Conditions: Postoperative Pain Inflammation Osteoarthritis
Keywords: Osteoarthritis Postoperative pain Total knee arthroplasty Orthopaedics Inflammation
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 1
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate if the use of two small doses of intravenous (IV) steroids around the time of knee replacement surgery decrease a patient's pain or use of pain medication. The investigators will also determine if the subjects receiving the steroid will have better pain control and better postoperative outcomes after their surgery.

Detailed description:
Adequate pain control after total knee arthroplasty (TKA) is of great importance not only to maximize patient comfort, but also to ensure optimal outcomes after surgery. This study is designed to assess whether the use of two small doses of intravenous (IV) steroids around the time of surgery decrease a patient's pain or use of pain medication. Secondly, the investigators will also determine if the use of these steroids as part of a multimodal pain management strategy leads to improved patient outcomes, including pain, nausea and vomiting, knee function and length of stay in the hospital after surgery. The study will compare the effect of two different doses of IV dexamethasone given preoperatively before TKA, when compared to placebo.

Arms:
arm 1: Subjects undergoing primary total joint arthroplasty of the knee will receive two doses of placebo intravenously in addition to a standard multimodal postoperative pain management regimen typically used for total knee arthroplasty. The first dose of placebo will be given preoperatively within 3 hours of surgery and the second dose will be administered 8 hours after the first dose in the inpatient setting. arm 2: Subjects undergoing primary total joint arthroplasty of the knee will receive two doses of 10 mg dexamethasone. The first dose will be given preoperatively within 3 hours of surgery and the second dose will be administered 8 hours after the first dose in the inpatient setting. Additionally, subjects will also receive a standard multimodal postoperative pain management regimen typically used for total knee arthroplasty. arm 3: Subjects undergoing primary total joint arthroplasty of the knee will receive two doses of 20 mg dexamethasone. The first dose will be given preoperatively within 3 hours of surgery and the second dose will be administered 8 hours after the first dose in the inpatient setting. Additionally, subjects will also receive a standard multimodal postoperative pain management regimen typically used for total knee arthroplasty.

Interventions: intervention 1: Dexamethasone 10 mg intervention 2: Dexamethasone 20 mg intervention 3: Standard multimodal pain management regimen intervention 4: Placebo
Intervention descriptions: intervention 1: Two doses of dexamethasone 10 mg will be given intravenously. The first dose will be given preoperatively within 3 hours of surgery and the second dose will be administered 8 hours after the first dose in the inpatient setting. intervention 2: Two doses of dexamethasone 20 mg will be given intravenously. The first dose will be given preoperatively within 3 hours of surgery and the second dose will be administered 8 hours after the first dose in the inpatient setting. intervention 3: The standard multimodal postoperative pain management regimen typically used for total knee arthroplasty consists of the following:

Preoperative:

* Decadron: 10 or 20mg IV x 1 2 doses, 8 hours apart (if randomized to study group)

Intraoperative:

* Ropivacaine: Given intraoperatively. Capsule, subcutaneous tissue/skin. Administered in standard fashion. (300mg)
* Toradol: 30mg q 6hr for 6 total doses. 1st dose given intraoperatively at incision. The dose is 15 mg for older patients or if creatinine clearance (CrCl) is low.

Postoperative

* Tylenol: 1000mg po q 8hr (scheduled)
* Oxycodone: 5mg or 10mg q 3-4hr prn pain, If intolerant to Oxycodone: second agent line is Hydrocodone or Oral Dilaudid
* IV Morphine (or Dilaudid): 1 or 2 mg q 2hr prn breakthrough pain
* Morphine patient-controlled analgesia (PCA): only for failure of the above
* Morphine Sulfate (MS) Contin: Use as backup prn pain intervention 4: Participants in the placebo arm will receive two doses of saline intravenously. The first dose will be given preoperatively within 3 hours of surgery and the second dose will be administered 8 hours after the first dose in the inpatient setting.

Protocol document:
Prot_SAP_000.pdf: 
1 
 
 
Study Title: Evaluation of Intravenous Glucocorticoid Therapy in Total Knee 
Arthroplasty 
 
Version:  12.0, August 1st, 2016 
 
NCT Number: NCT02219581 
 
Principal Investigator: Thomas L Bradbury, MD 
 
Co-Investigators: 
Jimmy H Daruwalla, MD 
Greg Erens, MD 
James Roberson, MD 
Christina Lomba, MS 
 
 
Introduction and Background 
 
Over the last decade, innovations in total joint arthroplasty have rendered 
joint reconstruction the gold standard for treatment of end-stage arthritis of the hip 
and knee.  Component design and survivability, infection control, rehabilitation 
protocols, and more recently, multimodal pain management, continue to improve 
patient outcomes in total joint arthroplasty.  Multimodal pain management, in 
particular, has improved patient satisfaction and outcomes following joint 
replacement surgery1, 2, 3.  
 
Data suggests that improved pain management has implications beyond the 
orthopaedist’s ethical obligation to provide adequate analgesia.  Poorly managed 
postoperative pain leads to prolonged hospital stays, increased risks of readmission, 
decreased postoperative range of motion, and substantial increases in opioid 
analgesia usage and associated side effects4-6.  Interestingly, in a review of 10,000 
patients undergoing ambulatory surgery, orthopaedic procedures had the highest 
incidence of postoperative pain in the post anesthesia care unit7.  Analgesia in the 
postoperative setting, therefore, is not only important for patient satisfaction, but also 
for patient safety and optimal surgical outcomes. 
 
Intravenous (IV) glucocorticoid therapy is an evolving concept in 
perioperative pain management in orthopaedics. Outside of the orthopaedic 
literature, level one evidence suggests that perioperative IV glucocorticoid 
administration is safe and improves pain, nausea, and vomiting in thyroid, abdominal, 
facial plastic, and oral surgery8-14.  Additionally, data from the facial plastic surgery 
literature suggests that postoperative swelling and tissue edema are improved with 
perioperative glucocorticoid administration without any concomitant increase in 
wound disturbances15-17.  
 
Within the orthopaedic literature, particularly in total joint arthroplasty, there 
is little evidence regarding perioperative IV glucocorticoid therapy.  Jules-Elysee et al. 
evaluated perioperative intravenous steroid administration in thirty-four patients 
undergoing bilateral knee arthroplasty and found improved outcomes in terms of 


2 
 
pain, nausea, and range of motion15-17.  The study found no increase in infection 
between control and treatment groups, but was underpowered to adequately assess 
this outcome.  In 2013, Lunn et al. showed that perioperative IV steroids improved 
pain in forty-eight total hip arthroplasty patients18.   
To date, the most comprehensive study on the use of IV steroids in total joint 
arthroplasty is a randomized controlled trial examining the effect of perioperative IV 
dexamethasone19. This study found significant reductions in anti-emetic and 
analgesic usage, superior VAS nausea and pain scores, and shorter length of stay 
compared to the control group. However, as this study investigated just one dosing 
regimen, the most efficacious dose and dosing regimen of perioperative 
dexamethasone is still unknown. Furthermore, this study had relatively short follow 
up, limiting its ability to determine the effect of IV steroids on long-term prosthetic 
knee function. 
 
It is likely that orthopaedic surgeons are wary of perioperative steroid therapy 
due to concern of infection and wound healing disturbance.  Certainly, these 
complications are devastating in the setting of arthroplasty.  However, data from 
plastic surgery, general surgery, oral surgery, and orthopaedic surgery suggest no 
increase in wound complications from perioperative IV steroid administration4.  
Taken together, the literature has shown that low-dose, short-course IV 
corticosteroid regimens appear to be safe with regard to wound healing and infection.  
Nevertheless, no single study that is powered to adequately evaluate infection risk 
with steroid therapy in total knee arthroplasty currently exists, given the low baseline 
incidence of infection.  
 
The proposed study seeks to comprehensively evaluate postoperative 
outcomes after total knee arthroplasty when using IV glucocorticoid therapy as part 
of a multi-modal pain control regimen.  This prospective, randomized, placebo-
controlled trial will build on previous studies by utilizing a superior study design with 
a larger sample size and evaluate a range of subjective and objective outcome 
measures with extended follow up of up to 1 year. More specifically, this study will 
assess the effect of different doses on key outcomes and also study the effect of 
perioperative dexamethasone on long-term knee function, considerations that have 
not yet been evaluated in the literature.  
 
 
Objectives 
Our objective is to determine the effect of and compare two different doses of 
IV dexamethasone given preoperatively before TKA, when compared to placebo, 
using the outcome measures listed below: 
 
Primary Outcome Measures  
• 
To assess patient reported visual analog pain scores.  
• 
To assess patient controlled analgesic usage. 
 
 
Secondary Outcome Measures 


3 
 
1. 
To assess the soft tissue swelling about the operative knee after steroid 
administration.  
2. 
To assess postoperative glucose levels after steroid administration. 
3. 
To assess rehabilitation parameters such as postoperative knee range of 
motion and time to physical therapy clearance. 
4. 
To assess incidence of nausea and vomiting postoperatively after steroid 
administration.  
5. 
To assess patient satisfaction and function scores at 4 months with both 
Short Form (SF) – 12 and Knee Injury and Osteoarthritis Outcome Score 
Short Form (KOOS, Jr.) scores.  
6. 
To assess hospital admission characteristics such as length of stay and rate 
of readmission.  
7. 
To assess the risk of infection at 4 months and wound drainage at 7 days 
after perioperative steroid administration in total knee arthroplasty. 
 
 
Study Design and Methods 
 
We plan to conduct a prospective, double-blinded, randomized, placebo-
controlled trial to evaluate perioperative glucocorticoid administration in total knee 
arthroplasty. There will be three arms in the study: 1) Placebo, 2) 10 mg 
dexamethasone, and 3) 20 mg dexamethasone. 
 
Consent to Participation in the Study 
Patients will be given the opportunity to participate in the study at the time of 
consent for surgery and blood product, which typically takes place in clinic during an 
evaluation for severe end-stage arthritis.  It will be emphasized that study 
participation is optional, and that patients may be randomized to the control or 
placebo group.  Patients will sign the combined informed consent and HIPAA form in 
order to participate in the study.  
 
Method of Randomization 
 
Once a patient chooses to be part of the study, he/she will be randomized in a 
blocked fashion to either the control group or to one of two intervention groups.  
Randomization will occur after informed consent has been obtained from the patients 
and after the preoperative screening examination is complete. Patients and 
investigators will be blinded to the randomization assignment. Emory’s 
Investigational Drug Services will randomize each patient prior to dispensing the 
blinded dexamethasone/placebo doses. 
 
Therapeutic Intervention 
 
Patients in the intervention arms will receive two doses of either 10 mg 
dexamethasone or 20 mg dexamethasone. The first dose will be administered 
preoperatively within three hours of surgery once the patient receives anesthesia. 
The second dose will be administered eight hours after the first dose in the inpatient 
setting by the nurse in that unit. The second dose will be administered using a 
piggyback setup. Patients in the placebo arm will receive two doses of saline/placebo. 


4 
 
This particular dosing is chosen based on available literature that suggests a safe and 
effective dose is between 4 and 20 mg of dexamethasone25-26.  
 
 
The administration of either steroid or placebo will occur in a double-blinded 
fashion.  For each study participant, two blinded doses will be sent over from Emory’s 
Investigational Drug Service (IDS).  Thus, neither the patient receiving the medication 
nor the health care professional administering the medication or collecting study 
outcome data will be aware of whether or not the patient received the steroid or the 
placebo.  
 
 
Both the intervention and control groups will receive spinal anesthesia using 
lidocaine and a standard multimodal postoperative pain management regimen 
typically used for total knee arthroplasty.   This regimen will be standardized across 
all three attending surgeons participating in the study.  The standard multimodal pain 
management regimen will be as follows: 
 
• Preoperative: 
o Decadron: 10 or 20mg IV x 2 doses, 8 hours apart (if randomized to 
study group) 
• Intraoperative: 
o Ropivacaine: 
Given 
intraoperatively. 
Injection, 
subcutaneous 
tissue/skin. Administered in standard fashion.  (300mg) 
o Toradol: 30mg q 6hr for 6 total doses. 1st dose given intraoperatively at 
incision.  (15 mg if patient is >65 years of age. Patients with Cr >1.5 
will not receive Toradol). 
• Postoperative 
o Tylenol: 1000mg po q 8hr (scheduled) 
o Oxycodone: 5mg or 10mg q 3-4hr prn pain, If intolerant to Oxycodone: 
second agent line is Hydrocodone or Oral Dilaudid (Tylenol will be 
adjusted accordingly if patient receives Hydrocodone). 
o IV Morphine (or Dilaudid): 1 or 2 mg q 2hr prn breakthrough pain 
o Morphine PCA: only for failure of the above 
o MS Contin: 15 mg BID for two weeks 
 
  On postoperative day (POD) 1, patients will be transitioned to oral (PO) and 
intravenous (IV) medications on an as-needed basis with a regimen that will be 
standardized across all study participants.  
 
Data Collection 
Data will be collected by a number of different health professionals during 
enrollment, during the patient’s postoperative hospital stay, by smart device 
application (app), and during the patient’s routine postoperative follow up visits (1 
month, 4 months, and 12 months).  After surgery, no participants in any group will be 
subjected to any extra invasive tests or interventions related to their involvement in 
the study.  Patients will not be informed whether or not they have received the study 


5 
 
drug until after all data collection is complete.  The schedule of study activities and 
data collection are shown in Table 1. 
 
1. Pain assessment: Postoperative pain will be assessed using the well-
standardized and accepted visual analog pain scale. This data will be recorded 
at baseline, during the hospital stay, and at all follow-up visits.   A smart device 
app will be used to record this information for the 7-day postoperative period. 
Questions will be asked morning, afternoon, and evening for every patient. 
Patients enter alarms for morning, afternoon, and evening the first time they 
use the app. Patients can later adjust these alarms if necessary. Timestamps 
will be recorded for each of these entries as patients will be asked about their 
'average' pain over the preceding 4 hours, and they will be able to edit/modify 
prior entries at any time. Patients will also be asked during the first entry for 
the day if they were awoken from pain or nausea during the previous night, 
and if they click yes, they will be prompted to select pain scores corresponding 
to this event. There will be a comments section to provide patients the ability 
to enter text. Furthermore, during the hospital stay this data will be recorded 
with each vital sign assessment by the nursing per standard of care. The 
following scale will be used to assess pain: 
 
 
 
2. Opioid analgesic usage: The amount of each patient’s postoperative opioid 
analgesic usage (converted into milligrams of morphine equivalents per day) 
will be recorded throughout the duration of their hospital stay.  After inpatient 
discharge, this data will be collected using the smart device app. Patients will 
track the use of both prescribed narcotic medications and over the counter 
non-steroidal 
anti-inflammatory 
medications 
use 
for 
knee 
pain.  
Once patients are discharged from the hospital, they will be asked each day to 
enter their medication usage from a preloaded list (number of pills/day). 
Patients may also choose to enter other medications not on the list. This 
information will be recorded for the two-week postoperative period. 
 
3. Soft tissue swelling: Soft tissue swelling will be evaluated using a 
measurement of knee circumference at the midpoint of the patella, with the 
knee in the maximum amount of extension allowed by the patient. This 


6 
 
measurement will be completed twice, and the average of the two 
measurements will be used as the value for that day. Knee circumference will 
be measured at baseline (time of enrollment), at POD 1 and each subsequent 
in-hospital POD, and at each follow up visit.  The measurements obtained at 
baseline and at each clinic visit will be conducted by the research coordinator 
or physician. Postoperative measurements obtained during the patient’s 
hospital stay will be conducted by the physical therapy staff, during the 
first/morning therapy session of each day. The non-operative knee will also 
be measured at the time of enrollment to use as a reference.   
 
4. Range of motion (ROM): maximum active and passive ROM allowed by the 
patient will be measured using a goniometer. This measurement is the amount 
of flexion and extension recorded in degrees. ROM will be measured at the 
following time points: preoperatively at baseline, at POD 1 and each 
subsequent in-hospital POD, and at each follow up visit.  ROM will be measured 
on postoperative in-hospital days by a physical therapist, whereas ROM at 
clinic visits will be measured by the research coordinator or physician. If more 
than one ROM measurement is obtained during an inpatient day, the numbers 
will be averaged to create one value for that day. 
 
5. Completion of physical therapy milestones: The POD when each patient is 
cleared by the physical therapy staff to go home will be recorded.  This will 
be evaluated by a physical therapist and documented in the medical record. 
The first physical therapy milestone is Bed Mobility in which patient will be 
able to go from supine to sit, get out of bed (without help, only supervision).  
The second milestone is Walking and Household Distance in which the 
patient will be able to walk 100 feet with a walking device (only supervision).  
The number of times physical therapy was aborted or not completed will be 
recorded along with the reason as to why it was not done. Patients who 
ultimately end up being transferred to a subacute rehabilitation facility will 
be excluded from length of stay analysis.  
 
6. Nausea/Vomiting Assessment: The use of as-needed antiemetics will be 
recorded for each patient.  Any incident of emesis will also be recorded by the 
patient’s nurse. A smart device app will be used to record this information for 
the 7-day postoperative period. Questions will be asked morning, afternoon, 
and evening for every patient. Patients enter alarms for morning, afternoon, 
and evening the first time they use the app. Patients can later adjust these 
alarms if necessary. Timestamps will be recorded for each of these entries as 
patients will be asked about their 'average' nausea over the preceding 4 hours, 
and they will be able to edit/modify prior entries at anytime. Patients will also 
be asked during the first entry for the day if they were awoken from pain or 
nausea during the previous night, and if they click yes, they will be prompted 
to select scores corresponding to this event. There will be a comments section 
to provide patients the ability to enter text. This data is being collected because 


7 
 
nausea and/or vomiting are well-known side effects of narcotic usage. The 
following scale will be used to evaluate nausea: 
 
 
BARF nausea scale. Published online May 29, 2011, doi: 10.1542/peds.2010-
1410 Pediatrics June 1, 2011 vol. 127 no. 6 e1542-e1549 doi: 
10.1542/peds.2010-1410. 
 
7. Blood Glucose Levels: The patient’s blood glucose level will be recorded once 
preoperatively at the pre-anesthesia clinic visit several days before surgery, at 
POD 1 and at each subsequent in-hospital POD using a hemocue.  These do not 
consist of extra blood tests, as blood draws at these time points are considered 
standard of care.  This data is being collected because hyperglycemia is a 
potential complication of IV steroid use. If patients experience ketoacidosis or 
hyperglycemia greater than 300, the study drug/placebo will be discontinued.  
 
8. Functionality scores: The Short Form (SF) – 12 and Knee Injury and 
Osteoarthritis Outcome Score Short Form (KOOS, Jr.)  questionnaires will be 
administered to patients at the baseline visit and at each follow up clinic visit.  
Both of these standardized function questionnaires are well validated and 
widely accepted in the literature. 
 
9. Hospital length of stay and readmission: We will record the length of each 
patient’s hospital stay and any readmission to our hospital for the 12-month 
duration of study. 
 
10. Infection: Patients will have standard follow up clinic appointments at 1 and 
4 months after surgery, at which time the clinical presence of possible wound 
drainage and periprosthetic infection will be evaluated.  Patients will be 
followed up to 1 year after surgery to monitor for latent infections.  
 
 


8 
 
Table 1: Outcome measure and data collection schedule 
 
Pre-
operative 
clinic visit 
Each 
inpatient 
day 
7 day app 
usage 
2 week 
app 
usage 
1 month 
clinic 
visit 
4 month 
clinic visit 
12 month 
clinic visit 
Consent, Enrollment, 
Randomization 
X 
 
 
 
 
 
 
Pain assessment 
X 
X 
X 
 
X 
X 
X 
Opioid usage 
 
X 
 
 
 
 
 
Pain medication log 
 
 
X 
X 
 
 
 
Knee swelling 
X 
X 
 
 
X 
X 
 
Knee ROM 
X 
X 
 
 
X 
X 
X 
Physical therapy 
milestones 
 
X 
 
 
 
 
 
Nausea/vomiting 
 
X 
X 
 
 
 
 
Blood glucose 
X 
X 
 
 
 
 
 
Postoperative 
infection/Wound 
drainage 
 
X 
 
 
X 
X 
X 
Length of stay 
 
X 
 
 
 
 
 
KOOS, Jr. and SF-12 
X 
 
 
 
X 
X 
X 
 
 
Consent Process 
Patients will be asked to participate in the study at a preoperative clinic visit. 
The risks, benefits and the optional nature of the study will be emphasized.  Patients 
may withdraw from the study at any given time.  Consent will be obtained from one 
or more of the following three people: the attending surgeon, the orthopaedic surgery 
resident, or the research coordinator.  
 
 
Participant Selection 
This study will be conducted at Emory University Orthopaedic and Spine 
Hospital and Clinic. The investigators perform over 500 total knee arthroplasty 
procedures per year. We estimate 75% (375) of the patients will be eligible and be 
willing to participate in the study. The Department of Orthopaedics staff performs 10-
20 clinical trials per year and therefore is well-trained and prepared to perform 
clinical trials of this magnitude. 
 
Inclusion Criteria 
1. Patients undergoing primary total joint arthroplasty of the knee 
2. Adult patients ages 18-100 years 
3. Patients must have smart phone and/or device for app usage 
 
 


9 
 
Exclusion Criteria 
1. Current chronic steroid use 
2. Patients undergoing revision knee surgery 
3. Patients ambulating preoperatively with assistive devices 
4. Patients with avascular necrosis of the operative knee 
5. Patients with a history of an adverse reaction to glucocorticoid steroids  
6. Patients unable to provide informed consent 
7. Patients with inflammatory arthritis 
8. Prisoners 
9. Current smokers 
10. Patients <18 years of age 
11. Any patient with a complicated postoperative course that requires transfer to 
the Intensive Care Unit (ICU) or to another facility for further management will 
be removed from the study.  
12. Any contraindication that would prevent the patient from being treated with 
the standard multimodal postoperative pain management regimen 
13. History of infection of surgical knee. 
14. Patients with diabetes. 
15. Patients that have an intolerance to Toradol. 
16. Patients that do not have smart phone and/or device for app usage 
 
 
Statistical Analysis 
 
In order to adequately examine our primary outcome measure of pain reduction, 
our target sample size was obtained by a power analysis using retrospective data.  
Assuming a mean difference in the VAS of 1.5 between placebo vs. low dose and 1.5 
for low dose vs. high dose (or 3 between placebo and high dose), in order to achieve 
90% power, we will need 47 patients per study arm. Thus, the total number of 
patients enrolled would need to be at least 141. Based upon historical data, we expect 
it to take 18 months to reach our target N of 141.  
 
 
After the study is complete, statistical analysis will be performed using de-
identified patient data to determine differences in primary and secondary outcomes.  
Repeated-measures analyses for VAS pain score (and change from baseline), knee 
ROM, functionality scores (SF-12 and KOOS, Jr.), and blood glucose will be done with 
a means model with SAS Proc Mixed (version 9, mixed linear models) providing 
separate estimates of the means by time on study (baseline, in hospital, day 7, and at 
1,4 and 12 months after total knee arthroplasty) and treatment group 
(dexamethasone or control).  A compound symmetry variance-covariance form 
among the repeated measurements will be assumed for each outcome and robust 
estimates of the standard errors of parameters will be used to perform statistical tests 
and construct 95% confidence intervals26.  T-tests will be used to compare the 
pairwise differences between the model-based treatment means (least-squares 
means) at each time point.  Mean changes over time within a treatment group will be 
tested for linear trend.  The model-based means are unbiased with unbalanced and 
missing data, so long as the missing data are non-informative (missing at random).  A 


10 
 
dropout process is assumed to be missing at random if; conditional on the observed 
data, the dropout is independent of the unobserved measurements.  Statistical tests 
will be two-sided.  A p value < 0.05 will be considered statistically significant.  
 
 
Adverse Event Reporting 
At a six-month time point following initiation of the study, we will assess our 
results for any reportable adverse events, including postoperative infections.  This 
data will be reported to the Emory Institutional Review Board (IRB). We will monitor 
for any adverse outcomes at each subsequent six-month interval.  
 
 
Data Safety and Monitoring Plan 
A subject key listing name, medical record number (MRN), age, sex, and study number 
will be kept in electronic format on a password-protected, encrypted computer, as 
well as in the research binder stored in a secure locked file cabinet.  Data will be 
collected on paper case report forms (CRFs) and using the smart device application. 
The CRFs will not have any identifiable subject information, only the study number 
and subject’s initials. Data will be entered into REDCap, a secure, web based 
application for building and managing online surveys and databases, by a study team 
member. The database will be made available to all investigators electronically. Data 
analysis will be performed by the investigators on a password-protected computer.  
 
Each subject's safety will be monitored by his/her physician/investigator as the study 
procedures are performed and follow-up visits are conducted. Information regarding 
complications and adverse events will be gathered at each of the study follow-up 
visits. During administration of the study drug or placebo, all patients will be under 
close monitoring by the anesthesia and/or nursing staff. Any difference in risk of 
infection between study groups will be assessed, and this data will be reported to the 
Emory IRB as necessary. We will also monitor for and report any adverse outcomes 
and report to the Emory IRB as necessary. Patients will be followed out to one year 
after 
surgery 
to 
ensure 
that 
the 
intervention 
is 
safe. 
Notification to the Emory IRB will be done according to the IRB’s specific procedures. 
 
No patient will be enrolled in the study and have any study-related procedures 
performed, including completing subject clinical assessments, before an 
approved Informed Consent Document is signed. 
 
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