A Pilot Study to Evaluate Single Dose Indocyanine Green 24 Hours Prior to Operative Treatment of Orthopaedic Infection
Conditions: Trauma Injury, Bone Infection
Sponsor: Dartmouth-Hitchcock Medical Center

PROTOCOL TITLE: A pilot study to evaluate single dose indocyanine green 
24 hours prior to operative treatment of orthopaedic infection.
Page 1 of 21
v.26Oct2022
D-HH IRB OVERSIGHT:
One of the following must be true in order to submit to the D-HH IRB. Please check all 
that apply:
☒ The Principal Investigator is employed by D-H
☒ The study will utilize any D-H data or specimens
☒ The study will enroll D-H patients or recruit from D-H sites
☒ The study will utilize any D-H resources, e.g. study procedures will occur at 
     D-H locations and/or use of D-H equipment or shared resources
PROTOCOL TITLE:
A pilot study to evaluate single dose indocyanine green 24 hours prior to operative 
treatment of orthopaedic infection.
PRINCIPAL INVESTIGATORs:
Ida Leah Gitajn
Orthopaedics
603-650-5133
Ida.leah.gitajn@hitchcock.org 
VERSION NUMBER/DATE:
Version 2: October 26, 2022 
REVISION HISTORY
Revision 
#
Version Date
Summary of Changes
Consent 
Change?
1
04Feb2022
Dosing of ICG in CRU
     Yes
2
26Oct2022
Removing Dr. Jevsevar
Yes

PROTOCOL TITLE: A pilot study to evaluate single dose indocyanine green 
24 hours prior to operative treatment of orthopaedic infection.
Page 2 of 21
v.26Oct2022
Table of Contents
1.0
Study Summary .......................................................................................................3
2.0
Objectives* ...............................................................................................................4
3.0
Background*.............................................................................................................4
4.0
Study Endpoints*......................................................................................................5
5.0
Study Intervention/Investigational Agent.................................................................5
6.0
Procedures Involved* ...............................................................................................6
7.0
Data and Specimen Banking*...................................................................................8
8.0
Sharing of Results with Subjects* ............................................................................8
9.0
Study Timelines*......................................................................................................9
10.0
Inclusion and Exclusion Criteria* ............................................................................9
11.0
Vulnerable Populations*.........................................................................................10
12.0
Local Number of Subjects ......................................................................................10
13.0
Recruitment Methods..............................................................................................11
14.0
Withdrawal of Subjects*.........................................................................................12
15.0
Risks to Subjects*...................................................................................................12
16.0
Potential Benefits to Subjects* ...............................................................................14
17.0
Data Management* and Confidentiality.................................................................14
18.0
Provisions to Monitor the Data to Ensure the Safety of Subjects*.........................15
19.0
Provisions to Protect the Privacy Interests of Subjects ..........................................15
20.0
Compensation for Research-Related Injury............................................................16
21.0
Economic Burden to Subjects.................................................................................16
22.0
Consent Process......................................................................................................17
23.0
Process to Document Consent in Writing...............................................................19
24.0
Setting.....................................................................................................................19
25.0
Resources Available ...............................................................................................19

PROTOCOL TITLE: A pilot study to evaluate single dose indocyanine green 
24 hours prior to operative treatment of orthopaedic infection.
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v.26Oct2022
1.0
Study Summary
Study Title
A pilot study to evaluate single dose indocyanine green 24 
hours prior to operative treatment of orthopaedic infection.
Study Design
Prospective  Observational Trial
Primary Objective
The primary study objective is to explore the variability 
associated with bone and soft tissue perfusion in infection 
patients, using ICG fluorescence imaging.
Secondary 
Objective(s)
The secondary study objective is to evaluate the change in 
single dose, 24h ICG distribution from pre to post 
debridement.
Research 
Intervention(s)/ 
Investigational 
Agent(s) 
Indocyanine green (ICG)-based dynamic contrast enhanced 
fluoresce imaging(diagnostic test)
IND/IDE # 
N/A
Study Population
Patients 18 years of age or older who present to DHMC 
with an orthopaedic infection
Sample Size
20 patients
Study Duration for 
individual 
participants
6 months
Study Specific 
Abbreviations/ 
Definitions 
CDC: Centers for Disease Control and Prevention 
CRU: Clinical Research Unit
CRF: Case Report Forms
DCE-FI: Dynamic Contrast Enhanced Fluorescence Imaging 
D-HH HRPP: Dartmouth-Hitchcock Human Research 
Protection Program
DHMC: Dartmouth Hitchcock Medical Center
FI: fluorescence imaging
GCP: Good Clinical Practice
GFR: glomerular filtration rate
ICG: Indocyanine Green
NSF: nephrogenic sclerosing fibrosis
ROI: Region of interest
SSI: Surgical Site Infection

PROTOCOL TITLE: A pilot study to evaluate single dose indocyanine green 
24 hours prior to operative treatment of orthopaedic infection.
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Objectives*
The primary study objective is to explore the variability associated with bone and soft 
tissue perfusion in infection patients, using ICG fluorescence imaging.
The secondary study objective is to evaluate the change in single dose, 24h ICG 
distribution from pre to post debridement.
The third study objective is to preliminarily determine whether a single dose of ICG 
given 24h preoperatively can predict recurrent infection/treatment failure
 
2.0
Background*
The focus of this study is to (1) Explore variability in distribution of 24h ICG in bone and 
soft tissue infection (2) Evaluate the change in 24h ICG distribution from pre to post 
debridement (3) Preliminarily determine whether 24h ICG has the possibility predict 
infection / treatment failure
Infection following trauma is one of the most prevalent and challenging complications 
faced by orthopedic surgeons in both military and civilian populations, occurring after up 
to 60% of open bone fractures1-7. Several factors specific to this trauma place patients at 
high risk for infectious complications, including: traumatized tissues, open contaminated 
fracture, soft tissue coverage issues, catabolic state due to poly-trauma, prolonged 
hospitalization with exposure to nosocomial bacteria, and presence of metallic implants8. 
Infection requires one or more unplanned surgical procedures and leads to prolonged 
morbidity, loss of function, and potential loss of limb1, 9-11. Failed treatment for bone 
infection results in recurrent infection, requiring repeat surgical procedures in 
approximately 30% of patients.12-15
We are currently enrolling patients into a study to evaluate the utility of first window ICG 
to identify areas of deficient perfusion.  This is based upon the concept deficient 
perfusion prevents delivery of antibiotics and endogenous immune cells to traumatized 
tissues. In the setting of established infection, poorly perfused bone can be a nidus for 
biofilm formation creating resistance to antibiotics. However, in the context of this work it 
is becoming increasingly clear that acute (rather than chronic) infections display hyper 
vascularity with increased blood flow and neovascularization.  Infection is known to display 
the enhanced permeability and retention effect with increased vascular permeability.  Second 
window or 24h ICG represents an ideal method to identify these areas of increased vascular 
permeability. In some instances infected tissue can be hard to distinguish from healthy 

PROTOCOL TITLE: A pilot study to evaluate single dose indocyanine green 
24 hours prior to operative treatment of orthopaedic infection.
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tissue when ICG is given immediately before optical imaging  Second window ICG will 
allow surgeons to better distinguish infected tissue from healthy tissue as the ICG will 
have a better opportunity to permeate the infected tissue while it will have been expelled 
from the health tissue.
There are currently no accepted intraoperative tools that can be used to make objective 
decisions about which bone and tissue is infected and which is normal. Methods currently 
used to guide debridement are quite rudimentary. Clinical judgement is based on the gross 
appearance of soft tissue and bone, including color, turgor, and extent of soft tissue 
stripping. A burr may be used to look for bleeding bone.  More extensive debridement is 
thought to minimize risk of index infection or reduce the rate of persistent infection; 
however, this comes at the cost of increasingly complex reconstructive procedures to fill 
bony defects22 23, 24. Clearly what is needed is a functional imaging system which can 
identify infected tissues to guide surgeons in the amount of tissue to debride. In turn, this 
will lead to fewer infections and a more effective treatment of SSIs at the fracture site. 
Both scenarios will allow patients to return to duty or work sooner.  
3.0
Study Endpoints*
The study endpoint is to determine the variability of bone and soft tissue perfusion in 
infection patients when given a single dose of ICG 24h prior to surgical debridement. The 
long term goal of this study is to aid in the development and optimization of bone specific 
imaging strategies that can be used to guide debridement and to optimize the quality of 
bone / tissue resection to minimize complications. 
4.0
Study Intervention/Investigational Agent
1.
Description: This study is neither a drug nor a device trial. Patients 
will be administered FDA approved ICG through intravenous injection 
and imaged by either  a FDA approved surgical fluorescence imaging 
device (Spy Elite) or  the Zeiss Penero 800 both of which are held approximately  
0.5 meter away from the subject. ICG fluorescence and both the Spy elite 
imaging system and the Zeiss Penero 800 surgical microscope have been used 
for routine clinical practice for many years. ICG fluorescence imaging 
utilizes intravenously injected ICG, which is a fluorescent dye that is 
FDA-approved for clinical use, illuminated with near-infrared light. 
The ICG dye is indirectly activated and the dynamic fluorescence due 
to bone perfusion can be captured by a video rate imaging system. 

PROTOCOL TITLE: A pilot study to evaluate single dose indocyanine green 
24 hours prior to operative treatment of orthopaedic infection.
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2.
Drug/Device Handling: Indocyanine green (ICG) study medication 
will be ordered and stored by the investigational pharmacy for 
administration pre operatively. 
ICG is FDA approved for routine clinical practice. No return or 
destruction of study drug is needed for this study.
3.
Dose Rationale: We plan a sample size of 20 patients in this open label 
prospective observational study of ICG fluorescence imaging for 
patients with orthopaedic infection No randomization will be performed. 
For each patient enrolled in the study 2.5 - 5mg/kg ICG will be injected 
intravenously 24h prior to surgical debridement. Previous studies by 
John Lee, MD have indicated that the upper range of the dose may be 
necessary to obtain acceptable imaging (letter of support attached).  
ICG fluorescence images will be acquired pre and post-surgical 
debridement.
5.0
Procedures Involved*
Eligible patients regardless of ethnicity or health status, will be identified and recruited 
subject to inclusion and exclusion criteria above. Patients who meet eligibility criteria 
will be asked to participate in the trial. If they agree, written informed consent will be 
obtained from the patient or their healthcare proxy. To obtain informed consent, study 
personnel (surgeon or research coordinator) will adhere to the following procedures: (1) 
present study information in a manner that is understandable to the patient; (2) discuss the 
study with the patient and answer any questions; (3) allow the patient an opportunity to 
discuss participation with their family; (4) confirm that the patient understands the risks and 
benefits of participating in the study and that their participation is voluntary; (5) complete the 
consent process and obtain signatures from the patient and research team. The process of 
obtaining and documenting informed consent forms will be completed in accordance with 
local Good Clinical Practice (GCP) recommendations.
If the research team member obtaining consent is at all unsure about the patient's ability to 
consent, s/he will consult with the study PI.
This study seeks to include individuals with lacking or limited decision making capacity. 
A legally authorized representative (LAR) with reasonable knowledge of the potential 
participant will be approached to consent on the patient’s behalf if the patient cannot 
adequately answer at least 2 questions about the study, or it is determined that the 
patient’s level of cognition is not likely to change before study medication (ICG) can be 
administered . These questions will be to assess the participant’s understanding of the study and 

PROTOCOL TITLE: A pilot study to evaluate single dose indocyanine green 
24 hours prior to operative treatment of orthopaedic infection.
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what it means to participate, their appreciation of the consequences of participation, and their 
ability to consider alternatives to participation. 
The choice of LAR will follow standard procedures. The following with be approached in 
this order of priority:
•
Legal guardian
•
Proxy (health care agent) named in an advance directive or durable power of attorney 
for health care;
•
Family member or other surrogate identified by the state law on health care decisions.
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.
If the patient is inpatient at the time of ICG administration then no additional IV access 
will need to be obtained. If the patient is dosed with ICG in the CRU then a qualified 
member of the CRU staff will insert the IV and then remove it before the patient leaves 
the CRU.
Patients will be administered a single, ICG, 2.5-5mg/kg dose 24 hours prior to surgery by 
a qualified member of their care team.  The patient will be prepared and transported to 
surgery as per routine at Dartmouth-Hitchcock. In the OR, patient positioning, 
preparation of the surgical field, and draping will follow standard practice, of fracture 
fixation or joint fusion or requiring open surgical debridement/saucerization for 
osteomyelitis.
ICG fluorescence images will be acquired prior to surgical debridement. Debridement will 
then proceed per standard of care. The wound will be irrigated with a minimum of 3 liters 
irrigation with normal saline. After irrigation and debridement is completed another ICG 
fluorescence image will be acquired. 

PROTOCOL TITLE: A pilot study to evaluate single dose indocyanine green 
24 hours prior to operative treatment of orthopaedic infection.
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Costs associated with the purchase and administration of ICG will be billed directly to the 
study.  Neither the patient or their health insurance provider will be responsible for any 
costs associated with the imaging procedures or the ICG administrations.  The patient and 
/ or their  insurance company will be billed for a pregnancy test as part of routine surgery 
precautions for women of childbearing potential. 
The need for repeat debridement or tissue cultures will be left up to the treating surgeon. If 
repeat debridement is needed, pre- and post-debridement quantitative ICG fluorescence 
images will be obtained at each procedure. In the situation where a debridement surgery is 
repeated on another date, the subject will undergo consent as outlined in the protocol for each 
additional surgery for which imaging will be obtained. If the skin wound is unable to be 
closed, it will be left open with a sterile dressing until delayed coverage in collaboration with 
plastic surgery.
ICG will be administered by a qualified member of the care team. During 
administration patients will either be under the care and observation of the inpatient 
care teams or closely monitored by a qualified member of the CRU for at least 30 minutes 
post ICG administration. Postoperatively, patients are transferred to the Post-Anesthesia 
Care Unit (PACU) where they are monitored continuously by nursing staff supervised by 
anesthesiologists. During this entire time vital signs (including temperature, pulse, 
respiratory rate and blood pressure) are collected as standard of care. All clinical data 
will be reviewed for adverse events for a period of 24 hours post-injection by members 
of the care team.
Day of Injection Procedures
Pre- Infusion
 Up To 24 Hours 
Post Injection
Pulse
X
X
Blood Pressure
X
X
Temperature
X
X
Respiratory Rate
X
X
Adverse Events
X
Upon admission and throughout the hospital course, patients will be treated with antibiotics 
per standard of care by the orthopaedic service or in collaboration with infectious disease 
recommendations. Management of study patients including clinical and radiographic 
assessments will not differ from standard of care.

PROTOCOL TITLE: A pilot study to evaluate single dose indocyanine green 
24 hours prior to operative treatment of orthopaedic infection.
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Study participants will be followed for a period of 6 months following injection of 24h 
ICG. Final follow-up will be at 6 months to capture all infectious complications (Figure 
C.2)35. If a participant does not return to clinic, follow-up may be conducted by telephone. 
SSI and unplanned fracture-related reoperations will be identified at the time of 
diagnosis/occurrence and/or during each participant clinical assessment and medical record 
review that will occur during their routine outpatient clinic visits.
Figure C.2 follow up assessments
6.0
Data and Specimen Banking*
Not Applicable 
7.0
Sharing of Results with Subjects*
Results will not be shared with subjects or others associated with the subject’s medical 
care
8.0
Study Timelines*
All patients will participate in the following events shown in Table C.2. Follow up visits 
will be conducted during standard postoperative clinical visits or over the phone.
We anticipate enrolling patients for 4 years with an additional 6 months needed to 
complete 6-month follow-up for all patients. We anticipate completing primary analyses 
at the end of 6 month follow-ups.
Assessment
Visit 1:
Enrollment
Visit 2:
6 months
Eligibility Screening
●
Informed Consent
●
Collection of Demographic and Fracture/Infection 
Data
●
Collection of Surgical Data
●
Collection of  Peri-Operative Data
●
Collection of  Outcome Data
●
Collection of Serious Adverse Events
●
●

PROTOCOL TITLE: A pilot study to evaluate single dose indocyanine green 
24 hours prior to operative treatment of orthopaedic infection.
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9.0
Inclusion and Exclusion Criteria*
Inclusion Criteria
1. Patients 18 years of age or older.
2. Extremity fracture.
3. Prior definitive fracture management with external fixation, 
internal fixation, or joint fusion.
4. Superficial, deep, or organ space SSI (as per CDC criteria) at the 
fracture site that requires operative management.
5. Will have all planned SSI care surgeries performed by a 
participating surgeon or delegate.
6. Provision of informed consent.
Exclusion Criteria
1. Fractures of the hand cannot be imaged.
2. Iodine allergy.
3. Burns at the SSI site.
4. Incarceration.
5. Expected survival of less than 90 days.
6. Problems, in the judgment of study personnel, with maintaining follow-up 
with the patient.
7. Adults unable to consent or whom do not have a LAR
8. Individuals who are not yet adults (infants, children, teenagers)
9. Pregnant or breastfeeding women
10.0
Vulnerable Populations*
In order to ensure that this study is not biased against patients with the most severe 
infections, who are most likely to benefit from this imaging device, patients who are 
cognitively impaired (most likely due to head trauma) will be eligible for this study.
A legally authorized representative (LAR) with reasonable knowledge of the potential 
participant will be approached to consent on the patient’s behalf if the patient cannot 
adequately answer at least 2 questions about the study or it is determined that the 
patient’s level of cognition is not likely to change before study medication (ICG) can be 
administered . These questions will be to assess the participant’s understanding of the study and 
what it means to participate, their appreciation of the consequences of participation, and their 
ability to consider alternatives to participation.

PROTOCOL TITLE: A pilot study to evaluate single dose indocyanine green 
24 hours prior to operative treatment of orthopaedic infection.
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The choice of LAR will follow standard procedures. The following with be approached in 
this order of priority:
•
Legal guardian
•
Proxy (health care agent) named in an advance directive or durable power of 
attorney for health care;
•
Family member or other surrogate identified by the state law on health care 
decisions.
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.
This is in compliance with Checklist HRP-417 (Cognitively Impaired Adults).
11.0
Local Number of Subjects
This is a pilot study to investigate the feasibility of obtaining fluorescence imaging 
following injection of ICG 24 hours prior to surgery for infection. This study seeks to 
enroll 20 patients.  Several studies by this investigator inject ICG during surgery, 
however none have investigated ICG injection prior to surgery.  The data collected in this 
pilot study will inform future studies involving ICG injection and the optimal time of 
injection.  
12.0
Recruitment Methods 
Participation in this research requires informed consent according to Institutional Review 
Board (IRB) guidelines and a signed IRB-approved Consent Form as the means of 
documenting this understanding.
Potential subjects will be identified either through the Orthopaedic outpatient clinic or by the 
patient’s primary attending when the patient is currently an in-patient. Subjects who have 
undergone previous trauma surgeries and have developed an infection will be assessed for 
protocol inclusion criteria. This study requests a partial waiver of HIPAA for recruitment 
purposes. The partial waiver would allow for the surgeon to share with the research coordinator 
the patient name, sex, MRN number, age, underlying conditions as well as type and location of 
injury. There is an adequate plan to protect identifiers from improper use and disclosure as 

PROTOCOL TITLE: A pilot study to evaluate single dose indocyanine green 
24 hours prior to operative treatment of orthopaedic infection.
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information will only be used by study team members to determine whether a patient may be 
eligible. Information will only be communicated and stored using D-HH approved secure 
platforms. Information is only being used to determine if a patient is eligible for the study, for 
recruitment purposes. Once approached, if a patient is not interested, information will be 
destroyed. Protected health information will not be re-used or disclosed for another purpose. It 
will only be used for recruitment. This research could not practically be done without a partial 
waiver of HIPAA. This information is needed for recruitment. Patients will sign a full HIPAA 
Authorization when consenting to the study.
Subjects will be invited to participate in this study by a member of the orthopaedic care 
team, which will occur either at the time of consultation with the surgeon about the 
candidate’s standard-of-care procedures or at another time agreed to by the potential 
participant, the candidate’s surgeon or their designee. No advertisements or other promotional 
material will be used. No finder fees or recruitment incentives will be offered. Women of 
child bearing potential are eligible for enrollment into this study because ICG administration 
is not considered to present any additional risk for these women. The study will exclude 
women who are pregnant or breast-feeding as indicated in the exclusion criteria. Women of 
child-bearing potential, if asked to participate, will be given a pregnancy test as part of their 
standard of care testing prior to surgery and before administration of ICG. 
All follow-up visits are within standard practice for these injuries/diagnoses.
Several additional strategies may be used to maximize follow-up including: 1) at the time of 
enrollment each participant will provide their own telephone number, as well as the name 
and address of a primary care physician, and the names and phone numbers of three people 
at different addresses with home the participant does not live and who are likely to be aware 
of the patient’s whereabouts; 2) participants will receive a reminder card upon discharge for 
their next follow-up visit by the clinical staff; 3) participants w h o  o p t  t o  receive text 
message reminders, will be given text message reminders; 4) follow-up will coincide with 
normal surgical infection clinic visits; and 5) if a participant refuses or is unable to return 
for the follow-up assessment, study personnel will determine his/her status with regards to 
major study outcomes by telephone.
13.0
Withdrawal of Subjects*
Participants will be removed from the protocol if:
•
Study imaging is not completed for any reason.
•
The subject withdraws consent.
•
The subject has an occurrence of a significant clinical event that precludes imaging.

PROTOCOL TITLE: A pilot study to evaluate single dose indocyanine green 
24 hours prior to operative treatment of orthopaedic infection.
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•
The subject becomes pregnant before injection of ICG
If a participant is withdrawn from the protocol, the PI will mark the data of this subject as 
"withdrawn" and will add a detailed explanation about the cause of withdrawal in the 
database.
Subjects  who withdraw after intraoperative imaging will be informed that data already 
collected may not be removed from the study database.  Subjects  will be asked if they 
would be willing to allow the investigator to collect data from their routine medical 
care.  If the patient agrees then the research coordinator will collect follow up data from 
the electronic medical record at each follow up visit pertaining to the injury.  The data 
collected will then be used in the statistical analysis portion that only involves the 
intraoperative image data and infection status. Those who do not wish to allow the 
investigator collect data from their electronic medical record will be asked to submit this 
request in writing to the investigator or a member of the research team. 
14.0
Risks to Subjects*
The risks to subjects are minimal in relation to anticipated benefits and/or knowledge that 
might reasonably be expected from the results of this clinical trial.
Risk of ICG injection: ICG (Indocyanine Green) will be administered intravenously 
once, 24h preoperatively. ICG is FDA approved for human use in angiography for 
ophthalmology and cardiology applications and is given routinely to patients in these 
clinical settings. The risks are considered minimal and consist of nausea, vomiting, hives, 
increased heart rate in subjects with particular sensitivity to the dye. ICG does contain 
sodium iodide and patients with a history of allergy to iodides will be excluded. 
Anaphylactic or urticardial reactions are rare but have been reported in patients both with 
and without a history of allergy to iodides. Anaphylactic deaths have been reported 
following IGG administration during cardiac catheterization. Reported rates of mild, 
moderate and severe adverse reactions to ICG are 0.15%, 0.2% and 0.05%. Every effort 
will be made to minimize this risk as much as possible. It is the standard of care at this 
institution to obtain information related to allergies, sensitivities and past medical 
histories upon patient arrival. Patients will also be monitored throughout their 
hospitalization, as is the standard of care, by everyone involved in their medical care for 
evidence of new or previously unknown reactions or sensitivities. Additionally, at all 
times ICG fluorescence imaging assessments are taking place, research staff and both 
surgical and anesthesia staff will monitor patients closely for any adverse reaction to 
ICG. Qualified inpatient medical staff or CRU staff will monitor patients for at least 30 

PROTOCOL TITLE: A pilot study to evaluate single dose indocyanine green 
24 hours prior to operative treatment of orthopaedic infection.
Page 14 of 21
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minutes after ICG fluorescence injection has been completed. In the event of an 
unexpected allergic reaction, Dartmouth-Hitchcock Medical Center and all affiliated 
groups within this institution have procedures in place for managing patients with 
unknown or unexpected allergic reactions. If such a reaction were to occur, all standard 
of care treatments will be provided including but not limited to treatment with 
appropriate agents such as epinephrine, antihistamines and corticosteroids. Risk of 
infection from IV injection is also extremely rare but can occur. Pregnant women are 
excluded from the study. A pregnancy test is administered to women of child-bearing age 
on request at no cost.
Risk of infection from IV injection is extremely rare but can occur. 
Prolonged operating room time: Because the ICG fluorescence assessments will take 
place in the operating room, participation in this study may increase the amount of time 
spent under surgical anesthesia in the operating room. For the average case, an additional 
10 minutes at most will be incurred. However, the research staff will make every effort to 
minimize this risk by performing the assessment test while other required operative 
procedures are being performed.
Risk of confidentiality breach: Subjects enrolled in research are always exposed to 
additional risks of a breach in confidentiality, for example, of some elements of their 
personal health information that is made available to study investigators as part of their 
participation. The risk is 100%, but the occurrence rate of an actual breach is < 1% (to 
date, we are not aware of any subject participating in our studies who has experienced a 
detrimental breach of confidentiality or confidential information).
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act of 1996 
(HIPAA). Risk of breach of confidentiality of the medical records and status of 
participants will be minimized. Databases which are used to store subject-sensitive 
information are password-protected and encrypted during file/data transfers from viewing 
terminals. Access will be limited to research team members who have undergone CPHS 
training at Dartmouth. Whenever possible and practical standard-of-care clinical data 
used in the research will be de-identified when under analysis.
15.0
Potential Benefits to Subjects*
Patients enrolling in this study will not benefit directly because no diagnostic or 
therapeutic decisions will occur based on the study, and thus, administration of the 
study is not intended to alter the surgical procedure. However, future patients may 

PROTOCOL TITLE: A pilot study to evaluate single dose indocyanine green 
24 hours prior to operative treatment of orthopaedic infection.
Page 15 of 21
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benefit from the knowledge gained from the study since this study may provide an 
objective, intraoperative, and real-time methodology to assess bone perfusion and 
thoroughness of debridement. This method may save the patients from unnecessarily 
high risk for index infection or nonunion—in the setting of open fracture—or 
recurrent infection in the setting of established infection, due to the substantial practice 
variation.
16.0
Data Management* and Confidentiality
Confidentiality
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act of 1996 
(HIPAA). Risk of breach of confidentiality of the medical records and status of 
participants will be minimized. Databases which are used to store subject-sensitive 
information are password-protected and encrypted during file/data transfers from viewing 
terminals. Access will be limited to research team members who have undergone CPHS 
training at Dartmouth. Whenever possible and practical standard-of-care clinical data 
used in the research will be de-identified when under analysis. All data will be 
communicated in a HIPAA-compliant manner using a HIPAA-compliant database for clinical 
data (REDCap) and a HIPAA-compliant storage drive for imaging data. Clinical and 
imaging data will be uploaded to the appropriate HIPAA-compliant site by the local research 
team at each institution and all data will be analyzed at either Dartmouth Hitchcock Medical 
Center or Dartmouth College/Thayer School of Engineering. De-identified patient 
information using a Study ID number will be utilized when possible.
Case Report Forms: Study case report forms (CRFs) will be the primary data collection 
instruments for the study. All data requested on CRFs will be recorded. Any missing data 
will be explained. If a space on the CRF is left blank because the procedure was not 
performed or the question was not asked, a written notation will be made. If an item is not 
applicable to an individual case, written notation will be made. Changes to the CRFs will be 
initialed and dated.
Record Retention: Following closure of the study, the investigator will maintain all site 
study records in a safe and secure location. The records are maintained to allow easy and 
timely retrieval when needed (e.g., audit or inspection) and, whenever feasible, to allow 
any subsequent review of data in conjunction with assessment of the facility, supporting 
systems, and staff. Upon completion of study analysis, research information is stored off 
site in accordance with the D-HH policy for retention of study records.

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17.0
Provisions to Monitor the Data to Ensure the Safety of Subjects*
Clinical research monitoring for regulatory compliance and data integrity will be 
conducted. Internal monitoring is conducted by appropriately trained staff of the Office 
of Clinical Research and Dartmouth- Hitchcock Medical Center Clinical Trials Office 
who are not involved in the study. This monitoring will include periodic assessment of 
the regulatory compliance, data quality, and study integrity. Study records will be 
reviewed and directly compared to source documents and the conduct of the study will 
be discussed with the investigator. Monitors may request access to all regulatory 
documents, source documents, CRFs, and other study documentation for on-site 
inspection. Direct access to these documents is guaranteed by the investigator, who 
must provide support at all times for these activities.
18.0
Provisions to Protect the Privacy Interests of Subjects
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act of 1996 
(HIPAA). Risk of breach of confidentiality of the medical records and status of 
participants will be minimized. Databases which are used to store subject-sensitive 
information are password-protected and encrypted during file/data transfers from viewing 
terminals. Access will be limited to research team members who have undergone CPHS 
training at Dartmouth. Whenever possible and practical standard-of-care clinical data 
used in the research will be de-identified when under analysis. All data will be 
communicated in a HIPAA-compliant manner using a HIPAA-compliant database for clinical 
data (REDCap) and a HIPAA-compliant storage drive for imaging data. Clinical and 
imaging data will be uploaded to the appropriate HIPAA-compliant site by the local research 
team at each institution and all data will be analyzed at either Dartmouth Hitchcock Medical 
Center or Dartmouth College/Thayer School of Engineering. De-identified patient 
information using a Study ID number will be utilized when possible.
This study is to be conducted according to US and international standards of Good 
Clinical Practice (FDA Title 21 part 312 and International Conference on Harmonization 
guidelines), applicable government regulations and Institutional research policies and 
procedures.
All subjects for this study will be provided a consent form describing this study and 
providing sufficient information for subjects to make an informed decision about their 

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participation in this study. See Attachment for a copy of the Subject Informed Consent 
Form. This consent form will be submitted with the protocol for review and approval by 
the IRB. The formal consent of a subject, using the IRB-approved consent form, will be 
obtained before that subject undergoes any study procedure. The consent form will be 
signed by the subject or legally acceptable surrogate, and the investigator-designated 
research professional obtaining the consent.
19.0
Compensation for Research-Related Injury
If in any case subjects are injured or become ill as a result of research procedures, the 
subjects will be provided with medical treatment, but the following organizations do not 
plan to pay for this treatment.
•
Mary Hitchcock Memorial Hospital
•
Dartmouth-Hitchcock Clinic
•
Dartmouth-Hitchcock Medical Center
•
Trustees of Dartmouth College
20.0
Economic Burden to Subjects
There are no additional costs that subjects will accrue in association with participating in this 
research. Costs associated with the purchase and administration of ICG will be billed 
directly to the study.  Neither the patient or their health insurance provider will be 
responsible for any costs associated with the imaging procedures or the ICG 
administrations.  The patient and / or their  insurance company will be billed for a 
pregnancy test as part of routine surgery precautions for women of childbearing potential. 
All follow-up visits will be conducted during standard of care follow-up visits or over the 
phone. Costs associated with the ICG and imaging device will be covered by the study and 
will not be billed to the patient.
21.0
Consent Process
To obtain informed consent, study personnel will adhere to the following procedures: (1) 
present study information in a manner that is understandable to the patient; (2) discuss the 
study with the patient and answer any questions; (3) allow the patient an opportunity to 
discuss participation with their family; (4) confirm that the patient understands the risks 
and benefits of participating in the study and that their participation is voluntary; and (5) 
complete the consent process and obtain signatures from the patient and research team. 
The process of obtaining and documenting informed consent will be completed in 

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accordance with Good Clinical Practice. If the research team member obtaining consent 
is at all unsure about the patient's ability to consent, s/he will consult with the study PI.
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.
This study will not involve the subjects who is under age 18.
The study team will comply with consent procedures outlined in SOP HRP-090.
Cognitively Impaired Adults
This study does not involve the assessment of an experimental treatment to the subjects 
enrolled. The subjects will undergo a method for collecting imaging data that has been fully 
vetted and utilized in other clinical settings. The purpose of this research it to evaluate the 
utility of this imaging technique in orthopaedic trauma patients who have developed an 
infection.
By virtue, as a result of high energy trauma that often precedes orthopaedic surgical site 
infections some percentage of the patients will have diminished cognitive impairment. It 
is important to not exclude these patients from the study as it would significantly reduce 
our ability to produce generalizable knowledge.
The risks to subjects are minimal in relation to anticipated benefits and/or knowledge that 
might reasonably be expected from the results of this clinical trial. ICG is FDA approved 
for human use in angiography for ophthalmology and cardiology applications and is 
given routinely to patients in these clinical settings. The risks are considered minimal and 
consist of nausea, vomiting, hives, increased heart rate in subjects with particular 
sensitivity to the dye. ICG does contain sodium iodide and patients with a history of 
allergy to iodides will be excluded. The ICG will be administered thru IV which the 
patient will have regardless of if they participate in this trial or not. There will be no 
additional study specific IV’s placed.
 ICG, the Spy Elite® imaging system and the Zeiss Pentero 800 surgical microscope are 
FDA approved for use in human subjects. Currently we are enrolling patients into a study 
to evaluate the utility of first window ICG to identify areas of deficient perfusion. This 
study seeks to evaluate ICG utility as a second window in areas of deficient perfusion. 
This study is to be conducted according to US and international standards of Good 
Clinical Practice (FDA Title 21 part 312 and International Conference on Harmonization 
guidelines), applicable government regulations and Institutional research policies and 
procedures.

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Patients with impaired decision-making capacity will be included in this study. If the patient 
is unable to provide informed consent (e.g. due to their injury) at the time they are identified, 
informed consent may be obtained from their legally authorized representative (LAR). 
Allowing informed consent from a patient’s LAR will reduce the risk of recruitment bias 
against the most severely infected patients.
For patient with impaired decision-making capacity, a LAR with knowledge of the potential 
participant will be approached to consent on the patient’s behalf. If the patient cannot 
adequately answer at least two questions about the study or it is determined that the patient’s 
level of cognition is not likely to change before study medication (ICG) can be 
administered, their LAR will be approached.. These questions will be to assess the participant’s 
understanding of the study and what it means to participate, their appreciation of the consequences 
of participation, and their ability to consider alternatives to participation. 
 The choice of LAR will follow standard procedures. The following will be approached in 
this order of priority:
•
Legal guardian
•
proxy (health care agent) named in an advanced directive or durable power of 
attorney for health- care
•
Family member or other surrogate identified by state law on health care decisions.
The LAR will be 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. 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.
Subjects participation in this study completely voluntary. If at any time a patient finds 
participation to be unduly stressful the patient or their legal authorized representative may 
withdraw the patient from the study with no repercussions.
Assent will not be requested from subjects unable to consent for themselves.
The study team will comply with consent procedures for cognitively impaired adults outlined 
in SOP HRP-013.
This study will not recruit non-English speaking subjects.  
This study will not involve the subjects who is under age 18. 

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No other vulnerable patient populations not outlined by this protocol will be included in 
this study.
22.0
Process to Document Consent in Writing
To obtain informed consent, study personnel will adhere to the following procedures: (1) 
present study information in a manner that is understandable to the patient; (2) discuss the 
study with the patient and answer any questions; (3) allow the patient an opportunity to 
discuss participation with their family; (4) confirm that the patient understands the risks 
and benefits of participating in the study and that their participation is voluntary; and (5) 
complete the consent process and obtain signatures from the patient and research team.  
The process of obtaining and documenting informed consent will be completed in 
accordance with Good Clinical Practice, outlined by the SOP HRP-090. The signed 
consent form will be uploaded to DHMC e-DH.
23.0
Setting
All consenting and imaging will be carried out in the orthopedic department, CRU clinic area or 
surgical unit at DHMC. All necessary patient follow-up with be conducted at the 
outpatient clinic. The data processing will be carried out by research staff within the 
administrative offices of the Orthopaedics Department located on level 5 of the Rubin 
building.  
24.0
Resources Available
The Department of Orthopaedics at DHMC, a level 1 tertiary care academic medical 
center, has a robust research infrastructure.  Research will be performed within the 
Orthopedic Surgery Department in the Rubin building, as well as in outpatient 
Orthopaedic clinics and CRU.  All research personnel have been thoroughly trained and 
have been involved in multiple orthopaedic research studies. The Orthopaedic surgeons 
have weekly meetings to address any issues that arise during the process of care as well 
as any issues with ongoing research projects.   While the medical and psychological risks 
from the study are minimal, and we do not anticipate any medical or psychological 
resources being needed for subjects enrolled in this study, should the need arise, subjects 
will be treated in accordance with usual standard of care for any medical or psychological 
issues, including but not limited to medical management, counselling, and appropriate 
consultation/referral.  

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All persons, including clinicians, faculty members, staff and students assisting with the 
research will receive instruction regarding the protocol, their duties and functions directly 
from the Principal Investigator.  Additionally all research staff are trained before 
engaging in any activities  in accordance with Dartmouth- Hitchcock policies for 
conducting research under Good Clinical Practices and have completed Collaborative 
Institutional Training Initiative (CITI) research ethics and compliance training.