Clinical trial NCT03671746
Conditions: Polytrauma
Keywords: Inflammatory cytokine inflammation trauma opioid
Sponsor: Arun Aneja
Start date: 2019-02-28; Completion date: 2023-06-20
Enrollment: 70 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
It is unknown whether early modulation of inflammatory cytokines is associated with improved patient outcomes, reduced narcotic requirements in orthopaedic patient population, and improved patient subjective pain after hospital discharge. Preliminary animal and clinical studies have shown correlation between elevated blood cytokine concentrations during the acute phase of trauma and the development of post-traumatic complications. Early administration of nonsteroidal anti-inflammatory drug (NSAID) in animals significantly reduced inflammatory profiles, improved pulmonary edema, and enhanced arteriole vasoconstriction in response to hemorrhage. The ability to modify post-traumatic physiologic response via short-term administration of a non-steroidal anti-inflammatory drug (NSAID) may lead to improved patient outcome. In addition, given the current landscape for opioid epidemic in the United States, alternative non-opioid pain management during acute trauma has the potential to reduce opioid consumption and represents a pivotal component of multimodal analgesia strategy.

By doing this study, the investigators hope to learn how to provide the best care for all patients in the state of Kentucky. Patient participation in this research will last about 1 year.

Detailed description:
Accidental trauma is the 4th leading cause of death in the United States, and it is associated with a complex inflammatory response. This response is associated with post-traumatic complications such as; multi-organ dysfunction syndrome (MODS), bacterial pneumonia, acute respiratory distress syndrome (ARDS), systemic inflammatory response syndrome (SIRS), and post-traumatic pain (PTP). It is unknown whether early modulation of inflammatory cytokines is associated with improved patient outcomes, reduced narcotic requirements, and improved patient subjective pain after hospital discharge.

Preliminary data has shown: (1) elevated blood cytokine concentrations during the acute phase of trauma are correlated with the development of fatal post-traumatic complications, (2) that early administration of a non-steroidal anti-inflammatory drug (NSAID) resulted in decreased blood serum levels of interleukin (IL-6), Prostaglandin E2 (PGE2), improved pulmonary edema, and enhanced arterioles ability to vasoconstrict in response to hemorrhage in animal models, and (3) that the addition of the internal physiologic parameters (inflammatory cytokines) to New Injury Severity Score (NISS - a marker of the external anatomical insult) significantly improves the ability to predict hospital length of stay of trauma patients when compared to NISS alone. The investigator's group is the first to use an integrative approach that combines the external anatomic injury data with the internal physiologic response for accurate prediction of a patient's clinical outcome. Therefore, if the investigators apply this same mindset to treatment, the investigators can improve the trauma patients' care by addressing both parameters as opposed to solely focusing on the external injury as done in the past. The ability to modify post-traumatic physiologic response via short-term administration of an NSAID may lead to improved patient outcomes.

Over the last decade, clinicians have remained puzzled over the safety of NSAID administration after fracture in terms of bone union. In addition, given the current landscape for the opioid epidemic in the United States, alternative non-opioid pain management during acute trauma has the potential to reduce opioid consumption and represents a pivotal component of multimodal analgesia strategy.

Arms: arm 1: Polytrauma participants will receive standard of care in addition to saline solution according to standard Advanced Trauma Life Support (ATLS) and standard ICU routine medical care. arm 2: Participants in the group will receive Ketorolac in addition to standard of care for the standard Advanced Trauma Life Support (ATLS) and standard ICU routine medical care.
Interventions: intervention 1: Ketorolac intervention 2: Saline Solution
Intervention descriptions: intervention 1: Participants will receive Ketorolac at 15 mg IV every 6 hours for their first 5 days of hospitalization intervention 2: Participants will receive 1 ml of saline solution IV every 6 hours for their first 5 days of hospitalization

Protocol documents:
Prot_SAP_000.pdf: 
Inflammatory Response to Trauma – Does Early 
Cytokine Modulation Improve Patient Outcome? 
NCT03671746 
08/22/2023


 TO:
Arun Aneja, MD, PhD 
Orthopaedic Surgery
PI phone #: 859-218-3063 
PI email: arun.aneja@uky.edu
 
 FROM:
Chairperson/Vice Chairperson
Medical Institutional Review Board (IRB)
 SUBJECT:
Approval for Continuation
 DATE:
8/22/2023
 
FL Continuation Review
 Approval Ends:
 IRB Number:
 8/21/2024
 43611
 
 
 
                               
                
                               
              
                   
 
On 8/22/2023, the Medical Institutional Review Board approved your protocol entitled:  
Inflammatory Response to Trauma – Does Early Cytokine Modulation Improve Patient Outcome?               
Approval is effective from 8/22/2023 until 8/21/2024 and extends to any consent/assent form, cover letter, and/or phone script. If applicable, the IRB approved
consent/assent document(s) to be used when enrolling subjects can be found in the "All Attachments" menu item of your E-IRB application.  [Note, subjects can
only be enrolled using consent/assent forms which have a valid "IRB Approval" stamp unless special waiver has been obtained from the IRB.]  Prior to the end of
this period, you will be sent a Continuation Review (CR)/Annual Administrative Review (AAR) request which must be completed and submitted to the Office of
Research Integrity so that the protocol can be reviewed and approved for the next period.   
In implementing the research activities, you are responsible for complying with IRB decisions, conditions and requirements.  The research procedures should be
implemented as approved in the IRB protocol.  It is the principal investigator's responsibility to ensure any changes planned for the research are submitted for
review and approval by the IRB prior to implementation.  Protocol changes made without prior IRB approval to eliminate apparent hazards to the subject(s)
should be reported in writing immediately to the IRB.  Furthermore, discontinuing a study or completion of a study is considered a change in the protocol’s status
and therefore the IRB should be promptly notified in writing.
For information describing investigator responsibilities after obtaining IRB approval, download and read the document "PI Guidance to Responsibilities,
Qualifications, Records and Documentation of Human Subjects Research" available in the online Office of Research Integrity's IRB Survival Handbook. Additional
information regarding IRB review, federal regulations, and institutional policies may be found through ORI's web site. If you have questions, need additional
information, or would like a paper copy of the above mentioned document, contact the Office of Research Integrity at 859-257-9428.
        
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PROTOCOL TYPE (VERSION 4)
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Which IRB
Medical
NonMedical
Protocol Process Type
Exemption
Expedited
Full
(Must be risk level 1)
 
IMPORTANT NOTE: You will not be able to change your selections for "Which IRB" and "Protocol Process Type" after
saving this section. If you select the wrong IRB or Protocol Process Type, you may need to create a new application. 
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(ORI) at 859-257-9428 with any questions prior to saving your selections.
 
*Which IRB*
The Medical IRB reviews research from the Colleges of:
Dentistry
Health Sciences
Medicine
Nursing
Pharmacy and Health Sciences
and Public Health.
 
The Nonmedical IRB reviews research from the Colleges of:
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Note: Studies that involve administration of drugs, testing safety or effectiveness of medical devices, or invasive medical procedures
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*Which Protocol Process Type* 
Under federal regulations, the IRB can process an application to conduct research involving human subjects in one of three ways: 
by exemption certification
by expedited review.
by full review;
The investigator makes the preliminary determination of the type of review for which a study is eligible. Please refer to ORI's "Getting
Started" page for more information about which activities are eligible for each type of review.
 
The revised Common Rule expanded exemption certification category 4 for certain secondary research with
identifiable information or biospecimens. The regulations no longer require the information or biospecimens to be
existing.  For more information see the Exemption Categories Tool.
Section 1 Page 1 of 2
IRB Approval
8/22/2023
IRB # 43611
IRB1


 
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CONTINUATION REVIEW/FINAL REVIEW
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In accordance with federal regulations and/or local policies, the IRB conducts periodic review of all currently approved projects. If
you need your IRB approval to continue and you do not complete and submit the required materials in a timely manner, IRB
approval will expire at the end of your current approval period.
If you have any questions, please contact the Office of Research Integrity at 859-257-9428 or email IRBsubmission@uky.edu.
To initiate your continuation review (CR)/annual administrative review (AAR), or properly close your study, complete this section
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1. Status of the Research
Check the statement(s) that best describe(s) the current status of your research: 
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Recruitment and/or enrollment of new subjects or review of records/specimens continue.
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The remaining research activities are limited only to data analysis. There is no subject/record/specimen identifying codes or links to
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All study activities are complete. IRB approval can be inactivated.
*Possibility that review will move from Full to Expedited.
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(Example: If 3 different approved consent forms were used since the last annual review, please provide the two most recent signed
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Attachments
Attach Type
File Name
Entire Signed Consent Form 20230731180556007-combined.pdf
Entire Signed Consent Form 20230731180652481.pdf
3. Informed Consent
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If the study is closed to subject enrollment, please go to the Informed Consent section of the E-IRB Application and remove
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Our records for the previously approved IRB application indicate the IRB approved estimate of subjects to be enrolled (or
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200
Enter the number of enrolled subjects (or records/specimens reviewed) that have not been previously reported to the IRB
1
Our records for the previously approved IRB application indicate the previous total # of subjects enrolled (or records/specimens
reviewed) since activation of the study is:
107
The new total number of subjects enrolled (or records/specimens reviewed) since activation of the study: 
108
Please review the Project Info section for the IRB approved estimate of subjects to be enrolled (or records/specimens reviewed).
If this new total exceeds your approved estimate of subjects to be enrolled (or records/specimens reviewed), please update the
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If your study is monitored by a DSMB or under a DSMP, attach all documentation (i.e. summary report; meeting minutes) representing
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7. Since the most recent IRB Initial/Continuation Review Approval:
Have there been any participant complaints regarding the research?
Yes
No
If yes, in the field below, provide a summary describing the complaints.
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Have any subjects withdrawn from the research voluntarily or by you as the PI for reasons related to safety, welfare, or problems
related to the conduct of the research? If a participant does not meet the screening criteria for a study even if they signed a screening
consent it is NOT considered a withdrawal.
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If yes, in the field below, provide a detailed explanation to the withdrawal(s) including if participants were lost to contact.
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Attach Type
File Name
Interim Findings OTA IM Abstract VAS and MME 2.10.23.docx
Have subjects experienced any benefits?
Yes
No
If yes, in the field below, provide a description of benefits subjects have experienced.
Results:
In total, 70 participants were enrolled, with 35 randomized to the ketorolac group and 35 to the placebo group.
Study groups were balanced with respect to age, BMI, and NISS. Over the 5-day treatment period, average
opioid intake (p = 0.0039) and VAS pain scores (p = 0.0481) were significantly reduced in the ketorolac group
compared to the placebo group. The ketorolac group experienced a 43.2% reduction in mean MME compared
to the placebo group.
Conclusion:
Scheduled, short-term use of low-dose ketorolac was associated with significantly reduced opioid use and pain
in orthopedic polytrauma patients with no apparent short-term adverse effects. The results support the use of
low-dose short-term schedule ketorolac for pain control among orthopaedic polytrauma patients.
Have there been any inspections/audits/quality improvement reviews of your research protocol resulting in the need for
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8. Risk Level:
Our records for the previously approved IRB application show your research is:
Risk
Level: 2
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Has something during the course of your research changed the level of risk?
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No
If yes, go to the Risk Level section, mark the appropriate risk level, and in the field below, describe why the risk level has changed:
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Our records for the previously approved IRB application indicate your research is being submitted to, supported by, or conducted in
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Yes
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N/A
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the study, please notify the IRB.
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Our records for the previously approved IRB application indicate your estimated project end date is:
08/31/2023
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Ending Date of Research Project.
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11. Study Personnel
Our records for the previously approved IRB application indicate the following individuals are study personnel on this project (if
applicable):
Last Name
First Name
Bernard
Andrew
Feola
David
Foster
Jeffrey
Griffin
Jarod
Herndon
Brooke
Matuszewski
Paul
Moghadamian
Eric
Noehren
Brian
Oyler
Douglas
Primm
Daniel
Wright
Raymond
Zuelzer
David
Please review the individuals listed above and update your records as needed in the Study Personnel section of the E-IRB application,
being sure that each individual listed has completed or is up-to-date on the mandatory human research protection training [see the
policy on Mandatory Human Subject Protection Training FAQs (required every three years)].
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To meet federal requirements the IRB is relying on your RESEARCH DESCRIPTION as a protocol summary and
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Review your Research Description section and update the Confidentiality portion, if necessary, to describe measures for security of
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14. Subject Demographics
Our records for the previously approved IRB application indicate the following categories of subjects and controls are
included in your research:
Children (individuals under age 18)
Wards of the State (Children)
Emancipated Minors
Students
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UK Medical Center Residents or
House Officers
Impaired Consent Capacity Adults
Pregnant Women/Neonates/Fetal
Material
Prisoners
Non-English Speaking
International Citizens
Normal Volunteers
Military Personnel and/or DoD
Civilian Employees
Patients
Appalachian Population
Please review the Subject Demographics section of your IRB application for accuracy, and note the following:
If during the course of your research 1) any prisoners have been enrolled, OR 2) subjects have been enrolled that became involuntarily
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Note: If either 1 or 2 above apply, and you have received funding from the Department of Health and Human Services (HHS), a
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have become involuntarily confined/detained in a penal institution cannot continue participation in the research until OHRP issues
approval. If the Certification has not been submitted, contact the Office of Research Integrity.
Based on the total # of subjects who have enrolled, complete the subject demographic section below:
     Participant Demographics
Cisgender Man 
Cisgender Woman 
TGNB/TGE 
Unknown/Not Reported
American
Indian/Alaskan
Native
Asian
Black or
African
American
Latinx
Native
Hawaiian or
Other Pacific
Islander
White
American
Arab/Middle
Eastern/North
African
Indigenous
People
3
1
40
26
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Around the
World
More than
One Race
Unknown or
Not Reported
                                                                                                   
If unknown, please explain why:
15. Research Sites
Our records for the previously approved IRB application indicate that you are conducting research at the following sites:
UK Sites
UK Classroom(s)/Lab(s)
UK Clinics in Lexington
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UK Hospital
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Institutions
Fayette Co. School Systems *
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Documents needing updating may include, but not limited to:
Consent forms (attachment under Informed Consent section)
Brochures (attachment under Additional Info section)
Advertisements (attachment under Research Description section) ;
Letter of support (attachment under Research Sites section)).
Please revise applicable sections and attachments as necessary.
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16. Disclosure of Significant Financial Interest
Disclosure of Significant Financial Interest:
Our records for the previously approved IRB application indicate that you, your investigators, and/or key personnel (KP) have a
significant financial interest (SFI) related to your/their responsibilities at the University of Kentucky (that requires disclosure per the
UK administrative regulation 7:2): 
Yes
No
If you need to update your records, please go to the PI Contact Information section and/or Details for individuals listed in the Study
Personnel section to change your response to the applicable question(s).
17. Supplementals
To ensure the IRB has the most accurate information for your protocol you are expected to re-visit the E-IRB application sections and
make corrections or updates as needed. At a minimum you are being asked to review the following sections for accuracy:
STUDY DRUG INFORMATION—Please review for accuracy.
STUDY DEVICE INFORMATION—Please review for accuracy.
RESEARCH ATTRIBUTES—Please review for accuracy.
OTHER REVIEW COMMITTEES -- Please review for accuracy.
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PROJECT INFORMATION
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Title of Project: (Use the exact title listed in the grant/contract application, if applicable). 
If your research investigates any aspect of COVID-19, please include "COVID19" at the beginning of your Project Title and Short Title 
Inflammatory Response to Trauma – Does Early Cytokine
Modulation Improve Patient Outcome?
Short Title Description 
Please use a few key words to easily identify your study - this text will be displayed in the Dashboard listing for your study.
Inflammatory Markers
Anticipated Ending Date of Research Project: 
Maximum number of human subjects (or records/specimens to be reviewed) 
200
After approval, will the study be open to enrollment of new subjects or new data/specimen collection? 
Yes
No
10/31/2023
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PI CONTACT INFORMATION
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Principal Investigator (PI) role for E-IRB access
The PI is the individual holding primary responsibility on the research project with the following permissions on the E-IRB application:
1. Read; 
2. write/edit;
3. receive communications; and 
4. submit to the IRB (IR, CR, MR, Other Review*).
If research is being submitted to or supported by an extramural funding agency such as NIH, a private foundation or a
pharmaceutical/manufacturing company, the PI listed on the grant application or the drug protocol must be listed as PI here. 
Please fill in any blank fields with the appropriate contact information (gray shaded fields are not editable). Required fields left blank will
be highlighted in pink after you click "Save".
To change home and work addresses, go to myUK and update using the Employee Self Service (ESS) portal. If name has changed,
the individual with the name change will need to submit a 'Name Change Form' to the Human Resources Benefits Office for entering
into SAP. The new name will need to be associated with the individual's Link Blue ID in SAP before the change is reflected in E-IRB.
Contact the HR Benefits Office for additional information.
The Principal Investigator's (PI) contact information is filled in automatically based on who logged in to create the application.
If you are not the Principal Investigator, do NOT add yourself as study personnel.
To change the PI contact information on an application in Researcher edit status:
click "Change Principal Investigator";
search for the PI's name using the search feature;
click "Select" by the name of the Principal Investigator, then "Save Contact Information".
You will automatically be added as study personnel with editing permissions to continue editing the application.
Change  Principal Investigator:
First Name: Arun
Room# &
Bldg: 740 S. Limestone,
Suite K401
Last Name: Aneja
Speed
Sort#: 
40536
Middle Name
Department:
Dept Code: 7H859
 
PI’s
Employee/Student
ID#:
12223247
Rank: 
 
PI's Telephone #: 859-218-3063
Degree: MD, PhD
PI's e-mail
address: arun.aneja@uky.edu
PI's FAX
Number:
PI is R.N.
Yes
No
HSP Trained: Yes
HSP Trained
Date: 6/9/2023
RCR Trained: Yes
Do you, the PI, have a significant financial interest related to your responsibilities at the University of Kentucky (that requires
disclosure per the UK administrative regulation 7:2)?
Yes
No
Orthopaedic Surgery - 7H859

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RISK LEVEL
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Indicate which of the categories listed below accurately describes this protocol
(Risk Level 1) Not greater than minimal risk
(Risk Level 2) Greater than minimal risk, but presenting the prospect of direct benefit to individual subjects
(Risk Level 3) Greater than minimal risk, no prospect of direct benefit to individual subjects, but likely to yield generalizable
knowledge about the subject's disorder or condition.
(Risk Level 4) Research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious
problem affecting the health or welfare of subjects.
*“Minimal risk” means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of
themselves from those ordinarily encountered in daily life or during the performance of routine physical or psychological
examination or tests.
***For Expedited and Exempt Applications, the research activities must be Risk Level 1 (no more than minimal risk to
human subjects).***
Refer to UK's guidance document on assessing the research risk for additional information.
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SUBJECT DEMOGRAPHICS
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Age level of human subjects: (i.e., 6 mths.; 2yrs., etc..) 18 to 75
Study Population:
Describe the characteristics of the subject population, including age range, gender, ethnic background and health status. Identify the criteria for inclusion and
exclusion. 
Provide the following information:
A description of the subject selection criteria and rationale for selection in terms of the scientific objectives and proposed study design;
A compelling rationale for proposed exclusion of any sex/gender or racial/ethnic group;
Justification for the inclusion of vulnerable groups such as children, prisoners, adults with impaired consent capacity, or others who may be vulnerable to
coercion or undue influence.
Please consider these resources: 
NIH Diversity Policy 
FDA Diversity Guidance 
The study population will consist of 200 patients (100 control, 100 treated with Ketorolac) that are admitted to the inpatient surgical service at our level I trauma
center for management of trauma care. Trauma patients that are between the ages of 18-75 and with NISS > 9 (moderate injury) will be enrolled [24, 25]. All
patients will be treated according to the standard Advance Trauma Life Support (ATLS) protocol. Those admitted to the ICU will be treated according to
standard ICU protocols. 
Patient demographics are expected to be consistent with the general trauma patient population in central Kentucky. We will prospectively identify skeletal
mature patients for inclusion in our research protocol. The detailed inclusion and exclusion criteria are listed in Table 1.
Attachments
Indicate the targeted/planned enrollment of the following members of minority groups and their subpopulations. Possible demographic
sources: Census Regional Analyst Edition, Kentucky Race/Ethnic Table, Kentucky Population Data. 
(Please note: The IRB will expect this information to be reported at Continuation Review time for Pre-2019 FDA-regulated
Expedited review and Full review applications):
Participant Demographics
Cisgender Man 
Cisgender Woman 
TGNB/TGE 
Unknown/Not Reported
American
Indian/Alaskan
Native:
Asian:
Black/African
American:
Latinx:
Native
Hawaiian/Pacific
Islander:
White:
American
Arab/Middle
Eastern/North
African:
Indigenous
People Around
the World:
More than One
Race:
Unknown or Not
Reported:
 
If unknown, please explain why:
Indicate the categories of subjects and controls to be included in the study. You may be required to complete additional forms depending on
the subject categories which apply to your research. If the study does not involve direct intervention or direct interaction with subjects, (e.g.,
record-review research, outcomes registries), do not check populations which the research does not specifically target. For example: a large
record review of a diverse population may incidentally include a prisoner or an international citizen, but you should not check those categories
if the focus of the study has nothing to do with that status.
3
3
3
3
94
94
Section 6 Page 1 of 3
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Check All That Apply (at least one item must be selected)
Children (individuals under age
18)
Wards of the State (Children)
Emancipated Minors
Students
College of Medicine Students
UK Medical Center Residents or
House Officers
Impaired Consent Capacity
Adults
Pregnant Women/Neonates/Fetal
Material
Prisoners
Non-English Speaking (translated
long or short form)
International Citizens
Normal Volunteers
Military Personnel and/or DoD
Civilian Employees
Patients
Appalachian Population
ADDITIONAL INFORMATION:
Please visit the IRB Survival Handbook for
more information on:
Children/Emancipated Minors
Students as Subjects
Prisoners
Impaired Consent Capacity Adults
Economically or Educationally
Disadvantaged Persons
Other Resources:
UKMC Residents or House Officers
[see requirement of GME]
Non-English Speaking [see also the
E-IRB Research Description section
on this same topic]
International Citizens [DoD SOP may
apply]
Military Personnel and/or DoD Civilian
Employees
Section 6 Page 2 of 3
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Traumatic brain injury or acquired brain
injury
Severe depressive disorders or Bipolar
disorders
Schizophrenia or other mental disorders
that
involve serious cognitive disturbances
Stroke
Developmental disabilities
Degenerative dementias
CNS cancers and other cancers with
possible CNS involvement
Late stage Parkinson’s Disease
Late stage persistent substance
dependence
Ischemic heart disease
HIV/AIDS
COPD
Renal insufficiency
Diabetes
Autoimmune or inflammatory disorders
Chronic non-malignant pain disorders
Drug effects
Other acute medical crises
Assessment of the potential recruitment of subjects with impaired consent capacity (or likelihood):
Check this box if your study does NOT involve direct intervention or direct interaction with subjects (e.g., record-review research, secondary
data analysis). If there is no direct intervention/interaction you will not need to answer the impaired consent capacity questions.
Does this study focus on adult subjects with any conditions that present a high likelihood of impaired consent capacity or fluctuations in
consent capacity? (see examples below)
Yes
No
If Yes and you are not filing for exemption certification, go to "Form T", complete the form, and attach it using the button below.
Examples of such conditions include:
Attachments
Section 6 Page 3 of 3
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INFORMED CONSENT/ASSENT PROCESS/WAIVER
0 unresolved
comment(s)
For creating your informed consent attachment(s), please download the most up-to-date version listed in "All Templates" under the
APPLICATION LINKS menu on the left, and edit to match your research project.
Additional Resources:
Informed Consent/Assent Website
Waiver of Consent vs. Waiver of Signatures
Sample Repository/Registry/Bank Consent Template
Consent/Assent Tips:
If you have multiple consent documents, be sure to upload each individually (not all in a combined file).
If another site is serving as the IRB for the project, attach the form as a “Reliance Consent Form” so the document will not receive
a UK IRB approval stamp; the reviewing IRB will need to stamp the consent forms.
Changes to consent documents (e.g., informed consent form, assent form, cover letter, etc...) should be reflected in a 'tracked
changes' version and uploaded separately with the Document Type "Highlighted Changes".
It is very important that only the documents you wish to have approved by the IRB are attached; DELETE OUTDATED FILES --
previously approved versions will still be available in Protocol History.
Attachments that are assigned a Document Type to which an IRB approval stamp applies will be considered the version(s) to be
used for enrolling subjects once IRB approval has been issued. 
Document Types that do NOT get an IRB approval stamp are:
"Highlighted Changes",
"Phone Script", and
"Reliance Consent Form",
"Sponsor's Sample Consent Form".
How to Get the Section Check Mark
1. You must:
a) provide a response in the text box below describing how investigators will obtain consent/assent, and 
b) check the box for at least one of the consent items and/or check mark one of the waivers
2. If applicable attach each corresponding document(s) as a read-only PDF.
3. If you no longer need a consent document approved (e.g., closed to enrollment), or, the consent document submitted does not
need a stamp for enrolling subjects (e.g., umbrella study, or sub-study), only select "Stamped Consent Doc(s) Not Needed".
4. After making your selection(s) be sure to scroll to the bottom of this section and SAVE your work!
Check All That Apply
Informed Consent Form (and/or Parental Permission Form and/or translated short form)
Assent Form
Cover Letter (for survey/questionnaire research)
Phone Script
Informed Consent/HIPAA Combined Form
Debriefing and/or Permission to Use Data Form
Reliance Consent Form
Sponsor's sample consent form for Dept. of Health and Human Services (DHHS)-approved protocol
Stamped Consent Doc(s) Not Needed
Attachments
Informed Consent Process:
Using active voice, describe how investigators will obtain consent/assent. Include:
the circumstances under which consent will be sought and obtained
the timing of the consent process (including any waiting period between providing information and obtaining consent)
Section 7 Page 1 of 4
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who will seek consent
how you will minimize the possibility of coercion or undue influence
the method used for documenting consent
if applicable, who is authorized to provide permission or consent on behalf of the subject
if applicable, specific instruments or techniques to assess and confirm potential subjects’ understanding of the information
Note: all individuals authorized to obtain informed consent should be designated as such in the E-IRB "Study Personnel" section of
this application.
Special considerations may include:
Obtaining consent/assent for special populations such as children, prisoners, or people with impaired decisional capacity
Research Involving Emancipated Individuals 
If you plan to enroll some or all prospective subjects as emancipated, consult with UK legal counsel prior to submitting this
application to the IRB. Include research legal counsel’s recommendations in the "Additional Information" section as a separate
document.
Research Involving Non-English Speaking Subjects 
For information on inclusion of non-English speaking subjects, or subjects from a foreign culture, see IRB Application Instructions
for Recruiting Non-English Speaking Participants or Participants from a Foreign Culture.
Research Repositories 
If the purpose of this submission is to establish a research repository describe the informed consent process. For guidance
regarding consent issues, process approaches, and sample language see the Sample Repository/Registry/Bank Consent
Template.
Consent and/or Authorization by a Legally Authorized Representative (LAR)
Eligible patients will be approached for their consent to participate. Informed consent will be obtained prior to the collection of any
study related data. To encourage a high level of participation from eligible patients, the attending surgeon may be involved in the
consent conversation. The research coordinator and surgeon may initiate the conversation together. 
By virtue of the types of injuries studied (resulting from high energy mechanisms such as high speed motor vehicle crashes, high
falls, and blast injuries) it is expected that a large proportion (> 30%) to have an associated traumatic brain injury which my render
them unable to provide consent for the study. It will be important not to exclude these patients from the study, as it would significantly
reduce our ability to produce generalizable knowledge. These patients are at no greater risk of adverse consequences by virtue of
their participation in the study, and should be given the same opportunity to participate. 
Consistent with Kentucky health care decision statutes for choosing a legally authorized representative for adult subjects unable to
consent, one of the following responsible parties, in the following order of priority (if no individual in a prior class is reasonably
available, willing, and competent to act), is authorized to make research participation decisions on behalf of the person: (a) the
judicially-appointed guardian of the person, if the guardian has been appointed and if the decisions to be made under the consent are
within the scope of the guardianship; (b) the attorney-in-fact named in a durable power of attorney, if the durable power of attorney
specifically includes authority for the decisions to be made under the consent; (c) the spouse of the person; (d) an adult child of the
person, or if the person has more than one (1) child, the majority of the adult children who are reasonably available for consultation;
(e) the parents of the subject; (f) the nearest living relative, or if more than one of the same relation, a majority of the nearest living
relatives.
Consent by a legally authorized representative should involve all the same considerations that informed consent from a competent
subject involves.
Guidance will be provided to assist the LAR in making the consent decision. They will advised to base the decision on the
participant’s expressed wishes, or, if these are not known, what they believe the participant would have desired under the
circumstances of the injury, their beliefs and values. If the LAR does not know what the participant would have wanted, the LAR will
advised to base the decision with the participant’s best interest in mind. They will be asked to carefully consider how much leeway the
participant would likely give the LAR in making the choice about participation in the study.
Recognizing that consent is an ongoing process, the study team will encourage the participants to ask additional questions that may
arise during the course of their participation in the study.
Not Applicable
Request for Waiver of Informed Consent Process
If you are requesting IRB approval to waive the requirement for the informed consent process, or to alter some or all of the
elements of informed consent, complete, Section 1 and Section 2 below.
Note: The IRB does not approve waiver or alteration of the consent process for greater than minimal risk research, except
for planned emergency/acute care research as provided under FDA regulations. Contact ORI for regulations that apply to
single emergency use waiver or acute care research waiver (859-257-9428).
Section 7 Page 2 of 4
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SECTION 1.
Check the appropriate item:
I am requesting a waiver of the requirement for the informed consent process.
I am requesting an alteration of the informed consent process.
If you checked the box for this item, describe which elements of consent will be altered and/or omitted, and justify the
alteration.
SECTION 2.
Explain how each condition applies to your research.
a) The research involves no more than minimal risk to the subject.
b) The rights and welfare of subjects will not be adversely affected.
c) The research could not practicably be carried out without the requested waiver or alteration.
d) Whenever possible, the subjects or legally authorized representatives will be provided with additional pertinent information
after they have participated in the study.
Section 7 Page 3 of 4
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Request for Waiver of Signatures
If you are requesting IRB approval to waive the requirement for signatures on informed consent forms, your research
activities must fit into one of three regulatory options:
1. The only record linking the participant and the research would be the consent document, and the principal risk would be
potential harm resulting from a breach of confidentiality (e.g., a study that involves participants who use illegal drugs).
2. The research presents no more than minimal risk to the participant and involves no procedures for which written consent
is normally required outside of the research context (e.g., a cover letter on a survey, or a phone script).
3. The participant (or legally authorized representative) is a member of a distinct cultural group or community in which
signing forms is not the norm, the research presents no more than minimal risk to the subject, and there is an appropriate
alternative mechanism for documenting that informed consent was obtained.
Select the option below that best fits your study. 
If the IRB approves a waiver of signatures, participants must still be provided oral or written information about the study.
To ensure you include required elements in your consent document, use the Cover Letter Template as a guide. There is
an English and a Spanish version.
 
Option 1
Describe how your study meets these criteria:
a) The only record linking the participant and the research would be the consent document:
b) The principal risk would be potential harm resulting from a breach of confidentiality (i.e., a study that involves subjects
who use illegal drugs).
Under this option, each participant (or legally authorized representative) must be asked whether (s)he wants to sign a
consent document; if the participant agrees to sign a consent document, only an IRB approved version should be
used.
Option 2
Describe how your study meets these criteria:
a) The research presents no more than minimal risk to the participant:
b) Involves no procedures for which written consent is normally required outside of the research context (i.e. a cover
letter on a survey, or a phone script):
Option 3
Describe how your study meets these criteria:
a) The subject (or legally authorized representative) is a member of a distinct cultural group or community in which
signing forms is not the norm.
b) The research presents no more than minimal risk to the subject.
c) There is an appropriate alternative mechanism for documenting that informed consent was obtained.
Section 7 Page 4 of 4
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STUDY PERSONNEL
1 unresolved comment(s)
Do you have study personnel who will be assisting with the research?
After selecting 'Yes' or 'No' you must click the 'Save Study Personnel Information' button. 
Yes
No
Manage Study Personnel
Identify other study personnel assisting in research project:
The individual listed as PI in the 'PI Contact Information' section should NOT be added to this section.
If the research is required for a University of Kentucky academic program, the faculty advisor is also considered study personnel and should be listed below.
***Residents and students who are PI’s are encouraged to designate the faculty advisor or at least one other individual as a contact with an editor role (DP).***
Role: DP = Editor (individual can view, navigate, and edit the application for any review phase (IR, CR/FR, MR) or 'Other Review", and submit Other Reviews on
behalf of the PI.)
Role: SP = Reader (individual can view and navigate through the currently approved application only.)
To add an individual via the below feature:
Search for personnel;
Click "select" by the listing for the person you want to add;
For each person, specify responsibility in the project, whether authorized to obtain informed consent, AND denote who should receive E-IRB notifications
(contact status).
NOTE: Study personnel must complete human subject protection (HSP) and Responsible Conduct of Research (RCR) training before implementing
any research procedures. For information about training requirements for study personnel, visit UK’s HSP FAQ page, the RCR Getting Started page, or
contact ORI at 859-257-9428. If you have documentation of current HSP training other than that acquired through UK CITI, you may submit it to ORI
(HSPTrainingSupport@uky.edu) for credit.
Study personnel assisting in research project: 
Last Name
First
Name
Responsibility
In Project
Role
A
C
Contact
Degree
StatusFlag
(HSP)
(HSP)Date
(RCR)
Removed?
Last
Updated
SFI
Bernard
Andrew
Co-
Investigator
DP
Y
N
 
P
Y
10/03/2021
Y
N
01/30/2018
N
Feola
David
Co-
Investigator
DP
Y
N
 
P
Y
12/29/2021
Y
N
01/30/2018
N
Foster
Jeffrey
Study
Coordinator
DP
Y
Y
MD
P
Y
05/18/2022
Y
N
05/19/2022
N
Griffin
Jarod
Study
Coordinator
DP
Y
Y
BS
P
Y
04/13/2021
Y
N
03/27/2023
N
Herndon
Brooke
Study
Coordinator
DP
Y
Y
 
P
Y
01/25/2021
Y
N
11/06/2019
N
Matuszewski
Paul
Sub-
Investigator
DP
Y
N
MD
P
Y
04/28/2021
Y
N
11/10/2020
N
Moghadamian
Eric
Sub-
Investigator
DP
Y
N
MD
P
Y
11/04/2022
Y
N
11/05/2022
N
Noehren
Brian
Co-
Investigator
DP
Y
N
 
P
Y
11/15/2020
Y
N
08/10/2020
N
Oyler
Douglas
Co-
Investigator
DP
Y
N
 
P
Y
02/25/2021
Y
N
01/30/2018
N
Primm
Daniel
Sub-
Investigator
DP
Y
N
MD
P
Y
09/08/2020
Y
N
11/10/2020
N
Wright
Raymond
Sub-
Investigator
DP
Y
N
MD
P
Y
11/29/2021
Y
N
11/10/2020
N
Zuelzer
David
Sub-
Investigator
DP
Y
N
MD
P
Y
11/30/2021
Y
N
11/10/2020
N
Abbenhaus
Eric
Study
Coordinator
DP
Y
N
MD
P
N
05/01/2020
Y
Y
01/13/2022
N
Albano
Ashley
Study
Coordinator
DP
Y
Y
 
P
N
07/21/2020
Y
Y
05/24/2022
N
Belza
Daniel
Data
Collection
SP
Y
N
 
S
N
09/30/2018
Y
Y
04/18/2022
N
Boyle
Maxwell
Data
Collection
SP
Y
N
 
S
Y
05/18/2021
 
Y
01/13/2022
N
Collofello
Brandon
Co-
Investigator
SP
Y
N
MD
P
Y
06/29/2022
N
Y
01/13/2022
N
Comadoll
Shea
Co-
Investigator
DP
Y
N
MD
P
N
07/09/2017
 
Y
04/18/2022
N
Section 8 Page 1 of 2
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Last Name
First
Name
Responsibility
In Project
Role
A
C
Contact
Degree
StatusFlag
(HSP)
(HSP)Date
(RCR)
Removed?
Last
Updated
SFI
Hautala
Gavin
Study
Coordinator
DP
Y
N
MD
P
Y
06/28/2022
Y
Y
01/13/2022
N
Isla
Alexander
Study
Coordinator
DP
Y
Y
 
P
Y
10/09/2020
N
Y
01/13/2022
N
Jacobs
Cale
Co-
Investigator
DP
Y
N
 
P
N
06/18/2020
Y
Y
03/10/2023
N
Kavolus
Matthew
Study
Coordinator
DP
Y
N
MD
P
Y
05/12/2021
Y
Y
03/10/2023
N
Kinchelow
Daria
Study
Coordinator
DP
Y
Y
BA
P
Y
07/08/2022
Y
Y
06/09/2023
N
Liu
Boshen
Co-
Investigator
DP
Y
N
MD
P
N
06/20/2020
 
Y
08/10/2020
N
Pease
Tyler
Study
Coordinator
DP
Y
N
BS
P
Y
04/18/2021
N
Y
03/10/2023
N
Pectol
Richard
Study
Coordinator
DP
Y
Y
B.S.
P
Y
12/13/2021
N
Y
03/10/2023
N
Raffetto
Michael
Study
Coordinator
DP
Y
Y
 
P
N
05/18/2020
N
Y
01/13/2022
N
Smith
April
Study
Coordinator
DP
Y
Y
 
P
N
03/02/2020
 
Y
08/10/2020
N
Sneed
Chandler
Study
Coordinator
DP
Y
Y
BS
P
Y
05/21/2021
Y
Y
06/09/2023
N
Stringer
Paul
Study
Coordinator
DP
Y
Y
 
P
Y
05/08/2023
Y
Y
01/13/2022
N
Teasdall
Robert
Study
Coordinator
DP
Y
Y
 
P
Y
12/11/2022
N
Y
01/13/2022
N
Section 8 Page 2 of 2
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RESEARCH DESCRIPTION
0 unresolved
comment(s)
You may attach a sponsor’s protocol pages in the “Additional Information” section and refer to them where necessary in
the Research Description. However, each prompt that applies to your study should contain at least a summary paragraph.
Pro Tips:
Save your work often to avoid losing data.
Use one of the attachment buttons in this section or under the Additional Information section to include supplemental
information with your application. During the document upload process, you will be able to provide a brief description
of the attachment.
Background
Include a brief review of existing literature in the area of your research. You should identify gaps in knowledge that should be addressed
and explain how your research will address those gaps or contribute to existing knowledge in this area. For interventional research,
search PubMed and ClinicalTrials.gov for duplicative ongoing and completed trials with same condition and intervention(s).
Accidental trauma is the 4th leading cause of death in the United States, and it is associated with a complex inflammatory response [1].
This response is associated with post-traumatic complications such as; multi-organ dysfunction syndrome (MODS), bacterial
pneumonia, acute respiratory distress syndrome (ARDS), systemic inflammatory response syndrome (SIRS), and post traumatic pain
(PTP) [2-7]. It is unknown whether early modulation of inflammatory cytokines is associated with improved patient outcomes, reduced
narcotic requirements, and improved patient subjective pain after hospital discharge. 
Our preliminary data has shown: (1) elevated blood cytokine concentrations during the acute phase of trauma are correlated with the
development of fatal post-traumatic complications [8], (2) that early administration of a non-steroidal anti-inflammatory drug (NSAID)
resulted in decreased blood serum levels of IL-6, Prostaglandin E2 (PGE2), improved pulmonary edema, and enhanced arterioles
ability to vasoconstrict in response to hemorrhage in animal models [9], and (3) that the addition of the internal physiologic parameters
(inflammatory cytokines) to New Injury Severity Score (NISS – a marker of the external anatomical insult) significantly improves the
ability to predict hospital length of stay of trauma patients when compared to NISS alone [10]. Our group is the first to use an
integrative approach that combines the external anatomic injury data with the internal physiologic response for accurate prediction of
patient’s clinical outcome. Therefore, if we apply this same mindset to treatment, we can improve the trauma patients’ care by
addressing both parameters as opposed to solely focusing on the external injury as done in the past. Our ability to modify post-
traumatic physiologic response via short-term administration of a NSAID may lead to improved patient outcome. 
Over the last decade, clinicians remain puzzled over the safety of NSAID administration after fracture in terms of bone union [11-15]. In
addition, given the current landscape for opioid epidemic in the United States [16, 17], alternative non-opioid pain management during
acute trauma has the potential to reduce opioid consumption and represents a pivotal component of multimodal analgesia strategy.
Objectives
List your research objectives. Please include a summary of intended research objectives in the box below.
Aim 1: Determine if a brief and low dose scheduled administration of an NSAID (Ketorolac) will reduce the inflammatory cascade and
improve the clinical outcomes of orthopaedic trauma patients. Ketorolac will be used as the NSAID of choice because it is of low cost
to patients, readily available intravenously, has few side effects, and also decrease opioid consumption in acute trauma [18-21]. 
Aim 2: Determine whether patients who received Ketorolac treatment require less opioid medication throughout their hospital and post-
operative course. The outcome variable will be patient’s subjective pain scores, morphine milligram equivalent intake along with other
pain modulating medication intake. Inpatient and outpatient subjective pain reports will be collected and analyzed for pain relief and
medication use.
Study Design
Describe and explain the study design (e.g., observational, secondary analysis, single/double blind, parallel, crossover, deception, etc.).
Clinical Research: Indicate whether subjects will be randomized and whether subjects will receive any placebo.
Community-Based Participatory Research: If you are conducting community-based participatory research (CBPR), describe
strategies for involvement of community members in the design and implementation of the study, and dissemination of results from
the study.
Qualitative research: Indicate ranges where flexibility is needed, if a fixed interview transcript is not available, describe interview
topics including the most sensitive potential questions.
Research Repositories: If the purpose of this submission is to establish a Research Repository (bank, registry) and the material
you plan to collect is already available from a commercial supplier, clinical lab, or established IRB approved research repository,
provide scientific justification for establishing an additional repository collecting duplicate material. Describe the repository design
and operating procedures. For relevant information to include, see the UK Research Biospecimen Bank Guidance or the UK
Research Registry Guidance.
Section 9 Page 1 of 8
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This study is a double blinded, randomized, prospective, and multi-specialty collaborative clinical trial to assess the effect of early
administration of Ketorolac as a preventative treatment for the post-traumatic complications associated with the hyperinflammatory
response in trauma patients. The second objective is to determine whether patients randomized to ketorolac treatment require less
opioid analgesics during their hospital and postoperative course than the standard of care (SOC). Please see protocol for full
description of study design.
Attachments
Subject Recruitment Methods & Advertising
Describe how the study team will identify and recruit subjects. Please consider the following items and provide additional information as
needed so that the IRB can follow each step of the recruitment process.
How will the study team identify potential participants?
Who will first contact the potential subjects, and how?
Will you use advertisements? If so, how will you distribute those?
How and where will the research team meet with potential participants?
If applicable, describe proposed outreach programs for recruiting women, minorities, or disparate populations.
How you will minimize undue influence in recruitment?
Attach copies of all recruiting and advertising materials (emails, verbal scripts, flyers, posts, messages, etc.).
For additional information on recruiting and advertising:
IRB Application Instructions - Advertisements
PI Guide to Identification and Recruitment of Human Subjects for Research
Potential patients will be prospectively identified either at the time of the initial consultation, at the morning fracture conference, based
on the orthopaedic injury diagnosis (Inclusion criteria noted above). Patients will be screened by their inclusion and exclusion criteria,
and if met will be considered for enrollment in the study.
Not Applicable
Attachments
Section 9 Page 2 of 8
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Back to Top
Research Procedures
Describe how the research will be conducted.
What experience will study participants have?
What will study participants be expected to do?
How long will the study last?
Outline the schedule and timing of study procedures.
Provide visit-by-visit listing of all procedures that will take place.
Identify all procedures that will be carried out with each group of participants.
Describe deception and debrief procedures if deception is involved.
Differentiate between procedures that involve standard/routine clinical care and those that will be performed specifically for this
research project. List medications that are explicitly forbidden or permitted during study participation.
Aim 1: The study population will consist of 200 patients (100 control, 100 treated with Ketorolac) that are admitted to the inpatient
surgical service at our level I trauma centers for management of orthopedic trauma care. All trauma patients that are between the ages
of 18-75 and with NISS > 9 (moderate injury) [33, 34] will be enrolled and treated according to the standard Advance Trauma Life
Support (ATLS) protocol. 100 patients in the control group will receive placebo intravenous saline every 6 hours for their initial 5 days
of hospitalization and no NSAID administration. 100 patients randomized to the treatment group will receive 15 mg of Ketorolac every
6 hours for their initial 5 days of hospitalization. A daily blood sample (10 cc) will be collected on Days 1–5 by blinded health care
personnel. These blood samples will be analyzed via sandwich ELISA method for concentrations of IL-1, IL-6, IL-10, and PGE2.
Serum concentrations will be compared between the treatment and control groups using two-tailed independent t-tests. In addition to
the standard trauma labs, patient demographics, injury data (gender, age, BMI, mechanism of injury, NISS, and types of
surgical/procedural interventions), injury outcomes (incidence of bacterial pneumonia, ARDS, SIRS, MODS), complications defined in
the National Trauma Dataset, and inflammatory data will be compiled, tracked, and maintained in our clinical database (REDCap).
Outcome variables (hospital and ICU length of stay and occurrence of pneumonia and/or ARDS and/or SIRS or death), and the
predictor variables of interest (inflammatory markers and NISS) will be compared using Poisson regression. The odds of developing
post traumatic complications in the different predictor groups will be determined using multiple logistic regressions. The covariates will
be adjusted for in the regression models: age, sex, injury severity, severity of head and/or extremity injury, injury mechanism, and injury
outcome. 
Aim 2: The enrolled patients will be followed daily by our trained clinical research coordinator. Patient’s subjective pain scores will be
assessed and documented by the trained nursing staff using Visual Analogue Scale (VAS) daily. Morphine milligram equivalent (MME)
along with other pain medication intake will be recorded per day for the duration of Ketorolac or placebo therapy. Patient’s clinical
course will be monitored closely and daily to ensure no NSAIDs will be administered to the control cohort to ensure consistency and
protocol adherence of the study. Once patients are discharged from the hospital, outpatient pain scores will be assessed during
routine clinic follow up visits using Patient-Reported Outcomes Measurement Information System (PROMIS) surveys. Opioid and pain
modulating medication prescription refills will be monitored using the State All Scheduled Prescription Electronic Reporting system.
Patient narcotic requirement will be assessed during all of the routine follow up visits by the same research coordinator in order to
maintain consistency. Patients’ inpatient and outpatient subjective pain score and MME intake will be compared between the control
and treatment groups using two-tailed independent t-tests. 
Aim 3: 
Finally, analysis will be performed to evaluate the treatment effects between two groups using fracture unions as a dependent variable.
The rate of fracture unions will be calculated at 3 month, 6 month and 12 month. Fractures will be considered united if they met the
criteria for clinical or radiological union. The baseline clinical factors that are independently associated with fracture unions will be
assessed from candidate variables and are entered using a forward (p<0.05) and backwards (p<0.10) stepwise selection procedure.
Finally, the multivariate model will be performed to assess the association of clinical factors with fracture unions starting at 3 month
between two groups.
Attachments
Data Collection & Research Materials
In this section, please provide the following:
Describe all sources or methods for obtaining research materials about or from living individuals (such as specimens, records,
surveys, interviews, participant observation, etc.), and explain why this information is needed to conduct the study.
For each source or method described, please list or attach all data to be collected (such as genetic information, interview scripts,
survey tools, data collection forms for existing data, etc.).
If you will conduct a record or chart review, list the beginning and end dates of the records you will view.
Please see above (Research Procedures Section) for detailed outcome variables
Attachments
Resources
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Describe the availability of the resources and adequacy of the facilities that you will use to perform the research. Such resources may
include:
Staffing and personnel, in terms of availability, number, expertise, and experience;
Computer or other technological resources, mobile or otherwise, required or created during the conduct of the research;
Psychological, social, or medical services, including equipment needed to protect subjects, medical monitoring, ancillary care, or
counseling or social support services that may be required because of research participation;
Resources for communication with subjects, such as language translation/interpretation services.
All chart reviews will occur at the in the Department of Orthopedics Surgery and Sports Medicine. Documented data will be stored in a
password-protected excel spreadsheet stored on a University of Kentucky password-encrypted computer that will be locked in Cale
Jacobs’ office (Kentucky Clinic, Room K426) when not being used for data collection. There will be a password-protected electronic
master list that connects the patient’s medical records number and/or encounter number with the spreadsheet being used for data
collection. This master list will be kept separate from the data collection spreadsheet file, and the master list will be stored on the
department’s password-protected network drive. Only study personnel identified in the IRB-approved study personnel list will have
access to the master list and data collection spreadsheet files. At this time, we expect that the current study personnel will perform all
the study statistical analyses. However, should additional statistical assistance be required, the statistician will be added to the study’s
personnel list prior to performing any study-related analyses.
Potential Risks & Benefits
Risks
Describe any potential risks – including physical, psychological, social, legal, ability to re-identify subjects, or other risks. Assess
the seriousness and likelihood of each risk.
Which risks may affect a subject’s willingness to participate in the study?
Describe likely adverse effects of drugs, biologics, devices or procedures participants may encounter while in the study.
Qualitative research - describe ethical issues that could arise while conducting research in the field and strategies you may use to
handle those situations.
Describe any steps to mitigate these risks.
Benefits
Describe potential direct benefits to study participants – including diagnostic or therapeutic, physical, psychological or emotional,
learning benefits. This cannot include incentives or payments.
State if there are no direct benefits.
Describe potential benefits to society and/or general knowledge to be gained.
Describe why potential benefits are reasonable in relation to potential risks. If applicable, justify why risks to vulnerable subjects are
reasonable to potential benefits.
Long-term non-steroidal anti-inflammatory drug (NSAID) intake has been correlated with impaired or delayed fracture healing in animal
and clinical studies with a dose dependent response. However, the evidence in animal studies is conflicting, and there are few
retrospective clinical studies and even fewer large scale prospective randomized trials. A recent meta-analysis demonstrated that
higher quality studies found no evidence of negative effect of NSAIDs on bone-healing [21]. To our knowledge, the present study will
be the largest prospective randomized clinical trial to evaluate the effect of short term and low dose administration of NSAID on trauma
patient outcomes, opioid consumption, and fracture union rates.
There is no guarantee that the patient will receive any personal benefit from taking part in this study; however, the collection of this
information will in the future, help clinicians better understand patients with similar injuries.
Available Alternative Opportunities/Treatments
Describe alternative treatments or opportunities that might be available to those who choose not to participate in the study, and which
offer the subject equal or greater advantages. If applicable, this should include a discussion of the current standard of care treatment(s).
There is no alternative treatment options. Should participants refused to participate in the present study, they will receive the standard
medical treatments per standard University of Kentucky Health Care protocols.
Back to Top
Records, Privacy, and Confidentiality
Specify where the data and/or specimens will be stored and how the researcher will ensure the privacy and confidentiality of both.
Specify who will have access to the data/specimens and why they need access.
Describe how data will be managed after the study is complete:
If data/specimens will be maintained, specify whether identifiers will be removed from the maintained information/material.
If identifiers will not be removed, provide justification for retaining them and describe how you will protect confidentiality.
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If the data/specimens will be destroyed, verify that this will not violate retention policies and will adhere to applicable facility
requirements.
If this study will use de-identified data from another source, describe what measures will be taken to ensure that subject identifiers are
not given to the investigator.
If applicable, describe procedures for sharing data/specimens with collaborators not affiliated with UK.
For additional considerations: 
Return of Research Results or Incidental Research Findings 
HIPAA policies 
FERPA policies 
Procedures for Transfer agreements 
Information regarding multi-site studies 
NIH Genomic Data Sharing (GDS) Policy 
Digital Data
The sources of research material for this study will include previous documentation of the patient’s initial injury and recovery course,
clinical documentation, and surgical documentation. Every attempt will be made to ensure patient confidentiality. All data will be stored
on a secured computer and backed up on a secured network, which can only be accessed by a member of the research team. The
computer and data will be stored inside a locked office when not being used for data collection.
The researchers involved with this study will keep private all research records that identify the subjects to the extent of the law. The
information obtained from the research may be combined and presented in written materials, but these materials will not contain any
identifying material specific to the patient. There will be a password-protected electronic master list that connects the patient’s medical
records number and/or encounter number with the spreadsheet being used for data collection. This master list will be kept separate
from the data collection spreadsheet file, and the master list will be stored on the department’s password-protected network drive.
Only study personnel identified in the IRB-approved study personnel list will have access to the master list and data collection
spreadsheet files. Immediately upon completion of data collection (estimated to be December, 2017), patient identifiers including
name, date of birth, and medical record number will be deleted from the spreadsheet and patients will be instead identified using a
study-specific ID number which is not the patient’s social security number or medical records number. The password-protected file will
be stored on the department’s password-protected network drive. Data and records will be kept for at least six years post study
closure.
A breach of confidentiality is a risk. Access to all patient information will be password protected and only available to listed research
personnel. All information will be kept in the University of Kentucky Department of Orthopedics and Sports Medicine password-
protected network drive and will only be available to listed research personnel. While every attempt will be made to prevent a breach of
confidentiality, should a breach occur, immediate measures will be taken to prevent further breach and any damage resulting from it.
The breach will be immediately reported to the IRB and, in a cooperative effort with the IRB and University, will contact the involved
study subject(s) to inform them of the breach and actions taken to resolve it.
UK IRB policies state that IRB-related research records must be retained for a minimum of 6 years after study closure. Do
you confirm that you will retain all IRB-related records for a minimum of 6 years after study closure?
Yes
No
Payment
Describe the incentives (monetary or other) being offered to subjects for their participation. If monetary compensation is offered,
indicate the amount and describe the terms and schedule of payment. Please review this guidance for more information on payments to
subjects, including restrictions and expectations.
Not Applicable
Costs to Subjects
Include a list of services and/or tests that will not be paid for by the sponsor and/or the study (e.g., MRI, HIV). Keep in mind that a
subject will not know what is “standard” – and thus not covered by the sponsor/study – unless you tell them.
Not Applicable. All of the costs of blood draws and Ketorolac administration will be covered by the principal investigator.
Data and Safety Monitoring
The IRB requires review and approval of data and safety monitoring plans for greater than minimal risk research or NIH-funded/FDA-
regulated clinical investigations.
If you are conducting greater than minimal risk research, or your clinical investigation is NIH-funded, describe your Data and Safety
Monitoring Plan (DSMP). Click here for additional guidance on developing a Data and Safety Monitoring Plan.
If this is a non-sponsored investigator-initiated protocol considered greater than minimal risk research, and if you are planning on
using a Data and Safety Monitoring Board (DSMB) as part of your DSMP, click here for additional guidance for information to
include with your IRB application.
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The study will monitor and report adverse events to ensure patient safety. Definitions and procedures for reporting adverse events are
designed to satisfy 45 CFR Part 46, Subpart A; the “Common Rule”, shared by 17 Departments and Agencies as well as 21 CFR
312, the FDA regulation for adverse events. The Common Rule requires written procedures and policies for ensuring reporting of
“unanticipated problems” involving risks to participants to IRBs, appropriate institutional officials, and the Department or Agency Head. 
Monitoring of the progress of clinical investigations and the safety of participants: The proposed medication for this investigation is a
commonly utilized substance for pain control. Patients will be monitored for adverse effects of these medications continuously while
they are an inpatient. Please refer to Study Drug information and Informed Consent Appendix B for further details. The research team
will work closely with the medical management team daily to note if any of these difficulties should arise. Other minor side effects will
be recorded and monitored through chart review (nausea, abdominal pain, minor bruising and bleeding) at the conclusion of the
inpatient admission. If necessary, blinding will be broken if any potential side effects are noted and the information regarding treatment
would be helpful to the treating team. The clinical medical monitor of the investigation will be obtained with the help of CCTS and that
person will be added to the study personnel. The PI will be blinded to the subject treatment arm, and thus limit bias in reporting. 
Compliance:
The research team will meet monthly to discuss and review any of the above recorded events and report adverse events to the IRB
accordingly. A yearly report will be filed with the IRB with regards to overall data safety. Study suspension/termination: In the event that
there is a noted increase in the serious side effects of taking the study drug, the study will be suspended for review. 
Data Accuracy:
The research team will meet monthly to go over the collected data and perform spot reviews to determine the accuracy of the data
collection from the medical record and study procedures.
Back to Top
Future Use and Sharing of Material (e.g., Data/Specimens/Information)
If the material collected for this study will be used by members of the research team or shared with other researchers for future studies,
please address the following:
list the biological specimens and/or information that will be kept
briefly describe the types, categories and/or purposes of the future research
describe any risks of the additional use
describe privacy/confidentiality protections that will be put into place
describe the period of time specimens/information may be used
describe procedures for sharing specimens/information with secondary researchers
describe the process for, and limitations to, withdrawal of specimens/data
Identifiable information such as the participant's name, medical record number, or date of birth may be removed from the
information or samples collected in this study. After removal, the information or samples may be used for future
research or shared with other researchers without the participant's additional informed consent.
In addition to the main study, the participant is being asked to allow us to keep and use their information and/or specimens
for future research that involves surgical complications and patient outcome research in the trauma patient
population. The specimens in this study consist of blood plasma that is being collected to measure inflammatory markers and cytokine
levels during the first 5 inpatient days.
Are you recruiting or expect to enroll Non-English Speaking Subjects or Subjects from a Foreign Culture? (does not include short
form use for incidentally encountered non-English subjects)
Yes
No
Non-English Speaking Subjects or Subjects from a Foreign Culture
Recruitment and Consent:
Describe how information about the study will be communicated to potential subjects appropriate for their culture, and if necessary,
how new information about the research may be relayed to subjects during the study. 
When recruiting Non-English-speaking subjects, provide a consent document in the subject’s primary language. After saving this
section, attach both the English and translated consent documents in the “Informed Consent" section. 
Cultural and Language Consultants:
The PI is required to identify someone who is willing to serve as the cultural consultant to the IRB.
This person should be familiar with the culture of the subject population and/or be able to verify that translated documents are
the equivalent of the English version of documents submitted.
The consultant should not be involved with the study or have any interest in its IRB approval.
Please include the name, address, telephone number, and email of the person who agrees to be the cultural consultant for
your study.
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ORI staff will facilitate the review process with your consultant. Please do not ask them to review your protocol separately.
For more details, see the IRB Application Instructions on Research Involving Non-English Speaking Subjects or Subjects from a
Foreign Culture. 
Local Requirements:
If you will conduct research at an international location, identify and describe:
relevant local regulations
data privacy regulations
applicable laws
ethics review requirements for human subject protection
Please provide links or sources where possible. If the project has been or will be reviewed by a local ethics review board, attach a
copy in the “Additional Information/Materials” section. You may also consult the current edition of the International Compilation of
Human Research Standards
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Does your study involve HIV/AIDS research and/or screening for other reportable diseases (e.g., Hepatitis C, etc…)?
Yes
No
HIV/AIDS Research
If you have questions about what constitutes a reportable disease and/or condition in the state of Kentucky, see ORI’s summary
sheet: “Reporting Requirements for Diseases and Conditions in Kentucky" [PDF].
HIV/AIDS Research: There are additional IRB requirements for designing and implementing the research and for obtaining
informed consent. Describe additional safeguards to minimize risk to subjects in the space provided below.
For additional information, visit the online IRB Survival Handbook to download a copy of the "Medical IRB's requirements for
Protection of Human Subjects in Research Involving HIV Testing" [D65.0000] [PDF], and visit the Office for Human Research
Protections web site for statements on AIDS research, or contact the Office of Research Integrity at 859-257-9428.
PI-Sponsored FDA-Regulated Research
Is this an investigator-initiated study that:
1) involves testing a Nonsignificant Risk (NSR) Device, or
2) is being conducted under an investigator-held Investigational New Drug (IND) or Investigational Device Exemption (IDE)?
Yes
No
PI-Sponsored FDA-Regulated Research
If the answer above is yes, then the investigator assumes the regulatory responsibilities of both the investigator and sponsor. The
Office of Research Integrity provides a summary list of sponsor IND regulatory requirements for drug trials [PDF], IDE regulatory
requirements for SR device trials [PDF], and abbreviated regulatory requirements for NSR device trials [PDF]. For detailed
descriptions see FDA Responsibilities for Device Study Sponsors or FDA Responsibilities for IND Drug Study Sponsor-
Investigators.
Describe the experience/knowledge/training (if any) of the investigator serving as a sponsor (e.g., previously held an
IND/IDE); and
Indicate if any sponsor obligations have been transferred to a commercial sponsor, contract research organization (CRO),
contract monitor, or other entity (provide details or attach FDA 1571).
IRB policy requires mandatory training for all investigators who are also FDA-regulated sponsors (see Sponsor-Investigator
FAQs). A sponsor-investigator must complete the applicable Office of Research Integrity web based training, (drug or device)
before final IRB approval is granted.
Has the sponsor-investigator completed the mandatory PI-sponsor training prior to this submission?
Yes
No
If the sponsor-investigator has completed equivalent sponsor-investigator training, submit documentation of the content for the
IRB’s consideration. 
Attachments
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HIPAA
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Is HIPAA applicable?
Yes
No
(Visit ORI's Health Insurance Portability and Accountability Act (HIPAA) web page to determine if your research falls under the HIPAA
Privacy Regulation.)
If yes, check below all that apply and attach the applicable document(s): 
HIPAA De-identification Certification Form
HIPAA Waiver of Authorization
Attachments
Attach Type File Name
Waiver
HIPAA-8-2.pdf
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STUDY DRUG INFORMATION
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The term drug may include:
FDA approved drugs,
unapproved use of approved drugs,
investigational drugs or biologics,
other compounds or products intended to affect structure or function of the body, and/or
complementary and alternative medicine products such as dietary supplements, substances generally recognized as safe (GRAS)
when used to diagnose, cure mitigate, treat or prevent disease, or clinical studies of e-cigarettes examining a potential therapeutic
purpose.
Does this protocol involve a drug including an FDA approved drug; unapproved use of an FDA approved drug; and/or an
investigational drug?
Yes
No
If yes, complete the questions below. Additional study drug guidance.
LIST EACH DRUG INVOLVED IN STUDY IN THE SPACE BELOW
Drug Name:
Ketorolac (Toradol)
Note: Inpatient studies are required by Hospital Policy to utilize Investigational Drug Service (IDS) pharmacies (Oncology or
Non-Oncology). Use of IDS is highly recommended, but optional for outpatient studies. Outpatient studies not using IDS
services are subject to periodic inspection by the IDS for compliance with drug accountability good clinical practices. 
Indicate where study drug(s) will be housed and managed:
Investigational Drug Service (IDS) UK Hospital
Other Location:
Is the study being conducted under a valid Investigational New Drug (IND) application?
Yes
No
If Yes, list IND #(s) and complete the following:
IND Submitted/Held by:
Sponsor:
Held By:
Investigator:
Held By:
Other:
Held By:
Checkmark if the study is being conducted under FDA’s Expanded Access Program (e.g., Treatment IND)
or if this is an Individual Patient Expanded Access IND (FDA Form 3926).
FDA's Expanded Access Program Information for Individual Patient Expanded Access INDs, and attach the
following:
FDA Form 3926;
FDA expanded access approval or correspondence;
Confirmation of agreement from manufacturer or entity authorized to provide access to the product.
For guidance and reporting requirements at the conclusion of treatment see the Expanded Access SOP.
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Complete and attach the required Study Drug Form picking "Study Drug Form" for the document type. Any
applicable drug documentation (e.g., Investigator Brochure; approved labeling; publication; FDA correspondence,
etc.) should be attached using "Other Drug Documentation" for the document type.
Attachments
Attach Type
File Name
Study Drug Form
Toradol.pdf
Study Drug Form
Form O - Inflammatory Markers.pdf
Study Drug Form
Ketorolac.pdf
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STUDY DEVICE INFORMATION
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A DEVICE may be a:
component, part, accessory;
assay, reagent, or in-vitro diagnostic device;
software, digital health, or mobile medical app;
other instrument if intended to affect the structure or function of the body, diagnose, cure, mitigate, treat or prevent disease; or
a homemade device developed by an investigator or other non-commercial entity and not approved for marketing by FDA.
For additional information, helpful resources, and definitions, see ORI's Use of Any Device Being Tested in Research web page.
Does this protocol involve testing (collecting safety or efficacy data) of a medical device including an FDA approved device,
unapproved use of an approved device, humanitarian use device, and/or an investigational device?
Yes
No
[Note: If a marketed device(s) is only being used to elicit or measure a physiologic response or clinical outcome, AND, NO data will
be collected on or about the device itself, you may answer “no” above, save and exit this section, (Examples: a chemo drug study
uses an MRI to measure tumor growth but does NOT assess how effective the MRI is at making the measurement; an exercise study
uses a heart monitor to measure athletic performance but no safety or efficacy information will be collected about the device itself, nor
will the data collected be used for comparative purposes against any other similar device).]
If you answered yes above, please complete the following questions.
LIST EACH DEVICE BEING TESTED IN STUDY IN THE SPACE BELOW
Device Name:
Is the study being conducted under a valid Investigational Device Exemption (IDE),
Humanitarian Device Exemption (HDE) or Compassionate Use?
Yes
No
If Yes, complete the following: 
IDE or HDE #(s)
IDE/HDE Submitted/Held by:
Sponsor:
Held By:
Investigator:
Held By:
Other:
Held By:
 Check if this is a Treatment IDE or Compassionate Use under the Food and Drug Administration (FDA)
Expanded Access program.
For Individual or Small Group Expanded Access, see FDA's Early Expanded Access Program Information,
and attach the following:
FDA expanded access approval or sponsor’s authorization;
An independent assessment from an uninvolved physician, if available;
Confirmation of agreement from manufacturer or entity authorized to provide access to the product.
For guidance and reporting requirements at the conclusion of treatment see the Medical Device SOP.
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Does the intended use of any research device being tested (not clinically observed) in this study meet the regulatory definition of
Significant Risk (SR) device?
Yes. Device(s) being tested in this study presents a potential for serious risk to the health, safety, or welfare of a subject and
(1) is intended as an implant; or (2) is used in supporting or sustaining human life; or (3) is of substantial importance in
diagnosing, curing, mitigating or treating disease, or otherwise prevents impairment of human health; or (4) otherwise presents
a potential for serious risk to the health, safety, or welfare of a subject.
No. All devices being tested in this study do not present a potential for serious risk to the health, safety, or welfare of
subjects/participants.
Complete and attach the required Study Device Form, picking the "Study Device Form" for the document type. Any
applicable device documentation (e.g., Manufacturer information; patient information packet; approved labeling; FDA
correspondence, etc.) should be attached using "Other Device Documentation" for the document type.
Attachments
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RESEARCH SITES
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To complete this section, ensure the responses are accurate then click "SAVE".
A) Check all the applicable sites listed below at which the research will be conducted. If none apply, you do not need to check any
boxes.
UK Sites
UK Classroom(s)/Lab(s)
UK Clinics in Lexington
UK Clinics outside of Lexington
UK Healthcare Good Samaritan Hospital
UK Hospital
Schools/Education Institutions
Fayette Co. School Systems *
Other State/Regional School Systems
Institutions of Higher Education (other than UK)
*Fayette Co. School systems, as well as other non-UK
sites, have additional requirements that must be
addressed. See ORI's IRB Application Instructions -
Off-site Research web page for details.
Other Medical Facilities
Bluegrass Regional Mental Health Retardation Board
Cardinal Hill Hospital
Eastern State Hospital
Norton Healthcare
Nursing Homes
Shriner’s Children’s Hospital
Veterans Affairs Medical Center
Other Hospitals and Med. Centers
Correctional Facilities
Home Health Agencies
International Sites
Research activities conducted at performance sites that are not owned or operated by the University of Kentucky, at sites
that are geographically separate from UK, or at sites that do not fall under the UK IRB’s authority, are subject to special
procedures for coordination of research review. Additional information is required (see IRB Application Instructions - Off-
Site Research web page), including:
A letter of support and local context is required from non-UK sites. See Letters of Support and Local Context on the
IRB Application Instructions - Off-Site Research web page for more information.
Supportive documentation, including letters of support, can be attached below.
NOTE: If the non-UK sites or non-UK personnel are engaged in the research, there are additional federal and
university requirements which need to be completed for their participation. For instance, the other site(s) may need
to complete their own IRB review, or a cooperative review arrangement may need to be established with non-UK
Section 13 Page 1 of 2
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sites.
Questions about the participation of non-UK sites/personnel should be discussed with the ORI staff at (859) 257-
9428.
List all other non-UK owned/operated locations where the research will be conducted:
Describe the role of any non-UK site(s) or non-UK personnel who will be participating in your research.
Attachments
B) Is this a multi-site study for which you are the lead investigator or UK is the lead site?
Yes
No
If YES, describe the plan for the management of reporting unanticipated problems, noncompliance, and submission of protocol
modifications and interim results from the non-UK sites:
C) If your research involves collaboration with any sites and/or personnel outside the University of Kentucky, then it is considered
multisite research and IRB reliance issues will need to be addressed. This may include national multi-center trials as well local studies
involving sites/personnel external to UK. If you would like to request that the University of Kentucky IRB (UK IRB) serve as the lead
IRB for your study, or if you would like the UK IRB to defer review to another IRB, please contact the IRBReliance@uky.edu.
Section 13 Page 2 of 2
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RESEARCH ATTRIBUTES
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comment(s)
Indicate the items below that apply to your research. Depending on the items applicable to your research, you may be required to
complete additional forms or meet additional requirements. Contact the ORI (859-257-9428) if you have questions about additional
requirements.
Not applicable
Check All That Apply
Academic Degree/Required Research
Alcohol/Drug/Substance Abuse Research
Biological Specimen Bank Creation (for sharing)
Cancer Research
CCTS-Center for Clinical & Translational Science
Certificate of Confidentiality
Clinical Research
Clinical Trial - Phase 1
Clinical Trial
Collection of Biological Specimens for internal banking and use
(not sharing)
Community-Based Participatory Research
Deception
Educational/Student Records (e.g., GPA, test scores)
Emergency Use (Single Patient)
Gene Transfer
Genetic Research
GWAS (Genome-Wide Association Study) or NIH Genomic Data
Sharing (GDS)
Human Cells, Tissues, and Cellular and Tissue Based Products
Individual Expanded Access or Compassionate Use
International Research
Planned Emergency Research Involving Exception from
Informed Consent
Recombinant DNA
Registry or data repository creation
Stem Cell Research
Suicide Ideation or Behavior Research
Survey Research
Transplants
Use, storage and disposal of radioactive material and radiation
producing devices
Vaccine Trials
For additional requirements and information:
Cancer Research (MCC PRMC)
Certificate of Confidentiality (look up
"Confidentiality/Privacy...")
CCTS (Center for Clinical and Translational
Science)
Clinical Research (look up "What is the definition
of....)
Clinical Trial
Collection of Biological Specimens for Banking
(look up "Specimen/Tissue Collection...")
Collection of Biological Specimens (look up
"Specimen/Tissue Collection...")
Community-Based Participatory Research (look
up "Community-Engaged...")
Data & Safety Monitoring Board (DSMB)
*For Medical IRB: Service Request Form for
CCTS DSMB
Data & Safety Monitoring Plan
Deception*
*For deception research, also go to the E-IRB
Application Informed Consent section,
checkmark and complete "Request for Waiver
of Informed Consent Process"
Emergency Use (Single Patient) [attach
Emergency Use Checklist] (PDF)
Genetic Research (look up "Specimen/Tissue
Collection...")
Gene Transfer
HIV/AIDS Research (look up "Reportable
Diseases/Conditions")
Screening for Reportable Diseases [E2.0000]
(PDF)
International Research (look up "International &
Non-English Speaking")
NIH Genomic Data Sharing (GDS) Policy (PDF)
Planned Emergency Research Involving Waiver
of Informed Consent*
*For Planned Emergency Research Involving
Waiver of Informed Consent, also go to the E-
IRB Application Informed Consent section,
checkmark and complete "Request for Waiver
of Informed Consent Process"
Use, storage and disposal of radioactive material
and radiation producing devices
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FUNDING/SUPPORT
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comment(s)
If the research is being submitted to, supported by, or conducted in cooperation with an external or internal agency or funding program,
indicate below all the categories that apply. 
Not applicable
Check All That Apply
Grant application pending
(HHS) Dept. of Health & Human Services
(NIH) National Institutes of Health
(CDC) Centers for Disease Control &
Prevention
(HRSA) Health Resources and Services
Administration
(SAMHSA) Substance Abuse and Mental
Health Services Administration
(DoJ) Department of Justice or Bureau of
Prisons
(DoE) Department of Energy
(EPA) Environmental Protection Agency
Federal Agencies Other Than Those Listed
Here
Industry (Other than Pharmaceutical
Companies)
Internal Grant Program w/ proposal
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Click applicable listing(s) for additional requirements and information:
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Specify the funding source and/or cooperating organization(s) (e.g., National Cancer Institute, Ford Foundation, Eli Lilly
& Company, South Western Oncology Group, Bureau of Prisons, etc.):
 
- University of Kentucky Center for
Clinical and Translational Science grant
- Orthopaedic Trauma Association
grant
Add Related Grants
If applicable, please search for and select the OSPA Account number or Electronic Internal Approval Form (eIAF) #
(notif #) associated with this IRB application using the "Add Related Grants" button. 
If required by your funding agency, upload your grant using the "Grant/Contract Attachments" button.
Add Related Grants
Grant/Contract Attachments
Section 15 Page 1 of 2
43611


The research involves use of Department of Defense (DoD) funding, military personnel, DoD facilities, or other DoD resources.
(See DoD SOP and DoD Summary for details)
Yes
No
Using the “attachments” button (below), attach applicable materials addressing the specific processes described in
the DoD SOP.
DOD SOP Attachments
Additional Certification: (If your project is federally funded, your funding agency may request an Assurance/ Certification/Declaration
of Exemption form.) Check the following if needed:
Protection of Human Subjects Assurance/Certification/Declaration of Exemption (Formerly Optional Form – 310)
Assurance/Certification Attachments
Section 15 Page 2 of 2
43611


OTHER REVIEW COMMITTEES
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comment(s)
If you check any of the below committees, additional materials may be required with your application submission.
Does your research fall under the purview of any of the other review committees listed below? [If yes, check all that apply and attach
applicable materials using the attachment button at the bottom of your screen.]
Yes
No
Institutional Biosafety Committee
Radiation Safety Committee
Radioactive Drug Research Committee
Markey Cancer Center (MCC) Protocol Review
and Monitoring Committee (PRMC)
Graduate Medical Education Committee (GME)
Office of Medical Education (OME)
Additional Information
Institutional Biosafety Committee (IBC) - Attach required IBC
materials
Radiation Safety Committee (RSC) - For applicability, see
instructions and attach form
Radioactive Drug Research Committee (RDRC)
Markey Cancer Center (MCC) Protocol Review and Monitoring
Committee (PRMC)** - Attach MCC PRMC materials, if any, per
instructions.
Office of Medical Education (OME)
Graduate Medical Education Committee (GME)
Attachments 
** If your study involves cancer research, be sure to select "Cancer Research" in the "Research Attributes"
section. ORI will send your research protocol to the Markey Cancer Center (MCC) Protocol Review and Monitoring
Committee (PRMC). The MCC PRMC is responsible for determining whether the study meets the National Cancer Institute
(NCI) definition of a clinical trial and for issuing documentation to you (the investigator) which confirms either that PRMC
approval has been obtained or that PRMC review is not required. Your IRB application will be processed and reviewed
independently from the PRMC review.
Section 16 Page 1 of 1
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ADDITIONAL INFORMATION/MATERIALS
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Do you want specific information inserted into your approval letter?
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No
Approval Letter Details:
If you wish to have specific language included in your approval letter (e.g., serial #, internal tracking identifier, etc…), type that
language in the box below exactly as it should appear in the letter. The text you enter will automatically appear at the top of all
approval letters, identical to how you typed it, until you update it. Don't include instructions or questions to ORI staff as those will
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content of this field.
Additional Materials:
If you have other materials you would like to include for the IRB's consideration, check all that apply and attach the corresponding
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Protocol/Other Attachments
Attach Type File Name
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Signed Inflammatory Marker Protocol Violation Letter.pdf
Other
Subject Enrollment Memo for IRB.docx
Protocol
CCTS Full Research Proposal.pdf
Protocol
OTA Full Grant Application.pdf
Protocol
IM Study- Protocol Changed- Clean.docx
Protocol
IM AE Risk Mitigation Plan Formal 4.17.20.docx
NOTE: Instructions for Dept. of Health & Human Services (DHHS)-approved protocol]
If you have password protected documents, that feature should be disabled prior to uploading to ensure access for IRB review.
To view the materials currently attached to your application, click “All Attachments” on the left menu bar.
Section 17 Page 1 of 1
43611


SIGNATURES (ASSURANCES)
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comment(s)
Introduction
All IRB applications require additional assurances by a Department Chairperson or equivalent (DA), and when applicable, a Faculty
Advisor or equivalent (FA). This signifies the acceptance of certain responsibilities and that the science is meritorious and deserving of
conduct in humans. The person assigned as DA should not also be listed in the Study Personnel section, and the individual assigned
as FA should be listed in the Study Personnel section.
For a list of responsibilities reflected by signing the Assurance Statement, refer to "What does the Department Chairperson’s
Assurance Statement on the IRB application mean?"
For a detailed illustration of how to complete this section, please review the short online video tutorial "Signatures
(Assurance) Section - How to Complete." Otherwise, follow the steps below.
Required Signatures:
First
Name
Last
Name
Role
Department
Date
Signed
 
Darren
Johnson
Department
Authorization
Orthopaedic
Surgery
02/09/2018
10:24 AM
View/Sign
Arun
Aneja
Principal
Investigator
Orthopaedic
Surgery
02/03/2018
11:57 AM
View/Sign
Department Authorization
 This is to certify that I have reviewed this research protocol and that I attest to the scientific validity and importance of
this study; to the qualifications of the investigator(s) to conduct the project and their time available for the project; that
facilities, equipment, and personnel are adequate to conduct the research; and that continued guidance will be provided
as appropriate. When the principal investigator assumes a sponsor function, the investigator has been notified of the
additional regulatory requirements of the sponsor and by signing the principal investigator Assurance Statement, confirms
he/she can comply with them.
*If the Principal Investigator is also the Chairperson of the department, the Vice Chairperson or equivalent should complete
the "Department Authorization".
**IF APPLICABLE FOR RELIANCE: I attest that the principal investigator has been notified of the regulatory requirements of
both the Reviewing and Relying IRBs, according to the information provided in the E-IRB application. The attached Reliance
Assurance Statement, signed by the principal investigator, confirms that he/she can comply with both sets of IRB
requirements.
Principal Investigator’s Assurance Statement
I understand the University of Kentucky's policies concerning research involving human subjects and I agree:
1. To comply with all IRB policies, decisions, conditions, and requirements;
2. To accept responsibility for the scientific and ethical conduct of this research study;
3. To obtain prior approval from the Institutional Review Board before amending or altering the research protocol or
implementing changes in the approved consent/assent form;
4. To report to the IRB in accord with IRB/IBC policy, any adverse event(s) and/or unanticipated problem(s) involving risks to
subjects;
5. To complete, on request by the IRB for Full and Expedited studies, the Continuation/Final Review Forms;
6. To notify the Office of Sponsored Projects Administration (OSPA) and/or the IRB (when applicable) of the development of
any financial interest not already disclosed;
7. Each individual listed as study personnel in this application has received the mandatory human research protections
education (e.g., CITI);
8. Each individual listed as study personnel in this application possesses the necessary experience for conducting research
Section 18 Page 1 of 2
43611


activities in the role described for this research study.
9. To recognize and accept additional regulatory responsibilities if serving as both a sponsor and investigator for FDA
regulated research.
Furthermore, by checking this box, I also attest that:
I have appropriate facilities and resources for conducting the study;
I am aware of and take full responsibility for the accuracy of all materials submitted to the IRB for review;
If applying for an exemption, I also certify that the only involvement of human subjects in this research study will be in the
categories specified in the Protocol Type: Exemption Categories section.
If applying for an Abbreviated Application (AA) to rely on an external IRB, I understand that certain items above (1, 3, 4, 7-8)
may not apply, or may be altered due to external institutional/IRB policies. I document my agreement with the Principal
Investigator Reliance Assurance Statement by digitally signing this application.
*You will be able to "sign" your assurance after you have sent your application for signatures (use Submission section). Please notify the
personnel required for signing your IRB application after sending for signatures. Once all signatures have been recorded, you will need
to return to this section to submit your application to ORI. 
Section 18 Page 2 of 2
43611


SUBMISSION INFORMATION
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comment(s)
*** If this Continuation Review entails a change in the scope of your activities to include COVID-19 related research, please
insert “COVID19” at the start of your Project and Short Titles.***
Each Section/Subsection in the menu on the left must have a checkmark beside it (except this Submission section) indicating the
Section/Subsection has been completed. Otherwise your submission for IRB review and approval cannot be sent to the Office of
Research Integrity/IRB.
If applicable, remember to update the Approval Letter Details text box under the Additional Information section
If your materials require review at a convened IRB meeting which you will be asked to attend, it will be scheduled on the next available
agenda and you will receive a message to notify you of the date.
If you are making a change to an attachment, you need to delete the attachment, upload a highlighted version that contains the changes
(use Document Type of "Highlighted Changes"), and a version that contains the changes without any highlights (use the appropriate
Document Type for the item(s)). Do not delete approved attachments that are still in use.
Principal Investigator’s Assurance Statement
I understand the University of Kentucky’s policies concerning research involving human subjects, and I attest to:
1. Having reviewed all the investigational data from this study, including a compilation of all internal and external unanticipated
problems.
2. Having reviewed, if applicable, information from the sponsor including updated investigator brochures and data and safety
monitoring board reports.
I also attest that I have reviewed pertinent materials concerning the research and concluded either:
A. The human subject risk/benefit relationship is NOT altered, and that it is not necessary to modify the protocol or the informed
consent process,
OR,
B. The human subject risk/benefit relationship has been altered, and have previously submitted or am including with this
continuation review submission, a modification of the research protocol and informed consent process.
By checking this box, I am providing assurances for the applicable items listed above. 
Your protocol has been submitted.
Section 19 Page 1 of 1
43611


 
Document Type
File Loaded
Document Description
File
Size
Modified
By
Mod Date
ApprovalLetter
ApprovalLetter.pdf
 
0.079
jlkear0
8/22/2023 8:16:23
AM
CR_InterimFindings OTA IM Abstract VAS and MME
2.10.23.docx
 
0.081
jtgr238
7/31/2023 6:17:19
PM
CR_EntireConsent
20230731180652481.pdf
 
0.758
jtgr238
7/31/2023 6:09:08
PM
CR_EntireConsent
20230731180556007-combined.pdf
 
0.901
jtgr238
7/31/2023 6:08:53
PM
AddInfoProduct
Subject Enrollment Memo for IRB.docx
Subject Enrollment Memo
0.050
jafo241
9/9/2022 2:46:26
PM
AddInfoProtocol
IM AE Risk Mitigation Plan Formal
4.17.20.docx
Risk Mitigation Plan
0.068
ejab226
6/11/2020
11:19:12 AM
AddInfoProduct
Signed Inflammatory Marker Protocol
Violation Letter.pdf
Preventative Action Plan
0.578
ejab226
7/15/2019 7:21:29
PM
AddInfoProtocol
IM Study- Protocol Changed- Clean.docx
Protocol
0.041
ejab226
7/3/2019 4:23:22
PM
Waiver
HIPAA-8-2.pdf
HIPAA-Waiver
0.152
smco282
8/2/2018 9:18:21
AM
AddInfoProtocol
OTA Full Grant Application.pdf
OTA Grant Submission
1.049
smco282
7/24/2018 2:21:34
PM
AddInfoProtocol
CCTS Full Research Proposal.pdf
CCTS Collaborative Grant-
UK/Wake
1.233
smco282
7/24/2018 2:21:06
PM
StudyDrug
Ketorolac.pdf
 
0.466
bli255
2/26/2018
12:38:14 PM
StudyDrug
Form O - Inflammatory Markers.pdf
 
0.322
bli255
2/26/2018
12:38:03 PM
StudyDrug
Toradol.pdf
Toradol Prescribing
Information
0.115
bli255
1/31/2018 1:25:48
PM
Download all
Section 20 Page 1 of 1
43611


Protocol Changes
Protocol Number: 43611
Click link to sort Changed Date
Study Personnel Changes:
Project Information IsSubEnrollDataSpecimen changed by jtgr238 on 8/7/2023 9:48:41 AM
YN
Project Information ProjectEndDate changed by jtgr238 on 8/7/2023 9:48:41 AM
810/31/2023 12:00:00 AM
Risk Level RiskCategory changed by jtgr238 on 8/7/2023 9:48:56 AM
21
No Changes
There are no recorded changes to study personnel.
Section 21 Page 1 of 1
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Protocol Type Comment by Samuel Bell - ORI to PI on 8/7/2023 9:25:12 AM
A few screening comments. Please see the following sections of the protocol for specifics: 
- Project Information
- Risk Level
- Study Personnel
Additionally, as the study is closed to new enrollment, please remove the approved version of the informed consent as it will no longer be 
needed and thus does not need a new IRB approval stamp.
Project Information Comment by Samuel Bell - ORI to PI on 8/7/2023 9:18:59 AM
Please also update the anticipated end date of the research project. 
Project Information Comment by Samuel Bell - ORI to PI on 8/7/2023 9:18:43 AM
As study is closed to new enrollment, please check "no" for "...will study be open to enrollment of new subjects..." 
Risk Level Comment by Samuel Bell - ORI to PI on 8/7/2023 9:19:27 AM
As the study is closed to enrollment, please reduce the risk level to risk level 1: not greater than minimal risk. 
Study Personnel Comment by Samuel Bell - ORI to PI on 8/7/2023 9:21:04 AM
Daniel Primm's human subject protection training is set to expire in early September, 2023. While this may not affect the CR approval, they 
should plan to complete HSP refresher training as soon as possible to remain on the study. More information on HSP refresher training can be 
found at the following link: https://www.research.uky.edu/office-research-integrity/three-year-refresher-hsp-training-faqs
Section 22 Page 1 of 1
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07-3-2019 
 
1. Title 
Inflammatory Response to Trauma – Does Early Cytokine Modulation Improve Patient Outcome? 
 
2. Study Design 
Primary Purpose: Treatment 
Allocation: Randomized 
Interventional Mode: Parallel Assignment 
Interventional Model Description: Compare the effectiveness of a NSAID to placebo in acute trauma setting. 
Masking: Triple (Participant, Care Provider, Investigator) 
Masking Description: Participant medical team will be blinded to the treatment or placebo intervention. 
3. Outcome Measures 
Primary Outcome: Length of Hospital Stay 
Secondary Outcomes: 
- 
Daily Concentrations of IL-1, IL-6, IL-10, and PGE2 
- 
Incidence of Post-Traumatic Complications (e.g., bacterial pneumonia, SIRS, MODS, ARDS, and AKI) 
- 
Mortality 
- 
Visual Analogue Pain Scores 
- 
Inpatient Morphine Milligram Equivalents 
- 
Change in Inpatient Subjective Pain Reports 
- 
Change in Outpatient Subjective Pain Reports 
 
4. Background 
Accidental trauma is the 4th leading cause of death in the United States, and it is associated with a 
complex inflammatory response. This response is associated with post-traumatic complications such as 
multi-organ dysfunction syndrome (MODS), bacterial pneumonia, acute respiratory distress syndrome 
(ARDS), systemic inflammatory response syndrome (SIRS), and post traumatic pain (PTP). It is unknown 
whether early modulation of inflammatory cytokines is associated with improved patient outcomes, 
reduced narcotic requirements, and improved patient subjective pain after hospital discharge. 
Our preliminary data has shown: (1) elevated blood cytokine concentrations during the acute phase of 
trauma are correlated with the development of fatal post-traumatic complications, (2) that early 
administration of a non-steroidal anti-inflammatory drug (NSAID) resulted in decreased blood serum 
levels of IL-6, Prostaglandin E2 (PGE2), improved pulmonary edema, and enhanced arterioles ability to 
vasoconstrict in response to hemorrhage in animal models, and (3) that the addition of the internal 
physiologic parameters (inflammatory cytokines) to New Injury Severity Score (NISS – a marker of the 
external anatomical insult) significantly improves the ability to predict hospital length of stay of trauma 
patients when compared to NISS alone. Our group is the first to use an integrative approach that 
combines the external anatomic injury data with the internal physiologic response for accurate 
prediction of patient’s clinical outcome. Therefore, if we apply this same mindset to treatment, we can 
improve the trauma patients’ care by addressing both parameters as opposed to solely focusing on the 
external injury as done in the past. Our ability to modify post-traumatic physiologic response via short- 
term administration of a NSAID may lead to improved patient outcome. 
Over the last decade, clinicians remain puzzled over the safety of NSAID administration after fracture in 
terms of bone union. In addition, given the current landscape for opioid epidemic in the United States, 
alternative non-opioid pain management during acute trauma has the potential to reduce opioid 
consumption and represents a pivotal component of multimodal analgesia strategy. 
5. Inclusion and Exclusion Criteria 


07-3-2019 
 
Inclusion Criteria 
• 
Patient aged 18-75 
a. Patient or legally authorized representative (LAR) able to provide consent. 
b. Patient with New Injury Severity Score (NISS) > 9 at time of admission determined by trauma staff. 
c. Anticipated admission ≥5 days 
 
Exclusion Criteria 
d. Patient age < 18 or > 75 
e. Patients with injury more than 24 hours prior to evaluation 
f. Hemorrhagic shock or risk of significant hemorrhage. 
g. Patients with preexisting inflammatory medical condition such as inflammatory arthropathy or 
inflammatory bowel disease 
h. Patients with acquired immunodeficiency syndrome (AIDS) 
i. 
Patients who are pregnant 
j. 
Patients with active GI bleed or ulceration 
k. Patients with chronic use of steroids or immune modulating drugs or history of organ 
transplantation 
l. 
Patients with preexisting chronic renal, liver, or lung disease 
m. Patients with history of myocardial infarctions 
n. Patients with chronic heart failure 
o. Patients with allergy to NSAID 
p. Patients with coagulation defects (e.g., clotting factor deficiencies, thrombophilia, or any 
bleeding disorder) 
q. Patients receiving chronic opioid therapy or treatment for opioid use disorder. 
 
6. Sample Size Calculation 
Pretrial sample size calculations were performed regarding LOS because this will be the primary 
outcome measure of the clinical trial. Using a significance level of 0.05 and an assumed SD of 1.5 days, a 
sample size of 42 patients per group (84 total) would yield 80% power to detect a difference of 0.928 
days in average LOS between the placebo and ketorolac groups. Allowing for a dropout rate up to 25%, 
the target enrollment will be 112 patients total, with 56 patients per group. Power calculations were 
performed using nQuery 8.5 (Statistical Solutions Ltd; Cork, Ireland). 
 
7. Statistical Analysis Plan 
Group-level summary statistics will be calculated for demographic and clinical variables, and differences 
between the 2 groups will be evaluated using two-sample t-tests for quantitative measures and Fisher 
exact tests for categorical measures, as appropriate. LOS and MME values will be summarized using 
medians and interquartile ranges for each group. Group-level VAS pain scores will be summarized using 
means and standard deviations. An analysis of variance model will be fit to compare log-transformed 
LOS between the 2 groups. Linear mixed models will be used to estimate differences in VAS pain scores 
and log-transformed MME values over time between the 2 groups. Time and group comparisons for 
each cytokine will be made using linear mixed models, with and without adjusting for selected 
covariates. Patient demographic variables and will be considered for inclusion as covariates in each 
model but will only be retained if they significantly improve the model. Linear mixed models may be log-
transformed, double-log-transformed, or square-root-transformed to correct for right skewness, as 
appropriate. Likelihood ratio testing and Akaike information criterion will be used to select appropriate 
covariance structures in each case. A Kenward–Roger adjustment will be used to correct for negative 
bias in the standard errors and degrees of freedom calculations. Throughout the study, a P value of less 
than 0.05 will be considered significant. All analyses will be completed in SAS 9.4 (SAS Institute Inc.; 
Cary, NC). 


07-3-2019 
 
 
8. Study-Wide Recruitment Methods 
Potential patients will be prospectively identified either at the time of the initial consultation, at the 
morning fracture conference, based on the orthopaedic injury diagnosis (inclusion criteria noted above). 
Patients will be screened by their inclusion and exclusion criteria and will be considered for enrollment 
in the study should they meet study criteria. 
 
9. Study Timeline 
After arrival, patient screening and enrollment is expected within 12 hours of arrival to ensure initial 
blood draw. Further participation of subjects will include blood draws and ketorolac administration 
through day 5. Patient participation will continue through to their follow-up visits and conclude with 
their 6 weeks post discharge clinic visit. Detailed project timeline and schedule of activities is listed in 
Table 1. 
 
 
Tentative time table of the proposed project 
 
Inpatient 
Outpatient 
 
Procedures 
Enrollment 
Day 
1 
Day 
2 
Day 
3 
Day 
4 
Day 
5 
Discharge 
2 
Week 
6 
Week 
3 
Month 
6 
Month 
12 
Month 
Inclusion/Exclusion 
Review 
X 
Informed Consent 
X 
Blood Sample 
X 
X 
X 
X 
X 
Ketorolac 
Intervention 
X 
X 
X 
X 
X 
MME 
X 
X 
X 
X 
X 
X 
VAS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Post-Traumatic 
Complications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
10.  Procedures Involved 
a. Patient identification: Patients will be identified on morning intake rounds by the trauma team and 
the research staff who are present daily to screen and enroll patients. 
b. Screening/Enrollment: Study population will consist of 112 patients (56 control, 56 treatment) 
admitted to the inpatient surgical service at University of Kentucky (UK) level I trauma center for 
management of trauma care. Trauma patients that are between the ages of 18-75 and with NISS > 9 
(moderate injury) with anticipated admission of ≥5 days (to ensure completion of the treatment) will 
be enrolled (Grisoni et al., 2001; Stevenson, Segui-Gomez, Lescohier, Di Scala, & McDonald-Smith, 
2001). All patients will be initially treated according to the standard Advance Trauma Life Support 
(ATLS) protocol and standard ICU protocols (if applicable). Experienced clinical research staff will 
prospectively identify patients who meet the inclusion criteria and none of the exclusion criteria 
detailed in table 2. 
c. Randomization: Consented patients will be randomized using a computer-generated algorithm to 
the control group (1-2 mL of intravenous saline every 6 hours for 5 days after admission) or 
treatment group (15 mg of intravenous ketorolac every 6 hours for 5 days after admission). 
d. Treatment: Ketorolac (15 mg) has been chosen as the treatment of choice for several  reasons: 
(1) Ketorolac has a similar pharmacodynamics profile as indomethacin, which was used 


07-3-2019 
 
in our previous animal model (Xiang et al., 2012). 
(2) It is readily available intravenously obviating limitations of oral intake. 
(3) In numerous prospective clinical studies, ketorolac infusion produced no change in 
cardiac or hemodynamic parameters in patients undergoing major vascular surgery 
(Camu, Van Overberge, Bullingham, & Lloyd, 1990; Peirce, Fragen, & Pemberton, 1990). 
(4) 30 mg is the approved dose that is consistent with United States Food and Drug 
Administration (FDA) labeling per the package 
(5) Ketorolac is part of the routine trauma acute pain protocol 
Patients with pre-existing medical co-morbidities and contraindications to ketorolac will be excluded 
from the study (see 5 for detailed exclusion criteria) 
Patients in the treatment group will receive 15 mg IV ketorolac every 6 hours for 5 days after 
admission. 
e. Post-operative inpatient care: Enrolled patients will have daily blood samples (10 cc) will be 
collected post-admission and at 24 hours intervals for 5 days by blinded health care personnel. The 
initial blood sample will be collected within 12 hours of initial injury and before the first scheduled 
administration of ketorolac to establish baseline cytokine profile. Subsequent blood sample 
collection will be 24 hours apart. Medication compliance and monitoring will be performed daily by 
the same research coordinators. 
 
Sandwich ELISA with be used to determine the concentrations of IL-1, IL-6, IL-10, and PGE2 in 
obtained blood samples. Blinded quality control samples will be included in every batch for each 
ELISA assay. This will allow for the calculation of coefficient of variation (CV) within and across 
patient cohorts. In the present study, the CV will be calculated for IL-1, IL-6, IL-10, and PGE2. If wide 
variations are observed among the analytes during the analysis, we will restrict our analysis to 
analytes in which the CV is less than 20%. 
 
In addition to the standard trauma labs (Sodium, Potassium, Creatinine, Lactic acid, Glucose, 
Platelet, blood urea nitrogen (BUN), hematocrit, and white blood cell count), patient demographics 
(sex, age, and BMI), injury data (mechanism of injury, NISS, and types of surgical/procedural 
interventions), posttraumatic complications (occurrence of bacterial pneumonia, ARDS, SIRS, 
MODS), complications defined in the National Trauma Dataset, and inflammatory data will be 
collected. This data will be maintained in our clinical database (REDCap) by a full-time Clinical Study 
Coordinator. 
 
Enrolled patients will be monitored daily by research staff throughout their hospital stay and routine 
outpatient clinic visits. Patient’s subjective pain scores will be assessed and documented by the 
trained nursing staff using Visual Analogue Scale (VAS) daily. Pre-injury narcotics use along with 
other pain modulating medication intake will be recorded per day in morphine milligram equivalent 
(MME) for the duration of ketorolac or placebo therapy in our password protected database. 
Patients’ clinical course will be monitored closely and daily by research staff to ensure no NSAIDs 
will be administered to the control cohort to ensure consistency and protocol adherence. After 
patient discharge, various patient surveys will be used to assess patient pain, function, and quality of 
life. Opioid and pain modulating medication prescription refills will be monitored using State 
Scheduled Prescription Electronic Reporting System. Patient narcotic requirement will be assessed 
during all the routine follow up visits by the same research staff to maintain consistency. 
 
11.  Data and Specimen Banking 
Blood sample specimens obtained from the research subjects will be labeled with the patient’s unique 
study ID number and will be stored in the CCTS lab until analysis. Following analysis, the specimens will 
be disposed of in accordance with UK policies. No specimens will be retained for future studies. The 
stored de-identified data from the study will be kept for a minimum of 6 years for records in the event 
follow- up studies are pursued and will remain protected and encrypted. Data will be permanently 


07-3-2019 
 
deleted following this time period. The banked data will be stored on a password-protected research 
drive.  Upon conclusion of the study, the data will be stored in a password encrypted file that only the PI 
has access to. 
 
12.  Data Management 
Following initial enrollment, each patient will be assigned a unique patient identifier. All electronic 
documentation containing total morphine equivalents, specimen results, and all other medical 
information will be associated with this unique patient identifier during analysis. All protected health 
information will be stored in a separate, password-protected research file that will not be accessed 
regularly. Following our secondary analysis, all personal health information will be removed from our 
electronic files and destroyed in accordance with patient privacy guidelines. 
 
Data obtained at the UK during the study will be recorded and stored using password protected 
spreadsheet on the department’s secure drive and will be maintained at the hospital by the research 
staff. Final analysis will be conducted using Excel spreadsheets. All documents will be stored on a 
password-protected research drive and only research personnel will have access to its content. Paper 
documents, including consent forms, will be stored in a locked cabinet in a secure research room in the 
Kentucky Clinic Suite K434. 
 
All study personnel have completed human subject protection, responsible conduct of research, and 
patient confidentiality training. Only IRB-approved research personnel will administer consents and 
perform phone surveys. All efforts will be made to maintain the confidentiality of the patient reported 
data. Only study personnel listed in eIRB will have access to identified study data. 
 
13.  Provisions to Monitor the Data to Ensure the Safety of Subjects 
Subjects in this study will be exposed to greater than minimal risk but presenting the prospect of direct 
benefit to individual in the study. The patients will be monitored continuously as inpatients post- 
operatively and any issues with medication effects, wound healing, or other medical complications will 
be logged as adverse events. Blinding will only be broken for unexpected complications potentially 
relating to ketorolac administration and the research study. The research team will meet monthly to 
monitor data collection and handling. During this time, study staff will also review adverse events logs. 
 
14.  Withdrawal of Subjects 
We do not anticipate any situation in which a subject would be withdrawn from the study by the 
researchers should they wish to remain. We anticipate analyzing the data via an intention to treat 
analysis and thus would include data from all subjects initially enrolled, even if they developed an 
intolerance or medical contraindication to continuing the study. 
 
However, a subject may choose to withdraw from the study on their own accord, at any time, for any 
reason. Contact information and instructions detailing how to withdraw from the study will be provided 
in the consent form and will involve contacting the principal investigator directly. If a subject chooses to 
withdraw, any and all data that was previously collected will be included in the analysis; however, we 
will cease any further data collection. All personal health information collected prior to a patient’s 
withdrawal from the study will be destroyed in accordance with patient privacy laws. In addition, any 
paper documents obtained will be destroyed in accordance with standard HIPPA guidelines. Upon being 
notified of a patient’s decision to withdraw from the study, researchers will no longer contact the 
patient via phone, administer in-office surveys, or access their medical information online. 
 


07-3-2019 
 
15.  Risks to Subjects 
Long-term non-steroidal anti-inflammatory drug (NSAID) intake has been correlated with impaired or 
delayed fracture healing in animal and clinical studies with a dose dependent response. However, the 
evidence in animal studies is conflicting, and there are few retrospective clinical studies and even fewer 
large scale prospective randomized trials. A recent meta-analysis demonstrated that higher quality 
studies found no evidence of negative effect of NSAIDs on bone-healing. To our knowledge, the present 
study will be the largest prospective randomized clinical trial to evaluate the effect of short term and 
low dose administration of NSAID on trauma patient outcomes, opioid consumption, and fracture union 
rates. 
 
Surgical risks are described to the patient prior to surgery and are part of standard of care procedures 
for hip fracture surgery. There are no additional surgical risks to patients who participate in this study. 
 
Although the treatment arm in this study involves randomization to ketorolac, standard ketorolac is 
commonly used as part of the acute trauma pain protocol. Risks commonly associated with ketorolac are 
listed in attachments to the eIRB. 
 
There is also a risk of a breach of confidentiality. All research team members are appropriately trained 
and understand the importance of confidentiality. 
 
16.  Potential Benefits to Subjects 
The use of ketorolac in the acute period could potentially decreasing the inflammatory cascade leading 
to a decrease in severe posttraumatic complications such as multi-organ dysfunction syndrome, 
bacterial pneumonia, acute respiratory distress syndrome, systemic inflammatory response syndrome, 
and post traumatic pain. Additionally this could result in decreased ICU stay and better postoperative 
pain control (decreasing opioid dependence/usage). 
 
17.  Vulnerable Populations 
At high energy trauma centers such as those participating in the study, some percentage of the patients 
will be eligible for the study but will not be able to consent due to traumatic brain injuries, or for other 
reasons related to their injury. We will consent these patients using the individuals’ legally authorized 
representative. The process for obtaining consent for surgery or study participation varies based upon 
the state the patient is being treated within, and as such the details of this process will be guided by the 
standard practice of the local IRB. 
Whenever possible, we will also discuss involvement in the study with the patient’s family (provided the 
patient gives permission for us to discuss with them) to ensure that the decision to participate in the 
study is made with appropriate consideration and that the entire family is comfortable with 
involvement. 
 
18.  Sharing of Results with Subjects 
To maintain the blinded nature of the study, the subjects will not be aware of which treatment group a 
subject has been randomly assigned to. At the conclusion of the study, following de-identification and 
data analysis, results of this data collection may be shared with patients who have participated in this 
research as it becomes available, if they request it verbally or in writing. This will only occur after final 
data analysis if a subject inquires. 
19.  Setting 
Research subjects will be identified, recruited, and followed post-operatively as inpatients at the 


07-3-2019 
 
University of Kentucky Chandler Hospital. They will be followed post-discharge at the Kentucky Clinic. 
Data analysis will primarily occur in locked, private offices at in one of two secure research offices 
located at the Kentucky Clinic. 
 
20.  Resources Available 
The University of Kentucky Chandler Hospital is a large level-1 Trauma center in eastern Kentucky. The 
Orthopedics Department has locations within the Kentucky clinic that serve as a dedicated research 
space, which contain computers with access to password-protected research drives. 
 
The Principle Investigator (PI) will be responsible for overseeing the study and ensuring consistency 
throughout the project. The orthopedic PI will serve as the research coordinator and assist in data 
collection and analysis. Recruitment and consent will be performed by the PI or the research assistant. 
Each member of the research staff has passed the CITI exam on ethical conduct of research and have 
received training and supervision regarding patient confidentiality and study protocol. The PI will meet 
with all research staff periodically to review each role and ensure adequate training for the respective 
positions. Upon enrollment of each patient, the corresponding surgical team will be counseled 
concerning the details of the study and their role, prior to admitting the patient into the OR. 
 
The PI and research assistant will be responsible for institutional /IRB communication as well as data 
review and assistance with follow-up patient coordination as needed. There are no anticipated adverse 
consequences associated with this study, however, the principal investigator and research assistant will 
both be available should any unexpected medical or psychological problems arise. The research subjects 
will be provided with appropriate contact information in the consent form and will be provided with the 
PIs contact information at the time of enrollment as well. 
 
21.  Recruitment Methods 
No formal external recruitment methods will be used for this study, as acute trauma patients that are 
moderately to severe injured are universally admitted to the hospital after injury while awaiting surgery. 
Patients will be identified, screened, and approached for enrollment in the study as noted above (see 8. 
Study Timeline). After review and screening, the patient will be given the opportunity to ask researchers 
questions about the study. There will be no financial compensation in return for participation in this 
study. 
 
22.  Confidentiality 
As part of our design, researchers will have access to patients’ names and phone numbers in order to 
collect the required data. Upon enrollment, each patient will also be assigned a unique identifier. All 
patient personal information will be stored in a master list that links the patient’s identifying 
information to their medical record number, which will be maintained in a separate, locked file that only 
approved research personnel will have access to. During the data collection period, researchers will not 
directly use this master list and, instead, will draw upon information from a separate that contains only 
the patient’s first name, phone number, and unique patient identifier 
 
All paper data collection documents are kept in locked file cabinets within locked offices that are 
accessible only to the project investigators and staff. All online databases are password protected to 
guard against unauthorized access and only approved research personnel will be granted access. 
 
23.  Provisions to Protect the Privacy Interests of Subjects (HIPAA) 


07-3-2019 
 
All eligible subjects will identified by orthopedic trauma team and researchers during morning fracture 
conference or upon presentation to the ED. After this point, only approved research personnel will have 
access to patients’ private health information. All research will be stored electronically on secure 
research drives or locked offices as described above. 
Only health information related to their orthopedic injury and surgery will be reviewed for the purposes 
of this study. Other unrelated personal health information will not be accessed or used in any way. All 
subjects will sign a HIPAA authorization form for use of any protected health information to be used for 
research purposes, as stated above. 
 
24.  Compensation for Research-Related Injury 
There will be no additional compensation for research related injury as all treatments/medications are 
approved for postoperative pain management. Patients would be treated for any complications of 
surgery including non-union or fractures that may be slow to heal using approved methods by their 
treating surgeon consistent with standard of care. The patient would be responsible for all costs 
associated with this treatment. 
 
25.  Economic Burden to Subjects 
Although ketorolac is part of the routine trauma acute pain protocol, the cost of the study medication 
(ketorolac) will be paid for by either an internal or external grant. All other treatment costs are within 
the standard of care and the expenses will be paid for by the patient and their health insurance. There is 
no additional post-operative follow-up required for this study beyond the surgeon’s standard follow-up 
routine. There will be no financial compensation in return for participation in this study. The cost to 
analyze and collect the specimens for analysis will also be covered by the internal or external grant.


07-3-2019 
 
26.  Consent Process 
Consent and/or Authorization by a Legally Authorized Representative (LAR) 
Eligible patients will be approached for their consent to participate. Informed consent will be obtained 
prior to the collection of any study related data. To encourage a high level of participation from eligible 
patients, the attending surgeon may be involved in the consent conversation. The research coordinator 
and surgeon may initiate the conversation together. 
By virtue of the types of injuries studied (resulting from high energy mechanisms such as high-speed 
motor vehicle crashes, high falls, and blast injuries) it is expected that a large proportion (> 30%) to have 
an associated traumatic brain injury which my render them unable to provide consent for the study. It 
will be important not to exclude these patients from the study, as it would significantly reduce our 
ability to produce generalizable knowledge. These patients are at no greater risk of adverse 
consequences by virtue of their participation in the study and should be given the same opportunity to 
participate. 
Consistent with Kentucky health care decision statutes for choosing a legally authorized representative 
for adult subjects unable to consent, one of the following responsible parties, in the following order of 
priority (if no individual in a prior class is reasonably available, willing, and competent to act), is 
authorized to make research participation decisions on behalf of the person: (a) the judicially-appointed 
guardian of the person, if the guardian has been appointed and if the decisions to be made under the 
consent are within the scope of the guardianship; (b) the attorney-in-fact named in a durable power of 
attorney, if the durable power of attorney specifically includes authority for the decisions to be made 
under the consent; (c) the spouse of the person; (d) an adult child of the person, or if the person has 
more than one (1) child, the majority of the adult children who are reasonably available for consultation; 
(e) the parents of the subject; (f) the nearest living relative, or if more than one of the same relation, a 
majority of the nearest living relatives. 
Consent by a legally authorized representative should involve all the same considerations that informed 
consent from a competent subject involves. 
Guidance will be provided to assist the LAR in making the consent decision. They will advised to base  
the decision on the participant’s expressed wishes, or, if these are not known, what they believe the 
participant would have desired under the circumstances of the injury, their beliefs and values. If the LAR 
does not know what the participant would have wanted, the LAR will advised to base the decision with 
the participant’s best interest in mind. They will be asked to carefully consider how much leeway the 
participant would likely give the LAR in making the choice about participation in the study. 
Recognizing that consent is an ongoing process, the study team will encourage the participants to ask 
additional questions that may arise during their participation in the study. 
27.  Process to Document Consent in Writing 
The consent will be documented in accordance with the guidelines set forth by the IRB and ORI at UK. 
The patient will receive a copy of this consent for their personal records during the enrollment process. 


07-3-2019 
 
The consent template provided by the IRB was used in the creation of the consent for this study and 
provides answers to many anticipated questions. Each signed consent will be stored in a locked cabinet 
in Kentucky clinic room k434 and only approved study personnel are able to access this. 
28.  Drugs or Devices 
Ketorolac is FDA approved, with a labeled indication for short-term (up to 5 days in adults), 
management of moderately sever acute pain that requires analgesia at the opioid level. As such, this 
study represents on-label use of the medication, but with investigation of potential additional benefits. 
Use of Toradol in this patient population does not involve a novel route or dosage, and is not being used 
in a patient population that would increase the risks. Toradol is used as part of the Acute Trauma pain 
protocol. 
 
Placebo will consist of normal saline. Additional treatment done by the surgical teams are determined 
by the attending surgeon based on the injury characteristics and are independent of involvement in this 
study. 
 
29.  References 
1) Camu, F., Van Overberge, L., Bullingham, R., & Lloyd, J. (1990). Hemodynamic effects of two 
intravenous doses of ketorolac tromethamine compared with morphine. Pharmacotherapy, 10(6 ( Pt 
2)), 122s-126s. 
2) Grisoni, E., Stallion, A., Nance, M. L., Lelli, J. L., Jr., Garcia, V. F., & Marsh, E. (2001). The New Injury 
Severity Score and the evaluation of pediatric trauma. J Trauma, 50(6), 1106-1110. 
3) Peirce, R. J., Fragen, R. J., & Pemberton, D. M. (1990). Intravenous ketorolac tromethamine versus 
morphine sulfate in the treatment of immediate postoperative pain. Pharmacotherapy, 10(6 ( Pt 2)), 
111s-115s. 
4) Stevenson, M., Segui-Gomez, M., Lescohier, I., Di Scala, C., & McDonald-Smith, G. (2001). An 
overview of the injury severity score and the new injury severity score. Inj Prev, 7(1), 10-13. 
5) Xiang, L., Lu, S., Fuller, W., Aneja, A., Russell, G. V., Jones, L. B., & Hester, R. (2012). Impaired blood 
pressure recovery to hemorrhage in obese Zucker rats with orthopedic trauma. Am J Physiol Heart 
Circ Physiol, 302(1), H340-348. doi:10.1152/ajpheart.00439.2011 

ICF_001.pdf: 
Inflammatory Response to Trauma – Does 
Early Cytokine Modulation Improve Patient 
Outcome? 
NCT03671746 
10/10/2022


Page 1 of 13 
 
Combined Consent and Authorization to Participate in a Research Study 
KEY INFORMATION FOR Inflammatory Response to Trauma – Does Early Cytokine 
Modulation Improve Patient Outcome? 
 
You are being invited to take part in a research study about early inflammatory modulation to improve surgical 
patient outcomes in trauma patient population 
 
WHAT IS THE PURPOSE, PROCEDURES, AND DURATION OF THIS STUDY? 
 
Dr. Aneja, MD, PhD, and his colleagues are asking you to participate in this research study because you suffer a 
traumatic injury to either your arm or leg or both due to a high energy mechanism, such as a car accident, farm 
injury, gun accident, a fall from > 15 feet, etc. This research is being done because accidental trauma is the 4th 
leading cause of death in the United States, and it is associated with a complex inflammatory response (you body’s 
response after an injury). We are attempting to see if a drug (Ketorolac) given early after trauma alters the clinical 
outcome of trauma patients. 
 
By doing this study, we hope to learn how to provide the best care for all of our patients in the state of Kentucky. 
Your participation in this research will last about 1 year. 
 
WHAT ARE REASONS YOU MIGHT CHOOSE TO VOLUNTEER FOR THIS STUDY? 
 
You are being asked to participate in this study because you are aged between18 to 75 and you have suffered a 
long bone fracture, meaning a broken bone in your upper or lower extremity (i.e. arm or leg), and you are 
currently admitted to the University of Kentucky Chandler Hospital Surgical Service. 
 
WHAT ARE REASONS YOU MIGHT CHOOSE NOT TO VOLUNTEER FOR THIS STUDY? 
 
You should not participate in this study if you: 
 
1. Are under the age of 18 or older than the age of 75 
2. Had your injury more than 24 hours prior to transfer to University of Kentucky 
3. Are currently in hemorrhagic shock or have significant risk of hemorrhage 
4. Suffered a thermal injury 
5. preexisting inflammatory medical condition such as: inflammatory arthropathy, inflammatory 
bowel disease (rheumatoid arthritis, crohn’s, ulcerative colitis, etc) 
6. Have acquired immunodeficiency syndrome (AIDS) 
7. Have active GI bleed or ulceration 
8. Chronically use steroids or immune modulating drugs or history of organ transplantation 
9. Have chronic liver, kidney, or lung disease 
10. Have a history of heart attacks or heart failure 
11. Are pregnant or incarcerated 
12. Have tested positive for H. pylori 
 
 
DO YOU HAVE TO TAKE PART IN THE STUDY? 
 
If you decide to take part in the study, it should be because you really want to volunteer. You will not lose any 
benefits or rights you would normally have if you choose not to volunteer. You can stop at any time during the 
study and still keep the benefits and rights you had before volunteering. If you decide not to take part in this 
study, your decision will have no effect on the quality of medical care you receive. 
 
Your alternative is to not take part in the study. If you choose not to take part, your healthcare at University of 
Kentucky will not be affected. 
 
WHAT IF YOU HAVE QUESTIONS, SUGGESTIONS OR CONCERNS? 
IRB Approval
10/10/2022
IRB # 43611
IRB1


Page 2 of 13 
 
The person in charge of this study is Arun Aneja, MD PhD of University of Kentucky, Department of Orthopaedic 
Traumatology There may be other people on the research team assisting at different times during the study. 
If you have questions, suggestions, or concerns regarding this study or you want to withdraw from the study his 
contact information is: 
 
Dr. Arun Aneja, MD PhD 
Department of Orthopaedic Surgery and Sports Medicine 
740 S Limestone, K400 
Lexington, KY 40536 
(859) 629-1970 
If you have any questions, suggestions or concerns about your rights as a volunteer in this research, contact staff 
in the University of Kentucky (UK) Office of Research Integrity (ORI) between the business hours of 8am and 5pm 
EST, Monday-Friday at 859-257-9428 or toll free at 1-866-400-9428. 
43611


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DETAILED CONSENT: 
 
WHERE IS THE STUDY GOING TO TAKE PLACE AND HOW LONG WILL IT LAST? 
 
The research will be conducted at UK Hospital. The screening visit will take place while you are hospitalized for 
your injury. You will need to come to the Kentucky Clinic 740 S. Limestone Street, Lexington KY, for your regular 
follow up visits (3 week, 6 week, 3 month, 6 month, 1 year after initial surgery or hospital discharge). Each of 
those visits will take about 1 hour. The total amount of time you will be asked to volunteer for this study overlaps 
with your regular medical care, therefore, no additional time outside of your routine medical follow up visit is 
necessary. We will observe and record information regarding your care conducted at the University of Kentucky. 
 
WHAT WILL YOU BE ASKED TO DO? 
 
If you agree to participate in this study, we will treat your broken bone as we normally would. The only change to 
normal care would be to randomize you to one of two groups and additional blood samples taken as part of your 
routine labs. 
 
If you agree to participate and are included in the study, you will be randomized into one of two groups: 
• 
Group 1 will get a brief and low dose administration of a non-steroidal anti-inflammatory drug Ketorolac 
(Toradol) 3 times a day for the initial 5 days of hospital admission 
OR 
• 
Group 2 will get the standard post surgery protocol, which you will NOT receive non-steroidal anti- 
inflammatory drug Ketorolac(Toradol). 
 
Randomization is like the flipping of a coin (based on chance). Randomization for this study will be in a 1:1 
fashion. This means that there is a 1 out of 2 (50%) chance that you will receive Toradol. 
 
After consent, we will collect the first blood sample. This will involve two tubes and we will make our best efforts 
to coordinate this with you next scheduled blood draw. Each day following your enrollment for five days total we 
will collect two additional tubes of blood that we will use to determine the level of inflammatory markers you’re 
your body is releasing. In total, we will collect 10 additional tubes of blood over a 6 day period. 
 
After your orthopaedic surgery consultation in the emergency room, your medical care will be exactly the same as 
if you were not in the study. You will be asked to come back to the clinic and follow up with us at 2 weeks, 3 
months, 6 months, and 1 year after your surgery or hospital discharge. These visits coincide with times you would 
normally come back to see your physician for a check-up. During these visits the following things will happen: 
 
• 
You will have a physical exam 
• 
Because you are in the study, you will be asked additional questions by a member of the study team. 
These questions will typically take about 5 minutes of your time and will usually be asked while you are 
waiting to see your surgeon. 
• 
Wewill check to see if you have been re-hospitalized for your injury since your last follow-up visit. If you 
have, we will gather the details about the hospitalization from your medical record. 
• 
We will ask you if you have had any problems with your treated fracture and if you have been told you 
have an infection by any of your doctors outside of this facility. 
• 
You will also be asked if you are taking any kind of medication for any kind of infection. 
• 
You will be evaluated by your primary orthopaedic surgeon for radiographic evidence of bone healing 
• 
You will be evaluated by experienced research coordinator, who will administer a patient center survey 
that will ask you about your daily pain level and functional status. 
 
In addition, at the 6 month study visit we would like to ask you some questions about pain, your health and 
general well-being. These questions are widely used in research and have been found to be useful in finding out 
how you are doing after your injury. These include the Short Form Musculoskeletal Assessment (SMFA) and 
Patient Reported Outcomes Measurement Information System (Promis). These questions should take you 
approximately 10 minutes to answer. 
 
Finally, we would like to contact you by phone for the final study visit at 12 months following your injury. At that 
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time we will check to see if you: 
 
• 
have been re-hospitalized for your injury since your last follow-up visit. 
 
• 
have had any problems with your treated fracture and if you have been told you have an infection by any 
of your doctors outside of this facility. 
 
• 
are taking any kind of medication for any kind of infection. 
 
This call should last approximately 5 to 10 minutes. 
 
 
WHAT ARE THE POSSIBLE RISKS AND DISCOMFORTS? 
There are standard risks with surgery. These will be explained to you along with your consent for surgery. 
 
The risks associated with getting Toradol treatment are low. Depending on your treatment group, you will be 
either receiving Toradol treatment for 5 days or just the standard of treatment. There is minimal risk associated 
with taking Toradol. The dose we provide is very low, and the duration is brief. If at any time you experience any 
discomfort, such as difficulty breathing, stomach pain, or bloody stools, please notify your health provider There 
is always a chance that any medical treatment can harm you, and the investigational treatment in this 
study is no different. There is always the possibility that taking Toradol may make worse your diagnosed medical 
comorbidities, such as peptic ulcer disease, or bleeding disorder. In addition to exacerbating pre-existing 
conditions, Toradol can also cause a new ulcer or bleeding incident to occur. Please alert your health care 
provider any prescription medication you are currently taking, or any family history of bleeding disorders. There 
will be orthopedic surgery resident physicians, nurses, physical therapists, and/or medical students that will 
check on you daily to prevent that from happening while you remain an inpatient. 
 
All treatments have potential to cause some side effects or other reactions; however, there are no treatments, 
therapies, or procedures directly involved with your participation in this research study. All treatments, therapies, 
or procedures you are receiving are part of standard of care and possible risks and discomforts from standard of 
care should be discussed with your primary care physician and your orthopaedic surgeon. 
 
WILL YOU BENEFIT FROM TAKING PART IN THIS STUDY? 
 
There is no guarantee that you will get any benefit from taking part in this study. Your willingness to take part, 
however, may help doctors better understand and/or treat others who have similar injuries in the future. 
 
WHAT WILL IT COST YOU TO PARTICIPATE? 
 
You and/or your insurance company, Medicare or Medicaid will be responsible for the costs of the overall care 
and treatment you receive during this study that you would normally receive for the treatment of your injury. By 
enrolling in the present study, no additional cost will be added to your overall medical cost. The University of 
Kentucky may not be allowed to bill your insurance company, Medicare or Medicaid for the medical procedures 
done strictly for research. The study sponsor will be paying for the 5 days of the study drug and its delivery 
 
WHO WILL SEE THE INFORMATION THAT YOU GIVE? 
 
The information we collect from you will be kept private to the best of our ability. Your name, birth date, medical 
record number and any other information that could identify you as an individual will be removed from all study 
forms. Instead, we will label your forms with a unique study number. The link between your name and your study 
number will be kept confidential to the greatest extent provided by law and removed once your final follow up has 
been completed. The information collected for the study will be stored in a password protected, HIPPA verified 
computer database that only authorized members of our research team can use. When we report the results of 
the study, we will combine the information about you with similar information about forty other patients so your 
individual information will not be identifiable in any reports or publications. 
We will make every effort to safeguard your data, but, the security of data obtained through commercial survey 
companies cannot be guaranteed. It is also possible the data collected for research purposes may be used for 
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marketing or reporting purposes by the company, depending on the company’s Terms of Service and Privacy 
policies. We will make every effort to prevent anyone who is not on the research team from knowing that you gave 
us information, or what that information is. You should know that there are some circumstances in which we may 
have to show your information to other people such as the The University of Kentucky’s Institutional Review 
Board/Office of Research Integrity, Law enforcement agencies when required by law, University of Kentucky 
representatives when situation arises, such as if you report information about a child being abused, or if you pose 
a danger to yourself or someone else. 
We will use your information only for the purposes of this study. The data from the study may be published. 
However, you will not be identified by name. People designated from the institutions where the study is being 
conducted will be allowed to inspect sections of your medical and research records related to the study. This 
includes people designated by the Institutional Review Board at the University of Kentucky who is overseeing this 
study. Everyone using study information will work to keep your personal information confidential. Your personal 
information will not be given out unless required by law. 
 
CAN YOU CHOOSE TO WITHDRAW FROM THE STUDY EARLY? 
Your participation in this study is voluntary. You have the right to withdraw from the research study at any time 
without penalty. Your decision will not affect the medical care you receive. If you decide to stop participating, you 
should notify the study doctor or the research coordinator. 
 
 
Dr. Arun Aneja, MD PhD 
Department of Orthopaedic Surgery and Sports Medicine 
740 S Limestone, K400 
Lexington, KY 40536 
(859) 629-1970 
 
Your participation in this research study could be ended without your consent. Possible reasons could include our 
decision to end the study early or other reasons. If you choose to leaqve the study early, the data up to that point 
will remain in the database and will not be removed. 
ARE YOU PARTICIPATING, OR CAN YOU PARTICIPATE, IN ANOTHER RESEARCH STUDY AT THE SAME 
TIME AS PARTICIPATING IN THIS ONE? 
You may not take part in this study if you are currently involved in another research study. It is important to let the 
investigator/your doctor know if you are in another research study. You should discuss this with the 
investigator/your doctor before you agree to participate in another research study while you are in this study. 
WHAT HAPPENS IF YOU GET HURT OR SICK DURING THE STUDY? 
 
If you believe you are hurt or if you get sick because of something that is due to the study, you should call Arun 
Aneja, MD PhD at (859) 629-1970 immediately. If you are hurt or become sick after normal business hours or on 
the weekend or holiday please call 859-323-5321 and ask to speak with the orthopaedic resident on call. Arun 
Aneja, MD PhD will determine what type of treatment, if any, that is best for you at that time. 
 
It is important for you to understand that the University of Kentucky does not have funds set aside to pay for the 
cost of any care or treatment that might be necessary because you get hurt or sick while taking part in this study. 
Also, the University of Kentucky will not pay for any wages you may lose if you are harmed by this study. 
 
If you are injured or become ill because of your participation in this study, you will receive emergency medical 
care if needed and you will receive assistance in getting other medical care as needed. You or your insurance 
carrier will be billed for the cost of care, just as you would be billed for any other medical care. If you have any 
costs that are not covered by insurance, they are your responsibility. 
 
You do not give up any of your legal rights by signing this form. 
 
WILL YOU RECEIVE ANY REWARDS FOR TAKING PART IN THIS STUDY? 
 
You will not be compensated by participating in the present study. However, the information and knowledge 
learned from the present study has the potential to benefit millions of trauma patients in the future. 
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WHAT IF NEW INFORMATION IS LEARNED DURING THE STUDY THAT MIGHT AFFECT YOUR DECISION 
TO PARTICIPATE? 
 
If the researcher learns of new information regarding to your medical care, and it might change your willingness to 
stay in this study, the information will be provided to you. You may be asked to sign a new informed consent form 
if the information is provided to you after you have joined the study. 
Do you give permission for Drs. Aneja and Bernard to contact you with information about research results or 
incidental findings that are determined to be important to you/your family’s health? (Incidental findings are 
unforeseen findings discovered during the course of the research that may affect you or your family’s health). 
Yes 
No 
  
Initials 
 
After signing the form, you can change your mind and NOT let the researcher(s) collect or release your 
health information (revoke the Authorization). If you revoke the authorization: 
 
• 
You will send a written letter to Arun Aneja, MD PhD (mailing address: K401 Kentucky Clinic 740 S. 
Limestone, KY 40536-0284) to inform him of your decision. 
• 
Researchers may use and release your health information already collected for this research study. 
• 
Your protected health information may still be used and released should you have a bad reaction 
(adverse event). 
 
WHAT ELSE DO YOU NEED TO KNOW? 
 
There is a possibility that the data collected from you may be shared with other investigators in the future. If that 
is the case the data will not contain information that can identify you unless you give your consent/authorization or 
the UK Institutional Review Board (IRB) approves the research. The IRB is a committee that reviews ethical 
issues, according to federal, state and local regulations on research with human subjects, to make sure the study 
complies with these before approval of a research study is issued. If you volunteer to take part in this study, you 
will be one of about 200 people at the University of Kentucky. A description of this clinical trial will be available on 
ClinicalTrial.gov as required by U.S. Law. This website will not include information that can identify you. At most, 
the website will include a summary of the results. You can search this website at any time. 
 
If you have not already received a copy of the Privacy Notice, you may request one. If you have any 
questions about your privacy rights, you should contact the University of Kentucky’s Privacy Officer 
between the business hours of 8am and 5pm EST, Mon-Fri at: (859) 323-1184. 
 
You are the subject or are authorized to act on behalf of the subject. You have read this information, and 
you will receive a copy of this form after it is signed. 
 
FUTURE USE OF YOUR PROTECTED HEALTH INFORMATIOON OR SPECIMEN(S) 
 
Identifiable information such as your name, medical record number, or date of birth may be removed from the 
information or samples collected in this study. After removal, the information or samples may be used for future 
research or shared with other researchers without your additional informed consent. 
 
In addition to the main study, you are being asked to allow us to keep and use your information and/or specimens 
for future research that involves surgical complications and patient outcome research in trauma patient 
population. 
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AUTHORIZATION TO DISCLOSE YOUR IDENTIFIABLE HEALTH INFORMATION 
The privacy law, HIPAA (Health Insurance Portability and Accountability Act), requires researchers to protect your 
health information. The following sections of the form describe how researchers may use your health information. 
 
Your health information that may be accessed, used and/or released includes: 
 
• 
Demographic information (name, initials, gender, race, age, height, weight, study number, mailing 
address, email address, and home/work cell initials, Social Security Number, Medical Record 
number, insurance information, marital status) 
• 
Medical history, Type of injury, Smoking Status, BMI, Activities you usually did before your injury, 
circumstances of your injury, X-rays of your fracture, length of time in ICU, 
• 
Medications taken prior to Injury, Medications used to treat your injury 
• 
Employment status, Workers compensation status, Income 
• 
Current Military Service 
The Researchers may use and share your health information with: 
 
• 
The University of Kentucky’s Institutional Review Board/Office of Research Integrity. 
• 
Law enforcement agencies when required by law. 
• 
University of Kentucky representatives. 
• 
University of Kentucky Center for Clinical and Translational Science and/or Orthopaedic Trauma 
Association if grant(s) are funded 
• 
Wake Forest University Clinical and Translation Science Institute (CTSI) if grant(s) are funded 
 
Should your health information be released to anyone that is not regulated by the privacy law, your health 
information may be shared with others without your permission; however, the use of your health information would 
still be regulated by applicable federal and state laws.  You may not be allowed to participate in the research 
study if you do not sign this form. If you decide not to sign the form, it will not affect your: 
• 
Current or future healthcare at the University of Kentucky 
• 
Current or future payments to the University of Kentucky 
• 
Ability to enroll in any health plans (if applicable) 
• 
Eligibility for benefits (if applicable) 
The registry will remove all information that could identify you such as your name, address, medical record 
number, etc., before sharing with investigators. The registry will not share information that could identify you 
without your permission. 
 
 
After Signing the form, you can change your mind and NOT let the researcher(s) collect or release your 
health information (revoke the Authorization). IF you revoke the authorization: 
• 
You will send a written letter to: Arun Aneja, MD to inform him of your decision. 
• 
Research may use and release your health information already collected for this research study. 
• 
Your protective health information may still be used and released should you have a bad reaction 
(adverse event). 
The use and sharing of your information has no time limit. 
 
 
If you have not already received a copy of the Privacy Notice, you may request one. If you have any 
questions about your privacy rights, you should contact the University of Kentucky’s Privacy Officer 
between the business hours of 8am and 5 pm EST, Monday-Friday at (859)323-1184. 
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Appendix A: Study Visits/Procedures 
Upon arrival to the emergency room, you will be treated according to the standard Advanced Trauma Life Support 
(ATLS) protocol. After careful screening by Dr. Aneja and the research team, you will be asked to enroll in our study 
group. Once you are discharged from the hospital, trained research personnel will follow up with you and document 
any subjective pain scores and additional pain modulating medication intake. At 6 weeks after your hospital 
discharge, the principal investigator will evaluate for evidence of bone healing on radiographic imaging. Please see 
table below for detailed project timeline and schedule of activities. 
 
Tentative time table of the proposed project 
Procedures 
Daily 
Screen 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
2 wk 
6 wk 
3 mon 
6 
mon 
12 
mon 
Inclusion/Exclusion 
Review 
x 
Informed consent 
x 
Blood Sample 
x 
x 
x 
x 
x 
Ketorolac 
intervention 
x 
x 
x 
x 
x 
Pain assessment 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Radiographic 
evaluation for 
fracture nonunion 
x 
x 
x 
x 
Data Analysis 
x 
Years 1 
Years 2 (12-18 mo) 
Active patient screening, enrollment, and data evaluation 
Data Analysis and 
Manuscript preparation 
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Appendix B: Risks 
 
There are standard risks with surgery. These will be explained to you along with your consent for surgery. 
 
The risks associated with getting Toradol treatment are low. Depending on your treatment group, you will be 
either receiving Toradol treatment for 5 days or just the standard of treatment. There is minimal risk associated 
with taking Toradol. The dose we provide is low, and the duration is brief. As a matter of fact, Toradol is a 
standard adjunctive pain medication in patients who receives colorectal surgery. If at any time you experience any 
discomfort, such as difficulty breathing, stomach pain, or bloody stools, please notify your health provider because 
it is our mission at UK that your health care will always come first. 
 
There is always a chance that any medical treatment can harm you, and the investigational treatment in this 
study is no different. There is always the possibility that taking Toradol may exacerbate your diagnosed medical 
comorbidities, such as peptic ulcer disease, or bleeding disorder. In addition to exacerbating pre-existing 
conditions, Toradol can also cause a new ulcer or bleeding incident to occur.  Please alert your health care 
provider any prescription medication you are currently taking, or any family history of bleeding disorders. There 
will be orthopedic surgery resident physicians, nurses, physical therapists, and/or medical students that will 
check on you daily to prevent that from happening while you remain inpatient. 
 
All treatments have potential to cause some side effects or other reactions; however, there are no treatments, 
therapies, or procedures directly involved with your participation in this research study. All treatments, therapies, 
or procedures you are receiving are part of standard of care and possible risks and discomforts from standard of 
care should be discussed with your primary care physician and your orthpaedic surgeon. 
 
WHAT ARE THE POSSIBLE RISKS AND DISCOMFORTS? 
 
Toradol (Ketorolac Tromethamine) is a nonsteroidal anti-inflammatory drug (NSAID) that is used to treat 
moderately severe pain and inflammation, usually after surgery. Toradol works by blocking the production of 
prostaglandins, compounds that cause pain, fever, and inflammation. The brand name Toradol is no longer 
available in the U.S. Generic versions may be available. Common side effects of Toradol include: 
 
Toradol (Ketorolac Tromethamine) is a nonsteroidal anti-inflammatory drug (NSAID) that is used to treat 
moderately severe pain and inflammation, usually after surgery. Toradol works by blocking the production of 
prostaglandins, compounds that cause pain, fever, and inflammation. The brand name Toradol is no longer 
available in the U.S. Generic versions may be available. Common side effects of Toradol include: 
 
• 
Headache 
• 
Heartburn 
• 
Upset Stomach 
• 
Nausea 
• 
Vomiting 
• 
Diarrhea 
• 
Stomach Pain 
• 
Bloating 
• 
Gas 
• 
Constipation 
• 
Dizziness 
• 
Drowsiness 
• 
Sweating 
• 
Ringing in the ears. 
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Stop taking ketorolac and seek medical attention or call your doctor at once if you have any of these serious side 
effects: 
 
• 
Chest pain, weakness, shortness of breath, slurred speech, problems with vision or balance; 
• 
Black, bloody, or tarry stools; 
• 
Coughing up blood or vomit that looks like coffee grounds; 
• 
Swelling or rapid weight gain; 
• 
Urinating less than usual or not at all; 
• 
Nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of 
the skin or eyes); 
• 
Fever, sore throat, and headache with a severe blistering, peeling, and red skin rash; 
• 
The first sign of any mouth sores or skin rash, no matter how mild; 
• 
Pale skin, easy bruising, severe tingling, numbness, pain, muscle weakness; or 
• 
Fever, headache, neck stiffness, chills, increased sensitivity to light, purple spots on the skin, and/or 
seizure (convulsions). 
 
Less serious side effects may include: 
 
• 
Upset stomach, mild nausea or vomiting, diarrhea, constipation; 
• 
Mild heartburn, stomach pain, bloating, gas; 
• 
Dizziness, headache, drowsiness; 
• 
Sweating; or 
• 
Ringing in your ears. 
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Appendix C: Subject information to be stored for future research 
 
WHAT IS A REGISTRY AND WHAT IS THE PURPOSE OF THE REGISTRY? 
A registry is a collection of medical information with pre-set definition of inclusion criteria. The purpose of 
the registry is to collect and store contact and/or health information for research purposes. Investigators 
can then use the stored information for future research studies to learn more about future treatment 
directions for providing the optimal care for trauma patients. The registry provides a ready supply of 
information, so investigators do not have to look for participants for each new study. 
The registry will enroll 200 participants. 
Participant Confidentiality: It is the investigator’s responsibility to conduct the protocol under the current version 
of Declaration of Helsinki, ICH Guidelines, Good Clinical Practice, and rules of local IRBs. The investigator will 
ensure that the patient’s anonymity be maintained in their data collection and submission. 
Patients will be identified only by an identification code but not by their name, SSN, or hospital medical record 
number. Study Site Investigators will maintain a separate confidential enrollment log which matches identifying 
codes with the patients’ names and addresses available only to local clinic staff to participate in the study. 
 
All study forms, reports, and other records that are part of the study data collection materials will be identified by 
coded number to maintain patient confidentiality. All paper records will be kept in locked file cabinets. All electronic 
records of study data will be identified by coded number. Clinical information will not be released without written 
permission of the patient, except as necessary for monitoring by the Institution Review Board (IRB). Consent 
procedures and forms, and the communication, transmission and storage of patient data will comply with University 
of Kentucky IRB requirements for compliance with The Health Insurance Portability and Accountability Act (HIPAA). 
 
Data Management: Following initial enrollment, each patient will be assigned a unique patient identifier. All 
electronic medical documentation will be associated with this unique patient identifier during analysis. All protected 
health information will be stored in a separate, password-protected research file that will not be accessed regularly. 
Following our secondary analysis, all personal health information will be removed from our electronic files and 
destroyed in accordance with patient privacy guidelines. 
 
Data obtained at University of Kentucky during the study will be recorded that will be maintained at the hospital by 
the research staff. Final analysis will be conducted using Excel spreadsheets. All documents will be stored on a 
password-protected research drive and only research personnel will have access to its content. Paper documents, 
including consent forms, will be stored in a locked cabinet in a secure research room. 
 
Each researcher on the project has passed the exam on ethical conduct of research and has received training and 
supervision regarding patient confidentiality. Only approved research personnel will administer consents and 
perform phone surveys. All efforts will be made to maintain the confidentiality of the patient reported data. Only 
study personnel listed will have access to identified study data. 
 
All other research-related files including but not limited to copies of consents and surveys will be stored on a 
password protected research drive or locked research cabinet. Research personnel also have allocated space with 
locked drawers for source document files and secure workspace apart from patient or public areas that is also 
locked. 
 
DOES TAKING PART IN THE REGISTRY COST ANYTHING? 
There will be no additional costs or charges to you for taking part in the registry. 
 
WHAT IF YOU CHOOSE NOT TO PARTICIPATE OR CHANGE YOUR MIND AND WANT TO WITHDRAW 
FROM TAKING PART IN THE REGISTRY? 
Taking part in the registry is voluntary. Choosing not to take part will not affect your care or cause you to lose 
benefits to which you are entitled. You may withdraw your permission to continue taking part in the registry at any 
time. To do so, you must send a written withdraw request to Arun Aneja, MD PhD (mailing address: K401 
Kentucky Clinic 740 S. Limestone, KY 40536-0284) to inform him of your decision. 
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The registry will destroy any remaining information that has been stored. In addition, it may be possible for the 
registry to destroy the code that links you with your medical information. However, the information that has 
already been shared with other investigators or placed in shared databases cannot be withdrawn. 
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Signature of Principal Investigator or Sub/Co-Investigator 
Date 
Printed name of [authorized] person obtaining informed consent/HIPAA authorization 
*If applicable, please explain Representative’s relationship to subject and include a description of 
representative’s authority to act on behalf of subject: 
*Printed name of research subject’s legal representative 
Printed name of research subject and, if applicable, 
Date 
Signature of research subject or, if applicable, 
*research subject’s legal representative 
INFORMED CONSENT SIGNATURE PAGE 
You are a participant or are authorized to act on behalf of the participant. This consent includes the 
following: 
• Key Information Page 
• Detailed Consent 
• Appendices A, B, and C. Please refer to above for further details 
You will receive a copy of this consent form after it has been signed. 
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