent  as  a  trauma  alert  again.  If  they  are  30  days  out  from  their  
initial enrollment, they would be eligible to participate again. However, this is very, very rare. 
 
Children and Adolescents 
We  do  not  routinely  treat  children  or  adolescents  at  the  Penn  Presbyterian  Trauma  Center.   Patients 
under the age of 18 will not be included in this study. 
 
Adult Subjects Not Competent to Give Consent 
see above 
 
2. Waiver of Consent 
 
Waiver or Alteration of Informed Consent* 
Waiver or alteration of required elements of consent 
 
Minimal Risk* 
This research involves minimal risk. The initial blood sample (15 ml) will be drawn at the time other 
blood  samples  are  taken  for  standard  clinical  care.  As  such,  it  does  not  require  an  additional 
venipuncture. In total, 7 blood samples (a max of 15 ml per sample) will be taken over the course of 5 
days. When  research  expertise  is  not  available  for  specific  assays  (e.g  microfluidics  or  respirometry) 
this  blood  volume  will  be  decreased  to  10  ml. Additionally,  collections  of  research  samples  will  
be deferred or delayed if the clinical team feels that collection would interfere with the clinical care of an 
unstable patient. Moreover, a volume of 15 ml X 7 times over 5 days is the maximum amount of blood 
that  will  be  collected.  Many  of  these  patients  will  be  bleeding  and  will  require  a  number  of  
blood transfusions because of their injuries. Each blood transfusion is 300 ml. We do not feel that a 
maximum of 105 ml of blood over 5 days will pose a higher risk to our patients. Residual blood collection 
(which would otherwise be discarded) involves obtaining samples from the clinical lab on day 0 and day 
2 and does not confer risk above loss of confidentiality. Lastly, sample collection of 10 ml of urine totaling 
70 ml over 5 days imposes only minimal risk to the patient as it is a prospective collection via noninvasive 
means. The urine specimen will be obtained at the time staff is performing a clinical draw and collected 
directly  from  a  Foley  catheter  or,  if  a  catheter  is  not  in  place  as  part  of  standard  care,  from  a 
spontaneous void. 
 
Impact on Subject Rights and Welfare* 
This  study  will  attempt  to  protect  the  patient's  rights  by  (1)  informing  and  consenting  the  patient  
or surrogate prior to the initial blood draw and urine collection whenever practicable (2) informing and 
obtaining  consent  for  continued  participation  when  a  surrogate  is  identified  and  (3)  informing  and 
consenting  the  patient  when  he/she  regains  capacity  to  make  an  informed  choice.  If  consent  is  
not obtained, the subject will be un-enrolled and the data and biological samples will be discarded. 
 
Waiver Essential to Research* 
Trauma remains the leading cause of death for those under the age of 40 in the United States, with a large 
percentage of patients dying from hemorrhagic shock within the initial post-injury hours. Potential 
therapeutic  interventions  will  have  the  most  impact  if  we  can  identify  which  patients  are  at  risk  
for developing trauma induced coagulopathy, exuberant inflammation, and multi-organ failure. In order 
to develop a robust model, data and biologic samples will need to be collected BEFORE interventions in 
order  to  determine  which  interventions  either  positively  or  negatively  influence  outcomes.  Given  
the unpredictability and emergent nature of trauma, potentially eligible patients cannot be identified prior 
to their  arrival  to  the  trauma  bay.  Moreover,  patients  who  are  severely  injured  and/or  
hemodynamically unstable  are  unable  to  consent  for  themselves.  Frequently,  these  patients  are  
rapidly  intubated, aggressively  resuscitated  with  blood  products  and  brought  to  the  operating  room  
or  IR  suite  for hemorrhage control within minutes of initial arrival. In general, the resuscitative effort is 
well on the way by the time the patient's family is located - a process that typically takes hours to days.

Page 11 of 11 
 
Additional Information to Subjects 
Contact  information  from  the  patient  and/or  the  surrogate  will  be  kept  in  a  separate  file  that  is  
not associated with any HIPPA or study data. Participants will have the option of receiving a copy of the 
study results or manuscript at the conclusion of the study either by email or standard post. 
 
Written Statement of Research* 
No 
 
If no written statement will be provided, please provide justificiation 
 
 
The following documents are currently attached to this item: 
 
There are no documents attached for this 
item. 
 
 
Risk / Benefit 
 
Potential Study Risks 
This study has minimal risk. Seven blood and urine samples with a maximum cumulative total volume of 
105 ml and 70 ml, respectively, over 5 days is well tolerated. Every attempt to will be made to collect 
research  samples  during  routine  clinical  phlebotomy  or  from  existing  lines.  Blood  samples  will  
be collected only by nursing/medical/phlebotomy staff in order to minimize the minimal risk of pain and 
infection associated with routine phlebotomy. 
 
Potential Study Benefits 
There are no direct benefits to study participants. The benefit will be toward advancing our knowledge of 
how severely injured patients develop complications such as coagulopathy and organ failure. This study 
will hopefully help us develop better assays to identify and treat patients at risk. 
 
Alternatives to Participation (optional) 
None. If a subject chooses not to participate he/she will receive standard care. 
 
Data and Safety Monitoring 
After each enrollment, the PARC research coordinator will audit the case report form in order to ensure 
proper consent procedures were performed, that data collection and entry are accurate and that personal 
data is stored properly. Data analysis will be performed after every 50th subject enrolled. 
 
The following documents are currently attached to this item: 
 
There are no documents attached for this 
item. 
 
Risk / Benefit Assessment 
This study presents minimal risk to patients.