Conditions: Post-operative Pain Management
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 102
Healthy volunteers: no

Brief summary:
This will be a comparative study between two cohorts of patients undergoing Roux-en-Y Gastric bypass. One cohort (75 patients) will receive FDA approved Exparel® (liposome bupivacaine injection solution) injections intra-operatively at time of incision site closure. The control cohort (75 patients) will receive 0.25% bupivacaine injection solution at the time of incision site closure. The medication for the control group is our current standard of care. The primary end point is post-operative pain at 24 and 48 hours measured by the Visual Analog Scale (VAS). Comparison will be made between cohorts. All subjects enrolled in the study will be evaluated per nursing protocol with the verbal numerical analog scale. At 24 and 48 hours a member of the research team will administer a 2-part questionnaire containing the VAS and the Revised American Pain Society Post-Operative Questionnaire (APS-POQ-R). The latter is validated for assessment of the patient's experience of pain and it hindrance to daily activity in the post operative period.

Detailed description:
The study will include up to 150 patients, and will consist of two cohort. The study cohort will include 75 patients who receive intraoperative Exparel® injections at the incision locations in addition to our standard multimodality post-operative analgesia. The control arm will include 75 patients who meet inclusion criteria but receive standard 0.25% bupivacaine and our standard multimodality post-operative analgesia. Patients will be randomized by REDCap™ database system in collaboration with Cleveland Clinic Pharmacy to receive either Exparel® or the control medication (0.25% Bupivacaine). Consent from patients will be obtained and documented by a dedicated research personnel prior to any enrollment.

Arms:
arm 1: Subjects in this arm will receive Exparel® liposomal bupivacaine injected concurrently with 0.25% bupivacaine at the incisional sites prior to closing arm 2: Subjects in this arm will receive 0.25% bupivacaine alone

Interventions: intervention 1: Exparel intervention 2: Bupivacaine
Intervention descriptions: intervention 1: Exparel liposomal bupivacaine - 20cc Exparel® + 60cc Bupivicaine intervention 2: 60cc Bupivacaine

Protocol document:
Prot_SAP_000.pdf: 
[KROH, ET AL. EFFICACY OF EXPAREL® ON POST-OPERATIVE 
PAIN AFTER RYGB USING EEA CIRCULAR STAPLER TECHNIQUE] 
NCT03187379 
Revised  
3/23/2020 
 
 
 
EFFICACY OF EXPAREL® ON POST-OPERATIVE PAIN AFTER RYGB USING EEA 
CIRCULAR STAPLER TECHNIQUE 
 
Summary 
This will be a head to head study that includes two cohorts of patients undergoing roux-en-y 
gastric bypass with the use of circular end to end anastomotic (EEA) stapler to create the 
gastro-jejunal anastomosis. One cohort (50 patients) will receive Exparel® (liposomal 
bupivacaine injection solution) injections intra-operatively at time of incision closure. The control 
cohort (50 patients) will receive standard bupivacaine injections at the time of incision closure, 
the current standard of care. Post-operative analgesia will be standardized and identical for both 
cohorts. The primary outcome will be pain scores and 24 and 48 hours post operatively, 
measure using the visual analog scale (VAS). Secondary outcomes will include the parameters 
included in the American Pain Society Post-Operative Questionnaire (APS-POQ-R), a validated 
measurement tool to assess how patients experience pain and how it may impact their ability to 
complete daily activity.  Readmission, ED visits, and phone calls to clinic related to pain control 
will be evaluated by retrospective chart review at day 30 postop.  This information may better 
direct surgeons in selecting type of injected medication at the incision site, in an effort to 
achieve better short-term results. 


[KROH, ET AL. EFFICACY OF EXPAREL® ON POST-OPERATIVE 
PAIN AFTER RYGB USING EEA CIRCULAR STAPLER TECHNIQUE] 
NCT03187379 
Revised  
3/23/2020 
 
 
 
Background 
Compared to open operation, laparoscopic surgery offers numerous benefits, including 
decreasing surgical trauma, improved cosmesis and decreased wound infection and wound 
related complications. Another significant advantage is the reduction of post-operative pain; 
however, effective post-operative analgesia following laparoscopy still often requires 
intravenous or oral narcotics. Several factors may contribute to the development of pain post-
laparoscopic surgery, including the stretching of the intra-abdominal cavity, peritoneal 
inflammation and neuro-vascular irritation [1–3]. Lower intensity and duration of pain associated 
with laparoscopic surgery has been well documented when compared to laparotomy. 
Nevertheless safe peri-operative analgesic regimen that effectively achieves pain relief with 
minimal side effects is required, and it likely best achieved by a multimodality approach 
Reduction of pain may be achieved by early administration of analgesics, typically prior to 
patient awakening from anesthesia [1, 4–7]. Preventive analgesia includes any intraoperative 
analgesic agents/techniques that provides the ability to control pain-induced sensitization of the 
central nervous system and decrease the development of ongoing pain [1, 8, 9].  
 
Commonly used non-opioid based medications such as acetaminophen (paracetamol) have 
been shown to reduce pain after various surgical procedures [1, 10, 11]. Local analgesia has 
also been shown to be effective adjunct in relieving pain related to laparoscopic surgery. [1, 9, 
12, 13]. Bupivacaine is an amide-based local anesthetic. The use of multiple analgesics 
medications when compared to a single analgesic medication for reduction in pain post-
operatively, allows more rapid post-operative recovery therefore allowing patients to resume 
normal activities of daily living sooner.[1, 11] Most enhanced recovery protocols as a result now 
include provisions for multimodal analgesia, in many cases beginning intraoperatively.  
 
Exparel® is a formulation of bupivacaine (Pacira Pharmaceuticals, Inc., San Diego), offering 
extended-release bupivacaine tissue release, and thus prolonged analgesia. In the Exparel® 
formulation, multi-vesicular liposomes (MVL) encapsulate the bupivacaine medication. The 
tightly packed multi-lamellar vesicles that comprise an Exparel® unit have proven to provide 
longer term drug release compared to other technologies using uni-lamellar vesicles. This 
arrangement of vesicles within the Exparel®, spans tens of micrometers in diameter and slows 
degradation in vivo, allowing for greater sustainability of medication release lasting days as 
opposed to hours. Several randomized clinical trials have been completed with this novel 
medication leading to is approval by the Food and Drug Administration (FDA). The outcome 
measures included verbal pain scores, amounts and duration of use of post-operative opioid 
analgesics and patient satisfaction. In post market studies, researchers have conducted a wide 
range of surgical studies assessing the use of Exparel® for a variety of surgical procedures. 
Currently there are no prospective studies evaluating post-operative pain after roux-en-y gastric 
bypass. Of particular interest is the use of the circular EEA, which requires a larger incision site 
in the left upper quadrant, and is typically the site of the greatest operative pain. 
 
A study conducted by Skolnik et al. assessing the use of Exparel® in ileostomy reversals 
indicates there was a statistically significant in reduction of post-operative opioid analgesic use, 
length of hospital stay, and maximal pain scores. A majority of the current studies support these 
findings, but the evaluation of Exparel® for post-bariatric pain is limited.  
 
Roux-en-Y gastric bypass (RYGB) is a well-studied bariatric surgical procedure that is not 


[KROH, ET AL. EFFICACY OF EXPAREL® ON POST-OPERATIVE 
PAIN AFTER RYGB USING EEA CIRCULAR STAPLER TECHNIQUE] 
NCT03187379 
Revised  
3/23/2020 
 
 
 
only a very effective procedure for weight loss, but is also associated with a reduction of 
significant co-morbid conditions. Roux-en-y gastric bypass operations involves the creation 
of  two new anastomoses, the gastrojejunal anastomosis linking the gastric pouch to the 
roux limb, and the jejuno-jejunal anastomosis connecting the bypassed biliopancreatic limb 
with the distal Roux limb.[14] Nationally the circular EEA stapler is the most common technique 
to form the gastrojejunal anastomosis. This stapler is ~40mm in diameter, and is introduced 
through an incision in the left upper quadrant incision. This is the largest incision created 
and is typically the site of the most intense postoperative pain.[14] Given the location next 
to the costal margin, pain at this location can also lead to patients self-splinting, limiting 
lung expansion and putting them at risk for post-operative atelectasis, respiratory 
insufficiency or pneumonia.  
 
Currently, there are no prospective trials for that examine post-operative pain management 
in patients undergoing laparoscopic roux-en-y gastric bypass utilizing a circular EEA staplers 
used to create gastrojejunal anastomosis. Objective data from such an investigation would 
serve to better direct patient care by providing needed information about the most 
appropriate medications to be used in reducing post-operative pain for this specific bariatric 
population, and resultant symptoms of pain and increased hospital resource use. 
 
 
 


[KROH, ET AL. EFFICACY OF EXPAREL® ON POST-OPERATIVE 
PAIN AFTER RYGB USING EEA CIRCULAR STAPLER TECHNIQUE] 
NCT03187379 
Revised  
3/23/2020 
 
 
 
Aims and Hypothesis 
 
Aim: To evaluate the efficacy in reducing post-operative pain with the use of Exparel® in 
comparison to bupivacaine injections in bariatric patients undergoing LRYGB with EEA stapler 
anastomosis at the incision sites. 
 
Hypothesis 1a.  Exparel® liposomal bupivacaine injected at the incisional sites prior to incision 
closure will reduce post-operative pain when compared to standard local analgesia using 
bupivacaine. 
 
Hypothesis 1b. Exparel® liposomal bupivacaine injected at the incisional sites prior incision 
closure will reduce post-operative opioid analgesic use when compared to standard local 
analgesia using bupivacaine. 
 
Hypothesis 1c. Exparel® liposomal bupivacaine injected at the incisional sites prior to incision 
closing will reduce unplanned readmission, and inquiries to medical providers regarding pain in 
the first 30 days post operatively compared to standard local analgesia using bupivacaine. 
 
 
 
 


[KROH, ET AL. EFFICACY OF EXPAREL® ON POST-OPERATIVE 
PAIN AFTER RYGB USING EEA CIRCULAR STAPLER TECHNIQUE] 
NCT03187379 
Revised  
3/23/2020 
 
 
 
Materials and Methodology 
 
Study Design 
 
The study will be composed of 100, and will consist of two cohorts of 50 patients. The study 
cohort will include 50 patients who receive intraoperative Exparel® injections at the incision locations in 
addition to our standard multimodality post-operative analgesia. The control arm will include 50 
patients who meet inclusion criteria but receive standard 0.25% bupivacaine and our standard 
multimodality post-operative analgesia. Patients will be randomized by REDCap™ database 
system in collaboration with Cleveland Clinic Pharmacy to receive either Exparel® or the control 
medication (0.25% Bupivacaine). Consent from patients will be obtained and documented 
by a dedicated research personnel prior to any enrollment. 
 
Inclusion Criteria: 
After Institutional Research Board (IRB) study approval, patients will be prospectively 
enrolled in to the study. The participants for this study will include bariatric patients who 
present at the Cleveland Clinic Bariatric Surgery Center of Excellence, over 18 years of age, 
fulfilling NIH criteria for bariatric surgery and will proceed with laparoscopic Roux-en-y 
gastric bypass with the use of EEA stapler anastomosis for the treatment of their obesity. 
Patients who fulfill the inclusion criteria and do not meet any of the exclusion criteria will be 
approached for participation. Patients will provide written personal signature on the 
consent/authorization form for enrollment in the study.  
 
Exclusion Criteria: 
Exclusion criteria includes age <18 years which is a contra-indication to laparoscopic roux-
en-y gastric bypass, patients with previous history of roux-en-y gastric bypass, or patients 
undergoing other bariatric procedures. Patients on pre-operative opioid analgesics will also 
be excluded from participating in the study. If the physician feels that the safety of the 
patient is at risk the participant will be excluded from the study, patients will be additionally 
excluded. Participants unwilling and unable to return for required follow-up visits will also be 
excluded. 
 
 
 


[KROH, ET AL. EFFICACY OF EXPAREL® ON POST-OPERATIVE 
PAIN AFTER RYGB USING EEA CIRCULAR STAPLER TECHNIQUE] 
NCT03187379 
Revised  
3/23/2020 
 
 
 
Methods 
Phase I: Preoperative Procedures 
All patients undergoing laparoscopic roux en Y gastric bypass will undergo pre-operative 
assessments. This includes appointments with internal medicine physicians specialized in care 
of the bariatric surgical population, nutrition counseling, psychological screening, demonstrated 
weight loss during a preoperative trial period, and additional evaluation and clearance by 
subspecialists based on co-morbid conditions. In addition patients have a complete history and 
physical examinations performed by or supervised by Dr. Matthew Kroh MD, and Dr. John 
Rodriguez, Staff Bariatric Surgeons that utilize the circular EEA technique. Consent for this 
study will occur during a preoperative visit.  
 
Phase II: Operative procedure 
The bariatric surgical procedure, (laparoscopic RYGB), will be performed at the Cleveland Clinic 
Main Campus Bariatric Surgery Center of Excellence. The gastro-jejunal anastomosis will be 
created through the use of a circular end to end anastomotic (circular EEA) stapler with a 
3.5mm staple height (Covidien, Dublin, Ireland). Patients will be randomized to receive either 
Exparel (R) (liposome bupivacaine injection solution), or standard bupivacaine, ~0.25%. 
Standardized injection volumes and technique will be performed. The study coordinator and/or 
the co-investigators on this study will notify the operative team prior to incision time to remind 
them of participation in this study. Those administering the study medication will not be blinded 
to the administration, since the appearance between the medications is significantly different.  
 
Phase Ill: Postoperative Procedures 
Patients have an initial stay in the Post Anesthesia Recovery Area, and then are typically 
admitted to a nursing unit specializing in post-operative bariatric care. Patients will be followed 
by the surgical team while in the hospital, and all will receive the same multimodal anesthetic 
regimen Patients are advanced on a diet along a pre-determined schedule, starting usually on 
post-operative day 1. 
 
At 24 hours a member of the research team will administer a 2-part questionnaire containing the 
VAS and the Revised American Pain Society Post-Operative Questionnaire (APS-POQ-R).[16]  
The latter is validated for assessment of the patient's experience of pain and it hindrance to 
daily activity in the post-operative period.  The VAS and APS-POQ-R assessment will be 
administered at 48 hours only if the patient is not discharged on post-operative day 1. 
Assessors will be blinded to the medication that was administered in the operating room.  
 
Following discharge from the hospital, standard follow up appointments are scheduled at 7-10 
days, 1 month, 3 months, 6 months, and 12 months. Patients are monitored for adverse events 
from bariatric surgery, enumerated and standardized by the American Society of Metabolic and 
Bariatric Surgeons.[15] 
 
.  ED visits and readmissions, as well as phone calls to clinic for issues related to pain will be 
evaluated at 30 days postop via a retrospective chart review to assess patient healthcare usage 
after discharge.  Assessors will be blinded to the medication that was administered in the 
operating room.  
 


[KROH, ET AL. EFFICACY OF EXPAREL® ON POST-OPERATIVE 
PAIN AFTER RYGB USING EEA CIRCULAR STAPLER TECHNIQUE] 
NCT03187379 
Revised  
3/23/2020 
 
 
 
Chart review will be completed to determine the amount of intravenous and oral narcotic pain 
medication used during the hospital stay, converted to morphine equivalents. Chart review will 
also be completed to detect narcotic related adverse events, similar to those used in prior 
studies of Exparel®.[17] 
 All data will be collected in a password-protected REDCap™ customized for this project.  Data 
points and schedule of assessment is provided in Table 2. 
 
Study Protocol 
CCF policy on the use of Exparel® will be followed throughout the study.  Specific but not 
comprehensive points include; 
 
 
Use of Exparel® is limited to one per patient 
 
All safety guidelines as outlined in IOH policy on use of Exparel® will be followed 
 
All patients will be provided safety information concerning Exparel® on discharge 
 
Local Analgesia Administration Technique for the Investigational Group (see Table 1) 
 
Dilute to final volume of 120mL 
(20mL Exparel® + 60mL Bupivacaine (0.25%) and 40mL 0.9% injectable saline) 
 
At the end of surgical procedure- inject 60mL around the left subcostal surgical site. 
Administer 40mL in the prefascial space, and 20mL at the dermal – subdermal junction 
 
inject 15mL at each remaining trocar site (4 trocar sites)= 60mL 
 
Local Analgesia Administration Technique for the Control Group     
 
60cc Bupivacaine (0.5%) and 60mL 0.9% injectable Saline (final concentration 0.25% 
bupivacaine) 
 
At the end of surgical procedure- inject 60mL around the left subcostal surgical site. 
Administer 40mL in the prefascial space, and 20mL at the dermal –subdermal junction 
 
Inject 15mL at each remaining trocar site (4 trocar sites)= 60mL 
 
All injections will use a spinal needle, part of the stand operative equipment for this procedure, 
and be administered with a moving needle technique.  
 
 
 
 


[KROH, ET AL. EFFICACY OF EXPAREL® ON POST-OPERATIVE 
PAIN AFTER RYGB USING EEA CIRCULAR STAPLER TECHNIQUE] 
NCT03187379 
Revised  
3/23/2020 
 
 
 
Table 1: Study Medication and Post-operative Multimodality Pain Regimen 
 
 
Investigational Group 
Control Group 
Intraoperative Analgesia 
Local anesthetic 
Administered as: 
½ administered in the LUQ 
port site 
- 40 mL in prefascial space 
around the LUQ port 
- 20mL at dermal / 
subdermal junction of the 
LUQ port site  
½ volume split among 
remaining ports 
20cc Exparel® 
60cc Bupivicaine (0.25%) 
40cc Normal Saline 
Final volume: 120cc 
 
60cc Bupivicaine (0.5%) 
20cc Normal Saline 
Final volume: 120cc 
IV analgesia 
1000mg IV acetaminophen once 
+ Additional medication administered by Anesthesia 
Providers 
Post-operative Analgesia 
If NPO 
Ketorolac IV 30mg q6 hours x 48 hours 
Hydromorphone IV 0.2mg q4 hours prn 
After taking liquids  
Acetaminophen po 1000 mg q8 hours 
Ketorolac IV 30mg q6 hours x 48 hours 
Roxicodone po 5-10 mg  q4 hours prn 
Hydromorphone IV 0.2mg q4 hours prn 
 
All injections will be documented in the intra-operative report including areas injected, and 
amount of Exparel® or Bupivacaine used.  Any adverse events are to be documented as well 
in the electronic medical record. 
 
 
 


[KROH, ET AL. EFFICACY OF EXPAREL® ON POST-OPERATIVE 
PAIN AFTER RYGB USING EEA CIRCULAR STAPLER TECHNIQUE] 
NCT03187379 
Revised  
3/23/2020 
 
 
 
Pain assessment:  
 
First assessment at 24 hours post operatively using In Hospital Pain Assessment 
Questionnaire, including  
o Visual Analog Scale (VAS) 
o American Pain Society Post-Operative Questionnaire-Revised (APS-POQ-R) 
 
Second assessment at 48 hours post operatively with the same assessment 
questionnaires if the patient was not discharged on post-operative day 1.  
 
Retrospective chart review for Narcotic Associated Adverse Events (NAE) 
NAEs include:  
o Somnolence 
o Respiratory depression 
o Hypoventilation 
o Hypoxia 
o Dry mouth 
o n/v 
o constipation 
o Sedation 
o Confusion 
o Pruritus 
o Urinary retention 
o Post op ileus 
 
Data Collection 
As confidentiality of patient health records is of significant importance, the data obtained or 
recorded from this study will be stored in a REDCap (Research Electronic Data Capture) 
database developed by the principal investigator and co-principal investigator, research 
fellows, and the bariatric research support staff at the Cleveland Clinic. REDCap is a secure, 
web-based application designed to support data capture for research studies and among 
many functions, includes an intuitive interface for data entry, audit trails for tracking data 
manipulation, and automated export procedures with integration into statistical packages. 
Only researchers listed and approved on the study protocol will have access to the data. If 
data should need to be provided to investigators outside of the protocol, it will be provided 
without identifying information in order to protect the patient's privacy and remain in 
compliance with HIPAA. The database will be maintained throughout the approved 
duration of the project. 
 
 
Table 2: Schedule of Assessments  
Study Day/Time Point 
 
Pre-op 
Operative 
encounter 
(24, 48 hours 
post op) 
7-10 
days post 
op 
1 month post 
op 


[KROH, ET AL. EFFICACY OF EXPAREL® ON POST-OPERATIVE 
PAIN AFTER RYGB USING EEA CIRCULAR STAPLER TECHNIQUE] 
NCT03187379 
Revised  
3/23/2020 
 
 
 
Questionnaire 
 
 
 
 
VAS 
 
I* 
 
 
APS-POQ-R 
 
I* 
 
 
Satisfaction and healthcare 
utilization survey  
 
 
 
 
General Procedures 
 
 
 
 
Informed consent 
I* 
 
 
 
Complete medical history 
S 
 
 
 
Updated medical history 
 
S 
S 
S 
Medication history 
S 
 
 
 
Medication changes 
 
S 
S 
S 
Vital Signs 
S 
S 
S 
S 
Physical exam 
S 
S 
S 
S 
Height 
S 
 
 
 
Body weight 
S 
S 
S 
S 
Body Mass Index 
S 
S 
S 
S 
Laboratory Tests 
 
 
 
 
CBC 
S 
 
 
 
Basic chemistry 
S 
 
 
 
- 
S=Standard of Care; I=Investigational Procedures; *= no additional costs for 
Investigational Procedures. 


[KROH, ET AL. EFFICACY OF EXPAREL® ON POST-OPERATIVE 
PAIN AFTER RYGB USING EEA CIRCULAR STAPLER TECHNIQUE] 
NCT03187379 
Revised  
3/23/2020 
 
 
 
APS-POQ-R 


[KROH, ET AL. EFFICACY OF EXPAREL® ON POST-OPERATIVE 
PAIN AFTER RYGB USING EEA CIRCULAR STAPLER TECHNIQUE] 
NCT03187379 
Revised  
3/23/2020 
 
 
 
 


[KROH, ET AL. EFFICACY OF EXPAREL® ON POST-OPERATIVE 
PAIN AFTER RYGB USING EEA CIRCULAR STAPLER TECHNIQUE] 
NCT03187379 
Revised  
3/23/2020 
 
 
 
Gordon, et al. J Pain. 2011; 11(11): 1172-86.  
 
Visual Analog Pain Scale 
 
How would you rate your current pain?  
 
Place a mark along the line below 
 
 
 
 
 


[KROH, ET AL. EFFICACY OF EXPAREL® ON POST-OPERATIVE 
PAIN AFTER RYGB USING EEA CIRCULAR STAPLER TECHNIQUE] 
NCT03187379 
Revised  
3/23/2020 
 
 
 
Interview at 1 Week and 1 Month Post-Operative Follow Up 
1. How satisfied were you with your post-operative analgesia  
Extremely 
dissatisfied 
Very 
dissatisfied 
Somewhat 
dissatisfied 
Somewhat 
satisfied 
Very 
satisfied 
Extremely 
Satisfied 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2. Were you readmitted to the hospital? 
Yes 
 
 
No  
 
If yes, for what reason?  
 
 
 
 
 
 
 
 
3. Did you have any unplanned medical visits?  
 
Yes 
 
 
No  
 
If yes, for what reason?  
 
 
 
 
 
 
 
 
 
4. Did you experience any health related problems during your recovery?  
 
Yes 
 
 
No  
 
If yes, what were they?  
 
 
 
 
 
 
 
 
5. Did you contact a medical provider about your recovery, apart from your scheduled post-
operative visits? 
 
Yes 
 
 
No  
 
If yes, for what reason?  
 
 
 
 
 
 
 
 
 


[KROH, ET AL. EFFICACY OF EXPAREL® ON POST-OPERATIVE 
PAIN AFTER RYGB USING EEA CIRCULAR STAPLER TECHNIQUE] 
NCT03187379 
Revised  
3/23/2020 
 
 
 
Statistical analysis 
Descriptive statistics will be computed for all variables. These include means, ranges, 
standard deviations, and percentiles for continuous variables and also frequencies and 
percentages for categorical variables. Data will be separated into two groups; investigational 
group and control group. Data will be presented as mean ± standard deviation, median 
[interquartile range] or N (%).  All analyses will be performed using SAS (version 9.2 or higher, 
The SAS Institute, Cary, NC) and R (version 2.13.1 or Higher, The R Foundation for Statistical 
Computing, Vienna Austria). A P < 0.05 will be considered statistically significant Results will 
be compared within each cohort and between cohorts. 
 
Power analysis 
This power analysis was calculated for the primary aim of the study to compare post-
operative pain reduction between both cohorts. Calculations were made based on results in 
the Butz et al. paper involving the use of the VAS scale in postoperative pain in breast 
reconstruction. Power was calculated assuming the use of a two-sample t test to compare mean 
VAS levels between Exparel® patients and patients given the standard of care treatment. The 
actual difference in means was assumed to be 1.5 mm and pooled standard deviation was 
varied across a range from 1 mm to 3 mm. For standard deviations similar to those seen in the 
Butz article, 50 patients are calculated to give > 85% power to detect a 1.5 mm difference in 
mean VAS at a standard deviation of 2.6 mm.  
 
Based on these calculations, a sample size of 50 patients per group is adequate under the 
conditions seen in the reference paper- a pooled standard deviation of about 2 mm and a 
difference in means of about 1.5mm. However, we see from the other conditions explored that 
the adequacy of this sample size (defined as having ≥ 80% power to detect a difference) is 
somewhat sensitive to either the true difference in means being less or the standard deviation 
larger.  
 
Timeline and Feasibility 
We fully expect to achieve our objectives upon completion of the funding period based on 
statistical and clinical resources available through the Digestive Disease and Surgery Institute, 
and Department of Quantitative Health Sciences.  
Risk/Benefit Analysis 
Benefits  
Participation in this study may help to improve post-operative pain.  There is no guarantee that 
all patients will benefit by participating in this research study. Participation in this study may 
provide information that may help other people in the future. 
 
Risks  
There may be risks or side effects related to the study drug that are unknown at this time. 
Patients and IRB will be notified of any significant new findings that become known that may 
affect the patient’s willingness to continue in the study. There are no additional risks related to 
this beyond those which would be routinely discussed related to surgery. The treating physician 
will counsel subjects regarding the surgical risks related to each procedure as part of obtaining 
informed consent.  


[KROH, ET AL. EFFICACY OF EXPAREL® ON POST-OPERATIVE 
PAIN AFTER RYGB USING EEA CIRCULAR STAPLER TECHNIQUE] 
NCT03187379 
Revised  
3/23/2020 
 
 
 
 
Complications 
Any complications, anticipated or unanticipated, will be monitored until they are resolved or 
explained. 
 
Protocol Changes  
Any changes to the study protocol will be reviewed and approved by the Cleveland Clinic IRB 
prior to implementation. 
 
Study Termination 
The investigator may terminate this study at any time. All data collected prior to termination of 
study can be used for analysis.    
 
Data Monitoring and Coordination Procedures  
The study investigator or his designee will monitor the study by frequent communications with 
all personnel engaged in the study to assure that the study is carried out according to protocol. 
Data will be entered into a database to facilitate data analysis.  Proper precautions will be taken 
to ensure the safety of patient information. The Principal Investigator or his designee will 
monitor the study at least once a year for data quality, subject recruitment, accrual, and 
retention, outcome and adverse event data, assessment of scientific reports or therapeutic 
development, results of related studies that impact subject safety, and procedures designed to 
protect the privacy of subjects. 
 
IRB Reporting 
Events requiring prompt reporting to the IRB will be done so in a timely manner.  At the time of 
continuing review, the following information will be provided: 1) summary of cumulative adverse 
events (if any); 2) assessment of external factors (i.e. scientific reports, therapeutic 
developments, results of related studies) that impacted the safety of subjects; and 3) any 
changes to the risk-benefit ratio. 
 
Consent Forms 
Each patient, prior to evaluation, will sign a consent form.  Copies will be distributed as follows: 
the original copy will be retained by the study coordinator, and one copy will be given to the 
patient. 
 
Study Records and Reports 
Investigator Records 
The investigator is responsible for the preparation, review, and retention of the records listed 
below: 
 
all correspondence that pertains to the study, 
 
source documents containing clinical results, 
 
documentation of date and reason for any deviation from protocol 


[KROH, ET AL. EFFICACY OF EXPAREL® ON POST-OPERATIVE 
PAIN AFTER RYGB USING EEA CIRCULAR STAPLER TECHNIQUE] 
NCT03187379 
Revised  
3/23/2020 
 
 
 
 
All applicable essential documents, as defined by Sections 8.2-8.4 of ICH E6 
Guidance on Good Clinical Practice 
 
Information Use 
Clinical information gathered from this study may be formalized in a manuscript and submitted 
for presentation or publication in a medical journal. 
 
 
Local/Institution Review Board 
The protocol for this investigation will be reviewed and by the Institutional Review Board 
(IRB). 
 
  
Available Resources 
There will be no dedicated space or equipment for the procedures specific to this 
investigation, however all shared facilities and equipment will be available. Procedures 
included in this study will occur at the standard facilities. At the Cleveland Clinic, these 
procedures take place in the operating theaters/suite. A research coordinator will be 
responsible for consenting patients prior to their involvement in this study. The surgical 
procedures for this study will be performed by Dr. Kroh, Director of Surgical Endoscopy, and 
Dr. Rodriguez. 
 
Office: Dr. Rodriguez and support staff have adequate office and clinic space in the Digestive 
Disease Institute.  
 
Operative theaters: Dr. Rodriguez and his co-investigators will have access to the Cleveland 
Clinic’s operative rooms in order to perform the operative procedure. These operative rooms 
are fully equipped for the desired bariatric procedure.  
 
Statistical Support: The Cleveland Clinic Digestive Disease and Surgery Institute has a 
dedicated biostatistician that will statistically support for the analysis associated with this 
study. 
 
Communication: Additional areas that are available to support this study include a conference 
room and library space with both teleconferencing and videoconferencing capabilities. 
 
 
 


[KROH, ET AL. EFFICACY OF EXPAREL® ON POST-OPERATIVE 
PAIN AFTER RYGB USING EEA CIRCULAR STAPLER TECHNIQUE] 
NCT03187379 
Revised  
3/23/2020 
 
 
 
  
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[KROH, ET AL. EFFICACY OF EXPAREL® ON POST-OPERATIVE 
PAIN AFTER RYGB USING EEA CIRCULAR STAPLER TECHNIQUE] 
NCT03187379 
Revised  
3/23/2020 
 
 
 
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