Clinical trial NCT03383198
Conditions: Pain, Postoperative
Sponsor: Prisma Health-Upstate
Start date: 2017-12-01; Completion date: 2019-08-30
Enrollment: 5 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a randomized controlled pilot study evaluating length of pain control with either liposomal bupivacaine or with bupivacaine plus decadron after PEC II injection in patients having bilateral mastectomies with immediate reconstruction.

Detailed description:
This research hopes to determine the duration of patient-reported analgesia provided by ultrasound guided PEC II field block injections. The design of the study randomly assigns the side of injection of the study drugs into each patient. All patients are having bilateral mastectomy with immediate reconstruction. Visual analog pain scores (VAS) will be recorded serially for both sides of the patient's chest in hopes of determining a difference in duration and efficacy of the two drugs. In addition to VAS scores, a subjective, binary question will be our primary outcome: does one side of your chest have more surgical pain than the other? We hope that his question, despite being entirely subjective, overcomes interpatient variability of numerical pain score reporting.

Arms: arm 1: Liposomal Bupivacaine left injection. Liposomal Bupivacaine is injected on the left, Bupivacaine plus Dexamethasone on the right arm 2: Liposomal Bupivacaine right injection. Liposomal Bupivacaine injected on the right, Bupivacaine plus Dexamethasone on the left
Interventions: intervention 1: Liposomal bupivacaine right injection intervention 2: Liposomal bupivacaine left injection
Intervention descriptions: intervention 1: Right side will have liposomal bupivacaine ultrasound guided PEC II field block injection ; the left side side will have bupivacaine plus dexamethasone ultrasound guided PEC II field block injection. intervention 2: Left side will have liposomal bupivacaine ultrasound guided PEC II field block injection ; the right side side will have bupivacaine plus dexamethasone ultrasound guided PEC II field block injection.

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
 
 
Pectoralis (II) Block with Liposomal Bupivacaine vs 
Bupivacaine plus Dexamethasone for Mastectomy 
with Immediate Reconstruction 
 
NCT Number: NCT03383198 
 
Date: 13Oct2017 


GHS Department of Anesthesiology  
IRB Study Protocol 
 
Date:  
13Oct2017 
Study Title:  
Pectoralis (II) Block with Liposomal Bupivacaine vs Bupivacaine plus 
Dexamethasone for Mastectomy with Immediate Reconstruction 
Principal Investigator:              William R Hand, MD 
Co-Investigators:  
 
Andrea Nisonson, MD 
Elizabeth Faucher, MD 
Wendy Cornett, MD 
Background: Regional anesthesia has multiple benefits to patients undergoing surgery related to 
both analgesia and avoidance of opioids.  Regional anesthesia requires accurate administration of 
local anesthetic medication to interrupt the function of sensory nerves to the surgical field.  
Multiple aqueous local anesthetics have been used for years, but in the past decade a liposomal 
formulation has been introduced with the reported ability to extend the duration of analgesia. 
Study Purpose: To evaluate the duration of analgesia provided by PEC II block with liposomal 
Bupivacaine compared to Bupivacaine with dexamethason. Our hypothesis is that the block 
performed with liposomal bupivacaine will result in longer duration of analgesia. 
Study Design: This pilot study is a self-controlled comparison of patients undergoing bilateral 
mastectomy with immediate reconstruction by breast surgeons at GHS.   Ten patients will be 
enrolled after completing informed consent.  Blocks will be performed and the duration of 
analgesia will be evaluated at regular intervals.  At each interval the patient will also be asked to 
identify whether they can discriminate the level of pain based on laterality.  
Our primary endpoint is the ability to discriminate analgesia.  Secondary outcomes will include 
visual analog pain scores (by side), total morphine equivalent consumption; time to the first 
opioid request, and non-opioid pain medication administration. We also are planning to obtain 
demographic characteristics, intraoperative consumption of pain medication, and length of stay 
data. We will exclude all patients younger than 18 years old, patients with BMI >30, pregnant 
patients, patients with severe hepatic disease and patients with an active opioid prescription 
before surgery. 
Methods and Duration:  
Prospective data will be collected on 10 patients undergoing bilateral mastectomy with immediate 
reconstruction at Greenville Memorial Hospital or Patewood Memorial Hospital. Following 
informed consent, patients will be randomized to have PEC II blocks with 10cc liposomal 
Bupivacaine (133mg) plus 20cc 0.25% Bupivacaine HCl on one side and 30cc 0.25% 
Bupivacaine plus 4mg Dexamethasone on the other.  Consistent with our current standard of care, 


all patients will receive oral medications before surgery (1g acetaminophen, 75mg pregabalin, 
400mg celecoxib) unless there are contraindications.  The blocks will be placed following 
induction of general anesthesia in the operating room under sterile conditions and procedures.  
The anesthesiologist performing the block will be unblinded to which medication is placed on 
either side, but the surgeon and care team for the remainder of the perioperative stay will be 
blinded.  All blocks will be performed by an anesthesiologist with expertise in regional anesthesia 
guided by ultrasonography.  Intraoperative management will be consistent with our standard of 
care: ASA monitoring, maintenance with isoflurane, boluses of fentanyl or hydromorphone as 
needed. 
Postoperative pain scores will be taken in throughout their hospitalization and by phone thereafter 
(2H, 4H, 6H, 8H, 12H, 18H, 24H, 30H, 36H, 42H, 48H +/- 1H after hour 6).  At each time point 
the patient will be asked if they can discriminate pain to either side of their chest, and if so, which 
side has more pain.  All pain scores will be taken at rest, if possible.  Patient records will be 
queried to determine length of stay, opioid consumption, and time to first dosage.  
Potential Risks to the Patients: 
• 
This study does not increase the patient risks related to surgery or the PEC II block, nor 
does it increase risk of local anesthetic toxicity (lower total dosage). 
Potential Benefits to the Patients:  
The information gained from this study may be used scientifically and may determine the drug of 
choice for PEC II blocks at GHS and beyond.  If liposomal Bupivacaine provides significantly 
longer analgesia, then patients would benefit from this pain relief on the side of liposomal 
Bupivacaine injection.  Currently no patients receive this drug for PEC II blocks because it is 
unclear whether the potential benefit justifies the cost of the medication. We hope the information 
will be of future benefit to others in relation to: 
• 
Better postoperative pain control 
• 
Avoidance of opioid-related adverse events such a respiratory depression, sedation, 
nausea and vomiting, pruritus, urinary retention, and ileus 
• 
Decrease length of stay and total cost  
Privacy and Confidentiality: 
The data collection sheets/jump-drives will be deposited in a locked collection box at the 
Department of Surgery at GMH. All collected data will be entered into a password-protected 
database (REDCap) in a password-protected GMH computer.  In the database, patients will be 
identified only by a medical record and/or birth date.  Only the PI and Co-Investigators will have 
access to this database.  
 
Data Analysis: 


Demographics, time to first narcotic request, and morphine equivalent pain medications will be 
described for the 10 patients.  Patient ability to correctly discriminate difference in pain between 
the two locations will also be described.  Additionally, intrapersonal differences in pain scores 
will be determined (liposomal Bupivacaine side - Bupivacaine plus Dexamethasone side) at each 
time interval.  The median differences across the 10 patients will be aggregated to determine any 
trend in differences across the time intervals, as tested with a Kruskal-Wallis test. 
 
Costs:  This will not incur any additional costs to participants.  Participants will not be 
compensated to take part in this study.  The cost of the medication and pharmacy related charges 
will be paid by the investigator department(s). 
References/Literature Review:  
1. Bashandy GM, Abbas DN. Pectoral nerves I and II blocks in multimodal analgesia for breast 
cancer surgery: a randomized clinical trial. Reg Anesth Pain Med 2015;40(1):68-74. 
- 120 Patients having mastectomy randomized to general anesthesia with or without PEC blocks.  
Lower pain scores and opioid consumption with the blocks.  No complications. 
2. Gorfine SR, Onel E, Patou G, Krivokapic ZV. Bupivacaine extended-release liposome 
injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a 
multicenter, randomized, double-blind, placebo-controlled trial. Dis Colon Rectum. 
2011;54(12):1552-1559. 
- Original prospective study with liposomal bupivacaine.  Showed decreased pain scores and 
prolonged time until first opioid vs placebo.  Multiple manuscripts available upon request, 
however PI endorses it remains unclear how much longer liposomal Bupivacaine lasts compared 
to aqueous Bupivacaine. 
3. Amundson AW, Johnson RL, Abdel MP, et al. A Three-arm Randomized Clinical Trial 
Comparing Continuous Femoral Plus Single-injection Sciatic Peripheral Nerve Blocks versus 
Periarticular Injection with Ropivacaine or Liposomal Bupivacaine for Patients Undergoing Total 
Knee Arthroplasty. Anesthesiology 2017;126(6):1139-1150. 
- Most recent article in quality anesthesia literature related to the multiple drug choices/modalities 
related to regional anesthesia.  Includes discussion of liposomal Bupivacaine vs aqueous local 
anesthetics.  Included to endorse the need for clarification of best practices. 
 
 
 
 
PEC II block: 


 
PEC II block ultrasound example 
 
Expected area of analgesia with PEC II block 
Reference for (modified) images (digital appendix): Blanco R, Fajardo M, Parras 
Maldonado T. Ultrasound description of Pecs II (modified Pecs I): a novel approach to 
breast surgery. Rev Esp Anestesiol Reanim. 2012 Nov;59(9):470-5. 

ICF_001.pdf: 
 
 
 
 
 
Pectoralis (II) Block with Liposomal Bupivacaine vs 
Bupivacaine plus Dexamethasone for Mastectomy 
with Immediate Reconstruction 
 
NCT Number: NCT03383198 
 
Date: 11Jan2019 


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                     _________________ 
 
                                                                                                                           Participant’s Initials 
Greenville Health System 
 IRB Number: Pro00072519 
Approved: 6/19/2019 
Expiration: 6/18/2020 
CONSENT TO PARTICIPATE IN A RESEARCH STUDY 
Pectoralis (II) Block with Liposomal Bupivacaine vs Bupivacaine with Dexamethasone for Mastectomy with 
Immediate Reconstruction  
 
Study to be conducted at: 
Greenville Health System 
 
 
 
 
Greenville Memorial Hospital 
 
 
 
 
701 Grove Road 
 
 
 
 
Greenville, SC. 29605 
 
 
 
 
 
Greenville Health System 
 
 
 
 
Patewood Memorial Hospital 
 
 
 
 
175 Patewood Drive 
 
 
 
 
Greenville, SC. 29615 
 
Sponsor Name: 
 
Greenville Health System 
 
Principal Investigator:  
William R Hand, MD (864-455-8300) 
 
INTRODUCTION 
You are being asked to participate in a research study.  The Institutional Review Board of the Greenville 
Health System has reviewed this study for the protection of the rights of human participants in research 
studies, in accordance with federal and state regulations.  However, before you choose to be a research 
participant, it is important that you read the following information and ask as many questions as necessary 
to be sure that you understand what your participation will involve.  Your signature on this consent form will 
acknowledge that you received all of the following information and explanations verbally and have been 
given an opportunity to discuss your questions and concerns with the principal investigator or a co-
investigator. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. 
This Web site will not include information that can identify you. At most, the Web site will include a summary 
of the results. You can search this Web site at any time. 
 
PURPOSE 
You are being asked to participate in this study because you are having breast surgery for a medical 
reason.  This surgery will require anesthesia, and one component of this anesthesia is the use of local 
anesthesia (numbing medicine) to help with pain during and after surgery.  This study is trying to better 
understand how long different local anesthetics (numbing medicines) last for this surgery. 
 
Approximately 10 participants will be enrolled in this study at either Patewood Memorial Hospital or 
Greenville Memorial Hospital. Your participation in this study is expected to last no longer than 72 hours.  
Participation will include questions about your medical history and what medications you are taking, having 
the medicine injected after you are asleep for surgery, and verbal pain scale ratings on a scale of 0-10 at 
several intervals after surgery.   Participation will also include us calling you after your hospital discharge to 
follow up on your pain or lack of pain.  This study is considered a pilot study.   
 


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                     _________________ 
 
                                                                                                                           Participant’s Initials 
Greenville Health System 
 IRB Number: Pro00072519 
Approved: 6/19/2019 
Expiration: 6/18/2020 
PROCEDURES 
If you decide to participate in the study, you will be asked to sign this informed consent form prior to 
beginning any study activities.  The study procedures are as follows: 
• The participants enrolled in this study will receive liposomal bupivacaine and aqueous bupivacaine 
injected near their armpit (PEC II block).  Enrollment in this study is not considered standard of 
care. 
• The side of your body that the liposomal bupivacaine will be placed on will be randomly 
determined. Randomization means the study team has no say in what side the medicine goes on. 
Your information is put into a computer and the computer picks what side to place the medicines. 
The study team will open an envelope, which will state which side the liposomal bupivacaine (right 
or left side) will be injected into. There is an equal chance for the liposomal bupivacaine to be 
placed on the right or left side. The use of liposomal bupivacaine is not considered standard of 
care, but the aqueous bupivacaine used on the other side is standard of care. 
• You will be asked to verbally rate your pain using a numerical rating scale (0 – 10) in relation to 
both sides of your wound after surgery.  You will also be asked if you feel pain any differently on 
either side of your body, and if so, what feels different between the sides.  You will be asked about 
your pain score at 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 18 hours, 24 hours, 30 hours, 36 
hours, and 48 hours after surgery.  Your pain score will be taken throughout your hospitalization 
and by phone after you leave the hospital.  Some of these time points will be considered standard 
of care and others will not.   
• Information from your medical records will be collected throughout this study. You will also be 
asked questions about your medical and surgical history as well as what medications you are 
currently taking.  This is considered standard of care.  
• Your demographic information will be collected, including your age, date of birth, race, sex, height, 
weight, and ethnicity.  This is considered standard of care. 
 
POSSIBLE RISKS   
Any treatment has possible side effects.  The treatments and procedures used in this study may cause all, 
some, or none of the side effects listed.  There is always the risk of very uncommon or previously unknown 
side effects happening. 
 
The possible risks associated with liposomal bupivacaine are reported to occur less commonly than with 
aqueous local anesthetics, and they include: 
• Ringing in ears 
• Numbness around the mouth 
• Seizure 
• Low blood pressure 
• Death (very rare) 
 
Other possible risks and discomforts may include: 
• An allergic reaction to the medicine(s). Allergic reactions may range from minor itching or rash to 
major reactions, which can lead to death. 
• The possible release of your personal health information. Your study records are considered 
confidential, but absolute confidentiality cannot be guaranteed. This study may result in 
presentations and publications, but steps will be taken to make sure you are not identified by 
name. 


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                                                                                                                           Participant’s Initials 
Greenville Health System 
 IRB Number: Pro00072519 
Approved: 6/19/2019 
Expiration: 6/18/2020 
 
 
POSSIBLE BENEFITS 
It is not possible to know whether or not you may benefit from participating in this study.  The treatment or 
procedures you receive may even be harmful.  The information gained from this study may be used 
scientifically and may be helpful to others. 
 
It is questionable that there will be any immediate benefit to you or the other participants in this study; 
however, future care may be enhanced. By evaluating whether the liposomal bupivacaine works longer, 
patient care could be impacted by reducing pain during and after surgery. 
 
ALTERNATIVE (OTHER) TREATMENTS 
You can still receive evaluation and treatment for your condition if you do not participate in this study.  
Discuss any alternative treatments with your regular doctor and/or the study doctor before you decide to 
participate in the study.  The decision to participate is entirely up to you.  If you decide not to participate in 
the study, you will not be penalized or lose any benefits, and your decision will not affect your relationship 
with your doctor or hospital. 
 
COST TO YOU FOR PARTICIPATING IN THIS STUDY 
Although study funds will pay for certain study-related items and services, we may bill your health insurer 
for routine items and services that you would have received even if you did not take part in the research.  
You will be responsible for payment of any deductibles and co-payments required by your insurer for this 
routine care or other billed care.  If you have any questions about costs to you that may result from taking 
part in the research, please speak with the study doctors and study staff.  If you are confused about what is 
or is not paid for in this study, please discuss this with your study doctor or study staff. 
 
Procedures performed as part of standard of care (routine) and procedures performed specifically for this 
study (not as part of standard of care) have been outlined in the procedure section of this informed consent 
form.  The procedures that are performed as part of standard of care will be billed to your insurance 
company.  You will be responsible for any co-payments, deductibles, or costs that your health insurer does 
not cover.  The cost of the liposomal bupivacaine and pharmacy charges related to liposomal bupivacaine 
will be paid for by the study. 
 
PAYMENT FOR PARTICIPATION  
To You: 
You will not be paid to participate in this study. 
 
To Investigators: 
The investigators will not be paid above their regular salaries for conducting this study. 
 
COMPENSATION FOR INJURY AS A RESULT OF STUDY PARTICIPATION 
The Greenville Health System will provide you the care needed to treat any injury or illness that directly 
results from taking part in this research study.  We reserve the right to bill your insurance company or other 
third parties for the care you get for the injury.  You may be responsible for these costs.  For example, if the 
care is billed to your insurer, you will be responsible for the payment of any deductibles and co-payments 
required by your insurer, or even possibly the entire cost of the service. 
 


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                     _________________ 
 
                                                                                                                           Participant’s Initials 
Greenville Health System 
 IRB Number: Pro00072519 
Approved: 6/19/2019 
Expiration: 6/18/2020 
Injuries sometimes happen in research even when no one is at fault. The Greenville Health System or the 
investigators as part of this study have no plans to pay you or give you other compensation for an injury, 
should one occur. However, you are not giving up any of your legal rights by signing this form.  
 
If you think you have been injured or have experienced a medical problem as a result of taking part in this 
research study, tell the person in charge of this study as soon as possible. The researcher’s name and 
phone number are listed in the ‘Contact for Questions’ section of this consent.  
 
VOLUNTARY PARTICIPATION 
Participation in this study is completely voluntary (your choice).  You may refuse to participate or withdraw 
from the study at any time.  If you refuse to participate or withdraw from the study, you will not be penalized 
or lose any benefits.  Your decision will not affect your relationship with your doctor or hospital. 
 
In addition, your study doctor may stop your participation in this study at any time if he/she believes it is in 
your best interest, if your medical condition changes or for any other reason.  Greenville Health System 
may also end the study at any time.   
 
If your participation in this study is stopped, your study doctor will discuss any tests or procedures that may 
be needed for your health and safety.  You may refuse any or all of these recommended tests.  
 
NEW INFORMATION 
During this study, you will be told of any important new information that may affect your willingness to 
participate in this study. 
 
AUTHORIZATION TO USE AND DISCLOSE (RELEASE) MEDICAL INFORMATION 
As part of this research study, your study doctor and his/her research team will keep records of your 
participation in this study.  These study records may be kept on a computer and will include all information 
collected during the research study, and any health information in your medical records that is related to the 
research study.   
 
Your study doctor and his/her research team will collect the following health information during the study:  
your gender, age, recent medical history, previous surgeries, recent hospitalizations, and current 
medications. Additionally the location of each medication injection will be documented and patient pain 
scale scores (0-10) will be collected throughout the study. 
 
Your study doctor and his/her research team will use and disclose (release) your health information to 
conduct this study.  To evaluate the results of the study and for compliance with federal and state law, your 
health information may be examined and copied by the Institutional Review Board of the Greenville Health 
System.  This study may result in scientific presentations and publications, but steps will be taken to make 
sure you are not identified.   
 
To help protect your confidentiality and to enhance the protection of your medical records the study 
physician will assign a coded patient ID number at the time of consent. The coded patient ID number will be 
tracked for study purposes and for data processing. The coded patient ID numbers will be placed on all 
study related items (standard numerical pain scale (0-10) scores and data collection sheets) for each 
participant. All data collected for this study will be stored in a GHS password-protected computer.  The 


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                                                                                                                           Participant’s Initials 
Greenville Health System 
 IRB Number: Pro00072519 
Approved: 6/19/2019 
Expiration: 6/18/2020 
digital data will be maintained on a password-protected GHS computer for 3 years after the study has 
ended. 
 
Under federal privacy laws, your study records cannot be used or released for research purposes unless 
you agree.  If you sign this consent form, you are agreeing to the use and release of your health 
information.  If you do not agree to this use, you will not be able to participate in this study.   
 
The right to use your health information for research purposes does not expire unless you withdraw your 
agreement.  You have the right to withdraw your agreement at any time.  You can do this by giving written 
notice to your study doctor.  If you withdraw your agreement, you will not be allowed to continue 
participation in this research study.  However, the information that has already been collected will still be 
used and released as described above.  You have the right to review your health information that is created 
during your participation in this study.  After the study is completed, you may request this information. 
 
Once your health information has been released, federal privacy laws may no longer protect it from further 
release and use. 
 
If you have any questions about the privacy of your health information please ask your study doctor. 
 
CONTACT FOR QUESTIONS 
For more information concerning this study and research-related risks or injuries, or to give comments or 
express concerns or complaints, you may contact the principal investigator, William R Hand, M.D. at (864)-
455-8300. 
 
You may also contact a representative of the Institutional Review Board of the Greenville Health System for 
information regarding your rights as a participant involved in a research study or to give comments or 
express concerns, complaints or offer input.  You may obtain the name and number of this person by 
calling (864) 455-8997. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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                     _________________ 
 
                                                                                                                           Participant’s Initials 
Greenville Health System 
 IRB Number: Pro00072519 
Approved: 6/19/2019 
Expiration: 6/18/2020 
CONSENT TO PARTICIPATE 
My study doctor, ____________________________________________, has explained the nature and 
purpose of this study to me.  I have been given the time and place to read and review this consent form and 
I choose to participate in this study.    I have been given the opportunity to ask questions about this study 
and my questions have been answered to my satisfaction.  I have been given a copy of my study doctor’s 
Notice of Privacy Practices.  I agree that my health information may be used and disclosed (released) as 
described in this consent form.  After I sign this consent form, I understand I will receive a copy of it for my 
own records.  I do not give up any of my legal rights by signing this consent form. 
 
 
_____________________________________________ 
Printed Name of Participant 
 
 
_____________________________________________   
_____________ 
____________ 
Signature of Participant  
 
 
 
 
Date 
 
 
Time 
 
 
_____________________________________________   
_____________ 
____________ 
Signature of Witness 
 
 
 
 
 
Date 
 
 
Time 
 
INVESTIGATOR STATEMENT 
I have carefully explained to the participant the nature and purpose of the above study. The participant 
signing this consent form has (1) been given the time and place to read and review this consent form; (2) 
been given an opportunity to ask questions regarding the nature, risks and benefits of participation in this 
research study; and (3) appears to understand the nature and purpose of the study and the demands 
required of participation. The participant has signed this consent form prior to having any study-related 
procedures performed. 
 
____________________________________ 
 
_______________ 
___________ 
Signature of Investigator  
 
 
 
Date 
 
 
Time 
 
 
Principal Investigator 
 
 
 
 
Phone 
William R Hand, MD 
 
 
 
 
 
(864) 455-3264 
 
Co-Investigators   
 
 
 
 
Phone 
 
Andrea Nisonson, MD  
 
 
 
 
(864) 455-3264 
Elizabeth Faucher, MD  
 
 
 
 
(864) 455-3264 
Wendy Cornett, MD 
 
 
 
 
 
(864) 455-7886 
Lily Fatula, MD  
 
 
 
 
 
(864) 455-3264