Safety and Tolerability Study of Antimicrobial TheraGauze for Skin Abscess
Phase: PHASE1
Conditions: Furunculosis
Sponsor: Eastern Virginia Medical School

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Protocol Title:   Safety and Tolerability Study of Antimicrobial TheraGauze for Skin 
Abscess - Pilot Study  
 
Phase of Study: I 
 
Version date:  30March2017 
 
Funding for this project is from the Department of Defense, through Soluble Systems, LLC 
 
Principle Investigator:  Kenji Cunnion, MD 
Eastern Virginia Medical School 
700 West Olney Road 
Norfolk, VA 23507 
Phone: 757-446-5125 
Mobile: 757-418-4842 
Fax: 757-668-8275 
Email: CunnionKM@evms.edu 
 
Institutional Review Board:  Eastern Virginia Medical School IRB (FWA00003956) 
 

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Background. Skin infections resulting in abscess, furunculosis, have become increasingly 
common in the past decade with the rapid emergence of community-associated methicillin-
resistant Staphylococcus aureus (MRSA).  The increasing incidence of these skin infections has 
stressed the medical system at the primary care, urgent and emergent care levels at significant 
cost.  Methicillin-resistant S. aureus (MRSA) killed 18,650 Americans in 2005, exceeding the 
number of deaths attributable to HIV/AIDS (Klevens, Morrison et al. 2007).  MRSA infections 
were identified for 368,600 hospitals stays in the U.S. in 2005 for an estimated $5 billion in 
hospitalization costs (Healthcare Cost and Utilization Project, DHHS).   
 
The primary endpoint of the study is to evaluate the safety of and identify side effects of 
TheraGauze/tobramycin wound packing compared with standard of care management for 
cutaneous abscesses requiring incision and drainage.  Current standard of care in most 
emergency and urgent care settings for community-acquired skin abscess is incision and 
drainage followed by packing with cotton wick (± iodoform) and anti-MRSA systemic antibiotics 
given orally for 5 – 7 days (Mistry, Weisz et al. , LoVecchio, Perera et al. 2009).  Commonly 
prescribed oral antibiotic regimens include trimethoprim-sufamethoxazol, doxycycline, and 
clindamycin.  Common side effects from these systemic antibiotics include diarrhea (~20%), 
nausea, and rash (Powell and Wenzel 2008).  Uncommon but severe side effects include C. 
difficile colitis, Stevens-Johnson Syndrome, toxic epidermal necrolysis, hepatitis, and aplastic 
anemia (Bell, Foster et al. , Mistry, Schwab et al. 2009).   
 
The primary likely benefit of this novel therapeutic strategy is avoiding the side effects of 
systemic antibiotics that cause significant additional morbidity and medical expense.  Other 
possible benefits of this novel strategy are improved wound healing time and less scar 
formation.  This work will capitalize on the polymer structure of TheraGauze that provides a 
platform for fluid redistribution within the wound bed without causing skin maceration 
(Landsman 2008).  We have developed an antimicrobial form of TheraGauze by loading 
TheraGauze with tobramycin (TheraGauze+tobramycin).  Prior in vitro testing demonstrated 
potent and sustained antibacterial activity for TheraGauze+tobramycin against a wide range of 
bacterial pathogens, including all strains of community-associated MRSA tested (Echague, Hair 
et al. 2010).  Lack of systemic absorption is a well-established property of tobramycin.  Thus, 
high concentrations can be delivered locally in the wound greatly exceeding typical minimum 
inhibitory concentrations (MICs) without concern for systemic toxicity. Additionally, tobramycin 
is a highly bactericidal antimicrobial compound.  Tobramycin is rarely used as a systemic 
antibiotic now having been largely replaced by fluoroquinolones.  Therefore, selective pressure 
that could promote development of antibiotic resistance and compromise systemic antibiotic 
therapy is not a concern. 
 
Tobramycin has been used for many years both as topical therapy applied to the eyes as well as 
in surgical wounds as tobramycin-containing polymethacrylate beads.  Topical application of 
tobramycin to cutaneous wounds has also been reported without evidence of local or systemic 
toxicity.  Andrew et al reported application of 3% (w/v) tobramycin with dexamethasone (i.e., 
Tobradex) ointment applied to post dermatological procedure surgical wounds twice-a-day for 2 
weeks. Eighteen human subjects were enrolled and no local or systemic side effects were noted 
(Andrew, Luecke et al. 2012)  
 

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In 2003 Simplex P with tobramycin was the first FDA approved antibiotic impregnated bone 
cement (ww.stryker.com). Preparations of tobramycin-impregnated bone cement appear to 
generally range from 1g to 1.2g in 20 ml (50 – 60 mg/ml) (Sterling, Crawford et al. 2003, 
McLaren, McLaren et al. 2008).  Tobramycin is reported to be the antibiotic of choice for bone 
cement for more than 75% of orthopedic surgeons (Fish, Hoffman et al. 1992) with excellent 
local tobramycin levels and minimal systemic tobramycin levels (Soto-Hall, Saenz et al. 1983, 
Eckman, Henry et al. 1988, Davies and Harris 1991, Pritchett and Bortel 1992, Brien, Salvati et al. 
1993, Sterling, Crawford et al. 2003, McKee, Li-Bland et al. 2010). Despite the extensive 
literature on tobramycin bone cement there are no mentions of local toxicity. It is notable that 
so little toxicity has been reported given the significantly varying amounts of tobramycin cement 
are used for different types of orthopedic procedures and depending on the amount of bone 
being replaced. The wounds the tobramycin cement are in deep tissue spaces that are highly 
vascular. In contrast, TheraGauze/tobramycin will be placed into small (2 - 10ml) cutaneous 
abscesses where the bacterial infection has been walled off to protect the body from spread. 
 
Tobramycin has also been used as a topical ophthalmic preparation for many years both as an 
ointment and drops (3 mg/ml) (e.g., Tobrex). Despite the very sensitive nature of topical 
application to the eye the package insert for Tobrex notes <1% hypersensitivity and eye or 
eyelid irritation is 3%, which is a typical rate for antibiotic eye drops.  Additionally, Tobramycin 
eye drops (3 mg/ml) have been shown to have no adverse effects on reepithelialization and be 
well tolerated after penetrating keratoplasty (Blavin, Sauer et al. 2012)  
 
Thus, there are several decades of human data demonstrating the safety of tobramycin when 
used topically for cutaneous and ocular wounds and in surgical wounds.  The data suggests that 
local or systemic toxicity is extremely rare when tobramycin is used in these ways. 
 
Primary Endpoint. The primary endpoint of the study is to evaluate the safety of and identify 
side effects of TheraGauze/tobramycin wound packing compared with standard of care 
management for cutaneous abscesses requiring incision and drainage.  
 
Methods.  
Design: 
This is a proof-of-concept, prospective, randomized clinical trial for safety of TheraGauze-
tobramycin in adult subjects who present to Emergency Department settings for care of skin 
abscess requiring incision and drainage.  A control, standard of care, arm is included to provide 
some data with respect to the side effect profile of current furunculosis management for 
comparison. 
 
Two arms are proposed for this study: 
1. Incision + TheraGauze+tobramycin packing (no systemic antibiotics) 
2. Incision + standard iodoform wick or plain cotton wick packing (± p.o. antibiotics) 
 
Anti-microbial TheraGauze (saturated with tobramycin ophthalmic solution at 3 mg/ml) will be 
packed into the drained wounds of the subjects in the study arm.  The control arm will receive 
current standard of care wound packing with a choice of iodoform wick or plain cotton wick, 
based on the preference of the ED physician.  After packing, the wound excess TheraGauze or 
wick will be cut away.  The ED physicians have the option to prescribe an oral antibiotic or not, 

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according to their preference.  The following oral antibiotic choices are available for subjects in 
the control arm only:  
 
Bactrim (TMP/SMX) 
 
Vibramycin (doxycycline) 
 
Cleocin (clindamycin) 
Antibiotics will be purchased by subjects from their local pharmacy. 
 
TheraGauze-tobramycin. 
We plan to use TheraGauze saturated with tobramycin ophthalmic solution (3 mg/ml).  The 
decades of efficacy and safety with tobramycin eye drops justifies using the 3 mg/ml 
concentration.  In vitro testing with TheraGauze/tobramycin (0.9 mg/ml), shows excellent 
broad-spectrum antibacterial activity against Gram-negative and Gram-positive bacterial 
pathogens including all clinical MRSA strains tested (Echague, Hair et al. 2010).  We expect that 
>85% of the cutaneous abscesses (furuncles) will be infected with MRSA (Demos, McLeod et al. 
2012). Additionally, tobramycin is a non-absorbable antibiotic and thus an excellent choice for 
achieving local antimicrobial activity with minimal risk of systemic side effects, which it is why it 
is the most common antibiotic bone cement.  
 
Furunculosis skin abscesses typically have a volume of 1 – 5 ml up to a maximum of 10 ml 
(Mistry, Marin et al. 2013).  Thus, a maximal volume of TheraGauze/tobramycin that can be 
packed in the wound will be 10 ml in the largest furuncles.  If the entire length of the 
TheraGauze/tobramycin is used, which will rarely occur, the 17 cm length will hold only 21 
grams of tobramycin, which will only be placed in the wound one time and not re-dosed.  
Standard intravenous dosing of tobramycin is 1 mg/kg/dose every 8 hours, thus ≥ 50 mg i.v. per 
dose for adults. The TheraGauze/tobramycin wound packing will be placed after the incision and 
drainage of the abscess and removed at the day 3 (- 1/+2) follow up visit in the Emergency 
Department.  TheraGauze/tobramycin will only be placed in the wound a single time.  
 
TheraGauze/Tobramycin creation   
1. TheraGauze commercial preparation will be dehydrated in the factory and spiral dye to 
yield a 17 cm strip of TheraGauze of uniform width. After cutting the dry TheraGauze 
will be packaged and sterilized by gamma radiation.  This follows all of the current steps 
of manufacturing only adding dehydration and cutting steps. 
2. Dried TG packages will be provided to the Sentara Norfolk General Hospital (SNGH) 
Emergency Department (ED).   
3. Commercial 10 ml vials of tobramycin ophthalmic solution (3 mg/ml) for human use will 
be provided by the SNGH pharmacy and stored in the temperature monitored med 
room in the SNGH ED. Each vial will be opened only once and then discarded. 
4. After randomization has been determined, a new 10 ml vial of tobramycin ophthalmic 
solution will be opened and added to newly opened TG in a sterile dish by the study 
coordinator and allowed to rehydrate to saturation (5 minutes). Maximal saturation of 
the 17 cm TheraGauze strip is achieved with only 7 ml of solution.  
5. The wound will be packed with the TheraGauze/tobramycin strip and any excess length 
will be cut off, measured and discarded.  
 
 
Methods: 

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Study Population: 
Subjects from the Hampton Roads region of southeastern Virginia will be recruited from the 
hospital emergency department site staffed by EVMS physicians at Sentara Norfolk General 
Hospital.   
 
Study Size: 
We anticipate screening 200 patients in order to enroll and randomize 100 subjects. Subjects 
will be randomized 2:1 to the TheraGauze+tobramycin or iodoform wick/ plain cotton wick, 
respectively.  We anticipate 50 participants completing the study.  The 50% retention rate is 
typical for emergency department populations. 
 
Subject Eligibility: 
Inclusion criteria: 
 
Ages >18 to <65 years  at time of enrollment 
 
Subject has skin abscess (furuncle) requiring incision and drainage  
 
Erythema surrounding abscess 
 
Induration of ≥2cm in maximal diameter 
 
Fluctuance or purulent head evident 
 
Tenderness at abscess 
 
No or mild fever ≤38.5⁰C 
 
Male or female 
 
Ability to read and understand the English language at a level sufficient to provide 
informed consent and comply with study requirements 
 
Subject is willing and able to comply with all study requirements 
Exclusion criteria: 
 
Systemic illness or deep-seated infection requiring inpatient admission (i.e. 
hypotension, tachycardia, or tachypnea) 
 
Deep seated infection requiring referral to surgery 
 
Subject requires intravenous antibiotics for suspicion of systemic spread of infection 
(i.e. suspicion of bacteremia) 
 
Extensive cellulitis extending > 6cm beyond the area of induration 
 
Fever >38.5⁰C 
 
Allergy to any aminoglycoside antibiotic, sulfamethoxazole-trimethoprim, 
doxycycline, clindamycin. 
 
An underlying medical condition that impairs normal immune function (e.g. AIDS, 
cancer, diabetes, lupus, rheumatoid arthritis, organ or marrow transplantation, 
ulcerative colitis, Crohn’s disease) 
 
Subject is pregnant or breastfeeding and/or a woman of childbearing potential who 
is not surgically sterile, not at least 2 years postmenopausal, or does not practice 
contraception methods, unless sexually abstinent for the duration of the study. 
 
Subject has any medical or psychiatric condition, in the opinion of the investigator, 
could jeopardize the subject’s health or compromise the subject’s ability to 
participate in the study. 
 
Subject has prior treatment with antibiotics in the preceding 7 (seven) days. 
 
Currently taking or has taken oral or injection steroid medication (e.g. prednisone or 
Medrol Dosepak) in the past 30 (thirty) days 

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 
Injection medications (Remicade, Humira, Cimzia, Simponi) other than vitamin (B6) 
 
Currently taking or has taken immune suppressing medications (e.g. methotrexate, 
Prograf, CellCept, Rapamune) in the past 30 (thirty) days 
 
Currently taking or has taken medications to treat cancer in the past 30 (thirty) days 
 
Subject is currently participating or has participated within the last two months in 
any study of an investigational drug or device. 
 
Recruitment and Retention: 
Subjects who present to Emergency Department setting for care of skin abscess requiring 
incision and drainage will be approached by on-site Study Coordinators for enrollment.  The 
study coordinators and physician investigators are trained in obtaining informed consent.  The 
potential subjects will be able to discuss participation with any family-member present, but due 
to the need for prompt treatment, the subject will need to make a decision regarding participate 
at the time of the Emergency Room visit.  Upon meeting eligibility criteria and willingness to 
participate, subjects/LARs will provide informed consent.  Complete demographic information 
to include residential and telephone contact information will be obtained.  Prior relevant 
medical history and usual primary care contact information will also be collected.  A medical 
information release will be obtained from the subject so that outcomes data can be collected 
related to additional unscheduled visits or adverse events cared for outside the emergency 
department setting. 
 
Women and minority participation: 
Adults up to 65 years of age will be enrolled regardless of gender and minority status as long as 
they are fluent in English.   
 
Randomization: 
A study subject identification number will be assigned.  Subjects will then be sequentially 
randomized to one of two treatment arms upon enrollment in a 2:1 ratio, using a prepared list.  
Each subject’s name will be recorded on the list next to his/her assigned subject number and 
randomization.  For example, the first subject enrolled will be randomized to Treatment 1; the 
next enrolled subjects will be enrolled to Treatment 1; the third subject to Treatment 2. The 
fourth subject will be randomized to Treatment 1 and so on.   
 
Study Treatments 
Visit 1 - Day 1: 
 
Informed consent will be obtained from subject.   
 
Review of Eligibility Criteria (Inclusion/Exclusion) 
 
Randomization to Treatment Arm 
 
Contact Information to include phone number(s), address, and primary care provider 
information will be collected. 
 
Treatment and discharge with instructions to return to the ED for revaluation per 
routine care.  The typical schedule is for the patients to return to the ED 2 days after 
initial wound care (Study Day 3 -1/+2).  
The following information will be collected and recorded on a hard copy Case Report Form at 
this visit. 
 
Subject ID number 
 
Demographics 

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o Date of visit 
o Age in years and months at time of enrollment 
o Race (white, non-white) 
o Ethnicity (Hispanic or non-Hispanic) 
 
Medical history 
o Chronic medical conditions: 
 
____ 
 
____ 
 
____ 
o Concomitant Medications 
 
____ 
 
____ 
 
____ 
o Allergies to medications 
 
____ 
 
____ 
 
____ 
 
Characteristics of symptoms and history 
o Duration of symptoms (number of days) 
o Fever > 38.0°C duration? (y/n, record number of days febrile at home prior to 
ED visit) 
o Fever > 38.0°C in ED? (y/n, record temp)  
o Spontaneous drainage (y/n) 
o Prior skin abscess (y/n) 
o Immediate family history (parent, sibling, child) of skin abscess (y/n) 
 
Abscess characteristics 
o Erythema at widest diameter (mm) 
o Abscess induration at widest diameter (mm) 
o Abscess location (e.g. trunk, extremity, buttocks, perineal, axilla, head/neck) 
 
 
Procedure information 
o Diameter of wound after incision (mm) 
o Treatment Arm: 
1. Anti-microbial TheraGauze (TheraGauze/tobramycin) 
2. Iodoform wick/ plain cotton wick 
o Length of packing used (mm) 
 
Laboratory Assessments – Per standard clinical care the abscess contents will be sent for 
routine Gram stain, bacterial culture and susceptibility testing as dictated by the 
patient’s insurance and ED policy.     
o Obtain results when available 
 
If patient is to receive iodoform wick/plain cotton wick then the care provider will have 
the option of prescribing a p.o. antibiotic, as is frequently done in these clinical settings. 
The following oral antibiotic choices are available for subjects in the control arm only:  
 
Bactrim (TMP/SMX) 
 
Vibramycin (doxycycline) 
 
Cleocin (clindamycin) 
 

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Phone Follow up Contact Day 2 (+2) 
Return visit reminder and wound status follow up performed by Sentara Study Coordinator.   
 
Questions 
o Fever since leaving ED? (y/n, record temp if taken) 
o If prescribed, was antibiotic prescription filled (y/n) 
o If prescribed, has antibiotic been taken (y/n, # doses) 
o If antibiotics taken, were any side-effects noted (y/n, list) 
o Increased or decreased pain (y/n, increased/decreased) 
o Increased or decreased size of redness (y/n, increased/decreased) 
o Any new symptoms? (y/n, list)  Specific questions will include: presence of rash, 
loose stool, nausea, vomiting, abdominal discomfort, headache, dizziness, 
drowsiness, thrush, as well as any change in local signs or symptoms including 
pain and redness, new skin lesions, enlarged lymph nodes, and sore or white 
spots in the mouth.   
 
Visit 2 - Day 3 -1/+2: (ED) 
Subjects’ wound status will be evaluated.   The following information will be collected and 
recorded on a hard copy Case Report Form at this visit: 
 
Questions about infection 
o Infection overall (better/same/worse) 
o Fever > 38°C at home since incision? (y/n) 
o Persistent discharge (y/n) 
o Pain (increased/same/decreased/resolved) 
o Medical evaluation between day 1 and day 3 visit (y/n) 
o New lesions (y/n) 
o Was an p.o. antibiotic prescribed (y/n) 
 
If yes, was the prescription filled (y/n) 
 
How many doses have been taken so far? (##) 
o Any diarrhea? (y/n) 
o Any nausea or vomiting? (y/n) 
o Any abdominal discomfort? (y/n) 
o Any new rash? (y/n) 
o Any other new symptoms including headache, dizziness, drowsiness, thrush, as 
well as any change in local symptoms. 
o  
 
Bacterial burden in wound bed – Wound culture performed using quantitative methods 
for culturing wound base (Gardner, Frantz et al. 2006).  Cultures taken to Cunnion lab 
for quantitation, swab may be stored at 4°C, if obtained after business hours. 
o Quantitation of bacteria present (colony counts performed in Cunnion lab) 
o Speciation of bacteria present (CHKD clinical microbiology laboratory using CLSI 
standards) 
o Antibiotic susceptibility testing of bacteria present (CHKD clinical microbiology 
laboratory using CLSI standards) 
 
Wound assessment 
o Fever > 38°C in ED? (y/n, record temp) 
o Packing present (y/n) 
o Erythema at widest diameter (mm) 

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o Abscess induration at widest diameter (mm) 
o Tenderness around the wound? (y/n) 
o Removal of packing 
o Does wound require repacking? (y/n) 
 
Clinical Options 
o Return to ED for additional clinical evaluation and management (y/n) 
 
Reason for reevaluation (infxn worsening/infxn non-
improvement/other) 
 
Another incision and drainage in the ED (y/n) 
 
Addition of oral antibiotics (y/n) 
 
Admission for i.v. Abx (y/n) 
 
Admission for surgical intervention (y/n) 
 
Return to ED in 2 more days (y/n) 
 
Schedule follow-up visit in Infectious Diseases Clinic at Children’s Hospital of The King’s 
Daughters (CHKD) in 5 ± 2 days 
 
Phone Follow up Contact Day Prior to CHKD visit: 
Return visit reminder performed by Study Coordinator.   
o Fever since leaving ED? (y/n, record temp if taken) 
o If prescribed, has antibiotic been taken (y/n, # doses) 
o If antibiotics taken, were any side-effects noted (y/n, list) 
o Increased or decreased pain (y/n, increased/decreased) 
o Increased or decreased size of redness (y/n, increased/decreased) 
o Any new symptoms? (y/n, list)  Specific questions will include: presence of rash, 
loose stool, nausea, vomiting, abdominal discomfort, headache, dizziness, 
drowsiness, thrush, as well as any change in local signs or symptoms including 
pain and redness, new skin lesions, enlarged lymph nodes, and sore or white 
spots in the mouth.   
 
Visit 3 - Day 7 ± 2: (CHKD Infectious Diseases Clinic):    
Follow up on subjects’ wound status.   The following information will be collected and recorded 
on a hard copy Case Report Form at this contact. 
 
Questions about infection 
o Fever > 38°C at home since incision? (y/n) 
o Pain (increased/same/decreased/resolved) 
o Redness (increased/same/decreased/resolved) 
o Persistent discharge (y/n) 
o Wound size (increased/same/decreased/resolved) 
 
If resolved, day of wound closure (day) 
o New lesions since day 3 visit (y/n) 
o Was an p.o. antibiotic prescribed (y/n) 
 
If yes, was the prescription filled (y/n) 
 
How many doses have been taken so far? (##) 
o Any diarrhea? (y/n) 
o Any nausea or vomiting? (y/n) 
o Any abdominal discomfort? (y/n) 
o Any new rash? (y/n) 

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o Any other new symptoms including headache, dizziness, drowsiness, thrush, as 
well as any change in local symptoms. 
 
 
Wound assessment 
o Fever > 38°C in CRU? (y/n, record temp) 
o Packing present (y/n) 
o Diameter of erythema (mm) at widest diameter 
o Diameter of wound (mm) at widest diameter 
o Tenderness around the wound? (y/n) 
 
 
Clinical Assessment (decided by PI or sub-I) 
o Infection worsening, non-improvement, improvement 
 
Clinical Options (decided by PI or sub-I) 
o No follow-up needed unless infection worsens 
o Suggest follow-up 
 
Clinical Follow-up, if applicable (obtained from subject or medical record after follow-
up) 
o Another incision and drainage in the ED (y/n) 
o Addition of oral antibiotics (y/n) 
o Admission for i.v. Abx (y/n) 
o Admission for surgical intervention (y/n) 
o Return to ED in 2 more days (y/n) 
 
 
 
PROTECTION OF HUMAN SUBJECTS: 
This research involves the recruitment, enrollment and management of human subjects 
participating in research.  Adults up to age 65 years at enrollment are being studied because 
adults commonly suffer skin abscesses.  Study oversight by the investigators will assure 
compliance with all regulatory requirements for Institutional Review Board approval prior to the 
initiation of the study, and will obtain annual re-approval for study activities.   
 
Potential risks and benefits to subjects and procedures to mitigate risks: 
 
Physical/Medical 
o Serious Adverse Events will be reported to EVMS IRB 
 
Confidentiality/PHI 
o All PHI will be maintained in an encrypted and password protected electronic 
file. 
 
RISKS AND SIDE EFFECTS  
Risks and side effects related to the anti-microbial TheraGauze we are studying include:   
 The skin abscess may re-accumulate and require a second drainage procedure 
and possibly evaluation for deeper infection. 
 A new skin abscess may arise while on the study. 
 A local allergic or irritation reaction to the wound packing. 
 Inadvertent release of PHI 

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POTENTIAL BENEFITS. 
There may or may not be direct benefit to subjects. Subjects will receive additional 
follow-up assessments. 
 
SUBJECT COMPENSATION. 
Subjects will receive a $40 gift card to a local merchant at each completed visit. 
 
ASSESSMENT OF SAFETY 
Subjects must be seen by a physician or an appropriately trained healthcare professional at 
every study visit, and the evaluation must be documented. 
 
Adverse Events.  An AE is any untoward medical occurrence in a clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have to have a causal 
relationship with this treatment. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding, for example), symptom, or disease temporally 
associated with the use of a medicinal product, whether or not considered related to the 
medicinal product. 
 
Causality Assessment. For all AEs, the PI will provide an assessment of causal relationship to the 
study drug. Causal relationship must be assessed by answering the following question: Is there a 
reasonable possibility the study drug caused the event? 
Yes: There is evidence to suggest a causal relationship between the study drug and AE, 
i.e.: there is a reasonable temporal relationship between the study drug and the 
event, and the event is unlikely to be attributed to underlying/concurrent disease, other 
drugs, or other factors. 
No: There is no evidence to suggest a causal relationship between the study drug and 
AE, ie: there is no reasonable temporal relationship between the study drug and the 
event, or the subject did not take the study drug, or the event is likely to be attributed to 
underlying/concurrent disease, other drugs, or other factors, or the event is commonly 
occurring in the (study) population independent of drug exposure. 
 
Adverse Reaction.  An AE assessed as likely having a causal relationship with the intervention 
(i.e., TheraGauze/tobramycin).  Specifically focusing on local-toxicity adverse reactions, we will 
evaluate for increasing redness, increasing pain or a new rash at the site of the packed wound. 
Increasing pain or redness could be due to progression of the infection (cellulitis/abscess) or 
local toxicity or reaction to the tobramycin in the TheraGauze/tobramycin packing.  This will be 
assessed by an Investigator.  Increasing purulent drainage or the identification of new areas of 
fluctuance requiring an additional incision and drainage procedure will be assessed as 
progression of the infection rather than evidence of local toxicity or reaction to the tobramycin.   
 
Severity Assessment. The PI must provide an assessment of the severity of each 
AE by recording a severity rating, which will be assessed as described below. Severity, which is a 
description of the intensity of manifestation of the AE, is distinct from seriousness, which implies 
a subject outcome or AE-required treatment measure associated with a threat to life or 
functionality. 
Guidelines for Adverse Event Severity Assessments 

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Mild. Minor awareness of signs or symptoms that are easily tolerated without specific 
medical intervention. 
Moderate. Discomfort that interferes with usual activities and may require minimal 
intervention. 
Severe. Significant signs or symptoms that are incapacitating with an inability to work or 
perform routine activities and/or that require medical intervention. 
 
Serious Adverse Events. An SAE is any untoward medical occurrence that at any dose: is life 
threatening, requires in-patient hospitalization or prolongation of existing hospitalization, 
results in persistent or significant disability/incapacity.  Important medical events may be 
considered serious when, based on appropriate medical judgment, they may jeopardize the 
subject and may require medical or surgical intervention to prevent one of the outcomes listed 
in this definition. If a serious and unexpected AE occurs for which there is evidence suggesting a 
causal relationship between the drug and the event the event must be reported as a serious and 
unexpected suspected adverse reaction.  SAE will be reported to the local IRB and the FDA 
within 5 calendar days.  
 
All unanticipated problems involving risk to subjects or others, serious adverse events related to 
participation in the study and subject deaths related to participation in the study should be 
promptly reported by phone (301-619-2165), by email (usarmy.detrick.medcom-
usamrmc.other.hrpo@mail.mil), or by facsimile (301-619-7803) to the USAMRMC, Office of 
Research Protections, Human Research Protection Office.  A complete written report will follow 
the initial notification.  In addition to the methods above, the complete report will be sent to the 
U.S. Army Medical Research and Materiel Command, ATTN: MCMR-ZB-PH, 504 Scott Street, Fort 
Detrick, Maryland 21702-5012. 
Stopping Rules. Adverse reactions, including local-toxicity adverse reactions, or SAEs will lead to 
immediate return to the SNGH ED for assessment and removal of the TheraGauze/tobramycin 
wound packing.  The investigator will assess the need for treatment of the adverse reaction or 
SAE and, if necessary, either treat or refer for treatment, as appropriate. The subject will 
continue with their scheduled follow up: Day 3 visit in the ED, Day 6 phone follow up, and Day7 
visit in the CHKD Infectious Diseases Clinic  
STATISTICAL ANALYSIS PLAN 
The research coordinators will collect data on a hard copy source document.  Clinical and 
laboratory data will then be entered into an Access database by the coordinator and lab 
personnel. 
 
The data will be analyzed using SAS 9.4 software.  All statistical tests will be two-sided with a 
significance level of 0.05.  Patients who withdraw while on treatment will be included in the 
data analysis for each time point before withdrawal.  Baseline and follow-up measurements of 
safety, tolerability, numbers of pathogenic bacteria, wound infection persistence or worsening, 
and gross effects on the rate of wound healing will be summarized using descriptive statistics 
such as mean, median, standard deviation, interquartile range, frequency, and percentage 
where appropriate.  Normality assessments for the continuous variables will be completed using 
Shapiro-Wilk tests and stem-and-leaf plots. 
  
Tests of equivalence between the TheraGauze + tobramycin and standard iodoform wick 
packing treatment groups will establish statistical significance if the two-sided 90% confidence 

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interval for the difference falls within the limits (-δ, δ), where δ is the margin of clinically 
accepted difference.  This analysis will determine whether the outcomes are equivalent 
between the TheraGauze+tobramycin and standard iodoform wick packing treatment groups. 
 
 
CONFIDENTIALITY. 
Subjects’ research charts will be maintained in the locked coordinators offices until each subject 
completes the study. Electronic data will be in an encrypted password-protected database, 
accessible only to the study coordinators, biostatistician, and PI.  Subjects’ research charts and 
laboratory specimens will be stored until the completion of the study. Research charts will be 
maintained in a secured facility for the length of time mandated by federal law. Laboratory 
specimens (i.e. bacterial culture isolates) will be destroyed at the completion of the study. 
 
AMENDMENTS. 
Any changes in procedures will be approved by the IRB prior to implementation, except for those 
necessary for subject safety.  Deviations that change the risk/benefit ratio will be reported to the 
IRB.   
 
ROLES OF RESEARCH TEAM MEMBERS 
Physician investigators and Emergency Room staff will identify potential subjects and will notify 
the coordinator.  The coordinator will explain the study and she or the physician will obtain 
informed consent.  The physician will collect medical history culture the wound, and care for the 
wound per standard of care, using TheraGauze with tobramycin or standard gauze per 
randomization.  The coordinators will ensure that all data are collected and recorded in the 
study chart, collect lab results, schedule follow-up appointments and make telephone contacts.  
Routine cultures and sensitivities will be performed in the hospital laboratories.  The research 
lab staff will perform quantitative analysis.  Coordinators and lab staff will enter data into the 
database.  The statistician, with the PI, will analyze the results.  The PI will oversee all of the 
above activities as well as performing most of the Visit 3 clinical assessments. and report 
findings to the sponsor. 
 
RESEARCH MONITOR. 
All Serious Adverse Event (SAE) reports will be sent to the Research Monitor, Ursula Kelly, MD, 
within 24 hours.  The Research Monitor will also review subject charts for safety  on a 3 to 6 
month basis, assessing for evidence of tolerability or superiority/inferiority between the arms, 
and will discuss her findings with the PI.  The Research Monitor may discuss the protocol with 
the investigators, interview subjects, and consult with others  outside the study about the 
research.  She shall have the authority to stop the protocol, remove subjects from the protocol, 
and take any necessary steps to protect the safety and well-being of subjects until the IRB can 
assess the Monitor's report.  The Research Monitor shall have the responsibility to promptly 
report her observations and findings to the IRB or other designated official.   The Research 
Monitor is required to review all unanticipated problems involving risks to subjects or others, 
serious adverse events and all subject deaths associated with the protocol and provide an 
unbiased written report of the event.  At a minimum, the research monitor must comment on 
the outcomes of the event or problem and in the case of a serious adverse event or death,  
comment on the relationship to participation in the study.  The research monitor must also 
indicate whether he/she concurs with the details of the report provided by the principal 

Safety and Tolerability Study of Antimicrobial TheraGauze for Skin Abscess CUNNION 
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investigator.  Reports for events determined by either the investigator or research monitor to be 
possibly or definitely related to participation and report of events resulting in death must be 
promptly forwarded to the USAMRMC ORP HRPO.  
 
 
 
 
Study Visit Schedule: 
 
PROCEDURE 
VISIT 1 
VISIT 2 
VISIT 3 
 
Screening/Day 1 
Day 3-1/+2 days 
Day 7±2 days 
Consent 
X 
 
 
Inclusion/exclusion 
X 
 
 
Demographics 
X 
 
 
Medical history 
X 
 
 
History and current 
symptoms 
 
X 
 
X 
X 
Temperature, wound 
assessment 
 
X 
 
X 
X 
Culture abscess 
X 
X 
 
Randomization 
X 
 
 
Apply wick 
X 
 
 
Provide prescription 
if applicable 
 
X 
 
 
Remove packing (if 
applicable) 
 
 
 
 
Follow-up phone call 
Day 2 (+2) 
 
X 
 
 
Follow-up phone call 
day prior to Day 7 
visit 
 
 
X 
 
 
 
 
 
 

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