Clinical trial NCT03587584
Conditions: Acute Pain
Sponsor: University of Minnesota
Start date: 2018-07-25; Completion date: 2021-06-08
Enrollment: 80 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to compare pain control after arthroscopic rotator cuff repair surgery using either liposomal bupivacaine or bupivacaine when injected in an interscalene block. Both medications, liposomal bupivacaine and bupivacaine, are standard of care in these types of surgeries.

Detailed description:
All patients will receive preoperative oral multimodal medications consisting of acetaminophen 975 mg, gabapentin 300 mg, and Celebrex 400 mg.

After completion of the preoperative process the patient will be placed in the supine position with the head of the bed elevated 30 degrees with standard ASA monitors applied. Sedation will be provided with midazolam 0-2 mg and propofol 50 mg. The interscalene groove will be identified with the ultrasound. Using sterile technique, a 21g Nerve block needle will then be inserted and advanced under ultrasound guidance until it is in the interscalene groove. Once in the interscalene, 20 mL of local anesthetic will be injected, with 10 mL deposited at the top of the brachial plexus and 10 mL at the bottom. In the study group, 5 mL of each 0.5% bupivacaine and LB will be injected at each location. The control group with have 20 mL of 0.5% bupivacaine divided between the injection sites. The patient will be monitored in the preoperative area until he/she is brought into the operating room for their procedure. A working block prior to surgery will be confirmed via sensory testing of the shoulder.

All patients will undergo a standard induction with propofol 1.5-3.0 mg/kg, ondansetron 4 mg, dexamethasone 10 mg and ketamine 0.25 mg/kg. A MAC or general with LMA or ETT will be placed and an opioid sparing technique will occur. Standardized maintenance will be a propofol infusion without neuromuscular blockers. 25-50 mcg of IV Fentanyl will be utilized for increases in heart rate greater than 20% or increases in systolic blood pressure above baseline.

Once in the operating room the surgeon will use 10 mL of 0.25% bupivacaine for skin, subcutaneous, and intraarticular injection.

When the operation is complete, the patient will be woken up and brought to the PACU. There the patient will receive IV fentanyl for a pain score of greater than 7. If more than 100 mcg of fentanyl is given and pain still remains above a 7 then IV hydromorphone will be used. A dose of 5-10 mg of oral oxycodone (or 2-4 mg of oral hydromorphone) will be given as soon as the patient is able to tolerate oral medication per standard protocol: If their pain score is 4-6 (on the Visual Analog Scale) then 5mg oral oxycodone (2 mg hydromorphone) can be administered, if their pain is between 7 to 10 then 10 mg of oxycodone (or 4 mg of hydromorphone) can be administered. Once the patient meets discharge criteria, they will be discharged home where each day they will fill out a pain diary. Additionally, a member of the research team will call the patient for signs of complications and ask the patient their current pain score, total opioid pills taken and non-opioid pain medication taken at 24, 48, and 72 hours postoperatively. Additionally, they will perform a Quality of Recovery Score survey at 72 hours, and 14 days postoperatively. An Ultrasound of the diaphragm will be completed by a blinded anesthesiologist in the PACU to assess diaphragm function.

All patients will be discharged with acetaminophen 975 mg q6 hours \& ibuprofen 600 mg q6 hours, taken in intervals such that the patient is taking one of these medications every 3 hours. And then hydromorphone 2mg pills #60 dosing 1-2 pills q4 hours prn severe pain or oxycodone 5 mg pills #60 dosing 1-2 pills q 4 hours prn severe pain.

Arms: arm 1: These patients receive an interscalene block with liposomal bupivacaine. arm 2: These patients receive an interscalene block with bupivacaine.
Interventions: intervention 1: liposomal bupivacaine intervention 2: Bupivacaine
Intervention descriptions: intervention 1: Experimental intervention 2: Active Comparator

Protocol documents:
Prot_SAP_000.pdf: 
PROTOCOL TITLE: Prospective Randomized controlled study comparing liposomal 
bupivacaine to bupivacaine interscalene blocks for arthroscopic rotator cuff repair surgery 
 
VERSION DATE: 8 5/11/2020 
1 
 
 


PROTOCOL TITLE: Prospective Randomized controlled study comparing liposomal 
bupivacaine to bupivacaine interscalene blocks for arthroscopic rotator cuff repair surgery 
 
VERSION DATE: 8 5/11/2020 
2 
PROTOCOL TITLE: 
Prospective Randomized controlled study comparing liposomal bupivacaine to bupivacaine 
interscalene blocks for arthroscopic rotator cuff repair surgery  
 
PRINCIPAL INVESTIGATOR or FACULTY ADVISOR: 
Name: Benjamin Matelich  
Department of Anesthesiology 
Phone 612-624-9990 
Email Address: mate0053@umn.edu 
STUDENT INVESTIGATOR: 
Name: NA 
Current Academic Level (e.g., Medical Student, Resident) 
Department 
Telephone Number 
Email Address (must not be a personal email address) 
VERSION NUMBER/DATE: 
5 5/21/19 
6 9/24/19 
7 12/4/19 
8 5/11/20 
 
 


PROTOCOL TITLE: Prospective Randomized controlled study comparing liposomal 
bupivacaine to bupivacaine interscalene blocks for arthroscopic rotator cuff repair surgery 
 
VERSION DATE: 8 5/11/2020 
3 
REVISION HISTORY 
 
Revision # 
Version Date Summary of Changes 
Consent Change? 
2 
6/29/18 
Clarified drug dosages and explained 
phone calls 
yes 
3 
8/10/18 
Removed one drug from preop 
multimodal regimen 
yes 
4 
12/19/18 
Added FV MG ASC as a site 
no 
5 
5/21/2019 
Added pregnant women to section 
8.2 exclusion criteria and multiple 
consent changes per IRB review 
yes 
6 
9/24/19 
Updated enrollment numbers and 
removed “pilot” from title 
yes 
7 
12/4/19 
Decreased discharge opioid amount no 
8 
5/11/20 
PI update  
yes 
 
 
 


PROTOCOL TITLE: Prospective Randomized controlled study comparing liposomal 
bupivacaine to bupivacaine interscalene blocks for arthroscopic rotator cuff repair surgery 
 
VERSION DATE: 8 5/11/2020 
4 
1.0 
Table of Contents 
 
1.0 
7 
2.0 
7 
3.0 
7 
4.0 
7 
5.0 
8 
6.0 
12 
7.0 
12 
8.0 
12 
9.0 
12 
10.0 13 
11.0 13 
12.0 14 
13.0 14 
14.0 16 
15.0 16 
16.0 17 
17.0 17 
18.0 18 
19.0 18 
20.0 18 
21.0 19 
22.0 19 
23.0 20 
24.0 20 
 


PROTOCOL TITLE: Prospective Randomized controlled study comparing liposomal 
bupivacaine to bupivacaine interscalene blocks for arthroscopic rotator cuff repair surgery 
 
VERSION DATE: 8 5/11/2020 
5 
ABBREVIATIONS/DEFINITIONS 
● LB/ liposomal bupivacaine 
● RCR/rotator cuff repair 
● QOR/Quality of Recovery 
●  
 
 


PROTOCOL TITLE: Prospective Randomized controlled study comparing liposomal 
bupivacaine to bupivacaine interscalene blocks for arthroscopic rotator cuff repair surgery 
 
VERSION DATE: 8 5/11/2020 
6 
STUDY SUMMARY 
 
Study Title 
Prospective Randomized controlled study comparing 
liposomal bupivacaine to bupivacaine interscalene 
blocks for arthroscopic rotator cuff repair surgery 
Study Design 
Prospective randomized double blind study 
Primary Objective 
Total opioids in 72 hours 
Secondary Objective(s) 
Pain scores within 72 hours, QOR at 72 hours, Number 
of phone calls to surgeon, adverse events, time to 
discharge 
Research 
Intervention(s)/Investigational 
Agents 
Liposomal bupivacaine and bupivacaine vs bupivacaine 
Scientific Assessment 
HRPP facilitated scientific assessment 
IND/IDE # (if applicable) 
Study Medication has been approved for use in 
shoulder surgery April 6, 2018 
IND/IDE Holder 
n/a 
Investigational Drug Services 
# (if applicable) 
n/a 
Study Population 
Adult patients aged 18 and older who are undergoing 
arthroscopic rotator cuff repair surgery 
Local Sample Size (number of 
participants recruited locally) 
90 
 
 
 


PROTOCOL TITLE: Prospective Randomized controlled study comparing liposomal 
bupivacaine to bupivacaine interscalene blocks for arthroscopic rotator cuff repair surgery 
 
VERSION DATE: 8 5/11/2020 
7 
2.0 
Objectives 
Purpose: To determine if LB plus bupivacaine provides superior pain control 
compared to bupivacaine alone when injected in an interscalene block for patients 
undergoing arthroscopic rotator cuff repair surgery.  
2.1  
3.0 
Background 
3.1 Significance of Research Question/Purpose: LB has not been adequately 
studied in peripheral nerve blocks. One study has been done in RCR surgery 
and showed superior analgesia compared to bupivacaine.   
3.2 Preliminary Data: It is our standard of care to use this medication in an 
interscalene block at the U of MN for patients undergoing RCR.  A 
retrospective study performed showed superior analgesia and less opioids 
for those who had LB plus bupivacaine.  
3.3 Existing Literature: Vandepitte et al showed that LB plus bupivacaine was 
superior to bupivacaine when used in interscalene nerve block for patients 
undergoing major shoulder surgery (both RCR and TSA).   
4.0 
Study Endpoints/Events/Outcomes 
4.1 Primary Endpoint/Event/Outcome: To determine if LB plus bupivacaine in 
an interscalene block results in less opioid use over 72 hours compared to 
bupivacaine only for RCR surgery.  
4.2 Secondary Endpoint(s)/Event(s)/Outcome(s):  
- 
To determine if LB plus bupivacaine in an interscalene block results in 
less pain over 72 hours as compared to bupivacaine only in an 
interscalene block for RCR surgery.  Assessed via total pain scores  
- 
To determine if LB plus bupivacaine in an interscalene block results in 
improved QOR at 72 hours as compared to bupivacaine only in an 
interscalene block for RCR surgery.  Assessed via QOR 15 patient 
survey.  
- 
To determine if LB plus bupivacaine in an interscalene block results in 
fewer phone calls to the surgeon within 72 hours as compared to 
bupivacaine only in an interscalene block for RCR surgery.   
- 
To determine if LB plus bupivacaine in an interscalene block hastens 
readiness for hospital discharge compared to bupivacaine only in an 
interscalene block for RCR surgery. Study 
Intervention(s)/Investigational Agent(s) 
4.3 Description: LB is a long acting local anesthetic.  It is liposome encapsulated 
bupivacaine which allows for prolonged release of bupivacaine over a 72 


PROTOCOL TITLE: Prospective Randomized controlled study comparing liposomal 
bupivacaine to bupivacaine interscalene blocks for arthroscopic rotator cuff repair surgery 
 
VERSION DATE: 8 5/11/2020 
8 
hour period.  Bupivacaine is a medium acting local anesthetic which 
provides between 6 and 24 hours of analgesia when used in a peripheral 
nerve block.  Both medications are standard of care for use in interscalene 
blocks here at the U of MN. Acetaminophen is a medication used to treat 
pain, gabapentin is a gabapentinoid which is used to treat postoperative 
pain.   
4.4 Drug/Device Handling: The LB will be stored in a locked pyxis fridge in a 
box labeled study LB.  It will be retrieved by the PI and sub I’s for use in the 
interscalene blocks.  
● The LB will be stored in a locked pyxis fridge in a box labeled 
Liposomal Bupivacaine.  The anesthesiologists in charge of 
regional anesthesia the day the procedure will be informed will 
write the order for dispensing the medication and the block per 
standard of care.  It will be retrieved by the PI and sub I’s for use 
in the interscalene blocks.  
4.5 
Biosafety: n/a  
4.6 
Stem Cells: n/a 
 
5.0 
Procedures Involved 
5.1 Study Design: Level I randomized prospective outcomes study 
comparing two groups of patients.  One group will receive LB plus 
bupivacaine for an interscalene block.  The other will receive 
bupivacaine for an interscalene block injection.  
Study Procedures: Patients will be identified in the pre-operative time period by the 
surgeons and if possible will be consented by the research coordinator or research 
assistant.  If that is unable to be accomplished the patient will be introduced to the study 
and given a copy of the consent form to evaluate prior to surgery.  On the day of surgery, 
the research coordinator, research assistant or primary or sub investigators will determine 
if the patient has any questions so that they can be answered.  After discussion with the 
person obtaining consent, consent will be obtained in the pre-operative area. A random 
number generator will be used to determine if the patient will have LB plus bupivacaine 
or bupivacaine for their interscalene block.  The primary investigator will access the 
number generator in the pre-op area immediately prior to block placement.  The website 
www.random.org will be used as the random number generator.   
 
Treatment technique: 
All patients will receive preoperative oral multimodal medications consisting of 
acetaminophen 975 mg and gabapentin 300 mg.   
After completion of the preoperative process the patient will be placed in the supine 
position with the head of the bed elevated 30 degrees with standard ASA monitors 
applied.  Sedation will be provided with midazolam 0-2 mg and propofol 50 mg. The 


PROTOCOL TITLE: Prospective Randomized controlled study comparing liposomal 
bupivacaine to bupivacaine interscalene blocks for arthroscopic rotator cuff repair surgery 
 
VERSION DATE: 8 5/11/2020 
9 
interscalene groove will be identified with the ultrasound.  Using sterile technique, a 21g 
Nerve block needle will then be inserted and advanced under ultrasound guidance until it 
is in the interscalene groove.  Once in the interscalene, 20 mL of local anesthetic will be 
injected, with 10 mL deposited at the top of the brachial plexus and 10 mL at the bottom.  
In the study group, 5 mL of each 0.5% bupivacaine and LB will be injected at each 
location.  The control group with have 20 mL of 0.5% bupivacaine divided between the 
injection sites (10 mL at each site). The patient will be monitored in the preoperative area 
until he/she is brought into the operating room for their procedure. A working block prior 
to surgery will be confirmed via sensory testing of the shoulder. 
 
All patients will undergo a standard induction with propofol 1.5-3.0 mg/kg, ondansetron 
4 mg, dexamethasone 10 mg and ketamine 0.25 mg/kg.  A MAC or general with LMA or 
ETT will be placed and an opioid sparing technique will occur. Standardized 
maintenance will be a propofol infusion without neuromuscular blockers.   25-50 mcg of 
IV Fentanyl will be utilized for increases in heart rate greater than 20% or increases in 
systolic blood pressure above baseline.   
 
Once in the operating room the surgeon will use an additional 10 mL of 0.25% 
bupivacaine for skin, subcutaneous, and intraarticular injection.  
 
When the operation is complete, the patient will be woken up and brought to the PACU.  
There the patient will receive IV fentanyl for a pain score of greater than 7 (50 mcg of 
Fentanyl x 2 if needed).  If more than 100 mcg of fentanyl is given and pain still remains 
above a 7 then IV hydromorphone will be used (max dose of 1 mg and given in 
increments of 0.3 mg q 10 minutes prn severe pain). Once the patient is able to tolerate 
oral medications a dose of 5 mg of oral oxycodone (or 2 mg of oral hydromorphone if 
allergic to oxycodone) will be given if their pain score is greater than 4 (on the Visual 
Analog Scale).  Once the patient meets discharge criteria, they will be discharged home 
where each day they will fill out a pain diary.  Additionally, a member of the research 
team will call the patient for signs of complications and ask the patient their current pain 
score, total opioid pills taken and non-opioid pain medication taken at 24, 48, and 72 
hours postoperatively.  Additionally, they will perform a Quality of Recovery Score 
survey at 72 hours, and 14 days postoperatively. An Ultrasound of the diaphragm will be 
completed by a blinded anesthesiologist in the PACU to assess diaphragm function. 
All patients will be discharged with instructions to take acetaminophen 975 mg q8 hours 
& ibuprofen 600 mg q6 hours. Additionally they will have opioid pain medication to take 
as needed for pain greater than 4.  They will either have hydromorphone 2mg, 30-40 
pills, with dosing being 1-2 pills q4 hours prn severe pain.  Or they will have a 
prescription for oxycodone 5 mg, 30-40 pills, dosing 1-2 pills q 4 hours prn severe pain.   
 
 
Enrollment procedures: Patients will be identified in the pre-operative time period by 
the surgeons and if possible will be consented by the research coordinator or research 
assistant.  If that is unable to be accomplished the patient will be introduced to the study 


PROTOCOL TITLE: Prospective Randomized controlled study comparing liposomal 
bupivacaine to bupivacaine interscalene blocks for arthroscopic rotator cuff repair surgery 
 
VERSION DATE: 8 5/11/2020 
10 
and given a copy of the consent form to evaluate prior to surgery.  On the day of surgery, 
the research coordinator, research assistant or primary or sub investigators will determine 
if the patient has any questions so that they can be answered.  After discussion with the 
person obtaining consent, consent will be obtained in the pre-operative area. Subjects 
interested in the study will be presented with consent and Health and Insurance 
Portability and Accountability Act (HIPAA) forms.  The patient will review the forms 
with the surgeon, research staff, or anesthesiologist.  Subjects will be reminded that 
participation is completely voluntary, and that they may stop participation at any time 
without question or penalty.  The surgeon, research staff, or anesthesiologist will answer 
any questions that the subjects may have about the study.  If the patient decides to 
participate, they will be asked to sign the consent and HIPAA forms.  One copy will be 
saved for study records, and the subject will be provided with a copy of the forms for 
their own records.  The patient will then have an opportunity to ask any questions of the 
surgeon regarding the treatment option that has been selected. All forms will be locked 
and stored in a file cabinet in the research department.  Enrollment will proceed from July 
2018 to July 2019.  Enrolling consecutive patients will help reduce selection bias.  
 
Assessments: Post-operatively patients will be evaluated at 2 and 6 hours post-
operatively by a blinded research staff.  This person will not be aware of the patient’s 
mode of analgesia. The patients will be contacted via in person assessment or via 
telephone at 24, 48, and 72 hours +/- 5 hours.  Patients will be asked to rate their pain on 
scale of 0-10.  The amount of opioids used by the patient will be recorded as will any 
other adjuvant pain medication used. The time in phase 1 and phase 2 of PACU will be 
recorded. The patients will be asked at 72 hours post-injection if they would undergo 
interscalene block with their medication again or if they would opt for a different form of 
pain management. Patients will fill out a Quality of Recovery Survey at 72 hours and 14 
days, and be assessed for block related complications at this time.  All complications will 
be recorded including:  
● Failure of the block 
● Wound infections 
● Subsequent procedures 
● Complications related to placement of the interscalene block including 
nerve injury, prolonged sensory loss greater than 3 days, prolonged arm 
weakness greater than 3 days 
● Opioid related side effects of nausea and/or vomiting 
● Local anesthetic toxicity as evidenced by seizures or cardiovascular 
collapse without other reasonable etiology 
Patients will be asked in the daily phone call if they or their family contacted anyone (any 
health care professional) regarding their pain overnight and that will be documented.   
 
All data will be recorded on the Clinical Diagnostic Sheet and will then be given to the 
research coordinator for manual data entry.  Data collection will continue until POD #14.  
At that time study participation will be terminated.  Should patients be re-admitted to the 


PROTOCOL TITLE: Prospective Randomized controlled study comparing liposomal 
bupivacaine to bupivacaine interscalene blocks for arthroscopic rotator cuff repair surgery 
 
VERSION DATE: 8 5/11/2020 
11 
hospital in the next two weeks (Up to POD #30) for pain, a notation will be made in 
study records. 
 
An analysis of the total cost of analgesics will be tabulated at the conclusion of the study 
to determine the most cost effective treatment option as this will be added into the cost of 
hospitalization including the number of days each patient spent in the hospital.   
 
Blinding Procedure:  The research assistant in this study will be blinded to the method 
of analgesia for the patient.  The research assistant will assess pain one time per day.  
This person will not be responsible for any clinical testing and will record all data in the 
protected database daily.  They will not have any access to the patients’ clinical records 
or chart.  Any questions from the patient will be referred to the on-call resident or 
staff on call.   
 
5.2  
Describe: 
● 
The interscalene block is standard of care for patients and would be 
performed regardless of patient’s participation in the study.  All 
patients still would get preoperative multimodal treatment as well as 
an opioid sparing anesthetic.   
● 
Patients would be required to take a dose of acetaminophen 975 mg 
oral and gabapentin 300 mg oral prior to surgery.  They would then be 
required to receive an interscalene block with either liposome 
bupivacaine and bupivacaine or bupivacaine.  Intraoperatively they 
would be required to receive propofol, lidocaine, ondansetron, 
dexamethasone, and ketamine for induction of anesthesia.    
● 
In addition to the surveys used to measure subjective and objective 
outcome, other data will be collected during patient interviews 
including:
o Demographic data 
o Age 
o Weight 
o ASA class 
o Duration of surgery 
o Pain Score at 2, and 6 hrs after surgery and once a day thereafter 
o Length of stay in recovery room both phase 1 and phase 2 
o Amount of opioids given intraoperatively and post-operatively 
o Satisfaction with treatment 
o Quality of recovery survey at 72 hours and 14 days 
o Non opioids used 
o Adverse events 
o Length of hospital stay 


PROTOCOL TITLE: Prospective Randomized controlled study comparing liposomal 
bupivacaine to bupivacaine interscalene blocks for arthroscopic rotator cuff repair surgery 
 
VERSION DATE: 8 5/11/2020 
12 
5.3 Study Duration: We anticipate the study to take from June 2018 to June 
2019.  Patients will be in the study for 14 days and then their chart 
monitored for up to 30 days post surgery.  The data analysis should take 
one month after full enrollment of the study.  
5.4 Individually Identifiable Health Information:This study involves the use of 
individually identifiable health information. Please see attached HIPAA 
authorization form.  
5.5 Use of radiation: n/a  
5.6 Use of Center for Magnetic Resonance Research: n/a 
6.0 
Data and Specimen Banking 
6.1 Storage and Access: All study data will be stored on excel spreadsheets 
stored in Box. Only the PI and members of the research team will have 
access to the data. 
6.2 Data: The data from this study will be collected both from Epic and directly 
from the patient. The data collected includes: demographic data, age, 
weight, ASA class, duration of surgery, length of stay in recovery room both 
phase 1 and 2, amount of opioids given intraoperatively and post-
operatively, non-opioid pain medication, pain score (0-10) at 2, 6, 24, 48, 
and 72 hours, satisfaction with treatment, Quality of Recovery survey at 72 
hours and 14 days, and any adverse events. 
6.3 Release/Sharing: N/A 
 
7.0 
Sharing of Results with Participants 
Results will not be shared with participants. 
 
8.0 
Study Population 
8.1 Inclusion Criteria: All adult patients aged greater than 18 years of age that 
are undergoing arthroscopic rotator cuff surgery  
8.2 Exclusion Criteria: Patients with allergy to local anesthetics, daily use of 
opioids for more than 3 weeks prior to surgery, patient refusal, patient 
with coagulopathy, non-english speaking patients, patients who are 
currently pregnant, and those who do not have access to a telephone.  
8.3 Screening: Patients will be screened at their preoperative visit either in the 
surgeon’s office or pre assessment center.   
9.0 
Vulnerable Populations 


PROTOCOL TITLE: Prospective Randomized controlled study comparing liposomal 
bupivacaine to bupivacaine interscalene blocks for arthroscopic rotator cuff repair surgery 
 
VERSION DATE: 8 5/11/2020 
13 
9.1 Vulnerable Populations:  
☐ Children 
☐ Pregnant women/Fetuses/Neonates 
☐ Prisoners 
☐ Adults lacking capacity to consent and/or adults with diminished 
capacity to consent, including, but not limited to, those with acute 
medical conditions, psychiatric disorders, neurologic disorders, 
developmental disorders, and behavioral disorders 
☐ Approached for participation in research during a stressful situation such 
as emergency room setting, childbirth (labor), etc. 
☐ Disadvantaged in the distribution of social goods and services such as 
income, housing, or healthcare 
☐ Serious health condition for which there are no satisfactory standard 
treatments 
☐ Fear of negative consequences for not participating in the research (e.g. 
institutionalization, deportation, disclosure of stigmatizing behavior) 
☐ Any other circumstance/dynamic that could increase vulnerability to 
coercion or exploitation that might influence consent to research or 
decision to continue in research 
☐ Undervalued or disenfranchised social group 
☐ Members of the military 
☐ Non-English speakers 
☐ Those unable to read (illiterate) 
☐ Employees of the researcher 
☐ Students of the researcher 
x None of the above 
9.2 Additional Safeguards:  
10.0 Local Number of Participants 
10.1 Local Number of Participants to be Consented: 90 patients as we expect a 
dropout or loss to follow up of 20%  
11.0 Local Recruitment Methods 
11.1 
Recruitment Process: Patients will be recruited from the group of adult 
surgical patients at the University of Minnesota undergoing RCR and receiving an 
interscalene block. Patients will be approached at the preoperative assessment 
clinic at the Clinic and Surgery Center if possible by a research staff member to 
determine their interest in participation.  If they decide to be a participant they 
will be consented and given a copy of their consent form for their records and a 
consent will be scanned and placed into EPIC.  If the patient is scheduled for a 
midday surgery, the research staff will approach them in the preoperative surgical 


PROTOCOL TITLE: Prospective Randomized controlled study comparing liposomal 
bupivacaine to bupivacaine interscalene blocks for arthroscopic rotator cuff repair surgery 
 
VERSION DATE: 8 5/11/2020 
14 
area.  These patients will have significant time to review the study with research 
staff as well as the physicians performing the procedure due to the fact they arrive 
several hours prior to their scheduled surgery.  All subjects will have enough time 
to ask questions about the study and the potential risks involved regardless of 
which venue they are consented. 
 
11.2 
Identification of Potential Participants: Patients will be identified by 
members of the treatment team in either the surgeon’s clinic, pre-assessment 
clinic, or preoperative area. Patients who have opted out of research will not be 
asked to participate in the study. Patients will be approached to consent for the 
study by a surgeon, anesthesiologist, or member of the research team. Patients 
who agree to participate in the study will sign both a study consent and HIPAA 
authorization allowing the use of specified information contained in medical 
records for research purposes. 
11.3 
Recruitment Materials: N/A 
11.4 
Payment: No payment will be provided to patients.   
12.0 Withdrawal of Participants 
12.1 
Withdrawal Circumstances:.  Subjects who have consented prior to the 
day of surgery and for some reason choose not to participate will be withdrawn 
and a notation will be made in the study records and these people will be 
considered screen failures.  The surgeon may choose to withdraw the patient from 
the study prior to surgery for  any medical reason or if they suffer a major life 
threatening  adverse event.  
12.2 
Withdrawal Procedures: If the patient is withdrawn from study prior to the 
procedure, they will be noted in study records as screen failures. If they undergo 
the procedure and they decide they no longer want to be a part of the study or 
withdrawn by the physician, they will be withdrawn and no further data will be 
collected.  This will also be noted in the study documentation. 
12.3 
Termination Procedures:  If the study is terminated for any reason, or there 
is more than 5 % major adverse events the data that is already collected will be 
stored in a secure location only accessible to research personnel on this study. No 
further data will be collected if the study is terminated. 
13.0 Risks to Participants 
13.1 Foreseeable Risks: The study has the following risks:  
·      infection 
·      bleeding 
·      nerve injury 
·      cardiac arrhythmias (irregular heartbeat) 
·      respiratory complications 


PROTOCOL TITLE: Prospective Randomized controlled study comparing liposomal 
bupivacaine to bupivacaine interscalene blocks for arthroscopic rotator cuff repair surgery 
 
VERSION DATE: 8 5/11/2020 
15 
·        
These complications all fall within the standard risks of surgery and the 
performance of the interscalene injection. Any intervention being provided as a 
part of this study falls within the standard of care as both medication options are 
within the standard treatments for post-operative pain and are currently used as 
analgesic options at UMMC. 
  
EXPAREL contains bupivacaine. Serious side effects related to bupivacaine are 
not common, but may occur if too much is given or if it is accidentally injected 
into a blood vessel. When given incorrectly, side effects may involve the brain or 
the heart. 
  
The effects on the brain and central nervous system may include: 
·      Restlessness (< 2%) 
·      Anxiety (<2%) 
·      Dizziness (<2%) 
·      Tinnitus (ringing in the ears) (<2%) 
·      Blurred vision (<2%) 
·      Tremors (shaking) possibly proceeding to convulsions (<2%). 
  
The effects on the heart appear when too much bupivacaine is given or when 
bupivacaine is injected in a blood vessel by accident. These effects cause a 
decrease of the heart function, including low heart rate or abnormal heart rhythm, 
decreased blood flow, low blood pressure, and, in extreme cases, heart attack. 
(<2%) 
  
The numbing sensation caused by bupivacaine may be persistent, with slow, 
incomplete, or no recovery. Sometimes a tingling sensation may appear in the 
area treated with bupivacaine. When injected next to a large nerve, bupivacaine 
may cause weakness or paralysis. 
  
Allergic reactions are rare, but may include rash, itching and redness of the skin, 
sneezing, nausea, vomiting, dizziness, fainting, sweating, fever, and low blood 
pressure. 
  
Other side effects of liposomal bupivacaine when given into the wound include: 


PROTOCOL TITLE: Prospective Randomized controlled study comparing liposomal 
bupivacaine to bupivacaine interscalene blocks for arthroscopic rotator cuff repair surgery 
 
VERSION DATE: 8 5/11/2020 
16 
·      Nausea  (22.6%) 
·      Constipation (8.7%) 
·      Vomiting (6%) 
·      High temperature (5.5%) 
·      Dizziness (<2%) 
·      Swelling (<1%) 
·      Low blood pressure (<2%) 
·      Anemia (<1%) 
·      Itching (2.4%) 
·      High heart rate (1.3%) 
·      Headache (5%) 
13.2 
Reproduction Risks: 
If the patient were pregnant we would not perform the study on them.  If they 
were to become pregnant there are no known risks to the patient. 
13.3 
Risks to Others: N/A 
 
14.0 Potential Benefits to Participants 
Potential Benefits: The potential benefits of participating in this study 
include reduced pain following shoulder surgery and shortened hospital 
stay.   
 
15.0 Statistical Considerations 
15.1 Data Analysis Plan: We plan to collect our data using excel, which will be 
maintained in box.  When the study is completed and ready for statistical 
analysis the data will be shared with our staff statistician. 
  
15.2 Power Analysis: Using the power analysis from our other ongoing 
interscalene block study (for total shoulder arthroplasty cases) we plan to 
continue to enroll to 70 total patients to reach an estimated 80% power.  
15.3 Statistical Analysis: This study will be analyzed by our staff biostatistician.  
The data will be deidentified and shared with him in box.  The statistician 
will be provided the protocol so they are able to analyze for primary and 
secondary objectives. 


PROTOCOL TITLE: Prospective Randomized controlled study comparing liposomal 
bupivacaine to bupivacaine interscalene blocks for arthroscopic rotator cuff repair surgery 
 
VERSION DATE: 8 5/11/2020 
17 
15.4 Data Integrity:  All patients will be assigned a unique patient identifier. The 
data that will be sent to the statistician will be deidentified.   
. 
16.0 Confidentiality 
16.1 
Data Security: All paper documents and consent forms will be stored in a 
locked cabinet in the anesthesia research office in B573 Mayo. All study data will 
be stored electronically in Box and only the PI and members of the research team 
will have access to the data.  
 
17.0 Provisions to Monitor the Data to Ensure the Safety of 
Participants 
 
17.1 Data Integrity Monitoring. 
The PI, co-investigators, and research assistants will all have access to the study 
data stored in the University’s Box storage system. All the research assistants 
have experience collecting pain scores and other relevant study information. The 
PI of the study will periodically review the study data to ensure accuracy and 
completeness of study data. 
17.2 
Data Safety Monitoring: The Department of Anesthesiology has 
established a Data and Safety Monitoring Committee consisting of several staff 
anesthesiologists which include persons who are board certified as pain 
specialists. Data will be transmitted in box to persons on the board on a monthly 
basis for review.  If there are patterns of adverse events, the board will meet as 
needed and provide recommendations. 
All safety data will be collected on a case report form and transferred into an 
excel spread sheet that will be stored in box. Also, all phone call data will be 
collected on a case report form and transferred into excel in box.  
All data will be collected by research assistants on a daily basis.  Subjects are 
monitored at several intervals on day of surgery and daily up to 72 hours.  If the 
patient is discharged prior to 72 hours they will Who will review the data. 
The data will be reviewed on a regular basis (weekly) by the PI and research 
staff.  If there are consistent complications noted a meeting will be convened by 
the DSMB for recommendations. 
The statistical tests for analyzing the safety data to determine whether harm is 
occurring. 
The statistician uses R or SAS for analysis.  Most likely  a regression analysis will 
be performed to see which event is most likely the contributor for the 


PROTOCOL TITLE: Prospective Randomized controlled study comparing liposomal 
bupivacaine to bupivacaine interscalene blocks for arthroscopic rotator cuff repair surgery 
 
VERSION DATE: 8 5/11/2020 
18 
complications  Also a chi-square analysis can be performed.  All is very 
dependent on data variability. 
A fatal or serious adverse event that is attributable to either the delivery or the 
study medication itself. 
  
18.0 Provisions to Protect the Privacy Interests of Participants 
18.1 
Protecting Privacy: 
Patients will be asked if this is a good time to answer questions.  All patients will 
have the right to refuse to answer questions when called. All calls will be done in 
a secure office and the data is deidentified when entered.  It will be stored using a 
unique study identifier.  
  
18.2 
Access to Participants: 
All patients are required to sign a consent that states their privacy of the data 
being collected.  In addition, they are required to sign a HIPAA consent that 
further describes the data being collected.  It also describes that all data is 
deidentified and stored in a secure database.  They will be informed that data is 
stored and reviewed in box which is HIPAA compliant and that only study 
personnel have accesss. 
 
19.0 Compensation for Research-Related Injury 
19.1 
Compensation for Research-Related Injury: 
In the event that this research activity results in an injury, treatment will be 
available, including first aid, emergency treatment and follow-up care as needed. 
Care for such injuries will be billed in the ordinary manner, to the patient and/or 
insurance company.  
19.2 
Contract Language: N/A 
 
20.0 Consent Process 
● Consent Process (when consent will be obtained): Patients will be 
identified in the pre-operative time period by the surgeons and if 
possible will be consented by the research coordinator or 
research assistant.   If patients have more questions and do not 
want to sign at their clinic will be asked if it is allowable for  a 
study staff member to contact them prior to surgery via phone to 
clarify if they have any questions.  On the day of surgery, if the 


PROTOCOL TITLE: Prospective Randomized controlled study comparing liposomal 
bupivacaine to bupivacaine interscalene blocks for arthroscopic rotator cuff repair surgery 
 
VERSION DATE: 8 5/11/2020 
19 
patient has not already signed consent and is still interested in 
participating in the study will be presented with consent and 
Health and Insurance Portability and Accountability Act (HIPAA) 
forms.  The patient will review the forms with the surgeon, 
research staff, or anesthesiologist.  Subjects will be reminded that 
participation is completely voluntary, and that they may stop 
participation at any time without question or penalty.  The 
surgeon, research staff, or anesthesiologist will answer any 
questions that the subjects may have about the study.  If the 
patient decides to participate, they will be asked to sign the 
consent and HIPAA forms.  One copy will be saved for study 
records, and the subject will be provided with a copy of the forms 
for their own records.  
● Waiver or Alteration of Consent Process: N/A 
● Non-English Speaking Participants: N/A- No Non-English speaking 
patients will be enrolled in this study. 
● Participants Who Are Not Yet Adults: N/A 
● Cognitively Impaired Adults, or adults with fluctuating or 
diminished capacity to consent: N/A 
● Adults Unable to Consent: N/A 
● 
  
21.0 Setting 
21.1 Research Sites: Patients will be consented in the surgeon’s clinic or pre 
assessment clinic.  The surgical procedures will take place at the M health 
Ambulatory Surgery Center or Fairview riverside campus or Fairview Maple 
Grove Clinics Ambulatory Surgery Center.   
21.2 International Research:n/a 
 
22.0 Multi-Site Research N/A 
23.0 Resources Available: 
Research assistants are available to aid in consent and data acquisition. All research assistants 
will be familiar with the study protocol and have experience working with similar studies. 
  
We plan to enroll 70 subjects.  The plan is to screen 90 subjects to research this target 
population.  This center performs approximately 300 RCRs annually. 


PROTOCOL TITLE: Prospective Randomized controlled study comparing liposomal 
bupivacaine to bupivacaine interscalene blocks for arthroscopic rotator cuff repair surgery 
 
VERSION DATE: 8 5/11/2020 
20 
We plan to conduct this study over 3 months.  Enrollment and data collection will be completed 
at this time.  Statistical Analysis will take approximately two months to complete. 
  
All procedures will be performed in the clinical facilities at the MHealth Clinics and Surgery 
Center and at the West and East Bank. Data storage and analysis will be done using 
desktop equipment which is available at the Research Office B573 Mayo. 
  
  
In the event that this research activity results in an injury, treatment will be available, including 
first aid, emergency treatment and follow-up care as needed. Care for such injuries will 
be billed in the ordinary manner, to the patient and/or insurance company.  
All study personnel will be adequately trained by the Principle Investigator on the study protocol 
and study conduct.  A log will be maintained to track which personnel are trained.  A 
delegation of authority log will also be maintained to track which personnel are 
responsible for specific duties. 
 
24.0 References 
1. Vandepitte C, Kuroda M, Witvrouw R et al.  Addition of liposome bupivacaine 
to bupivacaine HCl versus bupivacaine HCl alone for interscalene brachial 
plexus block in patients having major shoulder surgery. Reg Anesth Pain Med. 
2017;42:334-341.  

ICF_001.pdf: 
Approved for use by UMN IRB
Effective on 5/14/2020
IRB Study Number: STUDY00003350
Consent Form
Title of Research Study: Prospective randomized controlled study comparing liposomal 
bupivacaine to bupivacaine interscalene blocks for arthroscopic rotator cuff repair surgery
Investigator Team Contact Information:
For questions about research appointments, the research study, research results, or other 
concerns, contact the study team at:
Study Staff: Melissa Cohen, Jonah Pearson, 
Ryan Eskuri, Katherine Harmelink, Jessica 
Hatfield, Candace Nelson
Phone Number: 612-625-7116 
Email Address: cohen045@umn.edu 
Investigator Name: Dr. Ben Matelich 
Investigator Departmental Affiliation: 
Anesthesiology
Phone Number: 612-624-9990 
Email Address: mate0053@umn.edu
Supported By: This research is not supported by any company.
Page 1 of 8
Version Date: 5/11/2020


Approved for use by UMN IRB
Effective on 5/14/2020
IRB Study Number: STUDY00003350
Consent Form
Key Information About This Research Study
The following is a short summary to help you decide whether or not to be a part of this research study. 
More detailed information is listed later on in this form.
What is research?
Doctors and investigators are committed to your care and safety. There are important differences 
between research and treatment plans:
●
The goal of research is to learn new things in order to help groups of people in the future. 
Investigators learn things by following the same plan with a number of participants, so they do 
not usually make changes to the plan for individual research participants. You, as an individual, 
may or may not be helped by volunteering for a research study.
●
The goal of clinical care is to help you get better or to improve your quality of life. Doctors can 
make changes to your clinical care plan as needed.
Your doctor, who is also responsible for this research study, is interested in both your clinical care and 
the conduct of this research study. You have the right to discuss this study with another person who is 
not part of the research team before deciding whether to participate in the research.
Why am I being asked to take part in this research study?
We are asking you to take part in this research study because you are receiving an interscalene block for 
shoulder surgery.
What should I know about a research study?
●
Someone will explain this research study to you.
●
Whether or not you take part is up to you.
●
You can choose not to take part.
●
You can agree to take part and later change your mind.
●
Your decision will not be held against you.
●
You can ask all the questions you want before you decide.
Why is this research being done?
The purpose of this study is to determine if liposomal bupivacaine plus bupivacaine compared to 
bupivacaine alone when given in an interscalene block provides better and longer pain control for 
rotator cuff repair (RCR) surgery. An interscalene block is an injection of numbing medication near the 
nerves in your neck for the purpose of numbing your shoulder and decreasing pain in that area.
Liposomal bupivacaine is a long acting anesthetic. It is liposome encapsulated bupivacaine which allows 
for prolonged release of bupivacaine over a 72-hour period. Bupivacaine is a medium acting local 
anesthetic, which provides between 6 and 24 hours of pain relief. Currently it is the standard of care to 
give either of these medications in an interscalene block at the University of Minnesota, however their 
effectiveness has not been adequately compared against one another in interscalene blocks for RCR 
patients.
How long will the research last?
We expect that you will be in this research study for 14 days following RCR surgery. However, we will 
continue to monitor your chart for adverse events up to 30 days post-procedure.
Page 2 of 8
Version Date: 5/11/2020


Approved for use by UMN IRB
Effective on 5/14/2020
IRB Study Number: STUDY00003350
Consent Form
What will I need to do to participate?
You will be asked to consent to be randomized to receive either liposomal bupivacaine plus bupivacaine 
or bupivacaine alone in an interscalene block. In addition, we would ask you to have your pain scores 
and pain medication use evaluated by a member of the research staff at 2, 6, 24, 48, and 72 hours post 
procedure. This will be done in person or via telephone call. At 72 hours and 14 days post-procedure, 
you will be asked to complete a Quality of Recovery Survey and asked if you would undergo an 
interscalene block with your medication again or if you would opt for a different form of pain 
management. At 72 hours and 14 days you will also be assessed for any block related complications.
More detailed information about the study procedures can be found under “What happens if I say yes, I 
want to be in this research?”
Is there any way that being in this study could be bad for me?
There are complications associated with an interscalene block such as infection, bleeding, or nerve 
injury however, these complications all fall within the standard risks of surgery and the performance 
of the interscalene injection. Any intervention being provided as a part of this study falls within the 
standard of care as both medication options are within the standard treatments for post-operative 
pain and are currently used as analgesic (pain management) options at the University of Minnesota. 
Please see section “What are the risk of being in this study” on page 5 for a full description of risks to 
participating in the research.
Will being in this study help me in any way?
We cannot promise any benefits to you or others from your taking part in this research. However, 
possible benefits include reduced pain following your procedure and shortened hospital stay. Other 
possible benefits include increased knowledge that may be applied to future patients.
More detailed information about the benefits of this study can be found under “Will being in this study 
help me in any way? (Detailed Benefits)”
What happens if I do not want to be in this research?
You do not have to participate in this research. Choosing not to be in this study or to stop being in this 
study will not result in any penalty to you or loss of benefit to which you are entitled. This means that 
your choice not to be in this study will not negatively affect your right to any present or future medical 
care. If you choose not to participate you would not be randomized to receive one treatment over 
another. An interscalene block is the standard of care for patients undergoing this procedure and you 
would still receive an interscalene block regardless of your participation in this study.
Detailed Information About This Research Study
The following is more detailed information about this study in addition to the information listed above.
How many people will be studied?
We expect 90 patients will be enrolled in this research study.
Page 3 of 8
Version Date: 5/11/2020


Approved for use by UMN IRB
Effective on 5/14/2020
IRB Study Number: STUDY00003350
Consent Form
What happens if I say “Yes, I want to be in this research”?
If you choose to take part in this research you will be randomized to receive an injection near the nerves 
in your neck (interscalene block) with either a long acting numbing medicine (liposomal bupivacaine plus 
bupivacaine) or a medium acting numbing medicine (bupivacaine) alone. The interscalene block is part 
of the standard of care and would be performed regardless of your participation in this study. The 
treatment you get will be chosen by chance, like flipping a coin. Neither you nor the study doctor will 
choose what treatment you get. You will have an equal chance of being given either treatment. You will 
not be told which treatment you are getting, however your study doctor will know.
You will receive preoperative oral medications which are designed to minimize your pain after surgery. 
They consist of acetaminophen 975mg and gabapentin 300mg. This is part of the standard of care.
After completion of the pre-surgery check in process you will be placed in the lying down position with 
the head of the bed elevated 30 degrees with standard monitors applied to look at your heart, 
breathing, and blood pressure. Medication will be given to relax you called sedation will be provided 
with midazolam 0-2mg and propofol 0-50 mg . An area in your neck where your nerves to your shoulder 
lie called the interscalene groove will be identified with a machine that allows us to see the structures in 
your neck called an ultrasound. Using sterile technique, a needle will then be inserted and advanced 
using the ultrasound machine until it is in the interscalene groove. Once the needle is in position in your 
neck, local anesthetic or numbing medicine will be injected. You will be monitored in the preoperative 
area until you are brought into the operating room for your procedure.
You will be given medications to make you fall asleep which consist of propofol (an anesthetic 
medication) ondansetron (a nausea prevention medication), dexamethasone (another nausea 
prevention medication) and ketamine (a pain medication). A device that allows us to breath for you 
during surgery will be placed and an opioid sparing technique will occur. Medications to keep you asleep 
during surgery will be a propofol infusion without any medications that result in weak muscles. Pain 
medication such as intravenous Fentanyl will be utilized if your body is showing signes of pain during 
surgery. This is part of the standard of care.
While in the hospital you will receive a standardized pain medication regimen. Acetaminophen 975 mg 
q6 hours, ibuprofen 600mg and as needed opioid pain medication called oxycodone. You will be 
discharged with oral pain medications for postoperative pain control.
You will be evaluated at 2, 6, 24, 48, and 72 hours following your procedure by a member of the 
research staff for your pain scores using a 0-10 point scale, and for opioid usage and any other use of 
pain medications. This will be done in person or via telephone call. The research assistant will be blinded 
to which medication you have received. At 72 hours and at 14 days post-procedure you will be asked to 
complete a Quality of Recovery Survey and be assessed for any block related complications. Your chart 
will continue to be monitored up to 30 days post-procedure for any complications related to the 
procedure.
What are my responsibilities if I take part in this research?
You will be responsible for giving your pain scores and answering the questions of the Quality of 
Recovery survey to members of the research staff.
Page 4 of 8
Version Date: 5/11/2020


Approved for use by UMN IRB
Effective on 5/14/2020
IRB Study Number: STUDY00003350
Consent Form
What happens if I say “Yes”, but I change my mind later?
You can leave the research study at any time. You can leave the research study at any time and no one 
will be upset by your decision.
Choosing not to be in this study or to stop being in this study will not result in any penalty to you or loss 
of benefit to which you are entitled. This means that your choice not to be in this study will not 
negatively affect your right to any present or future medical care.
If you stop being in the research, information about you that has already been collected may not be 
removed from the study database. You will be asked whether the investigator can collect information 
from your routine medical care, such as your medical records. If you agree, this information will be 
handled the same as the information obtained for the research study.
What are the risks of being in this study? Is there any way being in this study could be 
bad for me? (Detailed Risks)
The study has the following risks. Risks to you of this study include:
•
infection (0.001%)
•
bleeding (0.1%)
•
nerve injury (0.0001%)
•
cardiac arrhythmias (irregular heartbeat) (0.0001%)
•
respiratory complications (0.0001%)
These complications all fall within the standard risks of surgery and the performance of the interscalene 
injection.  Any intervention being provided as a part of this study falls within the standard of care as 
both medication options are within the standard treatments for post-operative pain and are currently 
used as analgesic (pain management) options at UMMC. In addition, you risk having your day 
interrupted by the anesthesia team to ask about your pain control and side effects as well as having your 
record looked at to see opioid and non-opioid (are pain medications that are non-narcotic such as 
Acetaminophen and NSAIDS) use during your hospitalization. There is also a risk of loss of privacy if you 
participate in this study.
EXPAREL or liposome bupivacaine (the long-acting numbing medicine) contains bupivacaine. Serious 
side effects related to bupivacaine are not common, but may occur if too much is given or if it is 
accidentally injected into a blood vessel. When given incorrectly, side effects may involve the brain or 
the heart.
The effects on the brain and central nervous system may include:
•
Restlessness (< 2%)
•
Anxiety (<2%)
•
Dizziness (<2%)
•
Tinnitus (ringing in the ears) (<2%)
•
Blurred vision (<2%)
•
Tremors (shaking) possibly proceeding to convulsions (<2%).
The effects on the heart appear when too much bupivacaine is given or when bupivacaine is injected in 
a blood vessel by accident. These effects cause a decrease of the heart function, including low heart rate
Page 5 of 8
Version Date: 5/11/2020


Approved for use by UMN IRB
Effective on 5/14/2020
IRB Study Number: STUDY00003350
Consent Form
or abnormal heart rhythm, decreased blood flow, low blood pressure, and, in extreme cases, heart 
attack. (<2%)
The numbing sensation caused by bupivacaine may be persistent, with slow, incomplete, or no recovery. 
Sometimes a tingling sensation may appear in the area treated with bupivacaine. When injected next to 
a large nerve, bupivacaine may cause weakness or paralysis.
Allergic reactions are rare, but may include rash, itching and redness of the skin, sneezing, nausea, 
vomiting, dizziness, fainting, sweating, fever, and low blood pressure. If you have these symptoms, 
please call your study doctor.
Other side effects of liposomal bupivacaine when given into the wound include:
•
Nausea (22.6%)
•
Constipation (8.7%)
•
Vomiting (6%)
•
High temperature (5.5%)
•
Dizziness (<2%)
•
Swelling (<1%)
•
Low blood pressure (<2%)
•
Anemia (<1%)
•
Itching (2.4%)
•
High heart rate (1.3%)
•
Headache (5%)
In addition to these risks, this research may hurt you in ways that are unknown. These might be minor or 
be severe as to cause death.
An additional risk by participating in this study is a breach of confidentiality.
Will it cost me anything to participate in this research study?
You and your insurance company will be charged for the health care services that you would ordinarily 
be responsible to pay. In some cases, insurance will not pay for services ordinarily covered because 
these services are performed in a research study. You should check with your insurance to see what 
services will be covered by your insurance and what you will be responsible to pay.
What happens to the information collected for the research?
Efforts will be made to limit the use and disclosure of your personal information, including research 
study and medical records, to people who have a need to review this information. We cannot promise 
complete confidentiality. Organizations that may inspect and copy your information include the 
Institutional Review Board (IRB), the committee that provides ethical and regulatory oversight of 
research, and other representatives of this institution, including those that have responsibilities for 
monitoring or ensuring compliance.
The sponsor, monitors, auditors, the IRB, the University of Minnesota Research Compliance Office and 
other University compliance units, the US Office of Research Integrity (ORI), the US Office for the 
Protection of Human Research Protections (OHRP), the US Food and Drug Administration (FDA) may be
Page 6 of 8
Version Date: 5/11/2020


Approved for use by UMN IRB
Effective on 5/14/2020
IRB Study Number: STUDY00003350
Consent Form
granted direct access to your medical records to conduct and oversee the research. By signing this 
document you are authorizing this access. We may publish the results of this research. However, we will 
keep your name and other identifying information confidential.
A description of this clinical trial will be available at http://www.ClinicalTrials.gov, as required by U.S. 
Law. This Web site will not include information that can identify you. At most, the Web site will include a 
summary of the results. You can search this Web site at any time.
Will anyone besides the study team be at my consent meeting?
You may be asked by the study team for your permission for an auditor to observe your consent 
meeting. Observing the consent meeting is one way that the University of Minnesota makes sure that 
your rights as a research participant are protected. The auditor is there to observe the consent meeting, 
which will be carried out by the people on the study team. The auditor will not document any personal 
(e.g. name, date of birth) or confidential information about you. The auditor will not observe your 
consent meeting without your permission ahead of time.
Whom do I contact if I have questions, concerns or feedback about my experience? 
This research has been reviewed and approved by an IRB within the Human Research Protections 
Program (HRPP). To share feedback privately with the HRPP about your research experience, call the 
Research Participants’ Advocate Line at 612-625-1650  (Toll Free: 1-888-224-8636) or go to 
z.umn.edu/participants. You are encouraged to contact the HRPP if:
●
Your questions, concerns, or complaints are not being answered by the research team.
●
You cannot reach the research team.
●
You want to talk to someone besides the research team.
●
You have questions about your rights as a research participant.
●
You want to get information or provide input about this research.
Will I have a chance to provide feedback after the study is over?
The HRPP may ask you to complete a survey that asks about your experience as a research participant. 
You do not have to complete the survey if you do not want to. If you do choose to complete the survey, 
your responses will be anonymous.
If you are not asked to complete a survey, but you would like to share feedback, please contact the 
study team or the HRPP. See the “Investigator Contact Information” of this form for study team contact 
information and “Whom do I contact if I have questions, concerns or feedback about my experience?” of 
this form for HRPP contact information.
Can I be removed from the research?
The person in charge of the research study or the sponsor can remove you from the research study 
without your approval. We will tell you about any new information that may affect your health, welfare, 
or choice to stay in the research.
Page 7 of 8
Version Date:  5/11/2020


Approved for use by UMN IRB
Effective on 5/14/2020
IRB Study Number: STUDY00003350
Consent Form
What happens if I am injured while participating in this research?
In the event that this research activity results in an injury, treatment will be available, including first aid, 
emergency treatment and follow-up care as needed. Care for such injuries will be billed in the ordinary 
manner, to you or your insurance company. If you think that you have suffered a research related injury 
let the study physicians know right away.
Will I be compensated for my participation?
No compensation will be provided for participation in this study.
Use of Identifiable Health Information
We are committed to respect your privacy and to keep your personal information confidential. When 
choosing to take part in this study, you are giving us the permission to use your personal health 
information that includes health information in your medical records and information that can identify 
you. For example, personal health information may include your name, address, phone number or social 
security number. Those persons who get your health information may not be required by Federal 
privacy laws (such as the 1099 Rule) to protect it. Some of those persons may be able to share your 
information with others without your separate permission. Please read the HIPAA Authorization form 
that we have provided and discussed.
The results of this study may also be used for teaching, publications, or for presentation at scientific 
meetings.
Your signature documents your permission to take part in this research. You will be provided a copy of 
this signed document.
Signature of Participant
Date
Printed Name of Participant
Signature of Person Obtaining Consent
Date
Printed Name of Person Obtaining Consent
Page 8 of 8
Version Date: 5/11/2020