Conditions: Pain, Breast
Keywords: Bupivacaine Liposomal Bupivacaine Mastectomy Breast Reconstruction Pain Control
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 3
Healthy volunteers: no

Brief summary:
The purpose of this research study is to determine how well the local anesthetic, liposomal bupivacaine, controls postoperative pain after mastectomy and breast reconstruction.

Detailed description:
Eligible subjects will be identified prior to surgery. On the day of surgery, each patient will be randomized to be in either Local infiltration of bupivacaine OR liposomal bupivacaine. Study will be double blinded to patients and Investigators. Patients assigned to the local infiltration with bupivacaine group will receive a total 60 ml of 0.25% bupivacaine with 30 ml delivered to each breast. Patients assigned to the local infiltration of liposomal bupivacaine will receive a total of 20 ml liposomal bupivacaine (266 mg) with 10 ml of 0.25% bupivacaine and 30 ml of 0.9% sodium chloride. These injections will occur at the end of the mastectomy and prior to the insertion of the tissue expander implant. After this intraoperative injection, patients will not receive any more doses of local anesthetics.

Arms:
arm 1: Participants will be randomized to the Bupivacaine Group and receive a bilateral mastectomy with immediate implant based breast reconstruction arm 2: Participants will be randomized to the Liposomal Bupivacaine Group and receive a bilateral mastectomy with immediate implant based breast reconstruction

Interventions: intervention 1: Bupivacaine intervention 2: Liposomal Bupivacaine
Intervention descriptions: intervention 1: While in the operating room,if subject is randomized to bupivacaine, it will be injected into the surgical site. After surgery, oral and IV pain medications will be available to control pain. During the hospital stay, subject will rate pain on pain scales and monitor how much pain medications needed. Once discharged, PI/staff will provide a pain diary to record pain medication use and pain rating (0-10). Subjects will follow up with clinic at regularly scheduled appointment times at 1 week, 3 weeks and 5 weeks postoperatively. At those appointments, PI/staff will have subjects bring pain medication diary and fill out a pain assessment and a disability assessment related to recent surgery. intervention 2: While in the operating room,if subject is randomized to Liposomal Bupivacaine, it will be injected into the surgical site. After surgery, oral and IV pain medications will be available to control pain. During the hospital stay, subject will rate pain on pain scales and monitor how much pain medications needed. Once discharged, PI/staff will provide a pain diary to record pain medication use and pain rating (0-10). Subjects will follow up with clinic at regularly scheduled appointment times at 1 week, 3 weeks and 5 weeks postoperatively. At those appointments, PI/staff will have subjects bring pain medication diary and fill out a pain assessment and a disability assessment related to recent surgery.

Protocol document:
ICF_001.pdf: 
Page 1 of 9
Adult Consent Form
Version: _____________
IRB Template Version 6.7.2017
Department of Plastic Surgery
THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND BREAST RECONSTRUCTION
Informed Consent Form to Participate in Research
 Christopher Runyan, MD PhD, Principal Investigator
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 have breast cancer requiring 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.
WHY IS THIS STUDY BEING DONE?
The purpose of this research study is to determine how well the local anesthetic, liposomal 
bupivacaine, controls postoperative pain after mastectomy and breast reconstruction.  
Mastectomy is the surgery that is performed to remove tissue from a breast as a way to treat or 
prevent breast cancer. At this time, it is common practice to inject the local anesthetic, 
bupivacaine, into the breast at the time of mastectomy and breast reconstruction to improve post-
operative pain. A new formulation of this local anesthetic has been created in order for it to last 
for a longer period of time. This new formulation is called liposomal bupivacaine and it has been 
FDA approved for this use in local injection at the surgical site. The goal of this study is to 
compare the use of bupivacaine to liposomal bupivacaine to determine which medication better 
controls pain in the postoperative period.  
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY?
This study will require 50 patients to be enrolled at Wake Forest Baptist Medical Center. In order 
to identify the 50 subjects needed, we may need to screen as many as 70 because some people will 
not qualify to be included in the study.
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00045562
Meeting Date Approved 11/14/2019          
Version Valid Until: 8/4/2020


Page 2 of 9
Adult Consent Form
Version: _____________
IRB Template Version 6.7.2017
 
WHAT IS INVOLVED IN THE STUDY?
You will first be approached to be involved in our study at your pre-operative visit for your 
mastectomy and breast reconstruction at least 1 week before surgery. During the first visit we 
will ask you about your medical history, existing pain and any medications that you are taking. 
We will ask you to complete a pre-op questionnaire throughout the visit in addition to a baseline 
pain assessment. This should take approximately 30 minutes to complete. When you are asleep 
in the operating room, you will have either bupivacaine or liposomal bupivacaine injected into 
the surgical site. After surgery, you will have oral and IV pain medications available to control 
your pain. During your hospital stay we will rate your pain scales and monitor how much pain 
medications you need. When you are discharged home we will contact you by phone every 12 
hours, for the first 48 hours following discharge to record your pain rating. Also at discharge, we 
will provide you with a pain medication use diary to record your pain medication use, as well as 
your pain rating. 
You will follow up with our clinic at your regularly scheduled appointment times at 1 week, 3 
weeks and 5 weeks postoperatively. At those appointments, we will have you bring in your pain 
medication diary and fill out a follow-up questionnaire related to your recent surgery. This 
should take approximately 20 minutes to complete.  Your involvement in this study will be 
complete after the completion of your 5 week follow-up visit. 
Once you are enrolled into the study, you will be randomized into the bupivacaine or the 
liposomal bupivacaine group. Randomization means that you are put into a group by chance. It is 
like flipping a coin. You will have an equal chance of being placed in any group. Neither you nor 
the investigator injecting the medication will know which group you are assigned to. This is done 
so that a fair evaluation of results can be made. This information is available to the researchers if 
needed in an emergency.
If you take part in this study, you will have the following tests and procedures:
If you are in the bupivacaine local anesthetic group, you will have this medication injected into 
and around the breast at the end of surgery. This occurs when you are asleep in the operating 
room. This is a common practice in patients who are undergoing mastectomy who are not 
enrolled in the study. If you are in the liposomal bupivacaine group, you will have this 
medication injected into and around the breast. Similarly, this will occur when you are asleep in 
the operating room. 
HOW LONG WILL I BE IN THE STUDY?
You will be in the study for about 2 months. 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. There are no serious health consequences of sudden withdrawal from the study, 
however we will not be able use your experience in our research. 
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00045562
Meeting Date Approved 11/14/2019          
Version Valid Until: 8/4/2020


Page 3 of 9
Adult Consent Form
Version: _____________
IRB Template Version 6.7.2017
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. Because researchers do not know which drug is better at relieving pain and 
reducing side effects, there is a chance that you could be assigned to the arm of the study that 
performs better or worse than the other arm. Risks and side effects related to the liposomal 
bupivacaine that we are studying include:
More common immediate risks of receiving liposomal bupivacaine may include nausea (2-40%) 
and vomiting (28%). Uncommon risks include hypotension (low blood pressure) (2-10%), leg 
swelling (2-10%), insomnia (difficulty falling or staying asleep) (2-10%), itching (3%), anemia 
(blood has a lower than normal range of red blood cells which can lead to reduced oxygen flow 
to vital organs)(2-10%), muscle spasm (2-10%). Rare but serious side effects may include central 
nervous system excitation leading to convulsions or unconsciousness (<2%) and allergic 
reactions including anaphylaxis (a serious allergic reaction, which in rare cases can be fatal)  
(<2%).  Use of liposomal bupivacaine is contraindicated in pregnancy, but does not pose a long-
term reproductive risk to patients. Similar risks are associated with the use of bupivacaine 
injection. If a high dose is used such that toxicity occurs, this can result in a slow heart rate, 
cardiac arrest, cessation of breathing and possible death.  It should be used in caution with 
patients with moderate-severe hepatic or renal impairment because of the increased risk of 
toxicity.
In addition, there is a slight risk of a breach of confidentiality.  We will do our best to protect 
your confidential information.  There also may be other side effects that we cannot predict. 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.
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.
As part of this study, you will be asked questions about long-term quality of life which includes 
the presence of depression. If we learn that you or someone else is in danger of harm, the study 
team is required to report that information to the proper authorities. At the end of the consent 
there is a list of resources you may find helpful.
Reproductive Risks and other Issues to Participating in Research
Due to unknown risks and potential harm to the unborn fetus, sexually active women of 
childbearing potential must use a reliable method of birth control while participating in this 
study. Reliable methods of birth control are: abstinence (not having sex), oral contraceptives, 
intrauterine device (IUD), DepoProvera, tubal ligation, or vasectomy of the partner (with 
confirmed negative sperm counts) in a monogamous relationship (same partner). An acceptable, 
although less reliable, method involves the careful use of condoms and spermicidal foam or gel 
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00045562
Meeting Date Approved 11/14/2019          
Version Valid Until: 8/4/2020


Page 4 of 9
Adult Consent Form
Version: _____________
IRB Template Version 6.7.2017
and/or a cervical cap or sponge. We encourage you to discuss this issue further with your 
physicians if you have any questions.
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.
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. The benefits of 
participating in this study may be improved pain control after mastectomy and breast 
reconstruction with injection of liposomal bupivacaine.
WHAT OTHER CHOICES ARE THERE?
You do not have to be in this study to receive treatment. You should talk to your doctor about all 
the choices you have. Instead of being in this study, you have these options: undergo your 
scheduled mastectomy and breast reconstruction. 
WHAT ARE THE COSTS?
All study costs, including any study medications and procedures related directly to the study, will 
be paid for by the study. Costs for your regular medical care, which are not related to this study, 
will be your own responsibility. Neither you nor your insurance company will be billed for the 
medication used in this study as it will be funded by the study.
WILL YOUR RESEARCH RECORDS BE CONFIDENTIAL?
The results of this research study may be presented at scientific or medical meetings or published 
in scientific journals.  Your identity and/or your personal health information will not be disclosed 
unless it is authorized by you, required by law, or necessary to protect the safety of yourself or 
others.  There is always some risk that even de-identified information might be re-identified. 
Participant information may be provided to Federal and other regulatory agencies as required.  
The Food and Drug Administration (FDA), for example, may inspect research records and learn 
your identity if this study falls within its jurisdiction.
WILL YOU BE PAID FOR PARTICIPATING?
You will receive no payment or other compensation for taking part in this study.
WHO IS SPONSORING THIS STUDY?
This study is being sponsored by Wake Forest Baptist Medical Center, Department of Anesthesia 
and the Foundation for Anesthesia Education and Research. The researchers do not, however, 
hold a direct financial interest in the sponsor or the product being studied. There is no potential 
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00045562
Meeting Date Approved 11/14/2019          
Version Valid Until: 8/4/2020


Page 5 of 9
Adult Consent Form
Version: _____________
IRB Template Version 6.7.2017
conflict of interest between the authors of this study and the sponsors of this study. 
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 do 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 Christopher Runyan, MD PhD at telephone 
number: 
.
WHAT ABOUT MY HEALTH INFORMATION?
In this research study, any new information we collect from you and/or information we get from 
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: pain score, 
use of pain medications, side effects of local anesthetics including nausea and vomiting, length 
of hospital stay, and quality of life.
If this research study involves the diagnosis or treatment of a medical condition, then Protected 
Health Information collected from you during this study may be placed in your medical record, 
and may be used to help treat you, arrange payment for your care, or assist with Medical Center 
operations. 
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. 
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00045562
Meeting Date Approved 11/14/2019          
Version Valid Until: 8/4/2020


Page 6 of 9
Adult Consent Form
Version: _____________
IRB Template Version 6.7.2017
Your personal health information and information that identifies you (“your health information”) 
may be given to others during and after the study. This is for reasons such as to carry out the 
study, to determine the results of the study, to make sure the study is being done correctly, to 
provide required reports and to get approval for new products.  
Some of the people, agencies and businesses that may receive and use your health information 
are the research sponsor; representatives of the sponsor assisting with the research; investigators 
at other sites who are assisting with the research; central laboratories, reading centers or analysis 
centers; the Institutional Review Board; representatives of Wake Forest University Health 
Sciences and North Carolina Baptist Hospital; representatives from government agencies such as 
the Food and Drug Administration (FDA), the Department of Health and Human Services 
(DHHS) and similar agencies in other countries.
Some of these people, agencies and businesses may further disclose your health information. If 
disclosed by them, your health information may no longer be covered by federal or state privacy 
regulations.  Your health information may be disclosed if required by law. Your health 
information may be used to create information that does not directly identify you. This 
information may be used by other researchers. You will not be directly identified in any 
publication or presentation that may result from this study unless there are photographs or 
recorded media which are identifiable.
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 that is maintained in the 
research records will be kept for at least six years after the study is finished. At that time, any 
research information not already in your medical record will either be destroyed or it will be de-
identified. 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 Christopher Runyan, MD PhD 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:
Christopher Runyan, MD PhD
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.
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00045562
Meeting Date Approved 11/14/2019          
Version Valid Until: 8/4/2020


Page 7 of 9
Adult Consent Form
Version: _____________
IRB Template Version 6.7.2017
By signing this form you give us permission to use your Protected Health Information for this 
study.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This website will not include information that can identify you. At most, the 
website will include a summary of the results. You can search this Web site at any time.
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 worsened, 
you failed to follow instructions, or because the entire study has been stopped. 
Information that identifies you may be removed from the data or specimens that are collected as 
part of this study and could be used for future research or shared with others without additional 
consent.
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: IRB00045562
Meeting Date Approved 11/14/2019          
Version Valid Until: 8/4/2020


Page 8 of 9
Adult Consent Form
Version: _____________
IRB Template Version 6.7.2017
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, Christopher Runyan 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, or you 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: IRB00045562
Meeting Date Approved 11/14/2019          
Version Valid Until: 8/4/2020


Page 9 of 9
Adult Consent Form
Version: _____________
IRB Template Version 6.7.2017
Below is a list of resources which may you may find helpful: 
 
Emergencies:
Local Emergency Department
National Suicide Prevention Lifeline:  800-273-TALK (8255)
 
Non-Emergency:
Wake Forest Psychiatry (medical or counseling):  
Cancer Patient Support Program (CPSP) :
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00045562
Meeting Date Approved 11/14/2019          
Version Valid Until: 8/4/2020

Prot_SAP_002.pdf: 
THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 1 of 44 
Principal Investigator: 
 
Christopher Runyan, MD 
 
 
 
 
 
Plastic and Reconstructive Surgery 
 
 
 
 
 
Wake Forest School of Medicine 
 
 
 
 
 
Winston-Salem, NC 27157 
 
 
 
 
 
crunyan@wakehealth.edu 
 
 
 
 
 
336-716-5855 
 
 
Co-Investigator(s):  
 
J. Douglas Jaffe, DO 
 
 
 
 
 
Department of Anesthesiology 
 
 
 
 
 
Wake Forest School of Medicine 
 
 
 
 
 
jjaffe@wakehealth.edu 
 
 
 
 
 
 
James C. Eisenach, MD 
 
 
 
 
 
Department of Anesthesiology  
 
 
 
 
            Wake Forest School of Medicine 
 
 
 
 
 
Eisenach@wakehealth.edu 
 
 
Megan Rudolph, MD 
Plastic and Reconstructive Surgery 
Wake Forest School of Medicine 
mrudolph@wakehealth.edu 
 
Ryan Rebowe, MD 
 
 
 
 
 
Plastic and Reconstructive Surgery 
 
 
 
 
 
Wake Forest School of Medicine 
 
 
 
 
 
rrebowe@wakehealth.edu 
 
 
 
 
 
 
Nicholas Walker, MD 
 
 
 
 
 
Plastic and Reconstructive Surgery 
 
 
 
 
 
Wake Forest School of Medicine 
 
 
 
 
 
njwalker@wakehealth.edu 
 
 
Biostatistician: 
Greg Russell 
 
Department of Biostatistical Sciences 
 
Division of Public Health Sciences 
 
grussell@wakehealth.edu 
 
336-716-5449 
 
 
Study Coordinator:  
 
Caleb Suggs 
 
 
 
 
 
Plastic and Reconstructive Surgery 
 
 
 
 
 
Wake Forest School of Medicine 
 
 
 
 
 
csuggs@wakehealth.edu 
 
 
 
Protocol Editor: 
 
 
Mac Robinson, PhD 
Comprehensive Cancer Center of Wake Forest University 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 2 of 44 
Wake Forest University School of Medicine 
Medical Center Blvd 
Winston-Salem, NC 27157 
 
 
 
 
 
336-716-5096 
 
 
 
 
 
macrobin@wakehealth.edu 
 
 
Participating Institution(s): Wake Forest Baptist Health 
 
 
Version Date: 08/28/2017 
Amended: 
 
 
 
Confidential 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 3 of 44 
 
 
 
Table of Contents 
SCHEMA ................................................................................................................................................................ 5 
1.0 
Introduction and Background ..................................................................................................................... 6 
2.0 
Objectives ................................................................................................................................................... 7 
2.1 
Primary Objective(s) ............................................................................................................................... 7 
2.2 
Secondary Objective(s) ........................................................................................................................... 7 
3.0 
Patient Selection.......................................................................................................................................... 8 
3.1 
Inclusion Criteria .................................................................................................................................... 8 
3.2 
Exclusion Criteria ................................................................................................................................... 8 
3.3 
Inclusion of Women and Minorities ....................................................................................................... 8 
4.0 
Registration Procedures .............................................................................................................................. 9 
5.0 
Study Outcomes and Study Measures......................................................................................................... 9 
5.1 
Primary Outcome .................................................................................................................................... 9 
5.2 
Secondary Outcomes .............................................................................................................................. 9 
6.0 
Treatment Plan .......................................................................................................................................... 10 
6.1 
Study-Related Activities ....................................................................................................................... 11 
6.2 
Treatment Administration ..................................................................................................................... 13 
6.3 
General Concomitant Medication and Supportive Care Guidelines ..................................................... 13 
6.4 
Duration of Follow Up .......................................................................................................................... 13 
7.0 
Adverse Events List and Reporting Requirements ................................................................................... 13 
7.1 
Adverse Event List for Liposomal Bupivacaine: .................................................................................. 14 
7.2 
Adverse Event List for Bupivacaine: .................................................................................................... 14 
7.3 
Adverse Event Characteristics .............................................................................................................. 14 
7.4 
STRC SAE Reporting Requirements .................................................................................................... 15 
7.5 
WFUHS IRB AE Reporting Requirements .......................................................................................... 15 
8.0 
Pharmaceutical Information ...................................................................................................................... 15 
8.1 
Pharmaceutical Accountability ............................................................................................................. 16 
8.2 
Liposomal Bupivacaine ........................................................................................................................ 16 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 4 of 44 
8.3 
Bupivacaine........................................................................................................................................... 16 
9.0 
Data Management ..................................................................................................................................... 17 
10.0 
Statistical Considerations .......................................................................................................................... 18 
10.1 
Analysis of Primary Objective .............................................................................................................. 18 
10.2 
Analysis of Secondary Objective .......................................................................................................... 18 
10.3 
Power and Sample Size ......................................................................................................................... 19 
    10.4      Accrual Rate…………………………………………………………………………………………..20 
 
10.5 
Estimated Study Length ........................................................................................................................ 19 
10.6 
Interim Analysis Plan ............................................................................................................................ 19 
References ............................................................................................................................................................. 20 
Appendix A – Eligibility Checklist....................................................................................................................... 23 
Appendix B – Protocol Registration Form ........................................................................................................... 25 
Appendix C - Race & Ethnicity Verification Form .............................................................................................. 26 
Appendix D – Mandatory STRC SAE Reporting Guidelines .............................................................................. 27 
Appendix E – Adverse Event Log ........................................................................................................................ 32 
Appendix F – Pre-Operative Questionnaires ........................................................................................................ 33 
Appendix G – Daily Diary .................................................................................................................................... 37 
Appendix H - Weekly Assessment ....................................................................................................................... 39 
Appendix I- Visual Analog Scale ......................................................................................................................... 41 
Appendix J – Off-Study Form .............................................................................................................................. 41 
Appendix K- Pain Medication Diary…………………………………………………………………………….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 5 of 44 
 
 
 
SCHEMA 
 
 
 
 
 
 
Pre-operative consent and pre-study 
data collection 
Randomization 
Bupivacaine 
Liposomal bupivacaine  
Mastectomy and 
breast 
reconstruction 
Mastectomy and 
breast 
reconstruction 
Intraoperative surgical site 
infiltration 
Intraoperative surgical site 
infiltration 
Postoperative pain 
assessment and 
management in hospital 
Discharge and long 
term patient pain 
assessment 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 6 of 44 
1.0 
Introduction and Background 
Breast reconstruction defines the final step for many women on a long road to recovery from breast cancer. 
Reconstruction of the breast mound following mastectomy has several benefits in psychosocial functioning, 
body image and satisfaction with breast appearance, and sexual well-being1-4. However, reconstruction at the 
same time as mastectomy has been linked to higher post-operative pain5. As in any surgical procedure, post-
operative pain control has a major impact on patient satisfaction and important outcome measures such as 
length of stay, readmission rates, and overall hospital costs6-8. In particular, poor post-operative pain control in 
the cancer population has a negative impact on physical functioning, with decreased ability to perform activities 
of daily living, social functioning, with decreased interest in hobbies and contact with friends, and can increase 
feelings of anxiety and depression9. In fact, fear of post-surgical pain has been shown to be a major reason that 
women refuse breast reconstruction surgery10. 
 
Implant based breast reconstruction is a widely used and well accepted technique with 86,013 procedures 
performed in the United States in 2015 vs 20,325 flap based breast reconstruction procedures11. However, this 
technique has disadvantages in relation to post-operative pain. Compared to autologous breast reconstruction, 
implant based techniques have been linked to higher requirements of post-operative benzodiazepines, 
nonsteroidal anti-inflammatory drugs, and narcotics as well as higher pain scores in the immediate post-
operative period and one year after surgery5,12. Tissue expander based techniques in particular lead to even 
higher narcotic use and morphine equivalents than single staged implant reconstruction5.  
 
 In an effort to decrease pain control, it is common practice for local anesthetics to be infiltrated into the 
surgical wound. Individual studies have shown that infiltrations with bupivacaine specifically have decreased 
intraoperative and postoperative narcotic use, decreased pain scores in the immediate postoperative period 24-26. 
However, upon meta-analysis of randomized clinical trials studying the effect of wound infiltration with 
bupivacaine or ropivacaine it was found that postoperative pain severity was only decreased at 2 hours 
postoperatively and postoperative analgesic consumption did not change27. In light of this, there continues to be 
a need for improvement in postoperative pain management for mastectomy and subsequent breast 
reconstruction.  
 
One such medication which has been suggested for improvement in pain control after mastectomy and breast 
reconstruction is Exparel (Pacira Pharmaceuticals, Inc., San Diego, CA). It is a relatively recent bupivacaine 
multi-vesicular liposomal delivery system that allows slow release of bupivacaine, resulting in local anesthetic 
effects for up to 72-96 hours after injection. It is a safe pain control modality with a similar side effects profile 
to bupivacaine HCL and does not compromise breast implant integrity13-14.  
 
Side effects of Exparel primarily includes GI upset (nausea and vomiting) which can occur in greater than 10% 
of patients. More rare side effects include hypotension (2-10%), insomnia (2-10%), pruritus (3%), postoperative 
anemia (2-10%), and muscle spasm (2-10%). Similar to other local anesthetics, dose related toxicity can occur 
and can lead to central nervous system excitation or depression. Exparel has a half-life of 24-34 hours and is 
hepatically metabolized and renally excreted. It should be used in caution with patients with moderate-severe 
hepatic or renal impairment because of the increased risk of toxicity. Exparel may increase the toxicity of 
lidocaine and bupivacaine. Bupivacaine can be administered with or immediately before Exparel as long as the 
milligram dose ratio of bupivacaine to Exparel is not greater than 1:2. Furthermore, Exparel may increase the 
effect of neuromuscular blocking agents. Exparel is not recommended in pregnant patients as there have been 
no studies conducted in this population and high doses used in animal models have been shown to decrease fetal 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 7 of 44 
survival. It has been FDA approved for administration into the surgical site and the recommended a standard 
dosing for breast surgery of 266 mg (20 ml)28.  
 
Multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trials have been performed 
for Exparel use in postoperative pain control for bunionectomy and hemorrhoidectomy. In the bunionectomy 
trial, it was found that with injection of Exparel there was a statistically significant reduction of cumulative pain 
levels over the first 24 hours after surgery29. Similarly, in the hemorrhoidectomy trial, it was found that the 
Exparel group had a decreased cumulative pain score at 72 hours30.  
 
Furthermore, liposomal bupivacaine has been shown to improve outcome measures including mean hospital 
stay and post-operative pain scores in a wide range of procedures from abdominal wall reconstruction to 
thoracotomies and sternotomies15,16. In retrospective studies, the use of Exparel decreased immediate 
postoperative pain associated with breast reconstruction compared with IV and oral narcotics and bupivacaine 
pain pumps. It also showed a significant decrease in mean length of stay compared to IV and oral narcotic pain 
management18. Up to this point, there have been no prospective studies examining the effects of Exparel on 
outcome measures when used in tissue expander based breast reconstruction. We believe that its use will 
decrease post-operative pain and will lead to improved performance in outcome measures. 
2.0 
Objectives 
 
2.1 
Primary Objective(s) 
 
2.1.1 The primary objective of this clinical study is to evaluate the effect of Exparel on mean 
postoperative pain levels in patients who have undergone mastectomy and breast 
reconstruction within the first 48 hours. We hypothesize that Exparel will decrease mean 
postoperative pain levels within the first 48 hours.  
 
2.2 
Secondary Objective(s) 
 
2.2.1 To evaluate the effect of liposomal bupivacaine on cumulative pain control within the 
first 48 hours after mastectomy and breast reconstruction  
2.2.2 To evaluate the effect of liposomal bupivacaine on the amount of postoperative narcotic 
use after mastectomy and breast reconstruction for the first month after surgery 
2.2.3 To evaluate the effect of liposomal bupivacaine on length of hospital stay after 
mastectomy and breast reconstruction 
2.2.4 To evaluate the effect of liposomal bupivacaine on hospital readmission rates a within 2 
months after mastectomy and breast reconstruction  
2.2.5 To evaluate the effect of liposomal bupivacaine on the occurrence of opioid adverse 
effects within the first week of surgery after mastectomy and breast reconstruction 
2.2.6 To evaluate the effect of liposomal bupivacaine on the trajectory of postoperative pain 
control within 2 months after mastectomy and breast reconstruction 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 8 of 44 
3.0 
Patient Selection 
 
3.1 
Inclusion Criteria  
3.1.1 All patients who receive a bilateral mastectomy with only immediate sub-pectoral 
implant based breast reconstruction 
3.1.2 Age ≥ 18 years   
3.1.3 Ability to understand and the willingness to sign an IRB-approved informed consent 
document. 
3.1.4 Patients who receive tissue expander placement or direct permanent implant placement 
will be included in the study. 
3.1.5 ASA patient status I-III patients 
3.2 
Exclusion Criteria  
 
3.2.1 Patients who receive an autologous tissue reconstruction.  
3.2.2 Patients who receive a unilateral reconstruction. 
3.2.3 Patients who are expected to undergo axillary lymph node dissection 
3.2.4 Patients who have undergone breast irradiation 
3.2.5 Patients who abuse narcotics or have chronic pain (using greater than 40 mg equivalents 
of oxycodone per day) 
3.2.6 Patients who are wards of the state  
3.2.7 History of allergic reactions attributed to compounds of similar chemical or biologic 
composition to bupivacaine or liposomal bupivacaine. 
3.2.8  Pregnant women are excluded from this study because pregnancy precluded immediate 
breast reconstruction in our patient population. 
3.2.9 Patients who weigh less than 50 kg, as there can be dose related toxicities of the 
bupivacaine dosing used in this study 
3.2.10 Patients with moderate-severe hepatic or renal impairment because of the increased risk 
of toxicity. 
3.2.11 Patients receiving bilateral mastectomy with immediate pre-pectoral implant based breast 
reconstruction 
3.3 
Inclusion of Women and Minorities 
 
Women of all races and ethnicities who meet the above-described eligibility criteria are eligible 
to participate in this study.  
 
We expect approximately 5% of study participants to be Hispanic/Latino (N=5). We plan to 
enroll at least 10% Black or African American (N=10), 1% American Indian/Alaska Native 
(N=1), 5% Asian (N=5). Should we not meet or exceed these estimates, the PI will engage the 
Cancer Center Health Equity Advisory Group to discuss strategies to enhance recruitment in 
these target populations. 
 
 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 9 of 44 
 
 
 
4.0 
Registration Procedures 
 
All patients entered on any WFBCCC trial, whether treatment, companion, or cancer control trial, must be 
linked to the study in EPIC within 24 hours of Informed Consent. Patients must be registered in WISER prior to 
the initiation of treatment.   
 
You must perform the following steps in order to ensure prompt registration of your patient: All patients will be 
registered in WISER 
 
1.  
 
To complete the registration process, the study team  will:   
 
 assign a patient study number 
 notify the pharmacy via faxed physician order form 
 register the patient on the study 
5.0 
Study Outcomes and Study Measures 
5.1 
Primary Outcome 
 
5.1.1 The primary outcome of this study is the mean visual analog scores (scale of 0-10) within 
the first 48 hours postoperatively. This will be measured every 12 hours for the first 48 
hours and will be assessed by the level of breast pain associated with arm movements 
while eating.  
5.1.1.1 
Visual analog scores in mastectomy patients with oral and IV narcotics are 
approximately 5.0 at 24 hours and 4.8 at 48 hours17 
5.1.1.2 
For patients with local infiltration of Liposomal bupivacaine after implant 
based reconstruction, visual analog scores at 24hrs were 3.8 on average18  
5.2 
Secondary Outcomes 
 
5.2.1 Area under the curve visual analog scores (scale 0-10) during the first 48 hours 
postoperatively.  
5.2.1.1 
For patients undergoing submuscular augmentation mammoplasty, the area 
under the curve for pain scores at 72 hours for liposomal bupivacaine 
infiltration is 441 +/- 182 and for bupivacaine infiltration is 461 +/- 18120 
 
5.2.2 Morphine equivalents used within the first month postoperatively  


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 10 of 44 
5.2.2.1 
The number of doses of oral narcotics (hydrocodone-acetaminophen 1 tablet) 
for patients with immediate tissue expander reconstruction without other 
measure of pain control has been 4.2 at 24 hours and 4.0 at 48 hours17. This is 
approximately 3.3 morphine equivalents  
5.2.2.2 
We would expect the patients treated with liposomal bupivacaine to use an 
average of 2.5 intravenous morphine equivalents at the 48-hour point and 
decreased morphine equivalents in the liposomal bupivacaine over the first 
postoperative month. 
 
5.2.3 Length of stay for hospitalization after mastectomy and breast reconstruction 
5.2.3.1 
Length of stay for patients undergoing mastectomy and immediate 
reconstruction has been shown to be 41-47 hours on average21 
5.2.3.2 
We believe liposomal bupivacaine will shorten this time to 36 hours±12 in the 
liposomal bupivacaine group, but not in the bupivacaine groups. 
 
5.2.4 Readmission rates to the hospital within 2 months after mastectomy and breast 
reconstruction  
5.2.4.1 
Patients who underwent tissue expander breast reconstruction have a 
readmission rate of approximately 4.34%22. We anticipate a readmission rate 
of approximately 2% Patients will be informed that if they are expected to undergo 
an axillary lymph node dissection at the time of surgery then they will be excluded 
from the study. Patients who are undergoing sentinel lymph node biopsies will be 
included in the study, but if their nodes are positive and there is an intraoperative 
decision to pursue axillary lymph node dissection they will subsequently be excluded 
from the study. 
 
5.2.5 Frequency of postoperative opioid related adverse effects within the first week of 
surgery. This includes nausea, vomiting, pruritus, allergy, respiratory depression.  
5.2.5.1 
After immediate breast reconstruction with implants, patients receiving 
bupivacaine had a 40% incidence of nausea and vomiting. Those not receiving 
a local anesthetic had a 75% incidence of nausea and vomiting17 
5.2.5.2 
We predict a 30% incidence of opioid related adverse events in our liposomal 
bupivacaine group 
 
5.2.6 Trajectory of postoperative recovery from pain within the first 2 months 
5.2.6.1 
Growth curve analysis of pain intensity with movement scores over the first 
two months, using an initial log (time) model and a Bayesian change point 
analysis 
5.2.6.2 
Groups will be compared for intercept and slope of the trajectory of pain 
intensity up to the first change point  
5.2.6.3 
For the entire population, the impact of the optimism-catastrophizing 
continuum and other predictive factors for intercept and slope will be explored  
6.0 
Treatment Plan 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 11 of 44 
 
Preoperative 
Visit 
Day of 
Surgery 
Upon 
discharge 
home 
1st 12hr 
post 
discharge 
2nd 12hr 
post 
discharge 
3rd 12hr 
post 
discharge 
4th 12hr  
post 
discharge 
1 
week 
postop 
3 
weeks 
postop 
5 
weeks 
postop 
Life 
Orientation 
Test-Revised 
X 
 
 
 
 
 
 
 
 
 
PROMIS-
Depression 
X 
 
 
 
 
 
 
 
 
 
PROMIS-
Anxiety 
X 
 
 
 
 
 
 
 
 
 
Pain 
Catastrophizing 
Scale 
X 
 
 
 
 
 
 
 
 
 
Baseline Pain 
Assessment  
X 
 
 
 
 
 
 
 
 
 
Enrollment and 
informed 
consent 
X 
 
 
 
 
 
 
 
 
 
Receive 
surgical site 
infiltration of 
Exparel or 
bupivacaine 
 
X 
 
 
 
 
 
 
 
 
Q 12 hour pain 
scores 
 
 
 
X 
X 
X 
X 
 
 
 
Patent diary of 
narcotic use 
and pain rating 
 
 
X 
 
 
 
 
X 
 
 
Disability 
assessments 
 
 
 
 
 
 
 
X 
X 
X 
Pain 
assessments  
 
 
 
 
 
 
 
X 
X 
X 
 
6.1 
Study-Related Activities  
Patient involvement in the study will be initiated in the plastic surgery clinic. Eligible subjects will be identified 
prior to surgery.  Potential subjects will be contacted either by phone or during their clinic visit, informed 
consent will be obtained and a 30-minute preoperative assessment will be performed.  Patients will be informed 
that if they are expected to undergo an axillary lymph node dissection at the time of surgery then they will be 
excluded from the study. Patients who are undergoing sentinel lymph node biopsies will be included in the 
study, but if their nodes are positive and there is an intraoperative decision to pursue axillary lymph node 
dissection they will subsequently be excluded from the study. Also, we will record demographic and history 
information, including existing pain elsewhere, and administer questionnaire-based measures of psychological 
state, physical function, and baseline pain (Table 1, Appendix F). Questionnaire responses will be entered via 
the cancer center REDCap data entry form. From these questionnaires, we will place each participant on a 
dimensional continuum that describes their general cognitive style. We will use multidimensional scaling 
(MDS) to force catastrophizing and optimism as 2 ends of this continuum.  
 
Table 1.  Preoperative Questionnaires 
Life Orientation Test-Revised (LOT-R) 
PROMIS- Depression 
PROMIS- Anxiety 
Pain Catastrophizing Scale (PCS) 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 12 of 44 
 
These two constructs describe cognitive styles that are strongly inversely associated with each other; MDS will 
provide the optimal weights to best order individuals on this latent scale. Studies have examined the interplay of 
these constructs with other psychological concepts such as acceptance, pain-related disability and psychosocial 
adjustment and have found that both are reliably associated with the positive and negative aspects of the 
adjustment to pain.                                             
 
The research coordinator will then assign the patients a study number. On the day of surgery, each patient will 
be randomized to be in one of the following two groups for perioperative local anesthetic infiltration: 
 
1. Local infiltration of bupivacaine 
2. Local infiltration of liposomal bupivacaine 
 
The study will be double blinded to both patients and providers including plastic and general surgeons involved 
in their operative care. We will enroll our patients in pharmacy randomization program, in which the pharmacy 
will deliver the appropriate medication per assigned group.  
 
To monitor our primary outcomes, patients will be asked to rate their pain level on a visual analog scale (Table 
2, Appendix Z) with activity every 12-hours after surgery during their post-procedure stay. The activity for 
which they will rate their pain will be the arm movements associated with eating. In the hospital, their visual 
analog scores will be provided to each patient in person by their nurse every 12 hours. Subject’s pain scores will 
continue to be recorded every 12 hours via a phone call from a study team member for the first 48 hours after 
discharge. Additionally, while in the hospital, the amount of narcotics used will be recorded and converted into 
morphine equivalents.  
 
 
 
 
 
 
Table 2: Visual Analog Scale 
 
 
Upon discharge, patients will be given a sheet to record their pain level and the amount of narcotics & 
benzodiazepines used (Appendix K). Both the amount of narcotics & benzodiazepines and the pain level are to 
be reported at the time of taking any narcotics & benzodiazepines. Patients will follow up with our clinic at 1 
week, 3 weeks, and 5 weeks postoperatively. At week 1 patients will bring in their medication and pain diary, 
and fill out a pain assessment (Appendix G) in addition to a questionnaire assessing breast cancer surgery 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 13 of 44 
disability (Appendix H)23.  During subsequent appointments made at 3 and 5 weeks postoperatively, they will 
be assessed and receive the pain assessment and breast cancer surgery disability assessments as well. When 
tissue expansion is initiated will be determined by the primary surgeon, but we will track the dates of the 
initiation of expansion as this will impact pain scores within the electronic medical record.  
 
Secondary outcomes including length of hospital stay, adverse opioid effects and re-admission rate will be 
tracked by their electronic medical record. Upon reviewing the questionnaires, if a subject is determined to have 
high levels of depression, our team will make them aware of the resources available in the psychiatry 
department and a contact number will be provided to them.  
 
6.2 
Treatment Administration 
Patients assigned to the local infiltration with bupivacaine group will receive a total 60 ml of 0.25% bupivacaine 
with 30 ml delivered to each breast. Patients assigned to the local infiltration of liposomal bupivacaine will 
receive a total of 20 ml liposomal bupivacaine (266 mg) with 10 ml of 0.25% bupivacaine and 30 ml of 0.9% 
sodium chloride. These injections will occur at the end of the mastectomy and prior to the insertion of the tissue 
expander implant. The local anesthetic will be injected into the chest wall and skin flaps. Attending physicians 
and resident physicians will receive prior instruction regarding correct placement of the local anesthetic so that 
it will be consistently placed in the same locations with similar volume distribution. After this intraoperative 
injection, patients will not receive any more doses of local anesthetics.  
6.3 
General Concomitant Medication and Supportive Care Guidelines 
 
This local anesthetic will get delivered at the time of surgery in an opaque syringe. Standardized anesthetic 
criteria will be applied to all patients enrolled in the study. Pre-operatively, all patients will receive multi-modal 
therapy, such as acetaminophen, celecoxib, and gabapentin or pregabalin unless contraindicated. 
Intraoperatively, patients will only receive short acting fentanyl for analgesia. Intraoperative ketamine and 
dexamethasone will be avoided. A notification will populate in EPIC once the patient is linked to the study in 
WISER to notify the anesthesia provider.  Postoperative non-opioid medications will supplement as needed 
opioid mediations for analgesic management.  
 
 
Patients will receive full supportive care as medically necessary, including transfusions of blood and blood 
products, antibiotics, antiemetics, etc. Medications considered necessary for the patient's well-being may be 
given as long as they are considered safe in the postoperative period and clinically indicated. The reason(s) for 
treatment, dosage, and dates of treatment will be recorded on the flow sheets. 
6.4 
Duration of Follow Up 
 
Patients will be seen at one week, three weeks and five weeks postoperatively at which time they will receive 
pain and disability assessments.  
7.0 
Adverse Events List and Reporting Requirements 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 14 of 44 
7.1 
Adverse Event List for Liposomal Bupivacaine:  
 
 
Common adverse reactions (incidence 2-10%): pyrexia, dizziness, peripheral edema, anemia, hypotension, 
pruritis, tachycardia, headache, insomnia, anemia postoperative, muscle smasm, hemorrhagic anemic, back 
pain, somnolence, procedural pain. 28 
 
Rare adverse reactions (incidence <2%): chills, erythema, bradycardia, anxiety, urinary retention, pain, edema, 
tremor, dizziness postural, paresthesia, syncope, incision site edema, procedural hypertension, procedural 
hypotension, procedural nausea, muscular weakness, neck pain, pruritus generalized, rash pruritic, 
hyperhidrosis, cold sweat, urticaria, bradycardia, palpitations, sinus bradycardia, supraventricular extrasystoles, 
ventricular extrasystoles, ventricular tachycardia, hypertension, pallor, anxiety, confusional state, depression, 
agitation, restlessness, hypoxia, laryngospasm, apnea, respiratory depression, respiratory failure, body 
temperature increased, blood pressure increased, blood pressure decreased, oxygen saturation decreased, urinary 
incontinence, vision blurred, tinnitus, drug hypersensitivity, and hypersensitivity.28 
 
None of these adverse effects are expected to occur as a result of the administration of liposomal bupivacaine.  
7.2 
Adverse Event List for Bupivacaine: 
 
The major cause of adverse reactions is secondary to high plasma levels of the medication. In this setting, CNS 
reactions include restlessness, anxiety, dizziness, tinnitus, blurred vision, tremors, drowsiness, unconsciousness. 
High doses can depress the myocardium leading to decreased cardiac output, heart block, hypotension, 
bradycardia, arrhythmias, cardiac arrest. Allergic reactions are rare but can include urticarial, pruritus, 
erythema, angioneurotic edema, tachycardia, nausea, vomiting, anaphylactoid-like symtpoms31.   
 
None of these adverse effects are expected to occur as a result of the administration of liposomal bupivacaine.  
7.3 
Adverse Event Characteristics 
 
 
CTCAE term (AE description) and grade:  The descriptions and grading scales found in 
the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 
will be utilized for AE reporting. All appropriate treatment areas should have access to a 
copy of the CTCAE version 4.0. A copy of the CTCAE version 4.0 can be downloaded from 
the CTEP web site (http://ctep.cancer.gov). 
 
 
‘Expectedness’: AEs can be ‘Unexpected’ or ‘Expected’ (see Section 7.1 above) for 
expedited reporting purposes only.   
 
 
Attribution of the AE: 
 
- 
Definite – The AE is clearly related to the study treatment. 
- 
Probable – The AE is likely related to the study treatment. 
- 
Possible – The AE may be related to the study treatment. 
- 
Unlikely – The AE is doubtfully related to the study treatment. 
- 
Unrelated – The AE is clearly NOT related to the study treatment. 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 15 of 44 
7.4 
STRC SAE Reporting Requirements 
 
The Safety and Toxicity Reporting Committee (STRC) is responsible for reviewing SAEs for WFBCCC 
Institutional studies as outlined in Appendix B. STRC currently requires that all unexpected 4 and all 
grade 5 SAEs on these trials be reported to them for review. All WFBCCC Clinical Research 
Management (CRM) staff members assisting a Principal Investigator in investigating, documenting and 
reporting an SAE qualifying for STRC reporting are responsible for informing a clinical member of the 
STRC as well as the entire committee via the email notification procedure of the occurrence of an SAE. 
All adverse events will be recorded and the data will be managed in WISER. As such, the STRC will 
have access to all adverse events in the course of the study.  
7.5 
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. 
 
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. 
8.0 
Pharmaceutical Information 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 16 of 44 
A list of the adverse events and potential risks associated with the commercial agents administered in 
this study can be found in Section 7.1 and 7.2. 
 
8.1 
Pharmaceutical Accountability 
 
Drug accountability logs will be maintained for all agents used under this protocol. These logs 
shall record quantities of study drug received and quantities dispensed to patients, including lot 
number, date dispensed, patient identifier number, patient initials, protocol number, dose, 
quantity returned, balance remaining, and the initials of the person dispensing the medication.  
8.2 
Liposomal Bupivacaine 
 
Product description:  20 ml liposomal bupivacaine (266 mg)  
 
Solution preparation:  Will be diluted in 10 ml of 0.25% Bupivacaine and 30 ml of 0.9% NaCl 
for a total solution volume of 60 ml per patient (30 ml per breast) 
 
Storage requirements:  Vials of Exparel should be inverted multiple times to re-suspend the 
particles immediately prior to withdraw from the vial.  
 
Stability:  Diluted suspensions should be used within 4 hours of the preparation.  
 
Route of administration: Injection into surgical site including mastectomy skin flaps and 
wound bed after mastectomy and before breast reconstruction. 
 
Disposal:  There should be no additional product to dispose after injection  
 
8.3 
Bupivacaine  
 
Product description:  60 ml of 0.25% bupivacaine  
 
Solution preparation:  No further dilution is required. 30 ml of 0.25% bupivacaine will be 
delivered to each breast. 
 
Storage requirements:  Can be stored at room temperature. The pharmacy will store and create 
the syringes including the medications to be administered.  
 
Stability:  The dosage of the above bupivacaine is stable and will not change over time 
 
Route of administration:  Injection into surgical site including mastectomy skin flaps and 
wound bed after mastectomy and before breast reconstruction.  
 
Disposal:  There should be no additional product to dispose after injection  


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 17 of 44 
9.0 
Data Management 
 
Informed consent document 
EPIC 
Protocol registration form 
WISER/OnCore 
Life Orientation Test-Revised  
REDCap 
PROMIS- Depression  
REDCap 
PROMIS- Anxiety 
REDCap 
Pain Catastrophizing Scale 
REDCap 
Visual analog scores  
REDCap  
Daily Pain Diary and Pain Rating 
REDCap  
Weekly Disability Assessment  
REDCap 
Adverse Effects  
WISER 
 
 
 
 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 18 of 44 
10.0 Statistical Considerations 
 
10.1 Analysis of Primary Objective 
10.1.1 The study will allow for an attrition rate of 10%.  Assuming a similar standard deviation 
in pain score at 48 hours for the local infiltration of liposomal bupivacaine and 
bupivacaine arms, with a 2-sided alpha of 0.05 and power of 80%, the study would have 
the ability to detect an effect size (absolute value of difference in sample means divided 
by the standard deviation) of 0.6 between the 2 groups with 25 subjects per arm.  We will 
recruit 25 subjects per arm; if there is no attrition, with the same alpha and power as 
above, the study would have the ability to detect an effect size of 0.57. The primary 
outcome will be the pain score observed at 48 hours.  To test for differences in these 
scores between the 2 arms, an independent t-test will be used; if the observed p-value is 
<0.05, statistical significance will be assumed. Two-sided ANOVA will be performed for 
statistical analysis once data collection is complete.  
 
10.2 Analysis of Secondary Objective 
 
10.2.1 For the area under the curve of pain scores at 48 hours, prior studies have found that the 
area under the curve for pain scores at 72 hours for liposomal bupivacaine infiltration is 
441 +/- 182 and for bupivacaine infiltration is 461 +/- 18120. A sample size of 40 in each 
group will have 80% power to detect a difference in means of approximately 25% (115 
units) between a Bupivacaine mean, m1, of 461 and a Liposomal Bupivacaine mean, m2, 
of 346 assuming that the common standard deviation is 181 using a two group t-test with 
a 0.05 two-sided significance level. Our study will be powered to detect this difference; 
we will use an independent t-test to assess statistical significance. 
10.2.2 For postoperative narcotic use, prior studies have found the average use of morphine 
equivalents at 48 hours after mastectomy and tissue expander placement is 3.317. This 
study will also have the ability to detect an effect size of 0.6 between groups, with 45 per 
group, a two-sided alpha of 0.05, and 80% power.  We would expect the patients treated 
with liposomal bupivacaine to be have a lower average use. We will use an independent 
t-test to test for differences between groups; if the data are not normally distributed, a log 
transformation will be used prior to using the t-test. 
10.2.3 For length of stay, the reported LOS has been shown to be 41-47 hours on average 21. We 
believe Exparel will shorten this time; the study will have the ability to detect an effect 
size of 0.60 between the 2 groups.  We will use an independent t-test to test for 
differences between groups; if the data are not normally distributed, a log transformation 
will be used prior to using the t-test. 
10.2.4 For readmission rates, patients who underwent tissue expander breast reconstruction have 
a readmission rate of approximately 4.34%22. We anticipate a readmission rate of 
approximately 2%.  Our study is not powered to detect differences in the 2 arms in this 
parameter. 
10.2.5 For opioid related adverse effects, we predict a 50% incidence of opioid related adverse 
events in our study.  With 45 per group, our study is not powered to detect differences 
between the 2 arms unless the difference is much larger than anticipated.  With a 60% 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 19 of 44 
rate, 2-sided alpha of 0.05 and 80% power, we could detect a difference of 31% between 
the 2 arms using a Fisher’s Exact Test 
10.2.6 For trajectory of postoperative recovery from pain, Growth curve analysis of pain 
intensity with movement scores over the first two months, using an initial log (time) 
model and a Bayesian change point analysis  
10.2.6.1 
Groups will be compared for intercept and slope of the trajectory of pain 
intensity up to the first change point  
10.2.6.2 
For the entire population, the impact of the optimism-catastrophizing 
continuum and other predictive factors for intercept and slope will be explored 
10.3 Power and Sample Size 
We will have a power of 80%, as described in 10.1.1, with a sample size of 25 patients in each arm for a total of 
50 patients  
 
10.4 Accrual Rate  
We plan on accruing 25 new patients per year until the goal of 50 total patients is reached.   
10.5 Estimated Study Length 
Estimated study length will be approximately 2 years. This will include patient enrollment through the 5 week 
patient follow up period.  
10.6 Interim Analysis Plan 
We will plan on performing an interim analysis for the primary outcome and secondary outcomes after there are 
at least 10 patients in each treatment group in order to detect the evidence of severe side effects in either group. 
We will perform a secondary analysis after there are at least 20 patients in each group to monitor for more rare 
side effects including but not limited to bradycardia, tachycardia, respiratory distress, hypotension or 
neurological depression.  
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 20 of 44 
References 
 
1. Lovecchio F, Jordan SW, Lim S, Fine NA, Kim JY. Risk factors for complications differ between stages of 
tissue-expander breast reconstruction. Ann Plast Surg. Sept 2015. 75(3): 265-80. 
2. Butz DR, Shenaq DS, Rundell VL, Kepler B, Liederbach E, Thiel L, Pesce C, Murphy GS, Sisco M, Howard MA. 
Postoperative Pain and Length of Stay Lowered by Use of Exparel in Immediate, Implant-Based Breast 
Reconstruction. Plast Reconstr Surg Glob Open. Jun 2015. 5:3 (5) e391. 
3. Ng SK, Hare RM, Kuang RJ, Smith KM, Brown BJ, Hunter-Smith DJ. Breast Reconstruction Post Mastectomy: 
Patient Satisfactionand Recision Making. Ann Plast; Jun 2016. 76(6): 640-4. 
4. Shwkhawat L, Busheri L, Dixit S, Patel C,  Dhar U, Koppiker C. Patient-Reported Outcomes Following Breast 
Reconstruction Surgery and Therapeutic Mammoplasty: Prospectiv e Evaluation 1 year Post-Surgery with Breast-
Q Questionaire. Indian J Surg Oncol. Dec 2-15. 6(4): 356-62. 
5. Wallace MS, Wallace AM, Lee J, Dobke MK. Pain after breast surgery: a survey of 282 women. Pain. Aug 1996. 
66(2-3):195-205. 
6. Morrison JE Jr, Jacobs VR. Reduction or elimination of postoperative pain medication after mastectomy though 
use of a temporarily placed local anesthetic pump vs. control. Zentralbi Gynakol. Jan 2003. 125(1): 17-22. 
7. Lee MJ, Daniels SL, Wild JRL, Wilson TR. Readmission after general surgery: a prospective multicenter audit. J 
Surg Res. Mar 2017. 209:53-59.  
8. Bonnet F, Marret E. Influence of anaesthetic and analgesic techniques on outcome after surgery. Br J Anaesth. Jul 
2005. 95(1): 52-58.  
9. Strang P. Cancer pain- a provoker of emotional, social and existential distress. Acta Oncol. 1998. 37(7-8): 641-4.  
10. Zieliński T, Lorenc-Podgorska K, Antoszewski B. Why women who have mastectomy decide not to have breast 
reconstruction. Pol Przegl Chir. Feb 2015. 86(10): 451-5. 
11. American Society of Plastic Surgeons. (2015). Plastic surgery statistics report. Retrived from 
https://d2wirczt3b6wjm.cloudfront.net/News/Statistics/2015/plastic-surgery-statistics-full-report-2015.pdf 
12. Gassman AA, Yoon AP, Festekjian J, Da Lio AL, Tseng CY, Crisera C. Comparison of immediate postoperative 
pain in implant-based breast reconstruction. J Plast Reconstr Aesthet Surg. May 2016. 69(5): 604-16. 
13. Ilfled BM, Viscusi ER, Hadzic A, Minkowitz HS, Morren MD, Lookabaugh J, Joshi GP. Safety and side effect 
profile of liposomal bupivacaine (exparel) in peripheral nerve blocks. Reg Anesth Pain Med. Sept-Oct 2015. 40(5): 
572-82. 
14. Viscusi ER, Sinatra R, Onel E, Romamoorthy SL. The safety of liposomal bupivacaine, a novel local analgesic 
formulation. Clin J Pain. Feb 2014. 30(2): 102-10.  
15. Khalil KG. Boutrous ML. Irani AD, Miller CC 3rd, Pawelek TR, Estera AL, Safi HJ. Operative intercostal nerve 
blocks with long-acting bupivavaine liposome for pain control after thoracotomy. Ann Thorac Surg. Dec 2015. 
100 (6): 2013-8.  
16. Fayezizadeh M, Majumder A, Neupane R, Elliot HL, Novitsky YW. Efficacy of transervsus abdominis plane 
block with liposomal bupivacaine during open abdominal wall reconstruction. Am J Surg. Sept 2016.  212(3): 399-
405.  
17. Rawlani V, Kryger ZV, Lu L, Fine NA. A local anesthetic pump reduced postoperative pain and narcotic and 
antiemetic use in breast reconstruction surgery: a randomized controlled trial. Plast Reconstr Surg. Jul 2008. 
122(1):39-52. 
18. Butz Dr, Shenaq DS, Rundell VL, Kepler B, Liederback E, Thiel J, Pesce C, Murphy GS, Sisco M, Howard MA. 
Postoperative pain and length of stay lowered by use of exparel in immediate implant based breast reconstruction. 
Plast Reconstr Surg Glob Open. Jun 2015. 5(3): e391.  
19. Nadeu M, Saraswat A, Vasko A, Elliot J, Vasko S. Bupivacaine versus liposomal bupivacaine for postoperative 
pain control after augmentation mammoplasty: a prospective, randomized, double blind study. Aesthet Surg J. Feb 
2016. 36(2): NP47-52.  


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 21 of 44 
20. Smoot JD, Bergese S, Onel E, Williams H, Hedden W. The efficacy and safety of depofoam bupivacaine in 
patients undergoing bilateral cosmetic submuscular augmentation mammoplasty: a randomized double blind 
active-control trial. Aesthet Surg J. Jan 2012. 32(1): 69-76. 
21. Coopey SB, Specht MC, Warren L, Smith BL, Winograd JM, Fleischmann K. Use of preoperative paravertebral 
block decreases length of stay in patients undergoing mastectomy plus immediate reconstruction. Ann Surg Oncol. 
Apr 2013. 20(4): 1282-6.  
22. Mlodinow AS, Ver Halen JP, Lim S, Nguyen KT, Gaido JA, Kim JY. Predictors of readmission after breast 
reconstruction: a multi-institutional analysis of 5012 patients. Ann Plast Surg. Oct 2013. 71(4): 335-41.  
23. Andersen KG, Christensen KB, Kehlet H, Bidstup PE. The Effect of Pain on Physical Functioning after Breast 
Cancer Treatment: Development and Validation of an Assessment Tool. Clin J Pain 2014 Oct 10 [epub] DOI: 
10.1097/AJP.0000000000000156 
24. Campbell I, Cavanagh S, Creighton J, French R, Banerjee S, Kerr E, Shirley. To infiltrate or not? Acute effects of 
local anesthetic in breast surgery. ANZ J Surg. May 2015. 85(5): 353-7.  
25. Byager N, Hansen MS, Mathiesen O, Dahl JB.  The analgesic effect of wound infiltration with local anaesthetic 
after breast surgery: a qualitative systematic review. Acta Anesthesiol Scand. April 2014. 58(4): 402-10.  
26. Zielinski J, Jawarski R, Smietansk I, Irga N, Wujtewicz M, Jaskiewicz J. A randomized, double-blind, placebo-
controlled trial of preemptive analgesia with bupivacaine in patients undergoing mastectomy for carcinoma of the 
breast. Med Sci Monit. Oct 2011. 17(10): CR589-97.  
27. Tam KW, Chen SY, Huang TW, Lin CC, Su CM, Li CL, Ho YS, Wang WY, Wu CH. Effect of wound infiltration 
with ropivacaine or bupivacaine in breast cancer surgery: A meta-analysis of randomized controlled trials. Int J 
Surg. Oct 2015. 22:79-85.  
28. US Food and Drug Administration. FDA Label Approved on 10/28/2011 for Exparel. US Silver Spring, MD: US 
Food and Drug Administration. Available from: 
http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022496s000lbl.pdf.  
29. Golf M, Daniels SE, Onel E. A phase 3, randomized, placebo-controlled trial of DepoFoam bupivacaine 
(extended-release bupivacaine local analgesic) in bunionectomy. Adv Ther. 2011. 28(9):776-788.  
30. Gorfine SR, Onel E, Patou G, Krivokapic ZV. Bupivacaine extended-release liposomal injection for prolonged for 
prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, double-
blind, placebo-controlled trial. Dis Colon Rectum. 2011. 54(12): 1552-9.  
31. US Food and Drug Administration. Marcaine Bupivcacaine HCl Injection Label. US Silver Spring, MD: US Food 
and Drug Administration. Available from: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/018692s015lbl.pdf 
 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 22 of 44 
The following Appendices are required for all WFBCCC 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 
WFBCCC Protocol Review Committee (PRC) for review. 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 23 of 44 
Appendix A – Eligibility Checklist 
 
 
IRB Protocol No. ___ ___ ___ ___ ___ ___ ___ ___ 
WFBCCC Protocol No.___ ___ ___ ___ ___ 
Study Title: THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING MASTECTOMY AND BREAST 
RECONSTRUCTION 
Principal Investigator:  Christopher Runyan, M.D., Ph.D. 
 
Inclusion Criteria 
(as outlined in study protocol) 
Criteria 
is met 
Criteria is 
NOT met 
Source Used to Confirm * 
(Please document dates and lab results) 
All patients who receive a bilateral mastectomy with 
immediate implant based breast reconstruction 
 
□ 
□ 
 
Age >18 years  
□ 
□ 
 
Ability to understand and willingness to sign IRB-
approved informed consent document  
□ 
□ 
 
Patients who will receive a tissue expander or a direct 
permeant implant for breast reconstruction 
□ 
□ 
 
ASA patient status I-III 
□ 
□ 
 
Patients having sub-pectoral implant placement 
 
 
 
Exclusion Criteria 
(as outlined in study protocol) 
Criteria 
NOT 
present 
Criteria is 
present 
Source Used to Confirm * 
(Please document dates and lab results) 
Patients who receive an autologous tissue 
reconstruction 
□ 
□ 
 
Patients who receive a unilateral reconstruction 
□ 
□ 
 
Patients who weigh < 50 kg  
□ 
□ 
 
Patients who will undergo axillary lymph node 
dissection 
 
□ 
□ 
 
Patients who abuse narcotics or have chronic pain 
(using greater than 40 mg equivalents of oxycodone 
per day) 
 
□ 
□ 
 
Patients who are wards of the state  
 
□ 
□ 
 
History of allergic reactions attributed to compounds 
of similar chemical or biologic composition to 
bupivacaine or liposomal bupivacaine. 
 
□ 
□ 
 
Patients having pre-pectoral implant placement 
 
 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 24 of 44 
Pregnant women are excluded from this study because 
liposomal bupivacaine is a/an class C agent with the 
potential for teratogenic or abortifacient effects. 
Because there is an unknown but potential risk for 
adverse events in nursing infants secondary to 
treatment of the mother with liposomal bupivacaine, 
breastfeeding should be discontinued if the mother is 
treated with liposomal bupivacaine. 
□ 
□ 
 
 
This subject is      
 eligible / 
 ineligible     for participation in this study. 
 
ORIS Assigned PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
 
 
 
 
 
 
 
 
Signature of research professional confirming eligibility: _______________________  
 
Date: ___ ___ / ___ ___ / ___ ___ 
 
Signature of Treating Physician:  _____________________________________  
 
Date:  ___ ___ / ___ ___ / ___ ___ 
 
Signature of Principal Investigator**:  _____________________________________  
 
Date:  ___ ___ / ___ ___ / ___ ___ 
 
* Examples of source documents include clinic note, pathology report, laboratory results, etc. When listing the source, specifically 
state which document in the medical record was used to assess eligibility. Also include the date on the document. Example: 
“Pathology report, 01/01/14” or “Clinic note, 01/01/14” 
 
**Principal Investigator signature can be obtained following registration if needed 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 25 of 44 
Appendix B – Protocol Registration Form 
 
DEMOGRAPHICS 
Patient: Last Name: _____________________ 
First Name: ___________________________ 
MRN:          ___ ___ ___ ___ ___ ___ ___ ___ 
DOB (mm/dd/yy): ___ ___ / ___ ___ / ___ ___ 
ZIPCODE:  
___ ___ ___ ___ ___ 
 
 
SEX:   
  Male      Female 
Ethnicity (choose one):    Hispanic 
Non-Hispanic 
Race (choose all that 
apply): 
 WHITE           BLACK            ASIAN 
 PACIFIC ISLANDER                 NATIVE AMERICAN 
Height:   ___ ___.___ inches 
Weight: ___ ___ ___.___lbs.(actual) 
Surface Area: ___ ___.___m2   
 
Primary Diagnosis: ____________________________________________________________ 
Date of Diagnosis: ___ ___ /___ ___/___ ___ 
 
Performance Status: ___ ___ ___    ECOG   Karnofsky 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Registrar can be contact by calling 336-713-6767 between 8:30 AM and 4:00 PM, Monday – Friday. 
 
Completed Eligibility Checklist and Protocol Registration Form must be hand delivered, faxed or e-mailed to the registrar at 336-
7136772 or registra@wakehealth.edu. 
PROTOCOL INFORMATION 
Date of Registration: 
___ ___ / ___ ___ / ___ ___ 
MD Name (last) : 
______________________       
Date protocol treatment started: 
___ ___ / ___ ___ / ___ ___ 
Informed written consent: 
(consent must be signed prior to 
registration) 
 YES   NO 
 
Date Consent Signed: 
___ ___ / ___ ___ / ___ ___ 
 
PID # (to be assigned by ORIS): 
___ ___ ___ ___ ___ ___ ___ ___ 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 26 of 44 
Appendix C - Race & Ethnicity 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: 
 
 
 Name: ____________________ MRN#: ____________________  
 
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 USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST 
RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 27 of 44 
Appendix D – Mandatory STRC SAE Reporting Guidelines 
 
Safety and Toxicity Review Committee 
(STRC; previously known as CROC)  
Serious Adverse Event (SAE) Notification 
SOP 
     Date: 8/17/2016 
 
 
Mandatory STRC SAE Reporting Requirements  
 
This document describes STRC reporting and use of the electronic submission form that is 
submitted for unexpected grade 4 and any grade 5 (death during protocol intervention) 
SAEs on WFBCCC Institutional interventional trial patients. There are multiple entities that 
require reporting of SAEs. Each entity has different rules for what is reported, and how it is 
reported.  
 
Rules used by other entities (Institutional Review Board (IRB), AdEERS, MedWatch, etc.) 
should NOT be used to evaluate whether an event should be reported to STRC. Only the rules for 
reporting described in this document should be considered. 
 
As defined in the NCI Data Table 4 reporting guidelines, WFBCCC Institutional 
Interventional studies covered by these reporting requirements are defined as: In-house, 
internally reviewed trials, including those collaborative studies conducted with industry 
sponsorship in which the center is a primary contributor to the design, implementation, 
and monitoring of the trial, or participation in a multi-site trial initiated by an institutional 
investigator at another center.  Institutional trials are almost always authored by a researcher 
here at WFBCCC. Institutional protocols are labeled NCI Code=”I” for Institutional on the 
protocol screen in ORIS. Cooperative group protocols are not considered Institutional, but 
Research Base trials are classified as Institutional. 
 
The STRC is responsible for reviewing SAEs for WFBCCC Institutional Interventional studies, 
as defined above. STRC currently requires that unexpected grade 4 and all grade 5 SAEs on 
these trials be reported to the STRC for review. All Clinical Protocol and Data Management 
(CPDM) staff members assisting a PI in documenting and reporting an SAE that qualifies for 
STRC reporting are responsible for informing a clinical member of the STRC by phone (or in-
person), followed by informing the entire committee via the required email notification. 
 
THESE REPORTING REQUIREMENTS APPLY TO any faculty or staff member on the 
study team for a WFBCCC Institutional Interventional trial. Once an event is observed, it 
is the responsibility of the person who observed the event to be sure that it is reported. 
 
What is considered an SAE under this mandatory procedure? 
Any unexpected grade 4 event and all grade 5 events (death during protocol intervention) 
should be reported. These events should be reported if they occur while a patient is on study 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST 
RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 28 of 44 
treatment or if they occur within 30 days of last study treatment (even if patient begins a new 
treatment during the 30 days). This window of 30 days should be the standard window to be used 
in all protocols unless a specific scientific rationale is presented to suggest that a shorter window 
can be used to identify events.  In addition, if it is not clear whether the Grade 4 is unexpected it 
should be reported. 
 
 
Table 1: Summary of STRC Reporting Requirements for Institutional Pilot, Phase 1, Phase 
2  
and Phase 3 Interventional Trials  
STRC reporting may not be appropriate for specific expected adverse events for protocols. In 
those situations the adverse events that will not require STRC reporting must be specified in the 
text of the approved protocol. 
 
 
ADVERSE EVENT 
Grade 1, Grade 2, 
Grade 3 
 
Grade 4 
Grade 5 
Unexpected Expected 
Unexpected 
Expected 
Unexpected 
Expected 
Unrelated Not 
Required 
Not 
Required 
REPORT 
TO STRC 
Not 
Required 
REPORT 
TO STRC 
REPORT 
TO STRC 
Unlikely 
Not 
Required 
Not 
Required 
REPORT 
TO STRC 
Not 
Required 
REPORT 
TO STRC 
REPORT 
TO STRC 
Possible 
Not 
Required 
Not 
Required 
REPORT 
TO STRC 
Not 
Required 
REPORT 
TO STRC 
REPORT 
TO STRC 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST 
RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 29 of 44 
 
 
STRC notification responsibilities of the person handling the reporting/documenting of the 
SAE: 
1. Make a phone call (or speak in person) to the appropriate clinical member of the STRC as 
listed below (page if necessary)—see note 2 below 
2. Submit the STRC Notification Form WITHIN 24 HOURS of first knowledge of the event. 
This form is found at either the ORIS main menu page or by going to 
http://ccc.wfubmc.edu/oris/strc.aspx. 
This will ensure that all persons that need to be made aware of the event (i.e., study team 
members and STRC members) will be notified; remember to file a copy of your 
confirmation. (Form instructions will walk you through the required fields, consult the help 
page for further instructions.) 
3. Ensure that you document that the appropriate person(s) on the STRC has been contacted.  
This documentation is placed on the STRC Notification form described above. 
4. Follow up with/update the clinical member(s) of STRC regarding any new developments or 
information obtained during the course of the SAE investigation and reporting process. 
 
 
 
 
Elements to complete the electronic STRC form: 
Please use ‘reply to All’ when responding with one of these terms:  Definite, Probable, 
Possible, Unlikely, or Unrelated 
1. Patient ID (ORIS PID) 
2. Patient Name 
3. Patient MR# 
4. WFBCCC(ORIS) Study Number 
5. Title 
6. PI Name 
7. PI Contact Number 
8. PI Comments 
9. STRC Clinician notified by Phone 
10. Notified Date 
11. Notified Time 
12. STRC Clinician Comments 
13. Category [This is the Grade – Either Unexpected Grade 4 or Grade 5 should be entered] 
14. Additional Information (IRB Reporting)(after discussion with PI or STRC Clinician 
i. Is This Event Related to Protocol Treatment? 
Probable 
Not 
Required 
Not 
Required 
REPORT 
TO STRC 
Not 
Required 
REPORT 
TO STRC 
REPORT 
TO STRC 
Definite 
Not 
Required 
Not 
Required 
REPORT 
TO STRC 
Not 
Required 
REPORT 
TO STRC 
REPORT 
TO STRC 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST 
RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 30 of 44 
ii. Is Suspension of the Protocol Needed? 
iii. Any Changes to Consent or Protocol Needed? 
iv. Was Nature or Severity of Event Unexpected? 
15. Date of the event.  
16. Brief description (include brief clinical history relevant to this event, including therapies 
believed related to event).  
17. Date of Last Dose before event 
18. Relevant tests/labs.  
19. Other Relevant Treatment Information 
20. Other Comments/Notes (include regimen of chemo and dates the patient received them if 
known). 
21. Cc (email) (include treating Physician; separate email list with comma”,”) 
22. Your Name 
23. Your Email 
24. Confirm Your Email 
 
The Clinical Members of STRC to Notify by Phone or Page: 
 
Bayard Powell, MD – Director-at-Large, WFBCCC; Chair, PRC; Section Head, 
Hematology/Oncology.  6-7970 / 6-2701 / Pager 336-806-9308 
Antonius Miller, MD – Hematology Oncology 6-7970 / 6-7414 / Pager 704-637-8384 
Glenn Lesser, MD – Hematology Oncology 6-9527 / 6-7972 / Pager 336-806-8397 
Kathryn Greven, MD – Vice Chair – Radiation Oncology. 3-3600 / 3-6505 / Pager 336-
806-8314 
Marissa Howard-McNatt, MD – General Surgery 6-0545 / 336-806-6438 
Mercedes Porosnicu, MD- Hematology Oncology 6-7980 / 6-0230 / Pager 336-806-9150 
Definition of Unavailable:  
As a general guideline if the first clinician that is contacted does not respond to the phone call or 
page within a reasonable amount of time, then initiate contact with their backup.  Give the back-
up a reasonable amount of time to respond to a phone call or page before contacting another 
member. This is a general guideline.  You must use your best judgment as a clinical research 
professional given the time of day, severity of the SAE, and other circumstances as to when it is 
appropriate to contact backup clinicians.  If the event occurs near the end of day, then leave 
messages (voice or email) as appropriate and proceed with submitting your STRC notification 
form.  The important criteria is that you have taken reasonable steps to notify and document that 
you have initiated some type of contact to one or more of the clinical members of STRC. 
 
STRC CLINICAN RESPONSIBILITY: 
It is the responsibility of the STRC clinician to review all reported events, evaluate the events as 
they are reported; and communicate a response to the Investigator, event reporter and the 
members of STRC. The review will include but not be limited to the information reported; there 
may be times when additional information is needed in order for an assessment to be made and 
further communication directly with the investigator may be warranted. STRC reserves the right 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND IMMEDIATE IMPLANT BASED BREAST 
RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 31 of 44 
to agree with the investigator’s assessment if STRC does not agree with the investigator. STRC 
reserves the right to suspend the trial pending further investigation. 
Is there any immediate danger or harm that could be present for a future patient based on the 
information provided in the STRC report – and if so an immediate suspension of enrollment 
should take place. 
 
AMENDMENTS TO PREVIOUS REPORTS 
If you are not able to supply all pertinent information with the initial submission, once the 
additional information is available do not submit a new report. Go to the original email that 
was received by STRC and others “reply to all” and entitle your email “Amendment for (list 
date of event and patient ID) this will avoid duplications of the same event. List the additional 
information which you are reporting. 
 
Acronyms and Definitions 
STRC-Safety and Toxicity Review Committee 
SAE-Serious Adverse Event 
IRB-Institutional Review Board 
WFBCCC-Comprehensive Cancer Center Wake Forest University 
ORIS-Oncology Research Information System 
NCI-National Cancer Institute 
CPDM-Clinical Protocol and Data Management 
Interventional Trials-Therapeutic Level 1 and Level 2 trials 
Therapeutic Level 1-A cancer treatment protocol aimed at directly treating/curing the patient’s 
cancer. 
Therapeutic Level 2-A therapeutic protocol not cancer treatment involves clinical activity to 
treat symptoms, improve the patient’s quality of life, or prevent cancer. 
 
 
 
 
 
 
 
 
 
 
 
 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING MASTECTOMY AND 
IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # 99517 
 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 32 of 44 
Appendix E – Adverse Event Log 
WFBCCC Adverse Event (AE) Log 
PI: 
_________________ 
 
PID: _________________ 
 
MRN: ________________ 
 
 
 
Cycle Start Date: 
_____________ 
Cycle End Date: 
_______________ 
 
Cycle #: __________ 
 
 
 
 
Adverse 
Event CTC 
Term 
Value 
(-5 if 
non-
numeric) 
Grade  
(0-5) 
per CTC 
Start 
Date 
Attribution 
1=Related 
2=Probably 
3=Possible 
4=Unlikely 
5=Unrelate
d 
Treating 
MD 
Initials/D
ate 
End 
Date 
Expecte
d 1=Yes   
0=No 
*Serious 
Adverse 
Event 
(SAE)   
1=Yes 
0=No 
Dose 
Limiting 
Toxicity 
(DLT) 
1=Yes 
0=No 
Action 
Taken 
1=None    
2=Tx 
withheld 
3=Tx 
D/C   
4=Tx 
adjusted 
5=Other 
Reporta
ble?   
1=IRB  
2=STRC  
3=FDA  
4=Spons
or 
  
  
  
  
  
  
 
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
 
  
  
  
  
  
  
 
  
  
  
  
 
  
  
  
  
  
  
 
  
  
  
  
 
  
  
  
  
  
  
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
*Serious Adverse Event: Hospitalization; Disability; Birth Defect; Life-threatening; Death. 
CTCAE Version 4 - http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # TBD 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 33 of 44 
Appendix F – Pre-Operative Questionnaires 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # TBD 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 34 of 44 
 
 
 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # TBD 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 35 of 44 
 
 
 
 
 
 
 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # TBD 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 36 of 44 
 
 
 
 
 
 
 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # TBD 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 37 of 44 
 
 
 
Appendix G – Pain Assessment  
Subject Number:___ ___ ___ ___ ___ ___ ___ ___ DATE: __ __/__ __/__ __TIME: __ __:__ __AM/PM 
 
1 - Rate the intensity of your worst pain in the past 24 hours related to your operated 
breast/chest. 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
2 – Please rate the intensity of breast pain that you have while eating. 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10   Cannot Do 
 
3 – If it has been one month or longer since your surgery please complete the following 
question:  
 
Please lift your arms to the sides of your body at a 90-degree angle. Rate the intensity of 
breast pain that you have during this activity.  
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10   Cannot Do   
 
  Not Applicable  
 
4 - Rate your level of disability in the past 24 hours to do normal daily activities. 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
5 - Rate your level of disability in the past 24 hours to do activities you enjoy. 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
6 - Did you take prescription pain pills in the past 24 hours?   YES 
NO 
 
If yes please circle the medication below and complete question 5b 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # TBD 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 38 of 44 
 
6a1 – Oxycodone 
 
6a2 - Hydromorphone (Dilaudid) 
 
6a3 - Hydrocodone + acetaminophen (Vicodin, Norco) 
 
6a4 Valium 
 
 
6b - In the last 24 hours, how many prescription pills have you taken for your pain? 
 
______________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # TBD 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 39 of 44 
 
 
 
 
Appendix H - Disability Assessment 
For the following, indicate whether pain since your surgery has affected your ability to perform these activities: 
 
Subject Number:___ ___ ___ ___ ___ ___ ___ ___ DATE: __ __/__ __/__ __ TIME: __ __:__ __AM/PM 
6a: Carry or lift children 
1 - Not relevant, I don't do this 
2 - I can do this without any problem 
3 - I can do this but with difficulties due to pain  
4 - I can't do his due to pain from my surgery 
6b: Carrying grocery bags, luggage, or heavy bags 
1 - Not relevant, I don't do this 
2 - I can do this without any problem 
3 - I can do this but with difficulties due to pain  
4 - I can't do his due to pain from my surgery 
6c: Do Laundry 
1 - Not relevant, I don't do this 
2 - I can do this without any problem 
3 - I can do this but with difficulties due to pain  
4 - I can't do his due to pain from my surgery 
6d: Kitchen chores, cooking 
1 - Not relevant, I don't do this 
2 - I can do this without any problem 
3 - I can do this but with difficulties due to pain  
4 - I can't do his due to pain from my surgery 
6e: Opening a heavy door 
1 - Not relevant, I don't do this 
2 - I can do this without any problem 
3 - I can do this but with difficulties due to pain  
4 - I can't do his due to pain from my surgery 
6f: Put on a brassiere 
1 - Not relevant, I don't do this 
2 - I can do this without any problem 
3 - I can do this but with difficulties due to pain  
4 - I can't do his due to pain from my surgery 
6g: Put on a coat 
1 - Not relevant, I don't do this 
2 - I can do this without any problem 
3 - I can do this but with difficulties due to pain  
4 - I can't do his due to pain from my surgery 
6h: Reaching high shelves, over your head 
1 - Not relevant, I don't do this 
2 - I can do this without any problem 
3 - I can do this but with difficulties due to pain  
4 - I can't do his due to pain from my surgery 
6i: Sleep 
1 - Not relevant, I don't do this 
2 - I can do this without any problem 
3 - I can do this but with difficulties due to pain  
4 - I can't do his due to pain from my surgery 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # TBD 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 40 of 44 
6j: Take a sweater on or off 
1 - Not relevant, I don't do this 
2 - I can do this without any problem 
3 - I can do this but with difficulties due to pain  
4 - I can't do his due to pain from my surgery 
6k: Vacuuming or washing floors 
1 - Not relevant, I don't do this 
2 - I can do this without any problem 
3 - I can do this but with difficulties due to pain  
4 - I can't do his due to pain from my surgery 
6l: Washing hair / neck 
1 - Not relevant, I don't do this 
2 - I can do this without any problem 
3 - I can do this but with difficulties due to pain  
4 - I can't do his due to pain from my surgery 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # TBD 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 41 of 44 
 
 
Appendix I- Visual Analog Scale  
 
 
 
 
 
Appendix J – Off-Study Form  
 
Study Number: __ __ __ __ __ 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator: Christopher Runyan, M.D. 
Date: __ __/__ __/__ __ 
 
Name of Person Competing form_____________________________ 
 
Did the subject meet eligibility criteria for study enrollment?   Yes 
   No 
 
 
Was the subject withdrawn from the study?  Yes 
   No 
 
 
Reason(s) for withdrawal:  
1. 
 Patient exhibited progression of disease 
 
2. 
 Unacceptable toxicity   
If Yes, Please specify whether the toxicity was: 
 
 
 From Bupivacaine 
 From Liposomal Buvipucaine 
 From BOTH 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # TBD 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 42 of 44 
 Other _______________________ 
 
3. 
 Patient withdraw 
 
If Yes, Please specify what portion of the study the subject wishes to withdraw from: 
 
 
 
 For just the Drug A administration only 
 For just the Drug B administration only 
 For both 
 For all components of the research study (including follow up in the medical 
record)  
 
4. 
 Investigator’s discretion to withdraw patient from the study because continued 
participation in the study is not in the patient’s best interest (*Describe below) 
 
5. 
 Undercurrent illness: a condition, injury, or disease unrelated to the intended disease 
for which the study is investigating, that renders continuing the treatment unsafe or 
regular follow-up impossible (*Describe below) 
 
6. 
 General or specific changes in the patient’s condition that renders the patient 
ineligible for further investigational treatment (*Describe below) 
 
7. 
 Non-compliance with investigational treatment, protocol-required evaluations or 
follow-up visits (*Describe below) 
 
8. 
 Termination of the clinical trial by the clinical sponsor 
 
Comment: 
 
If reason for withdrawal includes #4, 5, 6, or 7 then please add comments clarifying this 
information)___________________________________________________________________
______________________________________________________________________________
______________________________________________________________________________
_______________________________________________________________________ 
 
 
 
 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # TBD 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 43 of 44 
 
 
 
 
Appendix K- Pain Medication Diary. Assists patients in recording the amount and time of 
narcotic and benzodiazepine use. 
 
 
Please use the scale below for reference when providing Pain Rating: 
 
 
 
 
Date 
Pain Medication 
Used (Include dose) 
Number of pills 
taken 
Time 
Pain 
Rating (see 
scale above 
for reference) 
1 
 
 
 
 
 
2 
 
 
 
 
 
3 
 
 
 
 
 
4 
 
 
 
 
 
5 
 
 
 
 
 
6 
 
 
 
 
 
7 
 
 
 
 
 
8 
 
 
 
 
 
9 
 
 
 
 
 
10 
 
 
 
 
 
11 
 
 
 
 
 
12 
 
 
 
 
 
13 
 
 
 
 
 
14 
 
 
 
 
 
15 
 
 
 
 
 


THE USE OF LIPOSOMAL BUPIVACAINE FOR PAIN CONTROL FOLLOWING 
MASTECTOMY AND BREAST RECONSTRUCTION 
Wake Forest Baptist Comprehensive Cancer Center 
CCCWFU # TBD 
Protocol version date 08/28/17 
 
 
 
 
 
 
Page 44 of 44 
16 
 
 
 
 
 
17 
 
 
 
 
 
18 
 
 
 
 
 
19 
 
 
 
 
 
20 
 
 
 
 
 
21 
 
 
 
 
 
22 
 
 
 
 
 
23 
 
 
 
 
 
24 
 
 
 
 
 
25 
 
 
 
 
 
26 
 
 
 
 
 
27 
 
 
 
 
 
28 
 
 
 
 
 
29 
 
 
 
 
 
30 
 
 
 
 
 
31 
 
 
 
 
 
32 
 
 
 
 
 
33 
 
 
 
 
 
34 
 
 
 
 
 
35 
 
 
 
 
 
36 
 
 
 
 
 
37 
 
 
 
 
 
39 
 
 
 
 
 
40 
 
 
 
 
 
41 
 
 
 
 
 
42 
 
 
 
 
 
43 
 
 
 
 
 
44 
 
 
 
 
 
45 
 
 
 
 
 
46 
 
 
 
 
 
47 
 
 
 
 
 
48 
 
 
 
 
 
49 
 
 
 
 
 
50