Randomized Clinical Trial Comparing 1-Port and 2-Port Tissue Expanders for Breast Reconstruction
Phase: NA
Conditions: Breast Cancer
Sponsor: Lesley Wong

PROTOCOL AND STATISTICAL ANALYSIS PLAN 
 
 Study Title: Comparison of One-Port and Two-Port Tissue Expanders for Breast 
Reconstruction 
Institution/Site:  
University of Kentucky 
Document (Approval/Update) Date: 
1/17/17 
NCT Number: 
NCT02725801 
IRB Number 
16-0064-F2L 
Coversheet created: 
07/29/20 
 
 

Form B:  Medical IRB Research Description 
Comparison of tissue expanders…               PI: Wong             1                     approved 1/17/2017 
7/29/2020 
Investigator:  Lesley Wong, M.D. 
Title:  Randomized Clinical Trial Comparing 1-Port and 2-Port Tissue Expanders for 
Breast Reconstruction 
1.  Background 
1 in 8 women in the United States will develop invasive breast cancer, and of these women, 
35-40% will be treated with a mastectomy.  Subsequent breast reconstruction has benefits 
for self-esteem and quality of life (Albornoz).  In 2013, over 95,000 reconstructive breast 
procedures were performed, 75,000 of which were expander/implant based reconstruction 
(ASPS). 
The majority of breast reconstruction procedures are done in a staged manner.  Tissue 
expanders are placed at the time of mastectomy.  These are then used to stretch the 
remaining skin to allow for eventual placement of an implant at the second stage of 
reconstruction.  The simultaneous use of acellular human dermal matrix (ADM) as an 
internal sling to support the expander is frequently used because of aesthetic benefits, 
reduced capsular contracture, reduced amount of submuscular dissection and decreased 
time to complete the reconstruction (Breuning, Sbitany).  With increased use of dermal 
matrices, increased complications have been documented, particularly infection and/or 
seroma, with rates up to 12-18% (Chun, Antony, Kim, Wiechman, Selber) and relative risks 
of 2.47-2.73 (Kim).  Complications can necessitate further surgical procedures, 
hospitalization and removal of the tissue expander, or the need to abandon reconstructive 
efforts.  Methods to reduce these complication rates would have substantial benefit for many 
breast cancer survivors. 
Seroma formation is thought to be caused by an inflammatory response to the biological 
material acting as a (initially) non-vascularized foreign body.  The presence of a seroma 
under the mastectomy skin flaps can lead to increased incidences of wound dehiscence, 
infection and/or asymmetry in the reconstructed breast appearance, both of which can lead 
to removal of the expander. 
Authors have described modifications in technique designed to minimize seroma formation.  
These include placing an additional drain to drain the sub-ADM space as well as the sub-
mastectomy skin flap space, leaving these drains in longer by lowering the threshold volume 
per 24 hour period, and applying postoperative soft compression dressings (Ganske).  
Traditional management of an established postoperative seroma consists of percutaneous 
aspiration, seroma catheter placement and/or operative exploration, irrigation and drain 
replacement.  Operative management is used for seromas refractory to aspiration or for 
suspected infected seromas. Imaged percutaneous drainage can also be used for aspiration 
and/or drain placement and cultures of the fluid can be obtained.  Even with this technique, 
persistent fluid collections and infection can still necessitate expander removal (Tong). The 
presence of seroma fluid is linked to other complications such as infection and skin flap 
necrosis (Brzezienski).  Thus, successful management of this complication may decrease 
other associated complications and the need to abandon the reconstructive efforts. 

Form B:  Medical IRB Research Description 
Comparison of tissue expanders…               PI: Wong             2                     approved 1/17/2017 
7/29/2020 
Methods to reduce and treat complications have focused on operative technique and not on 
the tissue expander itself.  The AlloX2 tissue expander has been developed specifically to 
reduce and treat these complications.  The traditional tissue expander has a single port to 
allow injection of saline through the skin directly into the expander for gradual stretching of 
the overlying skin.  The AlloX2 expander has the same injection port plus a second port which 
is connected to a perforated drain placed on the lower edge of the expander (see attached 
diagram).  The location of both ports are identified by a magnet placed over the breast skin.  
This second port gives percutaneous access to the peri-expander space, thus allowing 
removal of seroma fluid under the mastectomy skin flaps.  Seroma aspiration using this 
access port in the expander is safer than percutaneous aspiration, as it will reduce the 
potential for accidental puncture of the expander during standard percutaneous drainage.  
The aspirated fluid can be cultured in the setting of infection allowing identification of 
bacteria and determination of antibiotic sensitivities. Additionally, instillation of culture 
specific antibiotic solutions directly into the peri-expander space can be accomplished 
through the second port.  Thus, use of this second port in the expander can be both diagnostic 
as well as therapeutic. 
The AlloX2 expander is FDA approved, but randomized prospective controlled studies have 
not been done comparing it to the standard single port expander for equivalency.  The ability 
to decrease reconstructive failures related to seromas will benefit patients undergoing post-
mastectomy reconstruction and potentially will reduce the costs involved in treating 
complications. 
FDA Indications for Use:  510(k) Number K140383 (letter attached) 
“AlloX2 Tissue Expanders are intended for temporary (less than six months) subcutaneous 
or submuscular implantation to develop surgical flaps and additional tissue coverage 
required in a wide variety of applications, particularly to aid in reconstructions following 
mastectomy, to aid in the treatment of underdeveloped breasts and to aid in treatment of 
soft tissue deformities. 
Additionally, the AlloX2 Tissue Expanders contain a silicone drain component which allows 
access to and drainage of latent fluids from the periprosthetic space.  This drain component 
does not replace short-term, immediate, intraoperatively placed drains.” (FDA) 
2.  Objectives 
The goal of this study is to compare the AlloX2 expander with the traditional single port 
expander for equivalency.  Complication rates that will be tracked include seroma, 
mastectomy skin flap necrosis, infection, wound dehiscence, need for explantation of the 
expander.  Management of seromas will be compared between the two groups. We 
hypothesize that the AlloX2 expander will be as effective in achieving the final outcome of 
completion of the second stage of reconstruction with equal or improved complication rates. 
3. Study Design 
A prospective 1:1 randomized, single center, open label study will compare the traditional 
1-port tissue expander with the AlloX2 2-port expander placed during immediate tissue 

Form B:  Medical IRB Research Description 
Comparison of tissue expanders…               PI: Wong             3                     approved 1/17/2017 
7/29/2020 
expander breast reconstruction.  Due to the nature of the surgery, the study cannot be 
blinded.  Patients will be followed until completion of expansion and exchange for the 
permanent implant which typically takes 2 to 3 months.  Risks factors that have been 
previously identified to be associated with increased postoperative complications include 
smoking, obesity, breast size, diabetes, radiation therapy, and expander fill volume will be 
identified.  The final outcome is completion of expansion and exchange to permanent 
implant.   
Standard operative procedure and postoperative care will be done.  Both groups will have 
the same to external drains placed which is standard operative procedure.  Complications 
will be noted at each postoperative clinic visit and entered into a database.  Complication 
rates will be compared between the two groups and associations with risk factors will be 
analyzed.  There will be no cross-over into the other group in case of reconstructive failure.  
Treatment failures will be treated in the same fashion in the two groups. 
4. Study Population 
The study patients will be recruited from the University of Kentucky Plastic Surgery clinic.  
They will consist of patients referred for breast reconstruction following mastectomy(ies), 
unilateral or bilateral, for breast cancer or for positive gene mutation.  Only patients who are 
suitable candidates for and who agree to undergo tissue expander/implant reconstruction 
will be offered participation in the study. 
The anticipated number of patients to be enrolled is 60, 30 randomized to each type of 
expander.  The proposed study period for enrollment is January 2016 – December 2016.   
Exclusion criteria include age less than 18, patients who refuse expander/implant 
reconstruction, patients who are not medical candidates for expander/implant 
reconstruction from a soft tissue standpoint, patients who are anticipated to need 
postoperative radiation therapy.  Non-English speaking individuals or decisionally impaired 
individuals will not be enrolled. 
The study will not involve fetuses, neonates, children, pregnant women, prisoners, or 
institutionalized individuals. Due to the nature of this study, only women will be enrolled as 
this is the population that undergoes mastectomy and breast reconstruction.  Subjects will 
be chosen irrespective of ethnic background. 
5. Subject Recruitment Methods and Privacy 
Patients will be recruited from the University of Kentucky Plastic Surgery Clinic.  Lesley 
Wong, MD, will determine if a participant meets eligibility criteria and will approach the 
patients during regularly scheduled clinical appointments in order to assess if they are 
interested in learning more about the study. 
Eligible patients will be those undergoing immediate breast reconstruction with tissue 
expanders following mastectomy.  A patient’s acceptance or declination to be a part of this 
study will not affect the type of reconstruction performed on the patient, or their care in any 
way.   

Form B:  Medical IRB Research Description 
Comparison of tissue expanders…               PI: Wong             4                     approved 1/17/2017 
7/29/2020 
No advertisements of any form will be used with this study. 
6. Informed Consent Process 
Patients will be asked to sign the consent form after the investigators fully explain the study 
and risks.  This will be done prior to randomization into one of two groups.  There is no 
waiting period between informing the prospective subject and obtaining consent.  Voluntary 
consent may be obtained by the principal investigator (PI) (Dr. Lesley Wong), as well as 
collaborating investigators who are authorized to obtain informed consent.  The consent will 
contain information in line with IRB guidelines as to a brief background for the study, reason 
for their inclusion, risks, potential benefits, insurance coverage for injury, confidentiality, 
rights of the participant to refuse or withdraw, and guarantee to continuity of care should 
they refuse to participate or withdraw from the study, access to information, and payment 
for participation. 
Written informed consent from the participant will be placed in their medical record and 
documentation of the informed consent process will be placed in the participant’s progress 
notes.  A signed informed consent form will be obtained by the investigator.  The participant 
will receive a copy of the informed consent form.   
 
7. Research Procedures 
The study patients will be randomized into one of two groups, one using the AlloX2 two port 
tissue expander and the other using the existing single port expander (AllerganTM). The 
surgical procedure will follow standard acceptable guidelines for tissue expander 
reconstruction (Alderman).  Patients will receive IV prophylactic antibiotics and the surgical 
site is prepped with chloraprep.  The expander is placed under the elevated pectoralis 
muscle and an acellular dermal matrix which is pre-sterilized (AllodermTM).  The initial 
volume in the expander is recorded. Two standard suction drains are placed in the 
mastectomy defect and are removed when the output is <20cc/24 hours over two days. 
Patients will be followed weekly in clinic to observe for complications and expand the 
expander.  Filling of the expander is done weekly, or at an interval acceptable to the patient.  
When the desired volume is achieved, the patient will be scheduled for expander 
replacement with the permanent implant.  This procedure is the final endpoint for the study. 
If a seroma is suspected and there are no signs of infection, the expander is accessed through 
the second port of the AlloX2.  If seroma fluid is aspirated, the fluid is cultured.  If a seroma 
is suspected and there are signs of infection, the seroma cavity is drained with the second 
port and appropriate antibiotics can be ordered. 
Medical records are reviewed to collect patient demographics, co-morbidities (hypertension, 
diabetes), adjuvant/neoadjuvant chemotherapy, body mass index, smoking status, operative 
time, and area of dermal matrix used.  Postoperative complications include seroma, infection, 
skin flap necrosis.  Univariate analyses of independent variables will be done, with the use 
of dermal matrix and development of infection as the dichotomous dependent variable. 

Form B:  Medical IRB Research Description 
Comparison of tissue expanders…               PI: Wong             5                     approved 1/17/2017 
7/29/2020 
8. Resources: 
The research procedures will be conducted at UK Chandler Medical Center and University of 
Kentucky Plastic Surgery Clinic E-101 (Wing C, First Floor) 740 S. Limestone Street, 
Lexington, KY 40536-0284.  The participants will be followed by Lesley Wong, MD and her 
research team which includes physicians and certified nurse practitioners and clinical 
research coordinators during the study.  Emergency medical equipment, medications, and 
supplies will be at the physician’s disposal should the participant have an acute untoward 
reaction.   
9. Potential Risks:   
 
• 
ChloraPrep:  Blistering, burning, itching, peeling, skin rash, redness, swelling, or 
other signs of irritation on the skin, swelling of the face, hands, or feet, trouble breathing.  
A severe allergic may occur and could lead to death. 
 
• Allergan Natrelle Style 133V Tissue Expanders 
 
General Known Risks:  Any invasive surgical procedures has risks such as infection, 
hematoma, dysesthesia, postoperative pain and delayed healing.   
 
Specific Known Risks:   
 
 
Magnetic field.  The MAGNA-SITE® integral injection site contains a rare-
earth, permanent magnet.  If you already have an implanted device that would be 
affected by a magnetic field (e.g., pacemaker, drug infusion device, artificial sensing 
device) you must not have a MAGNA-SITE® tissue expander implanted.  In addition, 
patients with MAGNA-SITE® expanders in place should not undergo diagnostic testing 
with Magnetic Resonance Imaging (MRI).   
 
 
Deflation.  The expander and infection site may leak as a result of damage 
from surgical instruments or trauma.  Deflation release the saline filling and will require 
surgery to replace the expander to continue with the expansion process. 
 
 
Tissue damage.  Tissue damage may occur if the overlying skin is too weak to 
tolerate the pressure of expansion.  Tissue damage is most likely to occur with 
expansion against an unstable wound or tissue area, or expansion that occurs too 
rapidly, causing ischemia. 
 
 
Extrusion.  Extrusion of the expander may occur as a result of tissue damage.  
Extrusion may require removal of the expander. 
 
 
Capsular contracture.  The scar tissue that normally forms around any 
implanted device, including tissue expanders, may tighten and become firm around the 
expander.  Capsular contracture may make expansion difficult and painful, and 
necessitate surgical intervention. 
 
 
Premature explantation.  Adverse reactions may require premature 
explantation. 
 
 
Displacement.  Shifting and rotation of the expander/injection site may 
occur.  Displacement may make the injection site difficult to locate and require surgical 
intervention. 
 
 
Effects on bone.  Chest wall compression has been reported in association 
with the use of tissue expanders for breast reconstruction.   

Form B:  Medical IRB Research Description 
Comparison of tissue expanders…               PI: Wong             6                     approved 1/17/2017 
7/29/2020 
 
 
Changes in sensation.  The expansion process may affect sensation.  
Sensation may increase or decrease, temporarily or permanently.  
 
 
Discomfort/distortion.  Tissue expansion in an intensive process that causes 
temporary discomfort and distortion. 
 
10. Safety Precautions 
 
Provisions to guard against the potential risks and discomforts discussed in section 9 are as 
follows: Every precaution to prevent a direct study injury will be taken by medical personnel 
and the investigators. Should an adverse or serious adverse event occur, the research 
participant will be followed by physicians, registered nurses and other research staff 
members for the duration of the participant’s hospitalization and recovery.  Routine care will 
be provided by hospital staff.  Emergency medical equipment, medications and supplies will 
be at the physician’s disposal should the participants have an acute untoward reaction.   
 
All patient information used in this study will be de-identified for purposes of the study.  
Once enrolled in the study, the patient’s identifiable information will be replaced with a 
study number and will be followed using this number in all recording and correspondences 
throughout the study.  Only the PI and the PI’s team will have access to identifiable  
information prior to the patient’s enrollment into the study.   
 
11. Benefit vs. Risk: 
 
There is no guarantee that a participant will receive any benefit from taking part in this 
study.  The information from this research may decrease complications associated with 
breast reconstructive efforts.  This may benefit society in the future and is not expected to 
benefit the individual subject. The risks to subjects are no greater than those from the 
surgical procedure alone and are reasonable in relation to the importance of the potential 
knowledge to be gained. 
12. Available Alternative Treatments: 
If participants do not want to take part in the study, there are other choices such as: 
• No reconstruction 
• Use the existing single port expander 
• Autologous tissue reconstruction 
 
13. Research Materials, Records, and Privacy: 
For all participants, records from University of Kentucky Plastic Surgery Clinic will be 
reviewed to determine study inclusion by Dr. Wong.  Participants will be given a unique 
numerical identifier to be used to link Protected Health Information to study data, assigned 
by the principal investigator.  Protected Health Information will be kept in a separate 
password protected file on the desktop computer of the principal investigator, accessible 
only to the principal investigator and members of the research team. The computer is in a 
locked office. Demographic data on age (year of birth), race, gender and past medical history 

Form B:  Medical IRB Research Description 
Comparison of tissue expanders…               PI: Wong             7                     approved 1/17/2017 
7/29/2020 
will be collected from all participants.  This data will be stored in a password protected 
spreadsheet kept on the desktop computer.  Although all data will be entered on to the 
computer a printed copy of the datasheet is available upon request.  Data collected from the 
study will be linked to the numerical identifier and tabulated in a coded chart so as to keep 
the participant’s personal information private.   
14. Confidentiality: 
 
Data will be stored on the office computer of the principal investigator in password protected 
files.  The office is located in the Kentucky Clinic, Division of Plastic Surgery, 740 S. 
Limestone, Lexington, KY  40536.  Following review of all records and completion of data 
collection, all files containing Protected Health Information will be deleted so that no link 
exists between the data and the participant identifiers.  No personal identifiers beyond name 
and medical record number will be stored. Data collected are automatically entered into a 
spreadsheet table using numeric identifiers only used in analysis, further diminishing any 
link Protected Health Information.  This includes any and all dates, which cannot be back 
calculated.  The protected health information will be destroyed within six months of 
completion of the study.   
 
We will make every effort to keep confidential all research records that identify the 
participants to the extent allowed by law.   
 
Participant information will be combined with information from other people taking part in 
the study.  When we write about the study to share it with other researchers, we will write 
about the combined information we have gathered.  Participants will not be personally 
identified in these written materials.  We may publish the results of this study; however, we 
will keep the participant’s name and other identifying information private.   
 
Electronic data with PHI are stored in the University of Kentucky’s medical database that has 
limited medical personnel access, is password protected, and monitored for abnormal 
activity.  Incidental materials containing participant identifiers will be shredded or 
incinerated.   
 
Officials of the Food and Drug Administration, the University of Kentucky, and the 
manufacturer of the AlloX2 expander may look at pertinent portions of the records that 
identify the participant. 
 
 
15. Payment 
No incentives or monetary payment will be given in this study. 
16. Costs to Subjects 
Either the participant or their insurance company, Medicare or Medicaid will be responsible 
for the costs of all care and treatment a participant receives during this study that they would 
normally receive for their condition.  These costs that are considered medically reasonable 

Form B:  Medical IRB Research Description 
Comparison of tissue expanders…               PI: Wong             8                     approved 1/17/2017 
7/29/2020 
and necessary and will be part of the care a patient would receive if they did not take part in 
this study.  
 
The manufacturer of the AlloX2 expander is not offering any indemnification for their device 
as there are no increased risks over the other currently available types of expanders. 
17. 
Data and Safety Monitoring:  Not applicable 
18. 
Subject Complaints: Participants are free to ask any question they may have about the 
study.  Participants will be directed to the Principal Investigator if complaints, concerns, or 
questions arise and provided with contact information.  Participants will also be advised to contact 
the staff of the Office of Research Integrity at 859-257-9428 or toll free at 1-866-400-9428 with any 
concerns.  
19. 
Research Involving Non-English Speaking Subjects or Subjects from a Foreign 
Culture:  Not applicable.  
20. 
HIV/AIDS Research:  Not applicable  
21. 
PI-Sponsored FDA-Regulated Research: Not applicable.  
References 
Albornoz CR, Bach PB, Mehrara JB, et al.  A paradigm shift in U.S. breast reconstruction:  Increasing 
implant rates.  Plast Resconstr Surg 2013;131(1):15-23. 
American Society of Plastic Surgeons. 2014 report of the 2013 statistics: National Clearinghouse of 
Plastic 
Surgery 
Statistics. 
 
Available 
at 
http://plasticsurgery.org/Documents/news-
resources/statistics/2013-statistics/plastic-surgery-statistics-full-report-2013.pdf.  Accessed Sept 
11, 2015. 
Breuning KH, Warren SM. Immediate bilateral breast reconstruction with implants and inferolateral 
AlloDerm slings.  Ann Plast Surg. 2006;55:232-239. 
Sbitany H, Sandeen SN, Amalfi AN, et al.  Acellular dermis-assisted prosthetic  breast reconstruction 
versus complete submuscular  coverage: A head-to-head comparison of outcomes.  Plast Reconstr 
Surg 2009;124:1735-1740. 
Chun YS, Verma K, Rosen H, et al.  Implant-based breast reconstruction using acellular dermal matrix 
and the risk of postoperative complications.  Plast Reconstr Surg 2010;125:429-436. 
Antony AK, McCarthy CM, Cordeiro PG, et al.  Acellular human dermis implantation in 153 immediate 
two-stage tissue expander breast reconstructions:  Determining the incidence and significant 
predictors of complications.  Plast Reconstr Surg. 2010;125:1606-1614. 
Kim JYS, Davila AA, Persing S, et al  A meta-analysis of human acellular dermis and submuscular tissue 
expander breast reconstruction.  Plast Reconstr Surg 2012;129:28-41. 
Weichman KE, Wilson SC, Weinstein AL, et al.  The use of acellular dermal matrix in immediate two-
stage tissue expander breast reconstruction.  Plast Reconstr Surg. 2012;129;1049-1058. 

Form B:  Medical IRB Research Description 
Comparison of tissue expanders…               PI: Wong             9                     approved 1/17/2017 
7/29/2020 
Selber JC, Wren JH, Garvey PB, et al.  Critical evaluation of risk factors and early complications in 564 
consecutive two-stage implant-based breast reconstructions using acellular dermal matrix at a single 
center.  Plast Reconstr Surg. 2015;136:10-20. 
http://www.accessdata.fda.gov/cdrh_docs/pdf14/K140383.pdf 
Ganske I, Verma K, Rosen H, et al.  Minimizing complications with the use of acellular dermal matrix 
for immediate implant-based breast reconstruction.  Ann Plast Surg. 2013;71:464-470. 
Brzezienski MA, Jarrell JA, Mooty RC.  Classification and management of seromas in immediate breast 
reconstruction using the tissue expander and acellular dermal matrix technique.  Ann Plast Srug 
2013;70:488-492. 
Tong RT, Kohi M, Fidelman N, et al. Clinical outcomes of percutaneous drainage of breast fluid 
collections after mastectomy with expander-based breast reconstruction. J Vasc Interv Radiol. 
2013;24:1369-1374. 
Alderman A, Gutowski K, Ahuja A, et al. ASPS Clinical practice guideline summary on breast 
reconstruction with expanders and implants.  Plast Reconstr Surg 2014;134;648c.