Conditions: Shoulder Pain
Keywords: Total Shoulder Arthroplasty (TSA) Interscalene Nerve Block (ISB)
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 184
Healthy volunteers: yes

Brief summary:
This is a phase IV , randomized, single-blind, single-center study comparing patient related outcomes such as postoperative pain and opioid usage for patients who receive ISB 's containing liposomal bupivacaine (Exparel®) plus 0.5% bupivacaine HCL versus 0.5% bupivacaine HCL undergoing total shoulder arthroplasty. The objective of this study is to compare opioid utilization and pain management of patients who receive Exparel in an ISB vs standard 0.5% bupivacaine HCL during the initial 72 --- hour post --- operative period. Additionally, to understand the duration of block after addition of Exparel® to bupivacaine in an Interscalene block after TSA.

Detailed description:

Arms:
arm 1: None arm 2: Administered in an Interscalene block for TSA

Interventions: intervention 1: Liposomal Bupivacaine intervention 2: 0.5% Bupivacaine HCL
Intervention descriptions: intervention 1: Liposomal Bupivacaine Plus 0.5% Bupivacaine HCL intervention 2: 0.5% Bupivacaine HCL for Interscalene Nerve Block (ISB)

Protocol document:
Prot_SAP_000.pdf: 
 
 
Page 1 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
 
 
 
LIPOSOMAL BUPIVACAINE PLUS BUPIVACAINE VERSUS BUPIVACAINE 
HCL FOR INTERSCALENE BRACHIAL PLEXUS BLOCK IN PATIENTS 
UNDERGOING TOTAL SHOULDER ARTHROPLASTY 
 
A phase IV, randomized, single-blind, single-center study that measures the effects of interscalene brachial 
plexus blocks (ISB) containing Liposomal Bupivacaine plus 0.5% bupivacaine HCL versus 0.5% Bupivacaine 
HCL on postoperative pain and opioid utilization in participants who undergo primary total shoulder 
arthroplasty surgery. 
 
Principal Investigator: 
 
Uchenna O. Umeh, MD 
Department of Anesthesiology, Perioperative Care and Pain Med 
 
NYU Langone Health  
NYU Langone Orthopedic Hospital  
301 East 17th Street  
New York, NY 10003 
 
Uchenna.Umeh@nyulangone.org 
O: (212) 598-6085  
M:(917) 969-1551 
Additional Investigators: 
 
 
Arthur Atchabahian, MD 
Department of Anesthesiology, Perioperative Care and Pain Med 
 
NYU Langone Health  
NYU Langone Orthopedic Hospital  
301 East 17th Street  
New York, NY 10003 
 
Arthur.Atchabahian@nyulangone.org 
O: (212) 598-6085  
 
Mandeep Virk, MD 
Department of Orthopedic Surgery 
 
NYU Langone Health  
NYU Langone Orthopedic Hospital  
301 East 17th Street  
New York, NY 10003 
 
Mandeep.Virk@nyulangone.org 
O:(646) 754- 2100  
NYULMC Study Number: 
18-01183  
Study Product: 
Liposomal Bupivacaine (Exparel®) 
ClinicalTrials.gov Number  NCT03913091 
 
Initial version: 1/17/19 
Amended: 4/17/19  
 
Amended: 7/17/2019


Study number: S18-01183 
 
Version: 7/17/19 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 05 JAN 2017 
 
Statement of Compliance 
 
This study will be conducted in accordance with the Code of Federal Regulations on the Protection of Human 
Subjects (45 CFR Part 46), 21 CFR Parts 50, 56, 312, and 812 as applicable, any other applicable US 
government research regulations, and institutional research policies and procedures. The International 
Conference on Harmonisation (“ICH”) Guideline for Good Clinical Practice (“GCP”) (sometimes referred to as 
“ICH-GCP” or “E6”) will be applied only to the extent that it is compatible with FDA and DHHS regulations. 
The Principal Investigator will assure that no deviation from, or changes to the protocol will take place 
without prior agreement from the sponsor and documented approval from the Institutional Review Board 
(IRB), except where necessary to eliminate an immediate hazard(s) to the trial participants. All personnel 
involved in the conduct of this study have completed Human Subjects Protection Training. 
 
 


 
 
Page 3 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
Table of Contents 
 
STATEMENT OF COMPLIANCE .................................................................................................................... 2 
LIST OF ABBREVIATIONS ............................................................................................................................ 5 
PROTOCOL SUMMARY ................................................................................................................................. 6 
1 
KEY ROLES .......................................................................................................................................... 7 
2 
BACKGROUND AND SPECIFIC AIMS ................................................................................................... 7 
2.1 
SPECIFIC AIMS................................................................................................................................. 8 
2.1 
STATISTICAL HYPOTHESES ................................................................................................................. 8 
2.2 
OBJECTIVES AND PURPOSE ................................................................................................................. 8 
3 
STUDY DESIGN AND ENDPOINTS ....................................................................................................... 9 
3.1 
DESCRIPTION OF STUDY DESIGN ......................................................................................................... 9 
3.2 
SCHEMATIC OF STUDY DESIGN .......................................................................................................... 11 
4 
STUDY ENROLLMENT AND WITHDRAWAL ..................................................................................... 12 
4.1 
INCLUSION CRITERIA ...................................................................................................................... 12 
4.2 
EXCLUSION CRITERIA ...................................................................................................................... 12 
4.3 
VULNERABLE SUBJECTS ................................................................................................................... 12 
4.4 
RECRUITMENT AND CONSENT ........................................................................................................... 12 
4.5 
DURATION OF STUDY PARTICIPATION ................................................................................................ 13 
4.6 
TOTAL NUMBER OF PARTICIPANTS AND SITES ..................................................................................... 13 
4.7 
PARTICIPANT WITHDRAWAL OR TERMINATION ................................................................................... 13 
4.8 
PREMATURE TERMINATION OR SUSPENSION OF STUDY .......................................................................... 13 
5 
RISKS AND BENEFITS ....................................................................................................................... 14 
5.1 
POTENTIAL RISKS .......................................................................................................................... 14 
5.2 
POTENTIAL BENEFITS ..................................................................................................................... 14 
6 
STATISTICAL ANALYSIS.................................................................................................................... 14 
6.1 
GENERAL APPROACH ...................................................................................................................... 14 
6.2 
ANALYSIS OF ENDPOINTS ................................................................................................................. 14 
6.2.1 
Baseline Descriptive Statistics ................................................................................................. 15 
6.3 
SAMPLE SIZE................................................................................................................................. 15 
6.4 
ENROLLMENT/RANDOMIZATION/MASKING PROCEDURES...................................................................... 15 
6.5 
BREAKING THE STUDY BLIND/PARTICIPANT CODE ............................................................................... 15 
7 
ASSESSMENT OF SAFETY .................................................................................................................. 15 
7.1 
DEFINITION OF SERIOUS ADVERSE EVENTS (SAE) ................................................................................ 16 
7.2 
CLASSIFICATION OF AN ADVERSE EVENT ............................................................................................. 16 
7.2.1 
Severity of Event .................................................................................................................... 16 
7.2.2 
Relationship to Study Agent .................................................................................................... 16 
7.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP ............................................... 17 
7.4 
SAFETY OVERSIGHT ........................................................................................................................ 18 
8 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ............................................ 18 
9 
ETHICS/PROTECTION OF HUMAN SUBJECTS .................................................................................. 18 
9.1 
ETHICAL STANDARD ....................................................................................................................... 18 
9.2 
INSTITUTIONAL REVIEW BOARD ....................................................................................................... 18 
9.3 
PARTICIPANT AND DATA CONFIDENTIALITY ........................................................................................ 18 


 
 
Page 4 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
10 
DATA HANDLING AND RECORD KEEPING ....................................................................................... 19 
10.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES ..................................................................... 19 
10.2 
STUDY RECORDS RETENTION ........................................................................................................... 19 
10.3 
PROTOCOL DEVIATIONS .................................................................................................................. 20 
10.4 
PUBLICATION AND DATA SHARING POLICY .......................................................................................... 20 
10.5  
DATA SAFETY AND MONITORING (DSMB) …………………………………………………………………………………….. 19  
11 
STUDY FINANCES .............................................................................................................................. 21 
11.1 
FUNDING SOURCE .......................................................................................................................... 21 
11.2 
COSTS TO THE PARTICIPANT ............................................................................................................ 21 
11.3 
PARTICIPANT REIMBURSEMENTS OR PAYMENTS ................................................................................... 21 
12 
CONFLICT OF INTEREST POLICY ...................................................................................................... 21 
13 
REFERENCES ..................................................................................................................................... 22 
14 
ATTACHMENTS ................................................................................................................................. 23 
14.1 
OPIOID EQUIVALENTS .................................................................................................................. 23 
14.2 
PROMIS ASSESSMENT .......................................................................................................... 22 
14.3 
Medication Usage Record ........................................................................................................ 23 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
Page 5 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
 
List of Abbreviations 
 
ASA 
American Society of Anesthesiologist Score 
 
VAS 
Visual analog scale 
 
TSA 
Total Shoulder Arthroplasty 
 
ISB 
Interscalene Nerve Block 
 
DVT 
Deep vein thrombosis 
 
ER 
Emergency room  
 
AE 
Adverse event 
 
SAE 
Serious adverse event 
 
IV 
Intravenous 
 
PO 
Taken orally 
 
PRN 
Taken as needed 
 
TID 
Taken three times per day 
 
Q4h 
Taken every four hours 
 
CI 
Confidence interval 
 
SD 
Standard deviation; a parameter, which characterizes a population distribution 
 
SE 
Standard error 
 
ANOVA 
Analysis of variance; a linear model   
 
NSAID 
Non-steroidal anti-inflammatory drug 
 
 
 
 
 
 


 
 
Page 6 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
Protocol Summary 
Title 
Liposomal Bupivacaine (Exparel®) Plus 0.5% Bupivacaine HCL versus 0.5 % 
Bupivacaine HCL for Interscalene Nerve Block (ISB) for patients undergoing Total 
Shoulder Arthroplasty (TSA) 
Short Title 
Understanding the effects of Exparel® on post-operative pain management and 
opioid utilization for patients undergoing TSA 
Brief Summary 
This is a phase IV, randomized, single-blind, single-center study comparing patient 
related outcomes such as postoperative pain and opioid usage for patients who 
receive ISB’s containing liposomal bupivacaine (Exparel®) plus 0.5% bupivacaine 
HCL versus 0.5% bupivacaine HCL undergoing total shoulder arthroplasty.  
Phase 
Clinical study phase IV 
Objectives 
To compare opioid utilization and pain management of patients who receive 
Exparel in an ISB vs standard 0.5% bupivacaine HCL during the initial 72-hour 
post-operative period. Additionally, to understand the duration of block after 
addition of Exparel® to bupivacaine in an Interscalene block after TSA  
Methodology 
phase IV, randomized, single-blind, single-center study 
Endpoint 
Primary Endpoints: 
Opioid utilization expressed as (oral morphine mg equivalents) during the initial 
72-hour post-operative period.  
 
Secondary Endpoints: 
Duration of opioid use 
Patient reported pain scores (VAS) 
Length of stay 
Reported long-term narcotic use at home  
Documented opioid refills 
Adverse events such as respiratory depression, hypoventilation, reintubation, 
nausea, constipation 
Study Duration 
3 years 
Participant Duration 
Four weeks 
Duration of IP 
administration 
Once during surgery 
Population 
184 participants scheduled for total shoulder arthroplasty (TSA) 
Study Sites 
NYU Langone Orthopedic Hospital 
Number of 
participants 
184 
Description of Study 
Agent/Procedure 
Injection of 20mL 0.5% Bupivacaine HCL versus 10mL Liposomal Bupivacaine plus 
10mL Bupivacaine 0.5% in an Interscalene block for TSA 
Reference Therapy 
Reference is Bupivacaine 0.5% for Interscalene block 
Key Procedures 
Interscalene nerve block with Liposomal Bupivacaine + Bupivacaine 0.5% 
Statistical Analysis 
Intention-to-treat analysis will be performed with mean, t-tests, within and 
between group ANOVA and linear regression,  
 
 
 


 
 
Page 7 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
 
1 Key Roles 
 
Principal Investigator:    
 
Uchenna O. Umeh, MD 
Assistant Professor of Anesthesiology 
Department of Anesthesiology, Perioperative care and Pain Medicine 
NYU Langone Orthopedic Hospital 
NYU Langone Health 
301 East 17th street 
New York, NY 10003 
917-969-1551 
 
 
Co-Investigators:   
 
Arthur Atchabahian, MD 
Professor of Anesthesiology 
Department of Anesthesiology, Perioperative care and Pain Medicine 
NYU Langone Orthopedic Hospital 
NYU Langone Health 
301 East 17th street 
New York, NY 10003 
 
Mandeep Virk, MD 
Assistant Professor of Orthopedic Surgery 
Department of Orthopedic Surgery 
NYU Langone Orthopedic Hospital 
NYU Langone Health 
301 East 17th street 
New York, NY 10003 
 
 
2 Background and Specific Aims 
 
With the growing elderly population, the number of total shoulder arthroplasty (TSA) surgeries is 
increasing. Nationwide, the total and partial shoulder replacements increased from about 18,000 in 2000 to 
over 45,000 in 2013 according to the American Academy of Orthopedic surgeons (AAOS). One of the greatest 
drivers of cost following TSA has been shown to be discharge disposition. Effective pain control after 
surgery is paramount because it facilitates rehabilitation and decreases hospital length of stay. Additionally, 
it may increase the likelihood of patients being discharged to their home rather than a rehabilitation or 
skilled nursing facility.  
 
TSA is a procedure that is well confined within the dermatomal distribution of an interscalene brachial 
plexus nerve block (ISB), making it an ideal procedure to both evaluate and compare the regional potential 
of varying agents. Although the analgesic coverage is typically ideal, single shot injection of the long acting 


 
 
Page 8 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
local anesthetics, such as Bupivacaine, is limited in duration to the first postoperative day. Conversely, while 
interscalene perineural catheters offer the ability to continuously provide analgesia, they are time 
consuming to place, require daily maintenance, and often dislodge or migrate from the desired position.  
These limitations make interscalene perineural catheters problematic.  In order to offer the longevity of an 
appropriately positioned catheter while preserving the simplicity of a single injection nerve blockade, this 
group proposes to evaluate the efficacy of liposomal bupivacaine or Exparel® in the setting of TSA.   
 
Exparel® is a sterile, nonpyrogenic, preservative-free liposomal formulation of bupivacaine that provides a 
non-opioid option for postoperative pain control for up to 72 hours with single shot injection into the 
perineural space. The chemical and pharmacological nature of Exparel® allows for the encapsulated 
Bupivacaine to extend its duration of local anesthetic action by delaying medication release as compared to 
the injection of plain Bupivacaine. The FDA has recently approved Exparel® in its use for shoulder surgery 
via the interscalene nerve block. Exparel® has shown great potential with both its analgesic benefits and 
side effect profile; however, adequately powered trials are still necessary in order to compare its benefits to 
that of standard Bupivacaine. 
 
To date, only one study has been published comparing bupivacaine alone to bupivacaine plus liposomal 
bupivacaine (1). In that study, the reduction in pain scores was minimal. However, there are several 
methodological issues with that study: 0.25% bupivacaine was used rather than 0.5%, resulting in a nerve 
block that was less dense, and making it mandatory to use general anesthesia; the study was probably 
underpowered; and analgesic use was not quantified. 
 
2.1 
Specific Aims 
AIM 1:  To determine if Liposomal bupivacaine added to 0.5 % bupivacaine HCL in the interscalene nerve 
block during TSA surgery significantly changes post-operative opioid usage during the initial 72 hours post-
operative period. This will be evaluated by randomizing patients to either receive 0.5% Bupivacaine HCL or 
Bupivacaine 0.5% with Liposomal bupivacaine in the interscalene nerve block. Opioid consumption will be 
evaluated in the immediate post-operative period, up to 72 hours post op and for up to 4 weeks after 
surgery. 
 
AIM 2:  To determine if the addition of Liposomal bupivacaine to Bupivacaine 0.5% in an interscalene nerve 
block prolongs post-operative nerve block and hence reduces post-operative pain from during the initial 72 
hour post-operative period.  Using the same groups as above, the patient stated duration of block (record 
time of onset of pain) and post-operative VAS Pain scores will be recorded in both the hospital and 
outpatient settings. Physical therapy endpoints will also be monitored and recorded. 
 
2.1 Statistical Hypotheses 
We hypothesize that adding Liposomal bupivacaine to Bupivacaine 0.5% for the interscalene nerve block 
prior to TSA surgery will prolong the sensory block and reduce post-operative pain and opioid usage not 
only during the patients’ inpatient hospital stay but also after discharge from the hospital for up to 72 hours. 
Furthermore, combining Liposomal bupivacaine and Bupivacaine will reduce complications associated with 
opioids such as constipation, nausea, pruritus, ileus and opioid dependency. Failing to reject the null 
hypothesis would signify that Exparel® has no clinically relevant impact on post-operative outcomes in TSA 
surgery as compared to plain Bupivacaine.  
2.2 
Objectives and Purpose 
The goal of this study is to determine the effectiveness of Liposomal bupivacaine at reducing opioid 
consumption from 24-72 hours when used along with Bupivacaine 0.5% for single shot ISB for total 
shoulder arthroplasty. In addition, we would also like to determine if Liposomal bupivacaine is effective at 
prolonging the sensory block and reducing post-operative pain in patients after TSA surgery. We would also 


 
 
Page 9 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
like to determine how reduction in post-operative pain impacts a patient’s hospital stay in the short term.  
Primary outcomes measures will be opioid utilization (in morphine milligram equivalents [MME]) during a 
72-hour post-operative period.  Secondary outcomes include patient reported pain scores, VAS.  While it is 
expected that the greatest benefit of Liposomal bupivacaine plus Bupivacaine 0.5% will be seen within 24-
72 hours after surgery, it is possible that there will be in an overall reduction in long-term opioid use (up to 
4 weeks). Secondarily, function/rehabilitation, length of stay, and complications may be impacted by 
combined use of Liposomal bupivacaine plus Bupivacaine 0.5%. 
 
3 Study Design and Endpoints 
 
ARM 1: Experimental 
Sample Size: 
92 
10 mL Bupivacaine 0.5% 
+ 
10 mL Liposomal Bupivacaine 
 
ARM 2: Control 
Sample Size: 
92 
20 mL Bupivacaine 0.5% 
 
 
3.1 
Description of Study Design 
 
PRE-SCREENING PHASE/CONSENTING PHASE: 
Surgeons will inform eligible patients of the study during their pre-surgical visit in their office.  The surgeons 
will use an IRB-approved recruitment flyer to help explain the study to the eligible patient. If the patient is 
agreeable, a member of the research team will provide further details and ask the patient to participate on 
day of surgery.  Informed consent will be obtained on DOS when the patient is in the pre-operative holding 
room by an authorized research member.  
 
BASELINE ASSESSMENTS:  
After informed consent has been obtained, participants will complete a total of 3 PROMIS assessments 
(Upper Extremities, Pain Intensity and Global Physical Health) before undergoing their TSA surgery.  
 
RANDOMIZATION PHASE:  
Subjects scheduled to undergo TSA will be randomized to either the Bupivacaine 0.5% plus Liposomal 
bupivacaine Or Bupivacaine 0.5% group. Randomization of each subject will be done on day of surgery using 
randomization.com software to generate the assignment.  
 
TREATMENT PHASE:  
Subjects in the Bupivacaine plus Liposomal bupivacaine group will receive an interscalene nerve block with 
10mL 0.5% Bupivacaine and 10mL of Liposomal bupivacaine. The control group will receive an interscalene 
nerve block with 20mL 0.5% Bupivacaine HCL. The anesthesiologist will NOT be blinded to what solution is 
being injected, as liposomal bupivacaine is a white fluid while bupivacaine is clear. All other stakeholders 
(patient, surgeon, other caregivers, and research staff collecting the data) will be blinded to the patient’s 
group assignment. 
 
POST-OPERATIVE PHASE:  
After initial recruitment, subjects’ pain will be assessed via visual analog scale (VAS) by nursing staff during 
the post-operative period as per standard of care. The VAS pain scores are collected and documented in the 
patient’s electronic medical record. Additionally, a standardized regimen of pain medication will be given to 
all subjects who are enrolled. The pain medications given to patients are standard of care medications and 
vary based on pain level. The clinical staff determines this for each patient.  
 


 
 
Page 10 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
Occupational and physical therapy progress and activity goals will be reviewed. As per standard of care, 
motor testing of the operated shoulder and arm will be assessed during these visits. This includes: No 
weight bearing exercises will be performed as per surgeon’s instructions and the nursing staff will continue 
to obtain VAS pain scores.  
 
During the 24-72 hour post-operative period, research staff will visit the patient while they are in the 
hospital to obtain and verify the pain medication taken. If the patient is discharged before the 72-hour 
period, the research staff will give the patient a copy of a medication record diary to complete. Additionally, 
the staff member will call the patient within 1-2 business days to obtain the remaining opioid utilization 
information.  
 
After discharge, the research staff will continue to follow up with the patient on POD 7, POD 14 and POD 30 
to assess pain scores, opioid usage patterns, and functional status. The pain intensity PROMIS assessment 
will be administered during each phone call. Additionally, on POD 30, participants will complete the Upper 
Extremity PROMIS form. Research staff will verify documented opioid refills through Epic and pharmacy 
records.  
 
 


 
 
Page 11 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
 
3.2 
Schematic of Study Design 
 
 
184 subjects: Obtain informed consent. Screen potential subjects by inclusion and 
exclusion criteria; obtain history, document. 
Randomize 
ISB with:  
Bupi 0.5 % + Exparel  
92 Subjects 
ISB with:  
Bupi 0.5%  
92 Subjects 
VAS Scores, Opioid Consumption, Rehabilitation Progress, LOS 
Phone interviews: Opioid utilization (Medication Log), VAS (Pain Intensity 
Assessment)  
Final Assessments: Opioid Utilization, 
VAS pain scores and Upper Extremity 
questionnaire  
Inpatient 
Measurements 
Enrollment 
Outpatient 
Measurements 
(POD 7, 14) 
Outpatient 
Measurements 
(POD 30) 


 
 
Page 12 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
4 Study Enrollment and Withdrawal 
The researchers will approach patients scheduled for primary total shoulder arthroscopy who are eligible 
for participation in the study. Anesthesiology attendings, fellows, residents and authorized researchers will 
consent and enroll patients pre-operatively. 
4.1 
Inclusion Criteria 
1. 
Patients between 18 and 85 years of age 
2. 
Patients undergoing total shoulder arthroplasty; and 
3. 
Patients who consent to be randomized. 
4.2 
Exclusion Criteria 
1. Patients younger than 18 and older than 85; 
2. Patients with a history of chronic pain that have used opioids for pain management for 3 months or 
longer; 
3. Patients who are allergic to oxycodone; 
4. Patients who are unable to speak English; 
5. Patients with diagnosed or self-reported cognitive dysfunction; 
6. Patients with a history of neurologic disorder that can interfere with pain sensation; 
7. Patients with a history of drug or recorded alcohol abuse; 
8. Patients who are unable to understand or follow instructions; 
9. Patients with severe liver disease, renal insufficiency, congestive heart failure, and/or significant heart 
disease; 
10. Patients with an allergy or contraindication to any of the medications used in the study, or patients with a 
contraindication to any study procedures; 
11. Patients with BMI over 40;  
12. Any patient that the investigators feel cannot comply with all study related procedures; 
13. NYU Langone Health students, residents, faculty or staff members 
 
4.3 
Vulnerable Subjects 
No vulnerable populations will be intentionally solicited. It is possible that employees, economically 
disadvantaged persons and students will be solicited in the course of enrollment however no one will be 
specifically recruited for these reasons and no one with ties to the NYU Anesthesiology and Orthopedics 
department or NYU School of Medicine will be eligible for participation. 
4.4 Recruitment and Consent 
This study will utilize EPIC to identify subjects and use Redcap in addition to the firewall protected shared 
drive to manage and store relevant data.   
 
Process of Consent 
The consent for participation will be obtained on day of surgery in pre-operative holding room by the 
regional anesthesiology fellow, Attending Physician, or authorized researcher. Extensive discussion of risks 
and possible benefits of participation will be provided to the participants and their families. Consent forms 
will be IRB-approved and the participant will be asked to read and review the document. The investigator 
will explain the research study to the participant and answer any questions that may arise. All participants 
will receive a verbal explanation suited to their comprehension of the purposes, procedures, potential risks 
and their rights as research participants. Participants will have the opportunity to carefully review the 
written consent form and ask questions prior to signing. The participants will have the opportunity to 
discuss the study with their surrogates or think about it prior to agreeing to participate. The participant will 
sign the informed consent document prior to any procedures being done specifically for the study. The 
participants may withdraw consent at any time throughout the course of the trial. A copy of the signed 


 
 
Page 13 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
informed consent document will be given to the participants for their records. The rights and welfare of the 
participants will be protected by emphasizing that the quality of their medical care will not be adversely 
affected if they decline to participate in this study. 
 
A copy of the signed informed consent document will be given to the patient, placed in the patient’s 
electronic medical record and the original copy will be stored in the research regulatory binder.  Any 
alteration to the standard consent process (e.g. use of a translator, consent from a legally authorized 
representative, consent document presented orally, etc.) and the justification for such alteration will 
likewise be documented.  
 
Subject Capacity 
All subjects will be assessed for capacity to give informed consent. Capacity will be assessed through the 
subjects’ ability to express understanding of the information presented to them, their ability to express a 
choice, their appreciation of how this is relevant to them, and reasoning about how the study might impact 
them and others.  
 
Subject/Representative Comprehension 
The subject themselves will have to clearly state back the basic goals of the study (i.e. to look at the effect of 
different local anesthetics on post op pain after total shoulder replacement surgery) and state that they are 
willing to participate. This may be done in English or in their primary language with an interpreter.  
 
If a subject requests information regarding opting out of further recruitment for all research, subjects will be 
directed to contact research coordinator, Randy Cuevas at 212-598-6085. 
 
4.5 
Duration of Study Participation 
While the study will be open for 3 years after beginning enrollment, the actual length of a study subject’s 
participation is four weeks. 
4.6 
Total Number of Participants and Sites  
Recruitment will end when approximately 184 participants are enrolled. It is expected that approximately 
184 participants will be enrolled in order to produce 146 evaluable participants. The only site for 
enrollment will be the NYU Langone Orthopedic Hospital. 
 
4.7 
Participant Withdrawal or Termination 
Participants are free to withdraw from participation in the study at any time upon request. An investigator 
may terminate participation in the study if: 
 
• 
Any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest of the participant 
• 
The participant meets an exclusion criterion (either newly developed or not previously recognized) 
that precludes further study participation 
 
4.8 
Premature Termination or Suspension of Study 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable cause. 
If the study is prematurely terminated or suspended, the PI will promptly inform the IRB and will provide 
the reason(s) for the termination or suspension. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
1. 
Determination of unexpected, significant, or unacceptable risk to participants; 
2. 
Demonstration of efficacy that would warrant stopping; 


 
 
Page 14 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
3. 
Insufficient compliance to protocol requirements; 
4. 
Data that are not sufficiently complete and/or evaluable; or 
5. 
Determination of futility 
5 Risks and Benefits  
5.1 
Potential Risks  
Bupivacaine used for this study is the standard of care for ISB. Liposomal Bupivacaine (EXPAREL®), a 
second study drug, has recently been approved by the FDA for use in interscalene blocks. 
 
The potential risks associated with bupivacaine include neurologic and cardiac toxicity, if injected 
intravascularly. However, the risk is very low because a trained anesthesiologist using ultrasound guidance 
will perform the nerve block. This allows the anesthesiologist to see and avoid blood vessels when 
administering the medication. Additionally, the syringe of the local anesthetic will be aspirated prior to 
injection to ensure that the block needle tip is not intravascular.  
 
The use of Liposomal Bupivacaine or Exparel® in this study is experimental and may cause side effects. 
Exparel® has recently been approved by the FDA to be used in interscalene blocks. The potential risks 
associated with Exparel® include nausea, constipation, and fever. In addition, there can be temporary 
sensory and motor loss, depending on the dosage, site of injection and duration of the nerve block. However, 
the amount (10mL) used in this study meets FDA dosage-regulations for this medication.  
 
Potential Benefits 
Study subjects may experience better pain control, improved satisfaction, decreased need for opioids and 
reduced incidence of side effects. If the study is not inconclusive, the study’s results may benefit future 
patients by showcasing that Liposomal Bupivacaine improves pain control beyond 24hours in an ISB.  
Additionally, advocate for the use of Liposomal Bupivacaine as the standard of care for peri- and 
postoperative pain control in future patients undergoing TSA. 
 
6 Statistical Analysis 
6.1 
General Approach 
Intention-to treat. The primary analysis will follow the intention-to-treat (ITT) principle in order to evaluate 
the true outcome of the intervention as experienced by the patient who is blinded to the intervention. 
 
Missing Data. It is anticipated that the data for some subjects will be incomplete for various reasons:  
missing daily-diary entries, refusal to answer a sensitive question on a questionnaire, onset of illness, loss-
to-follow-up, etc. All occurrences of incomplete data will be investigated to carefully document the reasons 
for the missing data. If the primary outcome (amount of opioid used between 24 and 72 hours after surgery) 
cannot be ascertained with a reasonable degree of certainty, the patient will be excluded from the study. 
 
 
6.2 
Analysis of Endpoints 
Primary Endpoints: 
Opioid utilization (expressed as oral morphine mg equivalents) used during initial 24-72 hours post-
operative period after surgery. 
 
Secondary Endpoints: 


 
 
Page 15 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
Duration of opioid use 
Patient reported pain scores (VAS) 
Length of stay 
Progress with physical therapy 
Reported long-term narcotic use at home  
Discharge location: home, acute rehab or skilled nursing facility 
Documented opioid refills 
Adverse events such as respiratory depression, hypoventilation, reintubation, nausea, constipation 
 
The analysis of opioid use, VAS, and PROMIS assessments will rely on a univariate analysis of variance model 
for mean score.  This model is in the class of models commonly known as unirep-ANOVA models.  It assumes 
that the mean score is a function of elapsed time and the treatment regimen assigned.  This model considers 
the fact that the subject’s repeated measures are correlated.  The fitted model will provide statistical 
estimates of the mean levels, the treatment-effect differences between mean levels, the standard deviation, 
the intra-class correlation coefficient, 95% CIs, standard errors (SE), and statistical hypothesis tests.  The 
estimates of means will be used to compute summary criteria such as area under the curve (AUC) for each 
regimen.  All estimates reported will be presented their 95% CIs. 
 
All endpoints will be evaluated as fits the data set with graphical figures such as scatter plots, box-and-
whisker plots, and frequency histograms to visualize the distribution of these outcomes and their 
relationships to covariates and treatment assignment. When appropriate descriptive graphical and tabular 
methods will also be estimated and presented in a graphical figure. 
 
6.2.1 Baseline Descriptive Statistics 
The following patient data will be recorded: age, gender, height, weight, date of admission, date of discharge, 
laterality, surgical approach, implants used, duration of surgery, contamination, ASA, comorbidities 
(smoking, cardiac history, diabetes etc.), CBC (WBC, PCV, HGB, RBC, indices, platelet count, differential), and 
medications. All of this information will be accessible in the patient’s medical record.  
 
6.3 
Sample Size 
184 subjects will be enrolled 
6.4 Enrollment/Randomization/Masking Procedures 
We will utilize randomization.com to generate a randomization assignment for all 184 participants. 
Someone that is not a stakeholder in the study will make randomization envelopes, which include the study 
ID number, the treatment assignment, and dosage specifics. These randomization envelopes will then be 
distributed to the anesthesiologist pre-operatively by the authorized researcher after informed consent is 
obtained.  
6.5 Breaking the Study Blind/Participant Code 
If there is any adverse event related to the drug, we will break the blind for the subject and randomization 
will be disclosed to the patient. 
7 Assessment of Safety 
 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity 
during the course of the study.  Intercurrent illnesses or injuries should be regarded as adverse events.  
Abnormal results of diagnostic procedures are considered to be adverse events if the abnormality: 
• 
results in study withdrawal 


 
 
Page 16 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
• 
is associated with a serious adverse event 
• 
is associated with clinical signs or symptoms 
• 
leads to additional treatment or to further diagnostic tests 
• 
is considered by the investigator to be of clinical significance 
 
7.1 Definition of Serious Adverse Events (SAE) 
Serious Adverse Event 
Adverse events are classified as serious or non-serious.  A serious adverse event is any AE that is:  
• 
fatal 
• 
life-threatening 
• 
requires or prolongs hospital stay 
• 
results in persistent or significant disability or incapacity 
• 
a congenital anomaly or birth defect 
• 
an important medical event 
 
Important medical events are those that may not be immediately life threatening, but are clearly of major 
clinical significance. They may jeopardize the subject, and may require intervention to prevent one of the 
other serious outcomes noted above. For example, drug overdose or abuse, a seizure that did not result in in-
patient hospitalization or intensive treatment of bronchospasm in an emergency department would 
typically be considered serious.  
 
All adverse events that do not meet any of the criteria for serious will be regarded as non-serious adverse 
events.  
7.2 
Classification of an Adverse Event 
7.2.1 Severity of Event 
For AEs not included in the protocol defined grading system, the following guidelines will be used to 
describe severity. 
 
1. Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities. 
2. Moderate – Events result in a low level of inconvenience or concern with the therapeutic measures. 
Moderate events may cause some interference with functioning. 
3. Severe – Events interrupt a participant’s usual daily activity and may require systemic drug therapy or 
other treatment. Severe events are usually potentially life-threatening or incapacitating. 
 
7.2.2 Relationship to Study Agent 
The clinician’s assessment of an AE's relationship to study agent (drug, biologic, device) is part of the 
documentation process, but it is not a factor in determining what is or is not reported in the study. If there is 
any doubt as to whether a clinical observation is an AE, the event will be reported. All AEs must have their 
relationship to study agent assessed. For all collected AEs, the clinician who examines and evaluates the 
participant will determine the AE’s causality based on temporal relationship and his/her clinical judgment. 
The degree of certainty about causality will be graded using the categories below. 
1. Definitely Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal laboratory test result, 
occurs in a plausible time relationship to drug administration and cannot be explained by concurrent 
disease or other drugs or chemicals.  
2. Probably Related – There is evidence to suggest a causal relationship, and the influence of other factors 
is unlikely. The clinical event, including an abnormal laboratory test result, occurs within a reasonable 


 
 
Page 17 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
time after administration of the drug, is unlikely to be attributed to concurrent disease or other drugs or 
chemicals, and follows a clinically reasonable response on withdrawal).  
3. Possibly Related – There is some evidence to suggest a causal relationship (e.g., the event occurred 
within a reasonable time after administration of the trial medication). However, other factors may have 
contributed to the event (e.g., the participant’s clinical condition, other concomitant events). Although 
an AE may rate only as “possibly related” soon after discovery, it can be flagged as requiring more 
information and later be upgraded to “probably related” or “definitely related,” as appropriate. 
4. Unlikely to be related – A clinical event, including an abnormal laboratory test result, whose temporal 
relationship to drug administration makes a causal relationship improbable (e.g., the event did not occur 
within a reasonable time after administration of the trial medication) and in which other drugs or 
chemicals or underlying disease provides plausible explanations (e.g., the participant’s clinical 
condition, other concomitant treatments). 
5. Not Related – The AE is completely independent of study drug administration, and/or evidence exists 
that the event is definitely related to another etiology. There must be an alternative, definitive etiology 
documented by the clinician. 
 
Dr. Umeh will be responsible for determining whether an AE is expected or unexpected. An AE will be 
considered unexpected if the nature, severity, or frequency of the event is not consistent with the risk 
information previously described for the study agent. 
7.3 
Time Period and Frequency for Event Assessment and Follow-Up 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits and 
interviews of a study participant presenting for medical care, or upon review by a study monitor. All AEs 
including local and systemic reactions not meeting the criteria for SAEs will be captured on the appropriate 
RF. Information to be collected includes event description, time of onset, clinician’s assessment of severity, 
relationship to study product (assessed only by those with the training and authority to make a diagnosis), 
and time of resolution/stabilization of the event. All AEs occurring while on study must be documented 
appropriately regardless of relationship. All AEs will be followed to adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an AE. However, if the study participant’s condition deteriorates at any time 
during the study, it will be recorded as an AE. UPs will be recorded in the data collection system throughout 
the study. 
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event at 
each level of severity to be performed. AEs characterized as intermittent require documentation of onset 
and duration of each episode. 
 
The PI will record all reportable events with start dates occurring any time after informed consent is 
obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study participation. At each 
study visit, the investigator will inquire about the occurrence of AE/SAEs since the last visit. Events will be 
followed for outcome information until resolution or stabilization.  
 
All unresolved adverse events will be followed by the investigator until the events are resolved, the subject 
is lost to follow-up, or the adverse event is otherwise explained.  At the last scheduled visit, the investigator 
will instruct each subject to report any subsequent event(s) that the subject, or the subject’s personal 
physician, believes might reasonably be related to participation in this study.  The investigator will notify the 
study sponsor of any death or adverse event occurring at any time after a subject has discontinued or 
terminated study participation that may reasonably be related to this study.  The sponsor will also be 
notified if the investigator should become aware of the development of cancer or of a congenital anomaly in 
a subsequently conceived offspring of a subject that has participated in this study.  
 


 
 
Page 18 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
7.4 
Safety Oversight  
It is the responsibility of the Principal Investigator to oversee the safety of the study at his/her site.  This 
safety monitoring will include careful assessment and appropriate reporting of adverse events as noted 
above, as well as the construction and implementation of a site data and safety-monitoring plan. Medical 
monitoring will include a regular assessment of the number and type of serious adverse events. 
 
8 Source Documents and Access to Source Data/Documents  
Source data is all information, original records of clinical findings, observations, or other activities in a 
clinical trial necessary for the reconstruction and evaluation of the trial.  Source data are contained in source 
documents.  Examples of these original documents, and data records include: hospital records, clinical and 
office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing 
records, recorded data from automated instruments, copies or transcriptions certified after verification as 
being accurate and complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, 
subject files, and records kept at the pharmacy, at the laboratories, and at medico-technical departments 
involved in the clinical trial.  
 
The study case report form (CRF) is the primary data collection instrument for the study.  All data requested 
on the CRF must be recorded.  All missing data must be explained.  If a space on the CRF is left blank because 
the procedure was not done or the question was not asked, write “N/D”.  If the item is not applicable to the 
individual case, write “N/A”.  All entries will be printed legibly in black ink.  
 
Access to study records will be limited to IRB-approved members of the study team. The investigator will 
permit study-related monitoring, audits, and inspections by the IRB/EC, the sponsor, government regulatory 
bodies, and University compliance and quality assurance groups of all study related documents (e.g. source 
documents, regulatory documents, data collection instruments, study data etc.).  The investigator will ensure 
the capability for inspections of applicable study-related facilities (e.g. pharmacy, diagnostic laboratory, 
etc.). 
 
9 Ethics/Protection of Human Subjects 
9.1 
Ethical Standard 
The investigator will ensure that this study is conducted in full conformity with Regulations for the 
Protection of Human Subjects of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, and/or 
the ICH E6. 
9.2 
Institutional Review Board 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form must be 
obtained before any participant is enrolled. Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study. All changes to the consent form will 
be IRB approved; a determination will be made regarding whether previously consented participants need 
to be re-consented. 
9.3 
Participant and Data Confidentiality 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, and the 
sponsor(s) and their agents. Therefore, the study protocol, documentation, data, and all other information 
generated will be held in strict confidence. No information concerning the study or the data will be released 
to any unauthorized third party without prior written approval of the sponsor. 
 


 
 
Page 19 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
The study monitor, other authorized representatives of the sponsor, representatives of the IRB or 
pharmaceutical company supplying study product may inspect all documents and records required to be 
maintained by the investigator, including but not limited to, medical records (office, clinic, or hospital) and 
pharmacy records for the participants in this study. The clinical study site will permit access to such records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as long a 
period as dictated by local IRB and Institutional regulations. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will be 
transmitted to and stored at NYU Langone Medical Center. This will not include the participant’s contact or 
identifying information. Rather, individual participants and their research data will be identified by a unique 
study identification number. The study data entry and study management systems used by clinical sites and 
by NYU Langone Medical Center research staff will be secured and password protected. At the end of the 
study, all study databases will be de-identified and archived at the NYU Langone Medical Center. 
 
To further protect the privacy of study participants, a Certificate of Confidentiality will be obtained from the 
NIH. This certificate protects identifiable research information from forced disclosure. It allows the 
investigator and others who have access to research records to refuse to disclose identifying information on 
research participation in any civil, criminal, administrative, legislative, or other proceeding, whether at the 
federal, state, or local level. By protecting researchers and institutions from being compelled to disclose 
information that would identify research participants, Certificates of Confidentiality help achieve the 
research objectives and promote participation in studies by helping assure confidentiality and privacy to 
participants. 
 
10 Data Handling and Record Keeping 
10.1 
Data Collection and Management Responsibilities 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site PI. 
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the data 
reported. 
 
All source documents should be completed in a neat, legible manner to ensure accurate interpretation of 
data. Black ink is required to ensure clarity of reproduced copies. When making changes or corrections, 
cross out the original entry with a single line, and initial and date the change. DO NOT ERASE, OVERWRITE, 
OR USE CORRECTION FLUID OR TAPE ON THE ORIGINAL. 
 
Copies of the electronic CRF (eCRF) will be provided for use as source documents and maintained for 
recording data for each participant enrolled in the study. Data reported in the eCRF derived from source 
documents should be consistent with the source documents or the discrepancies should be explained and 
captured in a progress note and maintained in the participant’s official electronic study record. 
 
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and clinical 
laboratory data will be entered into Redcap. The data system includes password protection and internal 
quality checks, such as automatic range checks, to identify data that appear inconsistent, incomplete, or 
inaccurate. Clinical data will be entered directly from the source documents. 
 
10.2 
Study Records Retention 
Study documents will be retained for the longer of 3 years after close-out, 5 years after final 
reporting/publication, or 2 years after the last approval of a marketing application is approved for the drug 


 
 
Page 20 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
for the indication for which it is being investigated or 2 years after the investigation is discontinued and FDA 
is notified if no application is to be filed or if the application has not been approved for such indication. No 
records will be destroyed without the written consent of the sponsor, if applicable. It is the responsibility of 
the sponsor to inform the investigator when these documents no longer need to be retained. 
 
10.3 
Protocol Deviations 
It is the responsibility of the site PI/study staff to use continuous vigilance to identify and report deviations 
within 7 working days of identification of the protocol deviation, or within 7 working days of the scheduled 
protocol-required activity. 
 
Protocol deviations will be reported to the local IRB per their guidelines. The site PI/study staff is 
responsible for knowing and adhering to their IRB requirements.  
 
10.4 
Publication and Data Sharing Policy 
This study will comply with the NIH Public Access Policy, which ensures that the public has access to the 
published results of the research. This trial will be registered with clinicaltrials.gov as per the ICMJE policy, 
and the Section 801 of the Food and Drug Administration Amendments Act of 2007.  
10.5 
Data Safety and Monitoring 
The definition of unanticipated problems (UP) involving risk to subjects or others according to the NYU SOM 
IRB Drug Trial Protocol template is any incident, experience or outcome that meets all of the following 
criteria: unexpected in nature, severity or frequency, related or possibly related to participation in the 
research, suggests that the research places subjects or others at greater risk of harm. The definition of an 
adverse drug event according to the NYU SOM IRB Drug Trial Protocol is any symptom, sign, illness or 
experience that develops or worsens in severity during the course of the study.  
 
The DSMB will be made up of the Principal Investigator– Uchenna Umeh M.D. and Co-investigators- Arthur 
Atchabahian M.D. and Mandeep Virk M.D. All members of the DSMB are board certified physicians in their 
respective specialties.  
 
The DSMB will review safety data after the first five enrolled subjects and every three months thereafter. All 
unanticipated problems that increase risk to the subjects will be reported to the IRB per NYUSOM IRB policy. 
The time frame for reporting SAE and UP to the DSMB is by telephone within 24 hours of awareness of the 
event. The time frame for reporting SAE and UP to the IRB is to submit reports promptly but no later than 5 
working days from the time the investigator becomes aware of the event.  
 
During these meetings, the DSMB will review and analyze any unanticipated problems or adverse events 
involving risk to the patient including any neurological damage, significant delay in physical therapy 
progress, local anesthetic toxicity or allergic reaction to Exparel etc.   
 
Specific study stopping points is the occurrence of a serious adverse event such as a severe allergic reaction 
to Exparel. Additionally, after 5 patients in each group have completed all study related procedures, a brief 
safety analysis will be done by the Principal Investigator, Uchenna Umeh M.D., to check for evidence of 
systemic local anesthetic toxicity. Events will be reported to the anesthesia department QA.  
 
Additionally, the DSMB will perform an interim safety and data analysis after 50 patients have 
completed all study related visits.  
 
 


 
 
Page 21 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
 
 
 
11 Study Finances 
11.1 
Funding Source 
Both Anesthesiology and Orthopedic Surgery will use departmental funds to provide the Exparel used for 
this study.  
11.2 
Costs to the Participant 
There are no expected costs to the subjects. 
11.3 
Participant Reimbursements or Payments 
Participants will not receive any financial compensation for participation in this study. 
12 Conflict of Interest Policy 
 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical. Therefore, any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a way 
that is appropriate to their participation in the trial. The study leadership has established policies and 
procedures for all study group members to disclose all conflicts of interest and will establish a mechanism 
for the management of all reported dualities of interest.  
 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or financial gain 
greater than the minimum allowable by their institution, etc.) must have the conflict reviewed by the NYU 
Langone Conflict of Interest Management Unit (CIMU) with a Committee-sanctioned conflict management 
plan that has been reviewed and approved by the study sponsor prior to participation in this study. All 
NYULMC investigators will follow the applicable conflict of interest policies. 
 
 
 


 
 
Page 22 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
13 References 
1. Vandepitte C, Kuroda M, Witvrouw R, et al. Addition of Liposome Bupivacaine to Bupivacaine HCL Alone 
for Interscalene Brachial Plexus block in Patients Having Major Shoulder Surgery. Reg Anesth Pain Med. 
2017;42(3):334-341. 
2. Ilfeld BM, Viscusi ER, Hadzic A, et al.Safety and side effect profile of liposomal bupivacaine (Exparel) in 
peripheral nerve blocks. Reg Anesth Pain Med. 2015;40:572-582 
3. Ilfeld BM, Malhotra N, Furnish TJ, Donahue MC, Madison SJ. Liposomal bupivacaine as a single-injection as 
a single-injection peripheral nerve block: a dose-response study. Anesth Analg. 2013;117:1248–1256. 
4. Chahar P, Cummings KC 3rd. Liposomal Bupivacaine: a review of a new bupivacaine formulation. J Pain Res. 
2012;5:257–264. 
5. Hadzic A, Minkowitz HS,  Melson TI, et al. Liposomal Bupivacaine femoral nerve block for post surgical 
analgesia after total knee arthroplasty. Anesthesiology. 2016;124:1372–1383. 
 
 
 


 
 
Page 23 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
14 Attachments 
These documents are relevant to the protocol, but they are not considered part of the protocol.  They are 
stored and modified separately. As such, modifications to these documents do not require protocol 
amendments. 
 
14.1 Opioid Equivalents 
Notes from Lamplot (2013) 
 
Opioid and Route  
 
 
Dose (mg)  
Conversion Factor 
 
Morphine IM/IV   
 
 
10  
 
1.0 
 
Hydromorphone IM/IV   
 
1.67  
 
6.0 
 
Hydrocodone oral  
 
 
30  
 
0.3 
 
Tramadol oral   
 
 
100  
 
0.1 
 
Oxycodone oral   
 
 
20  
 
0.5 
 
Vicodin 5/500 oral  
 
 
6 tabs   
1.7 
 
Equianalgesic Doses of Opioids28 
Opioid 
Oral Equianalgesic Dose (mg) 
Buprenorphine 
0.3 
Oxymorphone 
1.5 
Butorphanol 
2 
Hydromorphone 
2 
Oxycodone 
7 
Hydrocodone 
10 
Morphine 
10 
Methadone 
10-20 
Tramadol 
40 
Propoxyphene 
43-45 
Codeine 
80 
Meperidine 
100 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
Page 24 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
14.2 PROMIS Assessments  
 
Upper Extremities Short Form (Administered Pre-Operatively in Holding Area):  
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
Page 25 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
Global Health Short Form (Baseline Assessment)   
 
 
 
Pain Intensity Scores:  
 
 
 
 
 
 
 
 
 


 
 
Page 26 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
14.3 Medication Usage Record  
 
Medication Record for TSA Surgery  
 
Thank you for participating in our research study and helping us improve pain control for 
patients undergoing total shoulder arthroplasty (TSA) surgery. 
Patient: ______________________ 
Pain medication:  Percocet 
Please record the following information in the log below:  
1. Time when you take your pain medication  
2. How many pills you took at each time  
3. Pain score on a scale of 0-10 (0 being no pain and 10 being the worst pain imaginable) 
4. Any additional pain medications (such as Advil), therapies (such as ice packs) and side 
effects (such as itching or nausea). 
 
Time 
Number of pills of 
Percocet 
Pain Score  
(scale of 0-10) 
Additional pain medications, 
therapy or side effects 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
We will call you within 1-2 business days after surgery to ask for the above information.  
Additionally, participants can also scan, photograph and email the medication record to  
Randy Cuevas at Randy.Cuevas@nyulangone.org  
 
 
Thank you for your participation.