Clinical trial NCT03716050
Conditions: Perfusion; Complications
Keywords: breast reconstruction Breast Cancer Implant Complication
Sponsor: Wake Forest University Health Sciences
Start date: 2018-01-30; Completion date: 2019-03-12
Enrollment: 17 participants; Allocation: RANDOMIZED; Intervention model: FACTORIAL

Brief summary:
This is a randomized study using a variety of techniques to compare and examine blood flow to the remaining skin after mastectomy. All treatments being used are considered standard of care and are not experimental. The objective is to compare the techniques and the incidence of perfusion related problems in patient's undergoing mastectomy with immediate breast reconstruction.

Detailed description:
This study's aim is to evaluate and compare a variety of interventions and their effect on the incidence of perfusion related problems in patients with breast cancer undergoing mastectomy and implant-based immediate breast reconstruction (IBR). The ability to identify, prevent and treat these perfusion related problems can help maximize aesthetic results after breast surgery, improve patient satisfaction with both mastectomy and breast reconstruction, and reduce healthcare cost associated with mastectomy and reconstruction complications.The study team will perform a randomized pilot study comprised of eight groups. All of these groups employ accepted techniques, medications and dressings and therefore are not experimental.

Group 1: Breast skin after mastectomy will be clinically examined by the surgeon to determine if there is adequate blood flow to the skin to allow safe coverage of the breast implant. No dye study, ointment, or vacuum dressing will be applied to the breast after implant placement.

Group 2 - Breast skin after mastectomy will be clinically examined by the surgeon, and nitroglycerin (NTG) cream will be applied to the breast skin after implant placement. This cream does not have systemic effects but may improve blood flow to the remnant breast skin after mastectomy.

Group 3 - Breast skin after mastectomy will be clinically examined by the surgeon, and an incisional vacuum-assisted dressing (iVAC) will be placed over the breast incisions after implant placement, which may improve blood flow to the skin and help wound healing.

Group 4 - Breast skin after mastectomy will be clinically examined by the surgeon, and both NTG cream will be applied to the breast skin and an iVAC will be placed over the incisions after implant placement.

Group 5 - Blood flow to breast skin after mastectomy will be examined using a fluorescent dye study called fluorescent angiography (FA) to determine if there is adequate blood flow to the skin to allow safe coverage of the breast implant. No further intervention will be used after implant placement.

Group 6 - Blood flow to breast skin breast skin will be examined using FA, and NTG cream will be applied to the skin after the implant is placed.

Group 7 - Blood flow to breast skin breast skin will be examined using FA, and an iVAC will be placed over breast skin incisions after the implant is placed.

Group 8 - Blood flow to breast skin breast skin will be examined using FA, and both NTG cream and iVAC will be used as interventions after the implant is placed.

The dosage of indocyanine-green (IC-green) to be used for assessment of mastectomy flaps will be in 10 mg boluses, not to exceed 5 mg/kg.

Nitro-Bid® (nitroglycerin ointment, 2%) at a dose of 45 mg (equal to 7.5 cm on the measuring strip provided with packaging) will be used. The paste will be applied to remnant breast skin after skin closure and surgical dressings placed over top.

Incisional negative pressure wound therapy will consist of a standard sponge dressing with adhesive drape, either Ioban® 2 (3M ™) or KCI-V.A.C.® Drape (KCI®), to continuous suction at 125 mm Hg while the patient is in hospital and not to exceed 4 days.

A physician will see the subjects on a regular weekly basis for up to 30 days once the procedure has been completed. These clinical visits are standard of care and the subject's health and well-being will be monitored rigorously during these visits. If during any of these visits, the physician deems a therapy necessary to prevent impairment/damage and improve well-being, the subject will be treated appropriately.

Arms: arm 1: Breast skin after mastectomy will be clinically examined by the surgeon to determine if there is adequate blood flow to the skin to allow safe coverage of the breast implant. No treatment, including dye study, ointment, or vacuum dressing will be applied to the breast after implant placement. arm 2: Breast skin after mastectomy will be clinically examined by the surgeon, and nitroglycerin (NTG) cream will be applied to the breast skin after implant placement. This cream does not have systemic effects but may improve blood flow to the remnant breast skin after mastectomy. arm 3: Breast skin after mastectomy will be clinically examined by the surgeon, and an incisional vacuum-assisted dressing (iVAC) will be placed over the breast incisions after implant placement, which may improve blood flow to the skin and help wound healing. arm 4: Breast skin after mastectomy will be clinically examined by the surgeon, and both NTG cream will be applied to the breast skin and an iVAC will be placed over the incisions after implant placement. arm 5: Blood flow to breast skin after mastectomy will be examined using a fluorescent dye study called fluorescent angiography (FA) to determine if there is adequate blood flow to the skin to allow safe coverage of the breast implant. No further intervention will be used after implant placement. arm 6: Blood flow to breast skin breast skin will be examined using FA, and NTG cream will be applied to the skin after the implant is placed. arm 7: Blood flow to breast skin breast skin will be examined using FA, and an iVAC will be placed over breast skin incisions after the implant is placed. arm 8: Blood flow to breast skin breast skin will be examined using FA, and both NTG cream and iVAC will be used as interventions after the implant is placed.
Interventions: intervention 1: Nitroglycerin intervention 2: Negative Pressure Wound Therapy/ Wound VAC intervention 3: Fluorescent Angiography with indocyanine-green (not to exceed 5mg/kg) intervention 4: No treatment
Intervention descriptions: intervention 1: Patient's will be randomized into one of eight groups and receive the intended treatment specified for that particular group. Groups 2,4,6, and 8 will include Nitroglycerin cream. intervention 2: Patient's will be randomized into one of eight groups and receive the intended treatment specified for that particular group. Groups 3,4,7,and 8 will receive iVAC therapy. intervention 3: Patient's will be randomized into one of eight groups and receive the intended treatment specified for that particular group. Groups 5,6,7,and 8 will receive angiography. intervention 4: Patient's will be randomized into one of eight groups and receive the intended treatment specified for that particular group. Groups 1 will include no treatment.

Protocol documents:
Prot_SAP_000.pdf: 
 
 The Effect of Nitroglycerin Ointment, Fluorescent Angiography, and Incisional NPWT on 
Mastectomy Skin Flap Perfusion-Related Problems Comprehensive Cancer Center of Wake 
Forest University (CCCWFU)  
PI: Ivo Pestana, MD  IRB #00038262 NCT03716050   Date of Document: 05/07/2019  
 
 
Principal Investigator:  
 
Ivo A. Pestana, MD 
 
 
 
 
 
Plastic and Reconstructive Surgery 
 
 
 
 
 
Wake Forest School of Medicine 
Winston-Salem, NC 27157 
336-716-4171 
ipestana@wakehealth.edu 
 
 
Co-Investigator(s): 
 
 
Austin M. Bond, MD 
Plastic and Reconstructive Surgery 
Wake Forest School of Medicine 
abond@wakehealth.edu 
 
Christine Velazquez, MD 
General Surgery 
Wake Forest School of Medicine 
cvelazq@wakehealth.edu 
 
Malcolm W. Marks, MD 
Plastic and Reconstructive Surgery 
Wake Forest School of Medicine 
mmarks@wakehealth.edu 
 
Lisa R. David, MD 
Plastic and Reconstructive Surgery 
Wake Forest School of Medicine 
ldavid@wakehealth.edu 
 
Anthony J. DeFranzo, MD 
Plastic and Reconstructive Surgery  
Wake Forest School of Medicine 
adefranzo@wakehealth.edu 
 
Christopher M. Runyan, MD. PhD 
Plastic and Reconstructive Surgery 
Wake Forest School of Medicine 
crunyan@wakehealth.edu 
 
Marissa Howard-McNatt, MD 
General Surgery 
Wake Forest School of Medicine 
mmcnatt@wakehealth.edu 
 
Biostatistician: 
Greg Russell 
Department of Biostatistical Sciences 
Division of Public Health Sciences 
336-716-5449 
grussell@wakehealth.edu 
 
 


 
 The Effect of Nitroglycerin Ointment, Fluorescent Angiography, and Incisional NPWT on 
Mastectomy Skin Flap Perfusion-Related Problems Comprehensive Cancer Center of Wake 
Forest University (CCCWFU)  
PI: Ivo Pestana, MD  IRB #00038262 NCT03716050   Date of Document: 05/07/2019  
 
 
Study Coordinator: 
 
 
Renea Jennings 
Plastic and Reconstructive Surgery 
Wake Forest School of Medicine 
rjenning@wakehealth.edu 
 
Regulatory Contact: 
 
 
TBD 
 
Protocol Editor: 
 
 
Bonny Morris, MSPH, BSN, RN 
Comprehensive Cancer Center of Wake Forest University 
 
 
 
 
 
336-713-6180 
 
 
 
 
 
bemorris@wakehealth.edu 
 
 
Participating Institution(s): 
 
Wake Forest Baptist Medical Center 
 
 
Version Date:  
 
 
05/07/2019 
Amended: 
 
 
 
Confidential
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 The Effect of Nitroglycerin Ointment, Fluorescent Angiography, and Incisional NPWT on 
Mastectomy Skin Flap Perfusion-Related Problems Comprehensive Cancer Center of Wake 
Forest University (CCCWFU)  
PI: Ivo Pestana, MD  IRB #00038262 NCT03716050   Date of Document: 05/07/2019  
Protocol version: 05/07/2019  
 
 
 
 
 
Page 3 of 19 
 
 
Table of Contents 
SCHEMA ................................................................................................................................... 4 
1.0 
Introduction and Background ............................................................................................. 5 
2.0 
Objectives ........................................................................................................................ 5 
3.0 
Patient Selection ............................................................................................................... 5 
3.1 Inclusion Criteria ................................................................................................................. 5 
3.2 Exclusion Criteria ................................................................................................................ 6 
3.3 Inclusion of Women and Minorities .................................................................................... 6 
4.0 Study Outcomes and Study Measures ........................................................................................ 7 
4.1 Primary Outcomes ............................................................................................................... 8 
5.0 
Treatment Plan ................................................................................................................. 9 
5.1 Study Related Activities .................................................................................................... 9 
5.2 Duration of Follow-up .........................................................................................................10 
6.0 
Adverse Events List and Reporting Requirements ................................................................10 
6.1 Adverse Event Characteristics ...........................................................................................10 
6.2  
WFUHS IRB AE Reporting Requirements ......................................................................10 
7.0 
Data Management ............................................................................................................11 
8.0 
Statistical Considerations ..................................................................................................11 
8.1 Estimated Accrual Rate ....................................................................................................11 
8.2 Estimated Study Length ....................................................................................................12 
9.0 
Registration Procedures ....................................................................................................13 
References ..................................................................................................................................13 
 
 
 
 
 
 
 
 
 


 
 The Effect of Nitroglycerin Ointment, Fluorescent Angiography, and Incisional NPWT on 
Mastectomy Skin Flap Perfusion-Related Problems Comprehensive Cancer Center of Wake 
Forest University (CCCWFU)  
PI: Ivo Pestana, MD  IRB #00038262 NCT03716050   Date of Document: 05/07/2019  
Protocol version: 05/07/2019  
 
 
 
 
 
Page 4 of 19 
SCHEMA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ensure subject fulfills inclusion/ exclusion criteria, obtain pre-
operative consent, and then obtain pre-operative pictures 
Randomization
1.
Group 1  
a.
 Clinical Examination 
b.
No therapy applied 
2.
Group 2  
a.
Clinical Examination 
b.
Nitroglycerin Cream applied 
3.
Group 3 
a.
Clinical Examination 
b.
Incisional Negative Pressure Wound 
Therapy applied 
4.
Group 4 
a.
Clinical Examination 
b.
Incisional Negative Pressure Wound 
Therapy + Nitroglycerin Cream 
applied 
CRF form completed and post-
operative photos taken at week 1 
(7 days after surgery), week 2, 
week 3 and week 4. 
Intraoperatively, perfusion of flap will be assessed by criteria a above to 
determine if subject is able to tolerate implant/tissue expander 
If plastic surgeon determines that 
the subject cannot tolerate 
implant/tissue expander, then no 
implant will be placed. Subject 
will continue to be followed for 
30 days but randomized therapy 
will be irrelevant. Thus a new 
envelope will be introduced to 
the pre-made envelopes 
5.
Group 5 
a.
Fluorescent Angiography 
b.
No therapy applied 
6.
Group 6 
a.
Fluorescent Angiography 
b.
Nitroglycerin Cream Applied 
7.
Group 7 
a.
Fluorescent Angiography 
b.
Incisional Negative Pressure Wound 
Therapy Applied 
8.
Group 8  
a.
Fluorescent Angiography 
b.
Incisional Negative Pressure Wound 
Therapy +Nitroglycerin Cream 
applied  
Subject continues with the study and 
randomized therapy if the surgeon 
determines perfusion is sufficient to 
support implant/tissue expander and 
intraoperative pictures will be taken 


 
 The Effect of Nitroglycerin Ointment, Fluorescent Angiography, and Incisional NPWT on 
Mastectomy Skin Flap Perfusion-Related Problems Comprehensive Cancer Center of Wake 
Forest University (CCCWFU)  
PI: Ivo Pestana, MD  IRB #00038262 NCT03716050   Date of Document: 05/07/2019  
Protocol version: 05/07/2019  
 
 
 
 
 
Page 5 of 19 
1.0 
Introduction and Background 
 
Breast cancer changes the lives of more and more women each year.  Despite its oncologic benefits, 
mastectomy results in disfigurement of the chest and women who undergo breast reconstruction 
demonstrate a profound psychosocial benefit.  The outcome of breast reconstruction is highly dependent on 
the remnant soft tissues and skin after mastectomy.  Unfortunately, vascular perfusion-related problems 
(PRPs) after mastectomy are common and may manifest as skin loss, wound dehiscence, delayed wound 
healing, or wound/ implant infections.  These, in turn, may result in significant patient morbidity as they 
undergo the process of breast reconstruction. Medications and technologies have been developed to aid in 
perfusion assessment (fluorescent angiography-FA), perfusion augmentation (nitroglycerin paste-NTG), 
and wound healing (incisional negative pressure wound therapy-iVAC), but their use and effect in 
minimizing mastectomy flap skin loss remains unclear.  
 
Indocyanine-green fluorescent angiography (FA) is a safe and efficient technology which implements laser 
excitation of indocyanine green (ICG) fluorescent dye to provide real-time angiography and assessment of 
tissue perfusion.  Our plastic and reconstructive surgery department and others have utilized FA since it is 
an accepted technique employed to identify perfusion-related problems in breast and free tissue transfer 
surgery.   
 
Nitroglycerin ointment exerts a vasodilatory effect on the soft tissue to which it is applied.  Thus, nitro paste 
may help to prevent perfusion-related problems when used in a prophylactic fashion after immediate breast 
reconstruction.  Most recently, a Level 1 evidenced randomized-controlled trial comparing nitroglycerin 
ointment to placebo in patients undergoing mastectomy with immediate reconstruction has shed new light 
on the use of this non-invasive treatment to decrease the incidence of potential ischemia-related 
complications postoperatively. 
 
Vacuum-assisted closure (VAC) dressings, also referred to as negative-pressure wound therapy (NPWT), 
have been employed since the early 1990’s to treat difficult open wounds, and recent evidence has 
elucidated their role in decreasing complications when placed over surgical closure sites (in which setting 
they are often referred to as “incisional NPWT” or iVAC).  A recent study has demonstrated decreased 
rates of mastectomy skin flap necrosis when incisional NPWT was placed over the surgical closure 
compared to no dressing placed over the incision.   
2.0 
Objectives 
 
Our aim is to evaluate and to compare the above described interventions and their effect on the incidence 
of PRPs in patients with breast cancer undergoing mastectomy and implant-based immediate breast 
reconstruction (IBR).  The ability to identify, prevent and treat these PRPs can help maximize aesthetic 
results after breast surgery, improve patient satisfaction with both mastectomy and breast reconstruction, 
and reduce healthcare cost associated with mastectomy and reconstruction complications. 
3.0 
Patient Selection 
 
3.1 Inclusion Criteria  
 


 
 The Effect of Nitroglycerin Ointment, Fluorescent Angiography, and Incisional NPWT on 
Mastectomy Skin Flap Perfusion-Related Problems Comprehensive Cancer Center of Wake 
Forest University (CCCWFU)  
PI: Ivo Pestana, MD  IRB #00038262 NCT03716050   Date of Document: 05/07/2019  
Protocol version: 05/07/2019  
 
 
 
 
 
Page 6 of 19 
3.1.1 
Patients must be female. 
 
3.1.2 
Patients must be between the ages of 18 and 99 years. 
 
 
 
3.1.3 
Patients must undergo mastectomy with our attending breast oncology surgeons 
followed by possible implant-based immediate breast reconstruction (IBR) performed 
by our attending plastic surgeons at WFBMC. 
 
3.1.4 
Patients must have the ability to understand and the willingness to sign an IRB-
approved informed consent document. 
 
3.2 Exclusion Criteria  
 
3.2.1 
Patients who are under the age of 18 or over the age of 99. 
 
3.2.2 
Patients who are undergoing mastectomy without immediate breast reconstruction 
including immediate breast reconstruction with autologous tissue (or combination of 
autologous tissue with tissue expanders or implants), or patients with a history of 
mastectomy presenting for delayed breast reconstruction. 
 
3.2.3 
Patients with pre-existing conditions in which use of indocyanine-green is 
contraindicated or must be used with caution, including those with a history of allergy 
to iodides or iodinated dye, those with chronic kidney disease, those with hepatic 
failure or cirrhosis of the liver, and females who are nursing, pregnant, or may become 
pregnant. 
 
3.2.4 
Pregnant women are excluded from this study because pregnancy precludes immediate 
breast reconstruction in our patient population. 
 
3.2.5 
Patients with pre-existing conditions in which use of nitroglycerin paste is 
contraindicated, including those with a history of cardiac insufficiency, hypotension, 
sensitivity to nitrites, severe liver impairment, glaucoma, hyperthyroidism, recent head 
trauma, severe anemia, or taking certain medication (i.e. alteplase, aspirin, beta-
blocker, calcium channel blocker, diuretics or thiazides). 
 
3.2.6  
Patients with pre-existing conditions in whom use of incisional negative pressure 
wound therapy is contraindicated including those with evidence of surgical site 
infection ( i.e. erythema, purulent drainage), clinical signs of hematoma (i.e. wound 
swelling, fluctuance, blood drainage), history of persistent cancer, exposed blood 
vessel on site of proposed therapeutic use, or allergy to acrylics and adhesives.   
 
3.3 Inclusion of Women and Minorities 
 
Females of any race or ethnicity who meet the above-described inclusion criteria are 
eligible to participate in this study.  


 
 The Effect of Nitroglycerin Ointment, Fluorescent Angiography, and Incisional NPWT on 
Mastectomy Skin Flap Perfusion-Related Problems Comprehensive Cancer Center of Wake 
Forest University (CCCWFU)  
PI: Ivo Pestana, MD  IRB #00038262 NCT03716050   Date of Document: 05/07/2019  
Protocol version: 05/07/2019  
 
 
 
 
 
Page 7 of 19 
4.0 Study Outcomes and Study Measures 
 
We will perform a randomized pilot study comprised of eight groups. All of these groups employ accepted 
techniques, medications and dressings and therefore are not experimental.   
 
Group 1: Breast skin after mastectomy will be clinically examined by the surgeon to determine if there is 
adequate blood flow to the skin to allow safe coverage of the breast implant. No dye study, ointment, or 
vacuum dressing will be applied to the breast after implant placement. 
 
Group 2 - Breast skin after mastectomy will be clinically examined by the surgeon, and nitroglycerin (NTG) 
cream will be applied to the breast skin after implant placement.  This cream does not have systemic effects 
but may improve blood flow to the remnant breast skin after mastectomy. 
 
Group 3 - Breast skin after mastectomy will be clinically examined by the surgeon, and an incisional 
vacuum-assisted dressing (iVAC) will be placed over the breast incisions after implant placement, which 
may improve blood flow to the skin and help wound healing. 
 
Group 4 - Breast skin after mastectomy will be clinically examined by the surgeon, and both NTG cream 
will be applied to the breast skin and an iVAC will be placed over the incisions after implant placement. 
 
Group 5 - Blood flow to breast skin after mastectomy will be examined using a fluorescent dye study called 
fluorescent angiography (FA) to determine if there is adequate blood flow to the skin to allow safe coverage 
of the breast implant.  No further intervention will be used after implant placement.   
 
Group 6 - Blood flow to breast skin breast skin will be examined using FA, and NTG cream will be applied 
to the skin after the implant is placed. 
 
Group 7 - Blood flow to breast skin breast skin will be examined using FA, and an iVAC will be placed 
over breast skin incisions after the implant is placed. 
 
Group 8 - Blood flow to breast skin breast skin will be examined using FA, and both NTG cream and iVAC 
will be used as interventions after the implant is placed.   
 
The dosage of indocyanine-green (IC-green) to be used for assessment of mastectomy flaps will be in 10 
mg boluses, not to exceed 5 mg/kg. 
 
Nitro-Bid® (nitroglycerin ointment, 2%) at a dose of 45 mg (equal to 7.5 cm on the measuring strip 
provided with packaging) will be used.  The paste will be applied to remnant breast skin after skin closure 
and surgical dressings placed over top. 
 
Incisional negative pressure wound therapy will consist of a standard sponge dressing with adhesive drape, 
either Ioban® 2 (3M ™) or KCI-V.A.C.® Drape (KCI®), to continuous suction at 125 mm Hg while the 
patient is in hospital and not to exceed 4 days. 
 
A physician will see the subjects on a regular weekly basis for up to 30 days once the procedure has been 
completed. These clinical visits are standard of care and the subject’s health and well-being will be 
monitored rigorously during these visits. If during any of these visits, the physician deems a therapy 
necessary to prevent impairment/damage and improve well-being, the subject will be treated appropriately. 


 
 The Effect of Nitroglycerin Ointment, Fluorescent Angiography, and Incisional NPWT on 
Mastectomy Skin Flap Perfusion-Related Problems Comprehensive Cancer Center of Wake 
Forest University (CCCWFU)  
PI: Ivo Pestana, MD  IRB #00038262 NCT03716050   Date of Document: 05/07/2019  
Protocol version: 05/07/2019  
 
 
 
 
 
Page 8 of 19 
At no point during this study will the needs of the randomized arm/research take priority over the subject’s 
health and well-being. 
 
Study Risks 
 
Risks of surgery may include bleeding, infection, hematoma/seroma formation, risks of anesthesia, 
implant/tissue expander failure, extrusion, or tissue necrosis. 
 
Risks with ICGLA may include a potential risk for anaphylaxis/urticarial reaction.   Caution must be taken 
with patients with iodine/iodinated contrast allergy.  There have been no studies performed to evaluate 
carcinogenicity, mutagenicity, or impairment of fertility. 
 
Risks associated with the use of nitroglycerin paste may include dizziness, light-headedness, blurred vision, 
fainting, increased risk of alcohol toxicity if consumed in conjunction with nitroglycerin use, headaches, 
severe allergic reactions (rash, hives, itching, difficulty breathing, tightness in chest, swelling of mouth, 
face, lips, throat or tongue), flushing and red, swollen, blistered or peeling skin. 
 
Vacuum-assisted closure is routinely used in the medical setting for various types of traumatic, surgically-
created, or chronic wounds.  The use of NPWT therapy is contraindicated when the system is in direct 
contact with vital structures (i.e. exposed vessels, anastomoses, organs, or nerves), or when the following 
are present in the wound: malignancy, untreated osteomyelitis, non-enteric and unexplored fistulas, or 
necrotic tissue with eschar present.Use of Ioban® drape is contraindicated in patients with a known 
sensitivity to iodine.  In these instances, the KCI-V.A.C.® drape will be used.  Patients with known allergy 
to acrylics or adhesives may develop an adverse hypersensitivity reaction to the KCI drape and will be 
excluded from the study.   
 
4.1 Primary Outcomes 
 
4.1.1 
The primary outcomes will be the following perfusion-related problems:  
 
 
Soft tissue ischemia/loss (i.e. partial and full thickness soft tissue defects 
identified postoperatively in clinic follow up) 
 
Surgical site infection (i.e. soft tissue cellulitis or abscess identified 
postoperatively either clinically or with wound culture) 
 
Delayed wound healing (manifesting as suture dehiscence and opening of 
an incisional wound) 
 
4.2 Secondary Outcomes 
 
 
4.2.1 
The secondary outcomes will be the following: 
 
 Rate of operative intervention secondary to perfusion related problems 
as listed in “Primary Outcomes” above, and surgical outcome with 
regards to mastectomy flaps 
 Rate of prescribing of outpatient antibiotics or admission for inpatient 
IV antibiotics for treatment of surgical site infection 


 
 The Effect of Nitroglycerin Ointment, Fluorescent Angiography, and Incisional NPWT on 
Mastectomy Skin Flap Perfusion-Related Problems Comprehensive Cancer Center of Wake 
Forest University (CCCWFU)  
PI: Ivo Pestana, MD  IRB #00038262 NCT03716050   Date of Document: 05/07/2019  
Protocol version: 05/07/2019  
 
 
 
 
 
Page 9 of 19 
 Wound care management modalities for treatment of delayed wound 
healing complications as listed in “Primary Outcomes” above, and 
wound healing outcomes 
 
5.0 
Treatment Plan 
 
 
Pre-
Operative 
Visit 
Day of 
Surgery 
Week 1 
Postop 
Week 2 
Postop 
Week 3 
Postop 
Week 4 
Postop 
Enrollment and informed consent 
X 
 
 
 
 
 
Clinical assessment to determine 
whether implant/tissue expander can be 
placed without compromising perfusion 
 
X 
 
 
 
 
Clinical photos of surgical site 
X 
X 
X 
X 
X 
X 
Data sheet documenting outcome 
 
 
X 
X 
X 
X 
 
5.1 
Study Related Activities 
 
Potential subjects will be identified by the physician, advanced practice provider, or research 
coordinator. This individual will discuss the study with the patient and answer any questions or 
concerns they may have. This will take place in an exam room, hospital room, or by phone 
depending on whether or not the patient is inpatient or a clinic patient. 
 
Signed informed consent will be obtained from each subject who will be undergoing mastectomy 
with immediate breast reconstruction using breast implants during a pre-operative appointment in 
the General Surgery (Breast Oncology) or Plastic Surgery clinic.  After the subject has been 
identified as meeting the inclusion criteria by the clinician or research coordinator, the study 
coordinator will obtain the signed informed consent. A signed copy of the consent form will be 
given to the subject. Once the patient has agreed to take part in the study and sign the consent form, 
pre-operative photos of the breast will be taken. Pregnancy tests performed 15 days apart (prior to 
surgery) is done as standard of care for all women of childbearing age potentially undergoing this 
surgery.  
 
Twenty subjects will be randomized to each arm of the study using sealed instructions provided by 
the study coordinator who will inform the clinician of the arm prior to surgery. The envelopes will 
be filled prior to the study with envelopes containing a document indicating to which group the 
patient will be a part of. The envelopes will be sealed and shuffled and then labeled from subject 1 
through 160.  
 
Once the subject is randomized to an arm of the study, the operating surgeon will be informed of 
the arm prior to the surgery. On the day of surgery, the surgeon will decide intraoperatively whether 
an implant/tissue expander can be safely placed without compromising perfusion of the flap. If the 
surgeon determines that an implant/tissue expander cannot be safely placed, they will continue to 
be followed as that indicates a perfusion related problem. At that point, another envelope will be 
introduced into the pre-made envelopes with that subject’s assigned arm. Pictures will be take pre-


 
 The Effect of Nitroglycerin Ointment, Fluorescent Angiography, and Incisional NPWT on 
Mastectomy Skin Flap Perfusion-Related Problems Comprehensive Cancer Center of Wake 
Forest University (CCCWFU)  
PI: Ivo Pestana, MD  IRB #00038262 NCT03716050   Date of Document: 05/07/2019  
Protocol version: 05/07/2019  
 
 
 
 
 
Page 10 of 19 
operatively, intraoperatively, and at week 1,2,3, and 4 post-operatively. In addition to these 
pictures, the data collecting sheet will be completed  by the physician, advanced practice provider 
or study coordinator at week 1, 2,3 and 4 post-operatively. 
 
This is not an intent-to-treat trial. In order to ensure that we are able to gather the most information 
from this study, we want to be able to closely monitor our enrolled subjects and remove any subjects 
that are non-compliant with their randomized arm. The study coordinator will be responsible for 
keeping a detailed Excel spreadsheet of the enrolled subjects and their respective arms of the study. 
If a subject comes off the study prematurely, another envelope will be introduced to the pre-made 
envelopes with the withdrawn subject’s arm – in this way the arms will never be unbalanced. 
 
This study will be monitored by the Cancer Center’s Safety and Toxicity Review (STRC) for 
SAEs and will also be monitored for accrual by the Clinical Research Oversight Committee 
(CROC) since this is an institutional intervention study. The standard operating procedures for the 
STRC can be found below in appendix c. 
 
 
5.2 Duration of Follow-up 
 
Patients will be followed for a minimum of 30 days after the procedure. Clinical assessments will 
occur weekly. 
6.0 
Adverse Events List and Reporting Requirements 
 
Any unanticipated problems, serious and unexpected adverse events, deviations or protocol changes will 
be promptly reported by the principal investigator or designated member of the research team to the IRB 
and sponsor or appropriate government agency if appropriate. 
6.1 Adverse Event Characteristics 
 
Adverse events may include, but are not limited to: anaphylaxis/urticarial reaction, dizziness, light-
headedness, blurred vision, fainting, severe allergic reactions (rash, hives, itching, difficulty 
breathing, tightness in chest, swelling of mouth, face, lips, throat or tongue), flushing and red, 
swollen, blistered or peeling skin, intraoperative or immediately postoperative/post-procedure 
death. 
6.2  
WFUHS IRB AE Reporting Requirements 
 
Any unanticipated problems involving risks to subjects or others and adverse events shall be 
promptly reported to the IRB, according to institutional policy. Reporting to the IRB is required 
regardless of the funding source, study sponsor, or whether the event involves an investigational or 
marketed drug, biologic or device. Reportable events are not limited to physical injury, but include 
psychological, economic and social harm. Reportable events may arise as a result of drugs, 
biological agents, devices, procedures or other interventions, or as a result of questionnaires, 
surveys, observations or other interactions with research subjects. 
 


 
 The Effect of Nitroglycerin Ointment, Fluorescent Angiography, and Incisional NPWT on 
Mastectomy Skin Flap Perfusion-Related Problems Comprehensive Cancer Center of Wake 
Forest University (CCCWFU)  
PI: Ivo Pestana, MD  IRB #00038262 NCT03716050   Date of Document: 05/07/2019  
Protocol version: 05/07/2019  
 
 
 
 
 
Page 11 of 19 
All members of the research team are responsible for the appropriate reporting to the IRB and other 
applicable parties of unanticipated problems involving risk to subjects or others. The Principal 
Investigator, however, is ultimately responsible for ensuring the prompt reporting of unanticipated 
problems involving risk to subjects or others to the IRB. The Principal Investigator is also 
responsible for ensuring that all reported unanticipated risks to subjects and others which they 
receive are reviewed to determine whether the report represents a change in the risks and/or benefits 
to study participants, and whether any changes in the informed consent, protocol or other study-
related documents are required. 
 
Any unanticipated problems involving risks to subjects or others occurring at a site where the study 
has been approved by the WFUHS IRB (internal events) must be reported to the WFUHS IRB 
within 7 calendar days of the investigator or other members of the study team becoming aware of 
the event. 
 
Any unanticipated problems involving risks to subjects or others occurring at another site 
conducting the same study that has been approved by the WFUHS IRB (external events) must be 
reported to the WFUHS IRB within 7 calendar days of the investigator or other members of the 
study team becoming aware of the event. 
 
Any event, incident, experience, or outcome that alters the risk versus potential benefit of the 
research and as a result warrants a substantive change in the research protocol or informed consent 
process/document in order to insure the safety, rights or welfare of research subjects. 
7.0 
Data Management 
 
 
Race Verification Form 
ORIS 
Protocol registration form 
ORIS 
Data Collection 
REDCap 
8.0 
Statistical Considerations 
 
This investigation will be designed as a pilot study, in which patients will be randomized to one of the eight 
groups described.  Once enrollment goals are met, outcomes data will be calculated for each of the primary 
and secondary measures.  Using these estimates, a larger randomized clinical trial will be designed to assess 
differences between study groups.  It is anticipated that the rate of study completion will be uniformly high 
across the study groups, with low rates of attrition.  For use in designing a future trial, we will calculate the 
rate of dropout for each group.  Reasons for dropout will be recorded and reported. 
 
 
8.1 
Estimated Accrual Rate 
8.1.1   We anticipate enrolling approximately 70-80 patients per year; With 8 study 
groups, with 20 subjects per group, the study will need 160 subjects to meet 
recruitment goals.  We will allow for attrition in our enrollment estimates, as our 
goal is to have 20 completed subjects in each arm.  Assuming a 15% dropout rate, 


 
 The Effect of Nitroglycerin Ointment, Fluorescent Angiography, and Incisional NPWT on 
Mastectomy Skin Flap Perfusion-Related Problems Comprehensive Cancer Center of Wake 
Forest University (CCCWFU)  
PI: Ivo Pestana, MD  IRB #00038262 NCT03716050   Date of Document: 05/07/2019  
Protocol version: 05/07/2019  
 
 
 
 
 
Page 12 of 19 
the study would need approximately 184 subjects.  Study recruitment should be 
completed within 2.5 years.   
 
 
8.2 
Estimated Study Length 
8.2.1 
The time Follow up time for each patient will be thirty days, which will allow 
enough time for mastectomy flap necrosis to develop.   
 
8.3 
Statistical Analyses 
8.3.1 
Estimates of all primary outcomes  (Soft tissue ischemia/loss, surgical site 
infection, delayed wound healing) and secondary outcomes (rate of operative 
intervention, rate of prescribing antibiotics or admission for IV antibiotic therapy, 
wound care management modalities and outcomes) will be calculated.  These data 
will provide estimates of rates for each outcome that will allow planning for future 
studies.  The rates of the primary outcomes will be reported, along with 
corresponding 95% confidence intervals.  With an anticipated sample size of 20 in 
each group, the width of the exact 95% confidence interval would be 
approximately +/- 22.8 if the observed rate was 50%.  The table below shows the 
power for testing against an observed rate of 10% (the anticipated average rate in 
the 8 study groups) in group 1 versus 20%, 30%, 40%, and 50% in other groups 
with an alpha of 0.20.  With group sample sizes of 20 in each of the 2 groups, the 
study would have 84% power to detect a difference of 30%. 
 
Numeric Results of Tests Based on the Difference: P1 - P2 
H0: P1 - P2 = 0.   H1: P1 - P2 = D1 ≠ 0.   Test Statistic: Z test with pooled variance 
  
                                                 
 
 
                  Trt|H1   Cntrl    Diff       Target       Actual 
Power              N1           N2             N          P1       P2        D1        Alpha        Alpha 
0.36453             20           20            40       0.10      0.20      -0.10       0.2000       0.1966 
0.62930             20           20            40       0.10      0.30      -0.20       0.2000       0.2228 
0.84713             20           20            40       0.10      0.40      -0.30       0.2000       0.2172 
0.95746             20           20            40       0.10      0.50      -0.40       0.2000       0.1920 
 
 
 
 
The table below shows the target and actual alpha and power if groups are 
combined to have 80 subjects in each one.  
 
Numeric Results of Tests Based on the Difference: P1 - P2 
H0: P1 - P2 = 0.   H1: P1 - P2 = D1 ≠ 0.   Test Statistic: Z test with pooled variance 
 
                                                                   
 
 
 Trt|H1     Cntrl     Diff      Target     Actual 
Power              N1           N2            N         P1          P2          D1      Alpha      Alpha 
0.42287             80           80           160       0.10      0.20      -0.10       0.05       0.0503 
0.71633             80           80           160       0.10      0.25      -0.15       0.05       0.0518 
0.90284             80           80           160       0.10      0.30      -0.20       0.05       0.0513 
0.97682             80           80           160       0.10      0.35      -0.25       0.05       0.0507 
0.99617             80           80           160       0.10      0.40      -0.30       0.05       0.0472 
 
With group sample sizes of 80 in each of the 2 groups, being compared, the study 
would have 90% power to detect a difference of 20%. 
 


 
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Mastectomy Skin Flap Perfusion-Related Problems Comprehensive Cancer Center of Wake 
Forest University (CCCWFU)  
PI: Ivo Pestana, MD  IRB #00038262 NCT03716050   Date of Document: 05/07/2019  
Protocol version: 05/07/2019  
 
 
 
 
 
Page 13 of 19 
8.3.2  The rate of attrition and reason for dropout will be reported for each of the study 
groups; these data will be used in adjusting the needed sample size for a larger 
study.  The rate of attrition and its corresponding 95% confidence interval will be 
calculated; attrition will be defined as the number of subjects who do not attend 
the final assessment, divided by the number accrued into the treatment group. 
9.0 
Registration Procedures 
 
All patients entered on any CCCWFU trial, whether treatment, companion, or cancer control trial, must 
be registered with the CCCWFU Protocol Registrar or entered into ORIS Screening Log. Patients must 
be registered prior to the initiation of treatment.   
 
You must perform the following steps in order to ensure prompt registration of your patient: 
 
1. Complete the Reduced Review Registration Form (Appendix A) 
2. Complete the Race Verification Form (Appendix B) 
3. Send the Reduced Review Protocol Registration Form and the Race Verification Form to the 
registrar, either by fax or email. 
 
 
Contact Information: 
Protocol Registrar PHONE (336) 713-6767 
Protocol Registrar FAX (336) 713-6772 
Protocol Registrar E-MAIL (registra@wakehealth.edu) 
            
*Protocol Registration is open from 8:30 AM - 4:00 PM, Monday-Friday. 
 
 
To complete the registration process, the Registrar will:   
 
 
register the patient on the study and assign the PID number 
 
References 
 
Burnier P, et al.  Indocyanine green applications in plastic surgery: A review of the literature.  J Plast 
Reconstr Aesthet Surg. 2017 Jun;70(6): 814-27. 
 
Dent BL, Small K, Swistel A, Talmor M.  Nipple-areolar complex ischemia after nipple-sparing 
mastectomy with immediate implant-based breast reconstruction: risk factors and the success of 
conservative treatment.  Aesth Surg J. 2014;34(4): 560-70. 
 
Duggal CS, Madni T, Losken A.  An outcome analysis of intraoperative angiography for postmastectomy 
breast reconstruction.  Aesthet Surg J. 2014 Jan;34(1): 61-5. 
 


 
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Mastectomy Skin Flap Perfusion-Related Problems Comprehensive Cancer Center of Wake 
Forest University (CCCWFU)  
PI: Ivo Pestana, MD  IRB #00038262 NCT03716050   Date of Document: 05/07/2019  
Protocol version: 05/07/2019  
 
 
 
 
 
Page 14 of 19 
Fan Z, He J.  Preventing necrosis of the skin flaps with nitroglycerin after radical resection for breast 
cancer.  J Surg Oncol.  1993 Jul;53(3): 210. 
 
Foglia E, et al.  Economic and organizational sustainability of a negative-pressure portable device for the 
prevention of surgical-site complications.  Clinicoecon Outcomes Res. 2017 Jun;12(9): 343-51. 
 
Gdalevitch P, et al.  Effects of nitroglycerin ointment on mastectomy flap necrosis in immediate breast 
reconstruction: a randomized controlled trial.  Plast Reconstr Surg.  2015 Jun;135(6): 1530-9. 
 
Gorai K, et al.  Prediction of skin necrosis after mastectomy for breast cancer using indocyanine green 
angiography imaging.  Plast Reconstr Surg Glob Open 2017 Apr;5(4): e1321. 
 
Griffiths M, Chae MP, Rozen WM.  Indocyanine green-based fluorescent angiography in breast 
reconstruction.  Gland Surg.  2016;5(2): 133-49. 
 
Harless CA, Jacobson SR.  Tailoring through technology: A retrospective review of a single surgeon’s 
experience with implant-based breast reconstruction before and after implementation of laser-assisted 
indocyanine green angiography.  Breast J.  2016 May;22(3): 274-81. 
 
Kim, DY, Park SJ, Bang SI, Mun GH, Pyon JK.  Does the use of incisional negative-pressure wound 
therapy prevent mastectomy flap necrosis in immediate expander-based breast reconstruction?  Plast 
Reconstr Surg.  2016 Sept;138(5): 558-66. 
 
Komorowska-Timek E, Gurtner GC.  Intraoperative perfusion mapping with laser-assisted indocyanine 
green imaging can predict and prevent complications in immediate breast reconstruction.  Plast Reconstr 
Surg.  2010 Apr;125(4): 1065-73. 
 
Kutun S, et al.  Is transdermal nitroglycerin application effective in preventing and healing flap ischaemia 
after modified radical mastectomy?  S Afr J Surg. 2010 Nov;48(4): 119-21. 
 
Matsen CB, et al.  Skin flap necrosis after mastectomy with reconstruction: A prospective study.  Ann 
Surg Oncol.  2016 Jan;23(1): 257-64. 
 
Munabi NCO, et al.  The ability of intra-operative perfusion mapping with laser-assisted indocyanine 
green angiography to predict mastectomy flap necrosis in breast reconstruction: A prospective trial.  J 
Plast Reconstr Aesthet Surg. 2014 Apr;67(4): 449-55. 
 
Newman MI, Samson MC, Tamburrino JF, Swartz KA.  Intraoperative laser-assisted indocyanine green 
angiography for the evaluation of mastectomy flaps in immediate breast reconstruction.  J Reconstr 
Microsurg. 2010 Sep;26(7): 487-92. 
 
Pestana IA, Campbell DC, Bharti G, Thompson JT.  Factors affecting complications in radiated breast 
reconstruction.  Ann Plast Surg. 2013 May;70(5):542-5. 
 
Phillips BT, et al.  Intraoperative perfusion techniques can accurately predict mastectomy skin flap 
necrosis in breast reconstruction: Results of a prospective trial.  Plast Reconstr Surg. 2012 May;129(5): 
778e-788e. 
 


 
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Mastectomy Skin Flap Perfusion-Related Problems Comprehensive Cancer Center of Wake 
Forest University (CCCWFU)  
PI: Ivo Pestana, MD  IRB #00038262 NCT03716050   Date of Document: 05/07/2019  
Protocol version: 05/07/2019  
 
 
 
 
 
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Robertson SA, Jeevaratnam JA, Agrawal A, Cutress RI.  Mastectomy skin flap necrosis: challenges and 
solutions.  Breast Cancer. 2017 Mar;9: 141-52. 
 
Xu K, Tzankova V, Li C, Sharma S.  Intravenous fluorescein angiography-associated adverse reactions.  
Can J Ophthalmol. 2016 Oct;51(5): 321-5. 
 
Zenn M, et al.  Optimizing outcomes of postmastectomy breast reconstruction with acellular dermal 
matrix: A review of recent clinical data.  Eplasty 2017;17(18): 156-71. 
 
 
 
 
 
 
 
 
 
 


 
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Mastectomy Skin Flap Perfusion-Related Problems Comprehensive Cancer Center of Wake 
Forest University (CCCWFU)  
PI: Ivo Pestana, MD  IRB #00038262 NCT03716050   Date of Document: 05/07/2019  
Protocol version: 05/07/2019  
 
 
 
 
 
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The following Appendices are required for all CCCWFU cancer treatment protocols. 
 
Add additional appendices as needed. 
 
ALL data collection forms must be included as protocol appendices at the time the protocol is submitted 
to the CCCWFU Protocol Review Committee (PRC) for review. 
 


 
 The Effect of Nitroglycerin Ointment, Fluorescent Angiography, and Incisional NPWT on 
Mastectomy Skin Flap Perfusion-Related Problems Comprehensive Cancer Center of Wake 
Forest University (CCCWFU)  
PI: Ivo Pestana, MD  IRB #00038262 NCT03716050   Date of Document: 05/07/2019  
Protocol version: 05/07/2019  
 
 
 
 
 
Page 17 of 19 
APPENDIX A: REDUCED REVIEW** REGISTRATION FORM 
 
Protocol#: 00038262 
 
 
 
 
 
 
*Required Field  
 
Protocol Title: The Effect of Nitroglycerin Ointment, Fluorescent Angiography, and Incisional NPWT on 
Mastectomy Skin Flap Perfusion-Related Problems     CCCWFU#00038262 
 
DEMOGRAPHICS 
 
Name (last, first) : ________________________, ________________________________ 
(or initials)  
 
UNIT # (MRN): _________________ (required if exists) 
Zip Code:__________ (required if no 
MRN) 
 
*SEX ﴾  ﴿ MALE 
(   ﴿ FEMALE  
 
*ETHNICITY (choose one): 
(   ﴿ HISPANIC ﴾   ﴿ NON-HISPANIC 
  
*RACE (choose all that apply):  WHITE 
 
 
 
 ASIAN 
 
  
 
 
 
 AFRICAN-AMERICAN 
 
 PACIFIC ISLANDER 
(HAWAIIAN) 
  
 
 
 
 
 NATIVE AMERICAN (ALASKAN) 
 Unknown (Other, Refused} 
 
*DIAGNOSIS : ____________________________________________________ 
 
 
BIRTH DATE: _______________________________(include if no MRN is provided) 
 
*MD Name (last, first): _________________________________ 
  
 
 
*DATE CONSENT WAS SIGNED: __________________ 
 
Date of Registration (if different): __________________________ 
 
PID#: ______________________ (to be completed by Registrar) 
 
The Comprehensive Cancer Center requires that all registrations be sent to the CCCWFU Centralized Registrar the 
day the patient is consented; if this is not possible we require that all registrations be communicated to the 
Centralized Registrar within 72 hours of consent. 
**Reduced review means eligibility and other review are not performed by CRM registrar. Questions: call 713-6767 
 
 
Submit by Email*** 
Print Form 
 
*** If not using the full wfubmc edu outlook client (full outlook, not web outlook), save this file and 
attach to an email to regjstra@wfubmc .edu  
Submitter  of this form is responsible for insuring that all regulatory and eligibility requirements are met 
for this registration. 


 
 The Effect of Nitroglycerin Ointment, Fluorescent Angiography, and Incisional NPWT on 
Mastectomy Skin Flap Perfusion-Related Problems Comprehensive Cancer Center of Wake 
Forest University (CCCWFU)  
PI: Ivo Pestana, MD  IRB #00038262 NCT03716050   Date of Document: 05/07/2019  
Protocol version: 05/07/2019  
 
 
 
 
 
Page 18 of 19 
Appendix B – Race Verification Form 
 
Thank you so much for helping us to verify your race and ethnicity to ensure the quality of our 
information. As a brief reminder, the information you provide today will be kept confidential. 
 
1. Are you: 
Hispanic or Latino/a   
Not Hispanic or Latino/a 
 
2. What is your race? One or more categories may be selected. 
White or Caucasian 
Black or African American American 
Indian or Alaskan Native Asian 
Native Hawaiian or Other Pacific Islander 
Other, Please Specify: _______________________________________ 
 
                                                            
Internal use only: 
Was the self-reported race and ethnicity of the participant verified at the time of consent? 
Yes       No 
 
Was a discrepancy found?       Yes        No 
If yes, please provide what is currently indicated in the EMR: 
 
Ethnicity: _____________________________   Race: _________________________________                                           
 
Additional comments:  ______________________________________________________________ 
___________________________________________________________________________________ 
___________________________________________________________________________________                             
 


 
 The Effect of Nitroglycerin Ointment, Fluorescent Angiography, and Incisional NPWT on 
Mastectomy Skin Flap Perfusion-Related Problems Comprehensive Cancer Center of Wake 
Forest University (CCCWFU)  
PI: Ivo Pestana, MD  IRB #00038262 NCT03716050   Date of Document: 05/07/2019  
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ICF_001.pdf: 
Page 1 of 7
Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 00038262
Department of Plastic & Reconstructive Surgery
THE EFFECT OF NITROGLYCERIN OINTMENT, FLUORESCENT ANGIOGRAPHY, AND 
INCISIONAL NEGATIVE-PRESSURE WOUND THERAPY ON MASTECTOMY SKIN FLAP 
PERFUSION-RELATED PROBLEMS
Informed Consent Form to Participate in Research
Ivo Pestana, MD, Principal Investigator
Austin Bond, MD, Christine Velazquez, MD, Malcolm W. Marks, MD, Lisa R. David, MD, 
Anthony J. DeFranzo, MD, Christopher M. Runyan MD, PhD, Marissa Howard-McNatt, MD, 
Co-Investigators
INTRODUCTION
You are invited to be in a research study. Research studies are designed to gain scientific 
knowledge that may help other people in the future. You are being asked to take part in this 
study because you will be undergoing a mastectomy with possible immediate breast 
reconstruction. Your participation is voluntary. Please take your time in making your decision 
as to whether or not you wish to participate. Ask your study doctor or the study staff to explain 
any words or information contained in this informed consent document that you do not 
understand. You may also discuss the study with your friends and family. Since researchers do 
not know which procedure/arm of the study will have the best outcome, it is possible that you 
could be assigned to the procedure that has a less favorable outcome than the others.
WHY IS THIS STUDY BEING DONE?
The purpose of this research study is to compare different ways of examining blood flow to the 
skin remaining after mastectomy as well as the effect of different ointments and dressings on 
breast skin after mastectomy. All of the examination techniques and treatments applied to the 
skin after mastectomy are well accepted techniques and may improve the outcome of your 
mastectomy and breast reconstruction. These therapies are contra-indicated in certain patients 
with pre-existing conditions and the doctor or study coordinator will speak with you more 
about these conditions.
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY?
One hundred sixty (160) people at Wake Forest Baptist Health will take part in the study. These 
people will be randomly assigned to one of eight groups detailed below.
WHAT IS INVOLVED IN THE STUDY?
You will be randomized into one of the study groups described below. Randomization means 
that you are put into a group by chance. It is like flipping a coin. You will have a one in eight 
chance of being placed into any group. All of these groups are considered standard of care 
and not investigational/experimental.
If you take part in this study, you will be randomized to one of the following groups before your
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00038262
Meeting Date Approved 6/17/2019          
Version Valid Until: 6/16/2020


Page 2 of 7
Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 00038262
surgery:
Group 1: Breast skin after mastectomy will be clinically examined by the surgeon to determine 
if there is adequate blood flow to the skin to allow safe coverage of the breast implant. No dye 
study, ointment, or vacuum dressing will be applied to the breast after implant placement.
Group 2 - Breast skin after mastectomy will be clinically examined by the surgeon, and 
nitroglycerin (NTG) cream will be applied to the breast skin after implant placement. This 
cream does not have systemic effects but may improve blood flow to the remnant breast 
skin after mastectomy.
Group 3 - Breast skin after mastectomy will be clinically examined by the surgeon and an 
incisional vacuum-assisted dressing (iVAC) will be placed over the breast incisions after implant 
placement, which may improve blood flow to the skin and help wound healing.
Group 4 - Breast skin after mastectomy will be clinically examined by the surgeon, and both 
NTG cream will be applied to the breast skin and an iVAC will be placed over the incisions 
after implant placement.
Group 5 - Blood flow to breast skin after mastectomy will be examined using a fluorescent 
dye study called fluorescent angiography (FA) to determine if there is adequate blood flow to 
the skin to allow safe coverage of the breast implant. No further intervention will be used after 
implant placement.
Group 6 - Blood flow to breast skin breast skin will be examined using FA. NTG cream will 
be applied to the skin after the implant is placed.
Group 7 - Blood flow to breast skin breast skin will be examined using FA. An iVAC will be 
placed over breast skin incisions after the implant is placed.
Group 8 - Blood flow to breast skin breast skin will be examined using FA. Both NTG cream 
and iVAC will be used as interventions after the implant is placed.
The assigned procedure will be performed at time of surgery. For research purposes, we are 
comparing the results of each of these groups. The decision of whether to insert a tissue 
expander or implant at the time of surgery will depend on the clinical appearance of the skin 
flaps and/or evidence of adequate blood flow to the skin through exam or intraoperative imaging 
(i.e. fluorescent angiography). If your skin flaps appear to be able to house a breast implant 
without negatively affecting blood flow, your surgeon may forego tissue expansion and place a 
final breast implant at the time of mastectomy (“Direct-to-implant” technique). Most frequently, 
however, tissue expansion is performed with an implant device that is filled with fluid through a 
port to gradually stretch the soft tissues.
As part of this research study, you will be photographed pre-operatively, intraoperatively and 
weekly during each follow-up. This is being done to follow your healing process post 
mastectomy with immediate breast reconstruction. You understand that you may request the
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00038262
Meeting Date Approved 6/17/2019          
Version Valid Until: 6/16/2020


Page 3 of 7
Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 00038262
filming or recording be stopped at any time during the course of the research study. You can also 
withdraw your consent to use and disclose the photograph/videotape/audiotape before it is used. 
You should also understand that you will not be able to inspect, review, or approve the 
photographs, videotapes, audiotapes or other media (including articles containing such) before 
they are used in this study.
Please choose one of the following regarding the use and disclosure of the 
photograph/videotape/audiotape used in this research study:
_____ I would like the photographs/videotapes/audiotapes of me to be destroyed once their use 
in this study is finished.
____ The photographs/videotapes/audiotapes of me can be kept for use in future studies 
provided they are kept secure and any future study will be reviewed by an IRB. I understand that 
I will not be able to inspect, review or approve their future use.
HOW LONG WILL I BE IN THE STUDY?
You will be in the study for at least thirty (30) days to allow us time to see you after your surgery 
for your post-operative clinic visits. If you have a tissue expander placed at the time of your 
mastectomy, your first clinic visit will be approximately one week post-operatively. After that, 
weekly clinic visits will be necessary for filling the tissue expander(s) with a small amount of 
fluid each time, in order to stretch the tissues so that they may house a final breast implant in the 
future. These clinic visits are routine for this form of breast reconstruction, and are the standard 
of care.
You can stop participating at any time. If you decide to stop participating in the study, we 
encourage you to talk to the investigators or study staff first to learn about any potential health 
or safety consequences.
WHAT ARE THE RISKS OF THE STUDY?
Being in this study involves some risk to you. You should discuss the risk of being in this study 
with the study staff. The following are some risks and side effects related to fluorescent 
angiography, nitroglycerin ointment, and the vacuum-assisted surgical dressing we are studying:
Risks associated with fluorescent angiography can include an allergic reaction that may result 
in hives or breathing problems. As a result, this therapy should not be used in people with 
allergies to iodine dye used for contrast.
Risks associated with the nitroglycerin ointment are: dizziness, light-headedness, blurred 
vision, fainting, increased risk of alcohol toxicity if consumed in conjunction with the ointment, 
headaches, severe allergic reactions (rash, hives, itching, difficulty breathing, tightness in chest, 
swelling of mouth, face, lips, throat or tongue), flushing, and red, swollen, blistered or peeling 
skin.
Risks associated with the vacuum-assisted closure dressing (“incisional VAC®”) include 
potential allergic reaction to one type of adhesive cover for the dressing (called Ioban®) in
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00038262
Meeting Date Approved 6/17/2019          
Version Valid Until: 6/16/2020


Page 4 of 7
Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 00038262
people with allergies to iodine and potential for irritation or a skin reaction to the adhesive 
used in people who are sensitive to tape being used on their skin. There is also a risk of 
pain/discomfort with removal of the VAC.
You should tell the research staff about all the medications, vitamins and supplements you take 
and any medical conditions you have. This may help avoid side effects, interactions and other 
risks in this study. There also may be other side effects that we cannot predict.
In addition, there is a slight risk of a breach of confidentiality. Taking part in this research study 
may involve providing information that you consider confidential or private. Efforts, such as 
coding research records, keeping research records secure and allowing only authorized people 
to have access to research records, will be made to keep your information safe. We will do our 
best to protect your confidential information.
Reproductive Risks and other Issues to Participating in Research
Pregnant women are excluded from participation in this study. If you are a sexually active 
woman of childbearing potential and have not been using a reliable method of birth control, 
two negative pregnancy tests performed 15 days apart are required to check for possible early 
pregnancy prior to starting treatment. Costs of pregnancy tests are not included in this research 
study.
Will I Be Paid?
You will receive no payment or other compensation for taking part in this study.
ARE THERE BENEFITS TO TAKING PART IN THE STUDY?
If you agree to take part in this study, there may or may not be direct benefit to you. We hope 
the information learned from this study will benefit other people in the future.
WHAT OTHER CHOICES ARE THERE?
Your alternative is to not participate in this study.
WHAT ABOUT MY HEALTH INFORMATION?
In this research study, any new information we collect from you, your medical records, or 
other facilities about your health or behaviors is considered Protected Health Information. The 
information we will collect for this research study includes:
Date of Birth, Date of Surgery, Age, BMI, co morbidities, tobacco use, complications related 
to surgery, intraoperative appearance of mastectomy flap, medical record and name.
We will make every effort to keep your Protected Health Information private. We will store 
records of your Protected Health Information in a cabinet in a locked office or on a password 
protected computer. Only the following people or organizations will be granted access to your 
Protected Health Information:
1) The study investigator and his/her staff, or others at Wake Forest University 
Health Sciences who oversee research
2) Other people or laboratories providing services for this research project on behalf of 
Wake Forest University Health Sciences and Wake Forest University Baptist Medical 
Center.  
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00038262
Meeting Date Approved 6/17/2019          
Version Valid Until: 6/16/2020


Page 5 of 7
3)Monitors, auditors, IRB or other regulatory agencies will be granted direct access to the 
participant’s original medical record for verification of clinical trial procedures or data, without 
violating confidentiality of the participant and to the extent permitted by other applicable laws.
If required by law or court order, we might also have to share your Protected Health 
Information with a judge, law enforcement officer, government agencies, or others. If your 
Protected Health Information is shared with any of these groups it may no longer be protected 
by federal or state privacy rules.
Any Protected Health Information collected from you in this study will be maintained in the 
research records. Any research information entered into your medical record will be kept for as 
long as your medical record is kept by the Medical Center. You will not be able to obtain a copy 
of your Protected Health Information in the research records until all activities in the study are 
completely finished.
You can tell Dr. Ivo A. Pestana that you want to take away your permission to use and 
share your Protected Health Information at any time by sending a letter to this address:
Dr. Ivo A. Pestana
However, if you take away permission to use your Protected Health Information you will not be 
able to be in the study any longer. We will stop collecting any more information about you, but 
any information we have already collected can still be used for the purposes of the research 
study.
By signing this form you give us permission to use your Protected Health Information for 
this study.
Laboratory test results and other medical reports created as a result of your participation in the 
research study may be entered into the computer systems of Wake Forest University Health 
Sciences and North Carolina Baptist Hospital. These will be kept secure, with access to this 
information limited to individuals with proper authority, but who may not be directly 
involved with this research study.
A North Carolina Baptist Hospital (NCBH) medical record will be created for all study 
participants. Information about your participation in the study will be placed in the NCBH 
medical record, along with any routine medical test results that are obtained at NCBH as part 
of this study.
WHAT ARE THE COSTS?
All of the arms of this study employ well accepted techniques, dressings, and medications and 
therefore are not considered experimental. Due to this, most costs associated with the interventions 
will be covered by your insurance, although some arms might require greater expense than other 
arms. Costs for your regular medical care, which are not related to this study 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00038262
Meeting Date Approved 6/17/2019          
Version Valid Until: 6/16/2020


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Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 00038262
will be your own responsibility.
WHO IS SPONSORING THIS STUDY?
This study is being sponsored by the Department of Plastic and Reconstructive Surgery. The 
sponsor is providing money or other support to Wake Forest University Health Sciences to 
help conduct this study. The researchers do not, however, hold a direct financial interest in the 
sponsor or the product being studied.
WHAT HAPPENS IF YOU EXPERIENCE AN INJURY OR ILLNESS AS 
A RESULT OF PARTICIPATING IN THIS STUDY?
Should you experience a physical injury or illness as a direct result of your participation in this 
study, Wake Forest University School of Medicine maintains limited research insurance 
coverage for the usual and customary medical fees for reasonable and necessary treatment of 
such injuries or illnesses. To the extent research insurance coverage is available under this 
policy; the reasonable costs of these necessary medical services will be paid up to a maximum of 
$25,000. Wake Forest University Baptist Medical Center holds the insurance policy for this 
coverage. It provides a maximum of $25,000 coverage for each claim and is limited to a total of 
$250,000 for all claims in any one year. The Wake Forest University School of Medicine, and 
the North Carolina Baptist Hospitals, Incorporated does not assume responsibility to pay for 
these medical services or to provide any other compensation for such injury or illness. 
Additional information may be obtained from the Medical Center’s Director of Risk and 
Insurance Management, at 
.
If you are injured, the insurer may require information such as your name, social security 
number, and date of birth in order to pay for your care. This is because the insurer is required by 
law to report any payments made to cover the care of any persons who are members of a 
government insurance plan to the Department of Health and Human Services.
You do not give up any legal rights as a research participant by signing this consent form. For 
more information on medical treatment for research related injuries, or to report a study 
related illness, adverse event, or injury you should call Dr. Ivo Pestana at 
.
WHAT ARE MY RIGHTS AS A RESEARCH STUDY PARTICIPANT?
Taking part in this study is voluntary. You may choose not to take part or you may leave the 
study at any time. Refusing to participate or leaving the study will not result in any penalty or 
loss of benefits to which you are entitled. If you decide to stop participating in the study we 
encourage you to talk to the investigators or study staff first to learn about any potential health 
or safety consequences. The investigators also have the right to stop your participation in the 
study at any time. This could be because it is in your best medical interest, your condition 
worsens, new information becomes available, you have an unexpected reaction, you fail to 
follow instructions, or because the entire study will be stopped.
You will be given any new information we become aware of that would affect your 
willingness to continue to participate in the study.
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00038262
Meeting Date Approved 6/17/2019          
Version Valid Until: 6/16/2020


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Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 00038262
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS?
For questions about the study or in the event of a research-related injury, contact the 
study investigator, Dr. Ivo Pestana at 
.
The Institutional Review Board (IRB) is a group of people who review the research to protect 
your rights. If you have a question about your rights as a research participant, would like to 
discuss problems or concerns, have questions or want to offer input, or you want to obtain 
additional information, you should contact the Chairman of the IRB at 
You will be given a copy of this signed consent form.
SIGNATURES
I agree to take part in this study. I authorize the use and disclosure of my health information 
as described in this consent and authorization form. If I have not already received a copy of 
the Privacy Notice, I may request one or one will be made available to me. I have had a 
chance to ask questions about being in this study and have those questions answered. By 
signing this consent and authorization form, I am not releasing or agreeing to release the 
investigator, the sponsor, the institution or its agents from liability for negligence.
Subject Name (Printed):_____________________________
Subject Signature: _________________________________ Date: ________Time:_______ am pm
Person Obtaining Consent (Printed):_____________________________
Person Obtaining Consent:___________________________ Date:_________ Time:________ am pm
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00038262
Meeting Date Approved 6/17/2019          
Version Valid Until: 6/16/2020