Clinical trial NCT04278846
Conditions: Pain, Postoperative Mammaplasty
Sponsor: The Cleveland Clinic
Start date: 2014-08-22; Completion date: 2019-05-15
Enrollment: 50 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Patients undergoing breast reconstruction with tissue expanders will be treated with a local anesthetic during their procedure and monitor their post-operative pain level and amount of oral pain medication taken. This information will be used to determine if liposomal bupivacaine provides better and longer pain control vs. bupivacaine HCl.

Detailed description:
Fifty consecutive (25 per arm) patients undergoing unilateral or bilateral breast reconstruction with tissue expanders will be administered intraoperatively in a standardized manner with either bupivicaine HCl (control group) or liposomal bupivacaine/Exparel (experimental group). Pain will be assessed qualitatively through the use of: 1) numeric rating scale during rest (NRS-R) and activity (NRS-A), 2) brief pain inventory (BPI) questionnaire, and 3) postoperative analgesia patient satisfaction scale. Furthermore, investigators will record the use of rescue analgesics for each patient. This part of the study will provide quantitative data that investigators can then use in comparison to the qualitative measurements (NSR, BPI, patient satisfaction scale rate). In turn, this will allow us to objectify patient's pain, thereby increasing the validity of our results. More importantly, this aspect of the investigation will enable us to study the impact that liposomal bupivacaine has in reducing the postoperative usage of opioid medications in this patient population. As this is a pilot study, a sample size of 50 total patients (25 per treatment group) is planned. This sample size should provide estimates of potential effect sizes and variability in the present setting to allow for future study planning. This study should provide adequate evidence of whether pain decreases of 15% or more are unlikely in this setting.

Investigators aim to evaluate the effectiveness of DepoFoam Bupivicaine (Exparel®) to reduce postoperative pain in breast reconstruction patients compared to the current standard treatment (bupivacaine HCl). Investigators hypothesize that patients undergoing breast reconstruction with tissue expander will achieve greater control of post-operative pain and longer lasting analgesia with the use of liposomal bupivacaine.

Arms: arm 1: local anesthetic arm 2: local anesthetic
Interventions: intervention 1: Depofoam bupivacaine intervention 2: Bupivacaine hydrochloride (HCl)
Intervention descriptions: intervention 1: The study drug Depofoam bupivacaine will be administered into the right and/or left breast of each patient 30 minutes prior to the creation of the subpectoral muscle pocket. intervention 2: The study drug bupivacaine HCl will be administered into the right and/or left breast of each patient 30 minutes prior to the creation of the subpectoral muscle pocket.

Protocol documents:
Prot_SAP_000.pdf: 
7/9/2014 
 
 
1
 
 
 
 
Efficacy of Liposomal Bupivacaine for Prolonged Postoperative 
Analgesia in Patient Undergoing Breast Reconstruction with Tissue 
Expander 
 
 
 
 
 
Cleveland Clinic Foundation 
Department of Plastic Surgery 
Cleveland, OH 
 
Principal Investigator 
Raymond Isakov, MD 
Department of Plastic Surgery 
Cleveland Clinic Foundation 
9500 Euclid Avenue 
Cleveland, OH 44195 
isakovr@ccf.org 
 
 
Grant Author 
Rafael A. Couto, MD 
Department of Plastic Surgery 
Cleveland Clinic Foundation 
9500 Euclid Avenue 
Cleveland, OH 44195 
coutor@ccf.org 
 
 
 
Sponsor Funder 
PACIRA Pharmaceuticals, Inc   
 
 
NCT04278846 
 
 
 
 
 
 
 
 
 
 


7/9/2014 
 
 
2
I. APPLICATION INFORMATION 
 
• Principal Investigator: Raymond Isakov, MD/ Staff & Associate Program Director 
• Institution/Organization: Plastic Surgery & Dermatology Institute 
                                             Cleveland Clinic Foundation Main Campus (Cleveland, OH) 
 
• Institution/ Organization Type: Academic 
• Mailing Address: Plastic Surgery & Dermatology Institute 
                                  Cleveland Clinic Foundation (CCF) 
                                  9500 Euclid Ave; Cleveland, OH 44195  
• E-mail:  isakovr@ccf.org 
• Phone: 216.445-3765                    Fax: 216.444.9419 
 
 
II. SUMMARY OF GRANT REQUEST 
 
• Title of Proposed Project:  
 
Efficacy of liposomal bupivacaine for Prolonged Postoperative Analgesia in Patient 
Undergoing Breast Reconstruction with Tissue Expander: Assess best technique for infiltration 
of liposomal bupivacaine and evaluate the effectiveness of DepoFoam Bupivicaine (Exparel®) 
to reduce postoperative pain in breast reconstruction patients compared to the current standard 
treatment (bupivacaine HCl). 
 
 
• Study Coordinator:  
     Rafael A. Couto, MD/ Resident: Plastic Surgery/ CCF 
 
• Institution/Organization:  
 
    Plastic Surgery & Dermatology Institute/ Cleveland Clinic Foundation Main Campus  
 
• Mailing Address: 
  
    Plastic Surgery & Dermatology Institute 
    Cleveland Clinic Foundation  
    9500 Euclid Avenue  
    Cleveland, OH 44195  
• E-mail:  
1) isakovr@ccf.org; 2) coutor@ccf.org; 3) kornj@ccf.org; 4) durandp@ccf.org;  
5)   ruedas@ccf.org 
 
• Phone: 216.445.3765                    Fax: 216.444.9419 


7/9/2014 
 
 
3
• Co-Investigators:  
 1) Steven Bernard, MD/ Staff & Program Director: Plastic Surgery CCF 
 2) Andrea Moreira, MD/ Staff: Plastic Surgery/ CCF 
 3) Risal Djohan, MD/ Staff: Plastic Surgery/ CCF 
 4) Graham Schwarz, MD/ Staff: Plastic Surgery/ CCF 
 5) Randal Yetman, MD/Staff: Plastic Surgery/ CCF 
 6) Rafael A. Couto, MD/ Resident: Plastic Surgery/CCF 
 7) Paul Durand, MD/ Resident: Plastic Surgery/ CCF 
 8) Steven Rueda, MD/ Resident: Plastic Surgery/ CCF 
 9) Jason Korn, MD/ Fellow: Plastic Surgery/ CCF 
   
 
 
 
• Product Support Requested from Pacira (description, dosage & quantity): 
    Description: Exparel® (liposomal bupivacaine) 
    Dosage: 266 mg 
    Quantity: Because we are planning to use 266mg, the final amount of units  
                    (266mg) of Exparel that will be requested will depend on number of unilateral and     
                    bilateral breast reconstruction included in the study. Therefore, the number of  
                    units requested will range  from 25 – 60 units.  
 
• Are you requesting Pacira to be the sole supporter of this study? 
    Yes 
 
• Please specify additional sources of support (if applicable) 
     Not applicable 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


7/9/2014 
 
 
4
 
III. 
STUDY INFORMATION 
 
• Study Design Abstract 
 
Study rationale:  
 
Control of postoperative analgesia has become a major topic in surgical awareness and it plays 
a crucial role in patient satisfaction and outcome.1,2 Breast reconstruction is associated with 
postoperative pain, which can result in patient discomfort, patient dissatisfaction, and 
unanticipated/extended hospital admission when undermanaged.2-4 Opioids continue to play an 
important role in postoperative pain management.5 However, their use concerns patients and 
physicians, 
since 
their 
side 
effects 
(e.g. 
nausea/vomiting, 
pruritus, 
sedation, 
respiratory/cardiovascular depression) can become detrimental to patient recovery. 2,5 
 
Long lasting local anesthetics (bupivicaine HCl) have become a useful tool to reduce 
postoperative pain and cumulative narcotics usage in breast reconstruction patients.2-4 
However, because bupivacaine HCl is only effective for a brief period of time (3-7 hours)6, 
postoperative pain control is then mostly achieved by intermittently administrating bupivacaine 
HCl through an indwelling catheter (ON Q pump) into the surgical site.2-4 This therapeutic 
modality  has several disadvantages: 1) patients must leave hospital with the device; 2) catheter 
can become dislodged; 3) seroma formation can occur; and 4) potential infections through the 
introduction of skin flora into a sterile pocket.7,8 In contrast to bupivicaine HCl, liposomal 
bupivacaine; Exparel®; Pacira Pharmaceuticals, San Diego, CA) has demonstrated a decrease 
in the use of rescue opioid analgesics and longer lasting postoperative pain control.9-11 
Therefore, in the breast reconstruction patient population, liposomal bupivacaine long-lasting 
effect not only allows us to treat postoperative pain without the need of a local anesthetic 
infusion pump, but also reduce postoperative opioid use.  
 
We believe that subjects undergoing breast reconstruction with tissue expander will achieve 
greater control of pain and longer lasting analgesia with the use of liposomal bupivacaine 
compared to bupivicaine HCl. Consequently, the group managed with liposomal bupivacaine 
will have less of a need for rescue analgesic medications, fewer narcotic adverse events (e.g. 
nausea/vomiting), and shorter hospital stays than subjects treated with bupivacaine HCl. We 
strongly believe that this study will be of great interest to the plastic and reconstructive surgery 


7/9/2014 
 
 
5
community, because it can significantly influence what may soon be considered ‘standard of 
care’ in this patient population.  
 
Objectives/Rationale/Hypothesis  
 
 
Objective 1:  
 
Evaluate the effectiveness of DepoFoam Bupivicaine (Exparel®) to reduce postoperative 
pain in breast reconstruction patients compared to the current standard treatment 
(bupivacaine HCl). 
 
We will assess pain utilizing methods that have been successfully employed in studies with 
similar experimental design.9-13 Pain will be assessed qualitatively through the use of: 1) 
numeric rating scale during rest (NRS-R) and activity (NRS-A), 2) brief pain inventory (BPI) 
questionnaire, and 3) postoperative analgesia patient satisfaction scale.  
 
The numeric rating scale of pain (NRS) will consist of an 11 point scale.  The end points are 
extremes of pain: no pain (NRS=0) and worst possible pain (NRS=10) (Appendix 1, Figure 1). 
We will also utilize the brief pain inventory (BPI) questionnaire to assess the patient’s quality 
of life after surgery (Appendix 2).  The BPI measures both the intensity of pain (sensory 
dimension) and interference of pain in the patient's life.  This questionnaire assesses pain relief, 
pain quality, and patient perception of the cause of pain (Appendix 2).14 Furthermore, 
postoperative analgesia satisfaction will be recorded through a 5-point scale (0= very 
unsatisfied to 5= very satisfied) (Appendix 1, Figure 2).   
 
Rationale:  
 
There is no current literature evaluating the effectiveness of DepoFoam Bupivicaine 
(Exparel®) in reducing postoperative pain in breast reconstruction patients compared to the 
current standard treatment (bupivacaine HCl).  
 
Hypothesis:  
 
We hypothesize that patients undergoing breast reconstruction with tissue expander will 
achieve greater control of post-operative pain and longer lasting analgesia with the use of 
liposomal bupivacaine. 
 


7/9/2014 
 
 
6
 
 
 
 
Objective 2:  
 
Evaluate and compare the usage of opiate rescue pain medications between the 
experimental (liposomal bupivacaine) and historical control (bupivacaine HCl) groups.  
 
Given the subjective nature behind pain assessment, we will record the use of rescue analgesics 
for each patient. This part of the study will provide quantitative data that we can then use in 
comparison to the qualitative measurements (NSR, BPI, patient satisfaction scale rate). In turn, 
this will allow us to objectify patient’s pain, thereby increasing the validity of our results. More 
importantly, this aspect of the investigation will enable us to study the impact that liposomal 
bupivacaine has in reducing the postoperative usage of opioid medications in this patient 
population. 
 
Rationale:  
 
There are no studies evaluating the effectiveness of liposomal bupivacaine in reducing the 
usage of opioid analgesics in breast reconstruction patients compared to the current standard 
treatment (bupivacaine HCl). 
 
Hypothesis:  
 
Patients managed with liposomal bupivacaine will have a reduced need for opioid medication 
management compared to subjects treated with bupivacaine HCl.  
 
Design of Study:  
 
The pilot study will be a prospective. 
 
Inclusion Criteria 
 
All eligible patients, 18 and over, undergo breast reconstruction with tissue expanders. 
 
 
Exclusion Criteria 
 
Exclusion criteria include the following patient populations: 1) history of adverse reaction to 
local anesthesia; 2) chronic liver disease; 3) history of chronic preoperative consumption of 
narcotics or opioids; 4) history of alcohol and/or illicit drug dependence; 5) undergoing 


7/9/2014 
 
 
7
combined procedures; 6) diagnosed with neuromuscular/neurosensory disorder; 7) positive 
pregnancy test; 8) previous breast conservation therapy (lumpectomy with radiation treatment; 
9) previous surgeries or trauma in the breast or chest region  (denervation may bias pain 
perception); 10) axillary node dissection; and 11) psychosis.  
 
Screening Visit 
 
Screening procedure will be performed within 30 days of the patient’s scheduled procedure. 
During screening visit: 1) informed consent will be obtained; 2) study eligibility will be 
confirmed; 3) evaluation will be performed (i.e. medical/surgical history, physical exam, vital 
signs, drug/alcohol screening, and clinical laboratory); and 4) patient will be trained on the pain 
assessment tools that will be used in the study.  
 
Preoperative 
 
Preoperative evaluation will be performed prior to the operation (e.g. eligibility reconfirmation, 
review of history, vital signs, physical exam, urine pregnancy test). Furthermore, patient’s 
baseline pain intensity will be assessed at this time. Pain intensity at both rest and with activity 
will be assessed using the numeric rating scale (NRS-R & NRS-A; 0= no pain & 10= worst 
possible pain, respectively). When assessing NRS-A pain intensity, we will ask the patient to 
raise both arms above the head and hold for five seconds.  Patient will be randomly assigned to 
either receive Depofoam bupivacaine (266mg per side) or bupivacaine HCl (2.5mg/kg) in a 1:1 
ratio. Randomization and allocation of the subjects chosen to be placed into the experimental 
group (DepoFoam bupivacaine) or control group (bupivicaine HCl) will be generated via a 
computer randomization system. (Note: A standard final dilution of the drugs will be 
established among the co-investigators prior to initiating the study). 
 
Intraoperative 
 
General Anesthesia Protocol: 
 
All eligible patients will receive the same anesthetic plan to minimize the incidence of 
postoperative nausea and vomiting: 
1. Premedication with midazolam 
2. Administration of decadron at induction to prevent nausea and vomiting 


7/9/2014 
 
 
8
3. Induction with propofol and alfentanyl, muscle relaxation with succinycholine, 
rocuronium or atracurium 
4. Anesthesia maintenance with propofol, alfentanyl, nitrous oxide, and oxygen 
5. Anesthesia reversal with neostigmine and glycopyrolate 
6. Dolasentron to be given within 30 minutes of emergence 
 
 
Local Anesthetics Protocol: (Depofoam bupivacaine & Bupivicaine HCl) 
 
The study drugs will be administered into the right and/or left breast of each patient 30 minutes 
prior to the creation of the subpectoral muscle pocket (where tissue expanders will be placed).  
 
The local anesthetic will be administered using a “field block” approach. The patient will be in 
supine position, with each arm abducted at the shoulder and placed on an arm board. We will 
administer the drug with a 10 or 20 ml syringe and 22- or 25-gauge. The local anesthetic will 
be locally infiltrated into the pocket (where implants are placed) and around the perimeter of 
the surgical site, including the drain sites. We will be infiltrating the drugs to soft tissue, chest 
wall and muscles. Because several surgeons will be involved in this study, we will develop a 
standardized protocol for administering the local anesthetic; not only this will reduce any 
potential confounding factors, but also will enable us to be consistent. Patients from surgeons 
that are not part of the study may be enrolled as long as the surgeon is familiarized with the 
protocol, agrees with it, and one of the co-investigators is present during the research related 
procedures to assure compliance. 
 
Postoperative 
 
Pain Assessment 
 
We will assess pain utilizing methods that have been successfully employed in studies with 
similar experimental design.9-13 Subjective evaluation of pain will be recorded on a Patient Data 
Collection Sheet. It will be performed by using numeric rating scale (Appendix 1; Table 1, 
Figure 1). Pain intensity at rest and with activity will be assessed using the numeric rating scale 
(NRS-R & NRS-A; 0= no pain & 10=worst possible pain, respectively). When assessing NRS-
A pain intensity, we will ask the patient to raise both arms above the head and hold for five 
seconds. NRS-R and NRS-A pain intensity assessment will be recorded at one, four, eight, 12, 
24, 36, 48, 60, 72, 84, and 96 hour time periods after the administration of the local anesthetic. 
Also patient’s quality of life will be assessed by asking her to complete the Brief Pain 


7/9/2014 
 
 
9
Inventory (BPI) questionnaire at 24, 48, 72, and 96 hours (Appendix 2). Furthermore, patient 
postoperative analgesia satisfaction will also be rated through the use of a 5-point categorical 
scale (0=very unsatisfied and 5=very satisfied) at 96 hours after local anesthetic administration 
(Appendix 1, Table 4).  
 
Objective evaluation of pain will be accomplished by assessing the amount and type of rescue 
analgesics used during hospitalization and post-operative days 1 through 4. This will be 
evaluated through nursing records available in our electronic medical record (EPIC; Verona, 
Wisconsin) that will be transferred to a Patient Data Collection Sheet (Appendix 1). During the 
hospitalization, for postoperative rescue analgesics, patients will have the following available: 
1) acetaminophen 650mg (Tylenol) every 4-6 hours as needed for mild pain (pain scale 1-3), 2) 
oxycodone 5mg/ acetaminophen 325 mg (Percocet) or hydrocodone 5 mg/ acetaminophen 300 
mg (Norco) every 4-6 hours as needed, for moderate pain (pain scale 4-6), and 3) IV opioid 
analgesics (e.g. Dilaudid, Fentanyl, or Morphine) every 4-6 hours as needed, for severe pain 
(pain scale 7-10). Patient will be discharged with a standardized oral pain medication regimen, 
which will consists of 1) acetaminophen 650mg and 2) oxycodone 5mg/acetaminophen 325 mg 
(Percocet) or hydrocodone 5 mg/ acetaminophen 300 mg every 4-6 hours as needed.  
 
Typically, patients undergoing this procedure are discharged from the hospital once tolerating 
oral pain medications, and no longer requiring IV rescue analgesics. Patients that are getting 
discharged will receive a similar Patient Data Collection Sheet used during their hospitalization 
to record their pain, use of rescue analgesics, and adverse events at the remaining time points. 
For example, if patient is discharged after 24 hours, we will have already assessed and recorded 
patient’s data as explained above at 1, 4, 8, 12, and 24 hour intervals. Then, we will ask the 
patient to record at home for the remaining intervals: 1) NRS-A and NRS-R at 36, 48, 60, 72, 
84, and 96 hours after drug administration; 2) rescue analgesics intake at 36, 48, 60, 72, 84, and 
96 hours after drug administration; 3) adverse events at 36, 48, 60, 72, 84, and 96 hours after 
drug administration; 3) BPI at 24, 48, 72, and 96 hours after drug administration; and 4) 5-point 
categorical scale at 96 hours (Appendix 1, 2). Patients will be seen at the Plastic Surgery office 
for their postoperative visit, usually within 7 to 14 days after surgery.  
 
Adverse Events: 
 
    The following adverse events will be evaluated: 1) nausea; 2) vomiting; 3) constipation; 4)     
    somnolence; 5) dizziness; 6) respiratory distress. They will be assessed at 1, 4, 8, 12, 24, 36,    


7/9/2014 
 
 
10 
    48, 60, 72, 84, and 96 hours after the administration of the local anesthetics and recorded in    
    the Patient Data Collection Sheet (Appendix 1, Table 3).  
 
 
 
 
 
Summary of Methods: 
 
Historical Comparator/Control 
 
The comparator/control of the study will be bupivicaine HCl (Marcaine 0.5% with epinephrine 
1:200,000). We are interested in utilizing bupivicaine HCl as the control because: 1) it has been 
shown to reduce pain scores and cumulative pain medications in breast reconstruction patients2-
4 and 2) the use of local anesthesia for reduction of postoperative analgesia following a breast 
reconstruction with tissue expander is a standard of treatment at our institution.  
 
Secondary Endpoints 
 
The secondary endpoints of this study will be: 1) adverse events (i.e. nausea/vomiting, 
somnolence, dizziness, constipation, respiratory distress); 2) overall patient satisfaction; 3) 
length of hospital stay. 
 
Predictive Variables:  
 
The predictive variables will include: 1) demographics (e.g. age, race/ethnicity, weight/BMI); 
2) 
unilateral/bilateral 
breast 
reconstruction; 
3) 
sentinel 
lymph 
node 
biopsy; 
4) 
therapeutic/prophylactic mastectomy; 5) use of acellular dermal matrix (ADM) for 
reconstruction of the lateral & inferior mammary fold (partial submuscular pocket with ADM); 
6)  elevation of the serratus anterior (complete submuscular pocket); 7) volume of saline in the 
tissue expander. 
 
Expected Results 
 
We hypothesize that patients undergoing breast reconstruction with tissue expander will 
achieve greater control of post-operative pain and longer lasting analgesia with the use of 
DepoFoam bupivacaine compared to bupivicaine HCl. Consequently, patients managed with 
DepoFoam bupivacaine will have lower use of opioid rescue medication, fewer narcotic 
adverse events, and shorter hospital stay than subjects treated with bupivacaine HCl.  
 


7/9/2014 
 
 
11 
Outcome Assessment 
 
Statistical analysis will be conducted on Stata 11.0 (College Station, TX). Patients will be 
randomly divided into an experimental and control group. Primary and secondary outcomes 
will be recorded.  
 
Patient population demographics in the two groups will be compared by Fisher’s exact test 
for nominal variables and Student t-test for quantitative variables. This will ensure that 
conclusions are not due to varying patient populations. Univariate analysis comparing 
primary outcome measures for both groups will be performed using Mann-Whitney test 
given expected non-normal distribution of values. The same will be done for secondary end 
points. Finally, exploratory multivariable regression analyses for each primary end point will 
be performed to control for the effect of differences in baseline variables between treatment 
groups on primary endpoint outcomes and avoid erroneous conclusions due to confounding; 
this will also enable us to evaluate if use of DepoFoam bupivicaine was an independent 
predictor of the primary and secondary outcomes of this study.   Continuous measures will 
be compared using linear regression techniques, while, if feasible, categorical outcomes will 
be evaluated using generalized linear models including logistic regression and Poisson 
regression as appropriate.  If necessary, transformations of outcome measures will be 
performed prior to analysis to meet model assumptions.  Analyses will be performed 
assuming a 0.05 significance level. 
 
• Therapeutics to Be Studied:  
 
1) Liposomal bupivacaine [bupivacaine extended-release liposome injection, (Exparel®)] 
     2) Bupivicaine HCl (Marcaine) 
 
• Pathology and Disease to be Studied and Incidence:  
No disease or pathology will be studied or treated in this investigation. We will be studying       
    the effectiveness of local anesthetics (liposomal bupivacaine & bupivacaine HCl) in post-  
    operative analgesia, following bilateral breast reconstruction with tissue expander. 
 
• Number of Study Subjects/Animals: 
As this is a pilot study, a sample size of 50 total patients (25 per treatment group) is planned. 
The goal is to have 25 completed patients in each group. Patients that for some reason did 
not complete the post-operative pain assessment will be replaced.    This sample size should 


7/9/2014 
 
 
12 
provide estimates of potential effect sizes and variability in the present setting to allow for 
future study planning.  In keeping with recommendations from Cocks et al15, if the 
variability is similar to what was observed in Smoot et al10, then this study should provide 
adequate evidence of whether pain decreases of 15% or more are unlikely in this setting.  
 
 
• Dosage Regimen: 
   Local Anesthetics: 
1) Liposomal bupivacaine: 266mg per side (Note: A standard final dilution of the drugs will 
be established among the co-investigators prior to initiating the study). 
2) Bupivicaine HCl: 2.5 mg/kg 
 
Postoperative Pain Rescue Medications During Hospitalization: 
1) Acetaminophen 650mg (Tylenol) for mild pain (pain scale 1-3). 
2) Oxycodone 5mg/acetaminophen 325mg (Percocet) or hydrocodone 5mg/acetaminophen 
300 mg (Norco) 4-6 hours as needed for moderate pain (pain scale 4-6). 
3)  IV opioid analgesics (e.g. Dilaudid, Fentanyl, or Morphine) for severe pain (pain 7-10). 
 
Pain Medications After Discharge: 
1) Acetaminophen 650mg every 6 hours as needed. 
2) Oxycodone 5mg/acetaminophen 325 mg (Percocet) or hydrocodone 5 mg/ acetaminophen   
    300 mg (Norco) 4-6 hours as needed. 
 
• Will IRB and/or Ethics Board Approval be Obtained?  
     Yes 
 
• Anticipated Date for Review and Approval 
    April 2013 
 
• Will Informed Consent be Obtained from All Study Subjects 
    Yes  
 
• Please Describe Your Process for Obtaining Informed Consent and Anticipated Timeline:  
For this investigation, patients will be interviewed at the CCF Plastic Surgery Clinic in a 
private office. Full explanation about the research will be provided. The patient will have the 
option to participate in the study, not participate, or decide at a later time.  If a subject 


7/9/2014 
 
 
13 
decides to participate in the study, a written consent document that includes all of the 
elements of this study will be provided to the patient. Her signature will be obtained on this 
consent. She will be consented by the PI or co-investigators only. If she decides to 
participate at a later time, we will discuss the study one more time before the surgery. This 
meeting will be documented in the patient’s electronic medical record (EPIC software) as an 
office encounter and signed by the person obtaining the consent. 
 
• Do you have a Plan for Documenting/Reporting Adverse Events?  
    Yes 
 
• Please Describe Plan for Documenting/Reporting Adverse Events 
    The following adverse events will be evaluated: 1) nausea; 2) vomiting; 3) constipation; 4)     
    somnolence; 5) dizziness; 6) respiratory distress. They will be assessed at 1, 4, 8, 12, 24, 36,    
    48, 60, 72, 84, and 96 hours after the administration of the local anesthetics and recorded in    
    the Patient Data Collection Sheet (Appendix 1, Table 3).  
 
• Study Duration 
   We estimate that the study will take approximately 6 months. 
 
• Anticipated Start Date:  
    We estimate to start the investigation in May 2014 
 
• Anticipated Finish Date:  
    We estimate to finish the study by November of 2014 
 
 
IV. 
PUBLICATION 
• 
Do you plan on registering this study on a public database?: No 
• 
Publication/Presentation Plan:  
           Peer-Reviewed Journals:  1) Plastic & Reconstructive Surgery  
                                                    2) Annals of Plastic Surgery 
 
           Meetings: 1) American Association of Plastic Surgeons (AAPS) Annual Meeting 
                            2) American Society of Plastic Surgeons (ASPS) Annual Meeting 
                            3) The Ohio Valley Society of Plastic Surgeons (OVSPS) Annual Meeting 
                            4) Plastic Surgery Research Council (PSRC) Annual Meeting 
 
 
 


7/9/2014 
 
 
14 
V. 
OTHER PACIRA SUPPORT REQUESTED  
 
    Description: Exparel® (Depo Foam bupivacaine) 
    Dosage: 266 mg 
    Quantity: Because we are planning to use 266mg per side, the final amount     
     of units (266mg) of Exparel that will be requested will depend on number of    
     unilateral and bilateral breast reconstruction included in the study.                                      
     Therefore, the number of units requested will range from 25 – 60 units.  
 
 
VI. 
APPENDIX 
 
Please see next page 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


7/9/2014 
 
 
15 
Appendix 1- Patient Data Collection Sheet 
 
Name:                                    
Subject Number:                          
 
Patient Data Collection Sheet 
Day 1: 
Table 1: Numeric Pain Rating Scale 
Instructions: Please record the number that best describes the level of pain (Figure 1) during rest 
and activity (raise both arms above the head and hold for five seconds) on the respective time 
points.  
Time 
Points 
Numeric Pain Scale 
(Rest) 
Numeric Pain Scale 
(Activity) 
 1 hour 
 
 
4 hours 
 
 
8 hours 
 
 
12 hours 
 
 
24 hours 
 
 
 
Table 2: Pain Medications 
Instructions: Please record the amount & frequency of each medication that you have taken on the 
respective time points. Only include medications that were taken, since the last time point. Do not 
include medications already included in previous time points (even if they overlap). 
Time 
Points 
Tylenol 
(Amt/Dose/ 
Freq) 
Percocet 
(Amt/Dose/ 
Freq) 
Norco 
(Amt/Dose/ 
Freq) 
Tramadol 
(Amt/Dose/ 
Freq) 
IV Opioid 
(Dilaudid, Fentanyl,Morphine) 
(Amt/Dose/ Freq) 
**circle the name of drug** 
Other  
Medication 
(specify) 
(Amt/Dose/ 
Freq)) 
 1 hour 
 
 
 
 
 
 
4 hours 
 
 
 
 
 
 
8 hours 
 
 
 
 
 
 
12 hours 
 
 
 
 
 
 
24 hours 
 
 
 
 
 
 
 
 
 
 
Figure 1: Numeric Pain Rating Scale 


7/9/2014 
 
 
16 
Table 3: Adverse Events  
Instructions: Please record any experienced adverse event on the respective time points. 
Time 
Points 
Nausea 
Vomiting 
Constipation 
Somnolence 
Dizziness 
Fatigue 
Other 
(specify) 
 1 hour 
 
 
 
 
 
 
 
4 hours 
 
 
 
 
 
 
 
8 hours 
 
 
 
 
 
 
 
12 hours 
 
 
 
 
 
 
 
24 hours 
 
 
 
 
 
 
 
 
 
Day 2: 
Table 1: Numeric Pain Rating Scale 
Instructions: Please record the number that best describes the level of pain (Figure 1) during rest 
and activity (raise both arms above the head and hold for five seconds) on the respective time 
points.  
Time 
Points 
Numeric Pain Scale 
(Rest) 
Numeric Pain Scale 
(Activity) 
36 hours 
(last 12 
hours) 
 
 
48 hours 
(last 12 
hours) 
 
 
 
Table 2: Pain Medications 
Instructions: Please record the amount & frequency of each medication that you have taken on the 
respective time points. Only include medications that were taken, since the last time point. Do not 
include medications already included in previous time points (even if they overlap). 
Time 
Points 
Tylenol 
(Amt/Dose/ 
Freq) 
Percocet 
(Amt/Dose/ 
Freq) 
Norco 
(Amt/Dose/ 
Freq) 
Tramadol 
(Amt/Dose/ 
Freq) 
IV Opioid 
(Dilaudid, Fentanyl,Morphine) 
(Amt/Dose/ Freq) 
**circle the name of drug** 
Other  
Medication 
(specify) 
 36 hours 
(last 12 
hours) 
 
 
 
 
 
 
48 hours 
(last 12 
hours) 
 
 
 
 
 
 
 
Figure 1: Numeric Pain Rating Scale 


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17 
Table 3: Adverse Events  
Instructions: Please record any experienced adverse event on the respective time points. 
Time 
Points 
Nausea 
Vomiting 
Constipation 
Somnolence 
Dizziness 
Fatigue 
Other 
(specify) 
36 hours  
(last 12 
hours) 
 
 
 
 
 
 
 
48 hours 
(last 12 
hours) 
 
 
 
 
 
 
 
 
 
Day 3: 
Table 1: Numeric Pain Rating Scale 
Instructions: Please record the number that best describes the level of pain (Figure 1) during rest 
and activity (raise both arms above the head and hold for five seconds) on the respective time 
points.  
Time 
Points 
Numeric Pain Scale 
(Rest) 
Numeric Pain Scale 
(Activity) 
60 hours 
 (last 12 
hours) 
 
 
72 hours 
(last 12 
hours) 
 
 
 
Table 2: Pain Medications 
Instructions: Please record the amount & frequency of each medication that you have taken on the 
respective time points. Only include medications that were taken, since the last time point. Do not 
include medications already included in previous time points (even if they overlap). 
 
Time 
Points 
Tylenol 
(Amt/Dose/ 
Freq) 
Percocet 
((Amt/Dose/ 
Freq) 
Norco 
((Amt/Dose
/ Freq) 
Tramadol 
(Amt/Dose/ 
Freq) 
IV Opioid 
(Dilaudid, Fentanyl,Morphine) 
(Amt/Dose/ Freq) 
**circle the name of drug** 
Other  
Medications 
(specify) 
60 hours 
(last 12 
hours) 
 
 
 
 
 
 
72 hours  
(last 12 
hours) 
 
 
 
 
 
 
 
Figure 1: Numeric Pain Rating Scale 


7/9/2014 
 
 
18 
Table 3: Adverse Events  
Instructions: Please record any experienced adverse event on the respective time points. 
Time 
Points 
Nausea 
Vomiting 
Constipation 
Somnolence 
Dizziness 
Fatigue 
Other 
(specify) 
60 hours  
(last 12 
hours) 
 
 
 
 
 
 
 
72 hours 
(last 12 
hours) 
 
 
 
 
 
 
 
 
 
Day 4: 
Table 1: Numeric Pain Rating Scale 
Instructions: Please record the number that best describes the level of pain (Figure 1) during rest 
and activity (raise both arms above the head and hold for five seconds) on the respective time 
points.  
Time 
Points 
Numeric Pain Scale 
(Rest) 
Numeric Pain Scale 
(Activity) 
84 hours 
(last 12 
hours) 
 
 
96 hours 
(last 12 
hours) 
 
 
 
Table 2: Pain Medications 
Instructions: Please record the amount & frequency of each medication that you have taken on the 
respective time points. Only include medications that were taken, since the last time point. Do not 
include medications already included in previous time points (even if they overlap). 
Time 
Points 
Tylenol 
(Amt/Dose/ 
Freq) 
Percocet 
(Amt/Dose/ 
Freq) 
Norco 
(Amt/Dose/ 
Freq) 
Tramadol 
(Amt/Dose/ 
Freq) 
IV Opioid 
(Dilaudid, Fentanyl,Morphine) 
(Amt/Dose/ Freq) 
**circle the name of drug** 
Other  
Medication 
(specify) 
 84 hours 
(last 12 
hours) 
 
 
 
 
 
 
96 hours 
(last 12 
hours) 
 
 
 
 
 
 
 
 
Figure 1: Numeric Pain Rating Scale 


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19 
Table 3: Adverse Events  
Instructions: Please record any experienced adverse event on the respective time points. 
Time 
Points 
Nausea 
Vomiting 
Constipation 
Somnolence 
Dizziness 
Fatigue 
Other 
(specify) 
84 hours 
(last 12 
hours) 
 
 
 
 
 
 
 
96 hours 
(last 12 
hours) 
 
 
 
 
 
 
 
 
Table 4: Patient Satisfaction: 
Instructions: Please circle the number that best describes the degree of satisfaction you 
experienced with the pain medication provided to you during the last 4 days after surgery. 
1- Very Unsatisfied        2- Unsatisfied          3- Neutral         4- Satisfied      5-Very Satisfied    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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20 
Appendix 2- Brief Pain Inventory 
 
Name:  
Subject #:  
 
 
1) Throughout our lives, most of us have had experience pain before (e.g. minor headaches, 
sprains, toothaches.) Have you had pain other than these kinds of pain today? (Circle 
Answer) 
 
                 Yes               No 
 
2) On the diagram, circle the areas where you feel pain. Put an X on the area that hurts the 
most.  
 
 
 
 
 
 
 
 
 
 
 
3) Circle the number that best describes your pain at its worst in the past 24 hours.  
 
 
 
 
4) Circle the number that best describes your pain at its least in the past 24 hours.  
 
 
 
 
5) Circle the number that best describes your pain on the average. 
 
 
 
 
6) Circle the number that best describes the pain you have right now 
 
 
 
7) What treatments/medications are you receiving for your pain? 
 
 
Right 
Left    
Right 
0   1   2    3    4    5    6    7    8    9    10 
0   1   2    3    4    5    6    7    8    9    10 
0   1   2    3    4    5    6    7    8    9    10 
0   1   2    3    4    5    6    7    8    9    10 
No Pain 
Worst Pain 
No Pain 
Worst Pain 
No Pain 
Worst Pain 
No Pain 
Worst Pain 
Brief Pain Inventory 


7/9/2014 
 
 
21 
8) Circle the percentage that most shows how much relief have pain medications provided.  
 
 
 
 
9) Circle the number that best describes how, during the past 24 hours, pain has interfered 
with: 
 
A. General Activity 
 
 
 
 
 
B. Mood 
 
 
 
 
C. Walking Ability 
 
 
 
 
D. Work (outside home & housework) 
 
 
 
 
E. Relation with other people 
 
 
 
 
F. Sleep 
 
 
 
G. Enjoyment of Life 
 
 
 
 
 
 
 
 
 
 
 
 
0% 10  20  30  40  50  60  70  80  90  100% 
0   1   2    3    4    5    6    7    8    9    10 
0   1   2    3    4    5    6    7    8    9    10 
Does not 
interfere 
Completely 
interferes 
Does not 
interfere 
 
 
Completely 
interferes 
No Relief 
Worst Pain 
0   1   2    3    4    5    6    7    8    9    10 
0   1   2    3    4    5    6    7    8    9    10 
Does not 
interfere 
Completely 
interferes 
Does not 
interfere 
Completely 
interferes 
0   1   2    3    4    5    6    7    8    9    10 
0   1   2    3    4    5    6    7    8    9    10 
Does not 
interfere 
Completely 
interferes 
Does not 
interfere 
Completely 
interferes 
0   1   2    3    4    5    6    7    8    9    10 
Does not 
interfere 
Completely 
interferes 


7/9/2014 
 
 
22 
 
VII. 
REFERENCES  
 
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