Pecto-Intercostal Fascial Plane Block for Enhanced Recovery After Cardiac Surgery
Phase: PHASE4
Conditions: Cardiac Surgery, Opioid Use, Unspecified
Sponsor: University of Wisconsin, Madison

 
 
August 1, 2024 
 
 
To whom it may concern, 
 
Please find attached, documents for the study entitled,” Pecto-Intercostal Fascial Plane 
Block for Enhanced Recovery After Cardiac Surgery, UW Madison: 2021-0111”. This 
study has a ClinicalTrials.gov ID of NCT04928339. The forms have an institutional review 
board stamp from January 11, 2021, the most recent approval of the study. 
 
Sincerely, 
Jeremy Sullivan, PhD 
 

HS IRB# 2021-0111
Lead Researchers: Patrick Meyer; MD, MS   608-263-8100,
                                  Eric Simon, MD  608-263-8100
Version Date: 11 Jan 2021
Page 1 of 10
University of Wisconsin-Madison
Consent to Participate in Research
And
Authorization to Use Protected Health Information for Research
Title of the Study: Pecto-Intercostal Fascial Plane Block for Enhanced Recovery After Cardiac 
Surgery
Lead Investigators:   Patrick Meyer, MD (Phone: 608-263-8100)
                                    Eric Simon, MD (Phone: 608-263-8100)
Where Lead Researchers work: University of Wisconsin- Madison, Department of 
Anesthesiology
UW HS-IRB # 2021-0111
__________________________
____________________
Subject name
MR#
Invitation
We invite you to take part in a research study about how the injection of numbing 
medication in a targeted area prior to surgery may improve pain control after surgery. 
We are inviting you because you are scheduled for a surgery where the block may be 
beneficial. 
The purpose of this consent form is to give you the information you need to decide 
whether to be in the study. It also explains how health information will be used for this 
study and requests your authorization (permission) to use your health information.  Ask 
questions about anything in this form that is not clear. If you want to talk to your family 
and friends before making your decision, you can. Once we have answered all your 
questions, you can decide if you want to be in the study.  This process is called 
“informed consent.”  
What is the purpose of this study?
The purpose of this research study is to understand if the injection of numbing 
medication (bupivacaine) injected in the area by your pectoral and rib muscles may 
improve your pain control after surgery. This injection procedure is called a pecto-
IRB Approval Date: 4/8/2021              
University of Wisconsin – Madison

HS IRB# 2021-0111
Lead Researchers: Patrick Meyer; MD, MS   608-263-8100,
                                  Eric Simon, MD  608-263-8100
Version Date: 11 Jan 2021
Page 2 of 10
intercostal fascial plane block. We are doing this research because there are studies 
indicating that this block may reduce pain experienced after different surgical 
procedures in the same area of the body and we want to study how it may affect 
recovery after a sternum incision. This research must be conducted to understand if the 
block can help improve pain control after surgery. Its use in this study is considered 
experimental.
This study is being conducted at University Hospital with funding from the UW 
Department of Anesthesiology. We plan to include 100 participants in this study.
What will happen in this study?
If you decide to participate in this research study you will be randomly assigned (like 
flipping a coin) to one of two groups. You will have an equal chance of being assigned 
to either of the two groups:
<0000>
Group 1: have the nerve block performed with bupivacaine injections.
 
Group 2: have the nerve block performed with placebo (saline solution) 
injections
If you are in group 1, you will have the nerve block performed with bupivacaine and 
liposomal bupivacaine (shorter and longer acting numbing medications) on both sides of 
your chest before surgery. This will be performed after you are asleep under general 
anesthesia before they start your surgery. An ultrasound machine will be used to see 
the muscles of your chest and a bupivacaine mixture will be injected through a small 
needle in the correct location. We believe the numbing medication injected may help 
provide additional pain control after your surgery so you do not require as much pain 
medication. You will receive pain medication as needed after surgery to ensure you are 
comfortable, just as you would if you did not participate in the study. 
If you are in group 2, you will have the nerve block performed with saline instead of any 
numbing medication. This will occur after you are asleep under general anesthesia 
before they begin your surgery. An ultrasound machine will be used to see the muscles 
of your chest and saline will be injected through a small needle in the correct location. 
We do not expect this group to have any benefit associated with your recovery after 
surgery. You will receive pain medication as needed after surgery to ensure you are 
comfortable, just as you would if you did not participate in the study. 
You will not know which group you were randomly selected to. Your involvement in the 
study will not impact the anesthesia or surgery you receive in the operating room. After 
the operation you will receive standard care.
If you elect to participate in the study, you will be contacted by telephone approximately 
ninety days following your surgery and will be administered a brief pain survey over the 
IRB Approval Date: 4/8/2021              
University of Wisconsin – Madison

HS IRB# 2021-0111
Lead Researchers: Patrick Meyer; MD, MS   608-263-8100,
                                  Eric Simon, MD  608-263-8100
Version Date: 11 Jan 2021
Page 3 of 10
telephone. The purpose of this survey is to evaluate your pain, if any, and if you are 
using pain medications at this time following your operation. Following this phone call 
and survey, your participation in the study will be complete. 
Protected health information (PHI) used in this study
Protected health information, also called PHI, is information about your physical or 
mental health that includes your name or other information that can identify you, like 
your date of birth or medical record number. From your medical records, health records, 
and/or billing records kept by the University of Wisconsin Hospital and Clinics we will 
collect the following:
 
Age, date of birth, medical record number, height, weight, body mass index, 
gender, which procedure you are scheduled for, date of procedure, creatine 
levels, time it takes your blood to clot (an INR test), your platelet count, 
anticoagulation levels, your left ventricle ejection fraction, your right ventricular 
function, if you have scarring on your liver or have a liver disease diagnosis, any 
opioid use prior to surgery, your baseline pain score, pro ICU and hospital length 
of stay and clinical data from your surgery and recovery such as opioid use 
during and after the surgery, pain scores, time until rescue pain medication is 
used, time until bowel function returns, and your answers to a pain questionnaire 
90 days after surgery.
How long will I be in this study?
You will receive the nerve block while you are asleep in your surgery. Your medical 
record will be used to follow the clinical data from your surgery and your recovery for 72 
hours after your operation. You will then receive a follow up call and pain survey 90 
days after your procedure. Following completion of this survey, your participation in the 
study will end. 
The researchers may take you out of the study, even if you want to continue, if
 
Any health change where the study is no longer in your best interest
 
The study is stopped by the researchers.
Could taking part in the study help me?
You are not guaranteed to benefit directly from participating in this study. If you are 
randomized to receive the block with the bupivacaine injections you may have improved 
pain control after surgery. If you receive the block with the placebo injections, we do not 
expect you to have any direct benefit from the study. Even if the study does not help 
you directly, your participation in this research study may benefit other people in the 
future by helping us learn whether there is a clinical difference with the addition of the 
nerve block. 
IRB Approval Date: 4/8/2021              
University of Wisconsin – Madison

HS IRB# 2021-0111
Lead Researchers: Patrick Meyer; MD, MS   608-263-8100,
                                  Eric Simon, MD  608-263-8100
Version Date: 11 Jan 2021
Page 4 of 10
How is being in this study different from my regular health care?
We do not routinely administer this nerve block for this surgery. If you take part in the 
study you will have the nerve block performed with either the bupivacaine injections or 
saline injections while you are asleep under anesthesia just prior to your surgery. You 
will also be contacted via telephone at approximately 90 days following your operation 
for a survey. The remainder of your care will be unchanged.  
Do I have to be in the study?  What if I say “yes” now and change my 
mind later?
No, you do not have to be in this study. Taking part in research is voluntary.  This 
means that you decide if you want to be in the study.  If you decide now to take part, 
you can choose to leave the study at any time.  
If you decide to be in the study, the researchers will tell you about new information or 
changes in the study that may affect your health or your willingness to continue in the 
study.
Let the researchers know if you choose to leave the study. If you decide not to take part 
in the study, or if you choose to leave the study, your choice will not affect any treatment 
relationship you have with healthcare providers at UW-Madison, UW Health or any 
affiliated organizations, or any services you receive from them.  No matter what decision 
you make, and even if your decision changes, there will be no penalty to you. You will 
not lose medical care or any legal rights.
What are my other choices if I do not take part in this study?
If you decide not to take part in the study, you may undergo the surgery with regular 
care without the additional study procedures. Regular care would involve no nerve 
blocks or injections and no telephone survey at 90 days. 
Are there any side effects or risks to me?
There are a few risks to this study that apply to all subjects. First, your study 
information could become known to someone who is not involved in performing or 
monitoring this study. A breach of confidentiality could result in damage to your 
reputation, but the chances of this happening are very small.
Nerve block injection risks (for both groups) include: bleeding, infection, nerve injury, 
injury to blood vessels, and the possibility your lung may collapse. These risks are 
very low and we will use an ultrasound machine during the injections to help reduce 
the chance of these risks occurring. 
IRB Approval Date: 4/8/2021              
University of Wisconsin – Madison

HS IRB# 2021-0111
Lead Researchers: Patrick Meyer; MD, MS   608-263-8100,
                                  Eric Simon, MD  608-263-8100
Version Date: 11 Jan 2021
Page 5 of 10
Potential adverse drug reactions for bupivacaine and liposomal bupivacaine include:
Numbness around your lips, tingling in your face, ringing in your ear, restlessness, 
anxiety, dizziness, seizure, coma, slowing of your heart rate, changes to the rhythm 
of your heart, decreased heart function, low blood pressure, allergic reactions. The 
reactions that could affect your nerves/brain and/or your heart/blood pressure are 
very rare and tend to result in the event of an overdose, inappropriate injection of the 
medicine into a blood vessel or due to your body not breaking down the medication 
appropriately. 
Specific to liposomal bupivacaine (10% or more): nausea, vomiting, constipation
Whenever an ultrasound is done, there is the chance of finding something unexpected. 
Unexpected findings can have clear clinical significance, or uncertain clinical 
significance. Clear clinical significance means that the ultrasound shows a problem 
that may be treatable and we generally know what the risks are of not treating the 
problem. Uncertain clinical significance means that the imaging shows something 
unusual in the spine, but we do not know if it might affect your health, and treatment 
may not be appropriate or possible. On this study, you will be informed of any findings 
of clear clinical significance that may be discovered during the imaging procedure, but 
you will not be informed if there are findings of uncertain clinical significance. In order 
to assist us in interpreting incidental findings in the ultrasound, we are also seeking 
your permission to review your medical records if you are or have been a patient at this 
hospital. 
There may be benefits to learning such results (such as early detection and treatment 
of a medical condition), but there are risks as well (such as problems with getting 
insurance or a job, or feeling worried about a finding for which no treatment is required 
or appropriate). The ultrasound we are using in this research study is used for 
guidance for the purpose of performing a block and is not meant as a diagnosis tool. If 
you believe you are having symptoms that may require clinical imaging, you should 
contact your primary care physician. 
You may also choose to have your physician informed of any findings of clear clinical 
significance that we report to you by checking the box below. Please note, however, 
that if you choose to have your physician informed of findings of clinical significance, 
that report will likely be placed in your medical record. Please indicate your preference 
by checking the appropriate box:
____     Yes, please inform my doctor of findings of clinical significance 
OR 
____     No, please do not inform my doctor of findings of clinical significance 
IRB Approval Date: 4/8/2021              
University of Wisconsin – Madison

HS IRB# 2021-0111
Lead Researchers: Patrick Meyer; MD, MS   608-263-8100,
                                  Eric Simon, MD  608-263-8100
Version Date: 11 Jan 2021
Page 6 of 10
If you do wish us to report any findings to your physician, you must provide us with the 
name and location of your primary physician. 
Name of primary physician______________________________________ 
City or clinic__________________________________________________
This study may also involve risks which are currently unforeseeable. We will inform you 
as soon as possible if we discover any information that may affect your health, welfare, 
or decision to be in this study.
Will being in this study cost me anything?
You or your insurance company will have to pay for all costs for medical care related to 
your surgery, including co-payments and deductibles. You will not incur any additional 
costs from participating in this research study. You will have to pay for any costs your 
insurance does not cover. If you have any questions about these costs, or what out-of-
pocket expenses you may have to pay, you should contact your insurance company.  
Will I be paid for my participation? 
You will not be paid for your participation in this study.
What happens if I am injured or get sick because of this study?
If you are injured or get sick because of this study, medical care is available to you 
through UW Health, your local provider, or emergency services, as it is to all sick or 
injured people. 
 
If it is an emergency, call 911 right away or go to the emergency room.
 
For non-emergency medical problems, contact your surgery team or your primary 
care physician. 
 
Call the Lead Researchers, Patrick Meyer or Eric Simon at 608-263-8100 to 
report your sickness or injury.
Here are some things you need to know if you get sick or are injured because of this 
research: 
 
If the sickness or injury requires medical care, the costs for the care will be billed 
to you or your insurance, just like any other medical costs. 
 
Your health insurance company may or may not pay for this care.
 
No other compensation (such as lost wages or damages) is usually available.
 
UW-Madison and UW Health do not have a program to pay you if you get sick or 
are injured because of this study.
IRB Approval Date: 4/8/2021              
University of Wisconsin – Madison

HS IRB# 2021-0111
Lead Researchers: Patrick Meyer; MD, MS   608-263-8100,
                                  Eric Simon, MD  608-263-8100
Version Date: 11 Jan 2021
Page 7 of 10
 
By signing this consent form and taking part in this study, you are not giving up 
any legal rights you may have. You keep your legal rights to seek payment for 
care required because of a sickness or injury resulting from this study. 
HOW WILL MY PRIVACY BE PROTECTED AND WHO WILL USE MY 
HEALTH INFORMATION?
We have strict rules to protect your personal information and protected health 
information (PHI).  We will limit who has access to your name, address, phone number, 
and other information that can identify you.  We will also store this information securely.  
We may publish and present what we learn from this study, but none of this information 
will identify you directly without your permission.
However, we cannot promise complete confidentiality. Federal or state laws may permit 
or require us to show information to university or government officials and to study 
sponsors responsible for monitoring this study. We may also have to tell appropriate 
authorities, such as child protective services or health care providers, if we learn during 
the study that you or others are at risk of harm (for example, due to child or elder abuse, 
or suicidal thoughts).
Authorizing the research team to use your PHI means that we can release it to the 
people or groups listed below for the purposes described in this form.  Once your health 
information is released outside UW-Madison or UW Health it may not be protected by 
privacy laws and might be shared with others.  Also, with appropriate institutional 
permissions and confidentiality protections, we might use information that we collect 
during this study for other research or share with other researchers without additional 
consent or authorization from you or your legally authorized representative.  
The information collected from you during this study and from your medical records 
will be used by the researchers and research staff of the UW-Madison and its 
affiliates (UW Health) for this study. It may also be shared with others at the UW-
Madison.
Others at UW-Madison and its affiliates who may need to use your health 
information in the course of this research:
●
UW-Madison regulatory and research oversight boards and offices
●
Research support services staff at the UW-Madison and its affiliates
●
Personnel who schedule or perform medical tests or procedures, handle 
accounting and billing, or do other tasks related to the study.
IRB Approval Date: 4/8/2021              
University of Wisconsin – Madison

HS IRB# 2021-0111
Lead Researchers: Patrick Meyer; MD, MS   608-263-8100,
                                  Eric Simon, MD  608-263-8100
Version Date: 11 Jan 2021
Page 8 of 10
Others outside of UW-Madison and its affiliates who may receive 
your health information in the course of this research:
●
The U.S. Food and Drug Administration
People outside the UW-Madison and its affiliates who receive your health information 
may not be covered by privacy laws and may be able to share your health information 
with others without your permission. 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. Law. This Web site will not include information that can identify you. 
At most, the Web site will include a summary of the results. You can search this Web 
site at any time.
Will information from this study go in my medical record?
 
Some of the information that we collect about you for this study will be put in your 
medical record. This includes information about the procedures performed in the 
hospital: We will record the associated drug administration, if applicable, as well 
as any unanticipated problems that result from your participation. Both you and 
your UW Health providers will be able to see these records.
 
A UW Health medical record will be created for you if you do not already have 
one. 
IS MY PERMISSION VOLUNTARY AND MAY I CHANGE MY MIND?
Your permission is voluntary. You do not have to sign this form and you may refuse to 
do so. If you refuse to sign this form, however, you cannot take part in this research 
study. You may completely withdraw from the study at any time. Tell the researchers if 
you’d like to withdraw by verbal communication to any member of the study team, or 
by letter as outlined below.
If you decide to be in the study, the researchers will tell you about new information or 
changes in the study that may affect your willingness to continue in the study.
If you decide not to participate in this study or if you stop while the study is underway, 
the health care you receive from the UW-Madison and its affiliates will not be affected 
in any way. No matter what decision you make, and even if your decision changes, 
there will be no penalty to you. You will not lose medical care or any legal rights.
HOW LONG WILL MY PERMISSION TO USE MY HEALTH INFORMATION LAST?
By signing this form you are giving permission for your health information to be used 
by and shared with the individuals or institutions described in this form. Unless you 
withdraw your permission in writing to stop the use of your health information, there is 
no end date for its use for this research study. You may withdraw your permission at 
IRB Approval Date: 4/8/2021              
University of Wisconsin – Madison

HS IRB# 2021-0111
Lead Researchers: Patrick Meyer; MD, MS   608-263-8100,
                                  Eric Simon, MD  608-263-8100
Version Date: 11 Jan 2021
Page 9 of 10
any time by writing to either person whose name is listed below:
Patrick Meyer, MD
600 Highland Avenue, B6/339 CSC 
Madison WI 53792
Eric Simon, MD
600 Highland Avenue, B6/339 CSC 
Madison WI 53792
Beginning on the date you withdraw your permission, no new information about you will 
be used. Any information that was shared before you withdrew your permission will 
continue to be used. If you withdraw your permission, you can no longer actively take 
part in this research study.
WHO SHOULD I CONTACT IF I HAVE QUESTIONS?
Please take as much time as you need to think over whether or not you wish to 
participate. If you have any questions about this study at any time, contact the 
Principal Investigators Patrick Meyer or Eric Simon at 608-263-8100.
If you are not satisfied with response of research team, have more questions, or want 
to speak with someone about your rights as a research participant, contact the UWHC 
Patient Relations Representative at 608-263-8009.
IRB Approval Date: 4/8/2021              
University of Wisconsin – Madison

HS IRB# 2021-0111
Lead Researchers: Patrick Meyer; MD, MS   608-263-8100,
                                  Eric Simon, MD  608-263-8100
Version Date: 11 Jan 2021
Page 10 of 10
Authorization to participate in the research study and permission to use and/or 
disclose my health information:

I have read this Consent and Authorization form describing the 
research study procedures, risks and benefits and how my health 
information will be used.

I have had a chance to ask questions about the research study, including the 
use of my health information.

I have received answers to my questions.

I voluntarily agree to participate in this research study and permit the 
researcher to use my health information as described above.

I will receive a copy of this form.
______________________________________________________________________
Printed Name of Research Participant
______________________________________________________________________
Signature of Research Participant
Date
______________________________________________________________________
Signature of Person Obtaining Consent
Date
**You will receive a copy of this form**
IRB Approval Date: 4/8/2021              
University of Wisconsin – Madison

 
 
 
 
 
 
 
Pecto-Intercostal Fascial Plane Block for Enhanced Recovery 
After Cardiac Surgery  
 
 
 
 
 
 
Protocol Number: IRB #2021-0111 
Multiple-Investigator: Patrick Meyer, MD  
Multiple-Investigator: Eric Simon, MD 
 
 
 
Funding will be provided by the Department of Anesthesiology’s Research and 
Development (R&D) Committee.  
 
 
This document is confidential. 
No part of it may be transmitted, reproduced, published, or used by other persons without prior 
authorization from the Principal Investigator. 
 
 
 
Protocol Version History 
 
Protocol 
Version 
Version 
Date 
Summary of Revisions Made 
Rationale 
1.0 
01/11/2021 
v1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

- i - 
 
 
Table of Contents 
 
1.0 
STATEMENT OF COMPLIANCE ............................................................................................................. 1 
2.0 
LIST OF ABBREVIATIONS ...................................................................................................................... 2 
3.0 
STUDY SUMMARY .................................................................................................................................. 3 
 
Synopsis ....................................................................................................................................... 3 
 
Schematic of Study Design ........................................................................................................... 5 
4.0 
KEY ROLES ............................................................................................................................................. 6 
5.0 
INTRODUCTION ...................................................................................................................................... 7 
 
Background ................................................................................................................................... 7 
 
Rationale ....................................................................................................................................... 8 
6.0 
STUDY OBJECTIVES AND ENDPOINTS ................................................................................................ 8 
7.0 
STUDY DESIGN ....................................................................................................................................... 9 
8.0 
SUBJECT SELECTION .......................................................................................................................... 10 
 
Inclusion Criteria ......................................................................................................................... 10 
 
Exclusion Criteria ........................................................................................................................ 10 
 
Vulnerable Populations ............................................................................................................... 10 
 
Subject Identification ................................................................................................................... 10 
 
Subject Recruitment and Informed Consent ................................................................................ 11 
 
Enrollment ................................................................................................................................... 11 
 
Early Termination and Withdrawal ............................................................................................... 11 
9.0 
PROCEDURAL INTERVENTION ........................................................................................................... 11 
 
Study Procedural Intervention(s) Description .............................................................................. 11 
 
Method for Assigning to Treatment Groups ................................................................................. 12 
 
Unblinding Procedures ................................................................................................................ 12 
10.0 STUDY CALENDAR, MEASUREMENTS, AND ACTIVITIES ................................................................. 12 
 
Study Calendar ........................................................................................................................... 12 
 
Study Measurements .................................................................................................................. 13 
10.2.1 
Preoperative Period - Screening (Visit 1) .......................................................................................................... 13 
10.2.2 
Intra-operative Period (Visit 2) .......................................................................................................................... 14 
10.2.3 
Postoperative Period – ICU (Visit 3) ................................................................................................................. 14 
10.2.4 
Postoperative Period - 24 hours (Visit 5) .......................................................................................................... 14 
10.2.5 
Postoperative Period - 48 hours (Visit 6) .......................................................................................................... 14 
10.2.6 
Postoperative Period - 72 hours (Visit 7) .......................................................................................................... 14 
10.2.7 
Follow Up - 90 days after DOS (phone) ............................................................................................................ 15 
 
Study Activities ............................................................................................................................ 15 
11.0 DATA HANDLING AND RECORD KEEPING ........................................................................................ 15 
 
Data Collection ............................................................................................................................ 15 
11.1.1 
Data Collection Forms ...................................................................................................................................... 15 
11.1.2 
Data Management Software System(s) ............................................................................................................ 16 
 
Confidentiality and Privacy .......................................................................................................... 16 
 
Records Retention ...................................................................................................................... 17 
 
Publication and Data Sharing Policies ......................................................................................... 17 
12.0 STUDY ANALYSIS ................................................................................................................................ 17 

- ii - 
 
Statistical Hypotheses ................................................................................................................. 17 
12.1.1 
Primary Efficacy Endpoint(s): ............................................................................................................................ 17 
12.1.2 
Secondary Efficacy Endpoint(s): ....................................................................................................................... 17 
 
Sample Size Justification ............................................................................................................ 17 
 
Subject Population(s) for Analysis ............................................................................................... 18 
 
Statistical Methods ...................................................................................................................... 18 
 
Handling of Missing Data ............................................................................................................ 18 
13.0 RISK/BENEFIT ASSESSMENT ............................................................................................................. 18 
 
Known Potential Benefits to the Subjects .................................................................................... 18 
 
Known Potential Risks ................................................................................................................. 18 
 
Risk/Benefit Analysis ................................................................................................................... 19 
14.0 DATA AND SAFETY MONITORING ...................................................................................................... 20 
 
Adverse Event (AE) Definition ..................................................................................................... 20 
 
Serious Adverse Event (SAE) Definition ...................................................................................... 20 
 
Classification of an Adverse Event .............................................................................................. 20 
14.3.1 
Severity of Event ............................................................................................................................................... 20 
14.3.2 
Relationship to Study, Study Procedure(s) and/or Study Intervention(s) .......................................................... 21 
 
Reporting AEs and SAEs ............................................................................................................ 21 
 
Unanticipated Problems .............................................................................................................. 21 
 
Other Reportable Events ............................................................................................................. 21 
 
Safety Oversight .......................................................................................................................... 24 
15.0 REFERENCES ....................................................................................................................................... 25 

PIFB and Recovery After Cardiac Surgery 
 
Meyer & Simon 
 
 
 
Version #: 1.0 
Version Date: 11/20/2020 
Page 1 of 27 
 
1.0 
STATEMENT OF COMPLIANCE 
1. I have read this protocol and agree to conduct this trial in accordance with Good Clinical Practice (GCP), all 
stipulations of the protocol, the Declaration of Helsinki, and applicable regulatory requirements as stated by 
my human subjects testing oversight body [e.g., independent ethics committee (IEC) or institutional review 
board (IRB)]. 
2. I will personally conduct or supervise the described investigation(s). This includes informing all associates, 
colleagues, and employees assisting in the conduct of the study about their obligations in meeting the 
above commitments. 
3. I agree to maintain the confidentiality of all information received or developed in connection with this 
protocol. 
4. I agree that all electronic signatures will be considered the equivalent of a handwritten signature and will be 
legally binding. 
 
 
Name 
Signature 
Date 
 
 
__________________________________ 
_____________________________ 
___________________ 
Principal Investigator 
 
 
__________________________________ 
_____________________________ 
___________________ 
Name of Principal Investigator  
(printed or typed) 
 
 
 
 
 
 
 
 

PIFB and Recovery After Cardiac Surgery 
 
Meyer & Simon 
 
 
 
Version #: 1.0 
Version Date: 11/20/2020 
Page 2 of 27 
 
2.0 
LIST OF ABBREVIATIONS 
 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Transaminase 
BMI 
Body Mass Index 
CABG 
Coronary Artery Bypass Graft 
CAM-ICU 
Confusion Assessment Method for the ICU 
CPOT 
Critical Care Pain Observation Tool 
CRF 
Case Report Form 
CTMS 
Clinical Trial Management Software 
DOS 
Day of Surgery 
DSMB 
Data & Safety Monitoring Board  
DSMC 
Data & Safety Monitoring Committee 
FDA 
Food and Drug Administration 
eCRF 
Electronic Case Report Forms 
ERAS 
Enhanced Recovery After Surgery 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
ICU 
Intensive Care Unit 
IMA 
Internal Mammary Artery 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
MME 
Morphine Milligram Equivalents 
NIH 
National Institutes of Health  
NRS 
Numeric Rating Scale 
OHRP 
Office for Human Research Protections 
OnCore 
Online Collaborative Research Environment 
PACU 
Post-Anesthesia Care Unit 
PHI 
Protected Health Information 
PI 
Principal Investigator 
PIFB 
Pecto-Intercostal Fascial Plane Block 
POD 
Postoperative Day 
PTT 
Partial Thromboplastin Time 
SAE 
Serious Adverse Event 
SOC 
Standard of Care 
TTP 
Transversus Thoracic Plane 
UP 
Unanticipated Problem 
X 
Applies to Research Only 
 
 
 
 
 

PIFB and Recovery After Cardiac Surgery 
 
Meyer & Simon 
 
 
 
Version #: 1.0 
Version Date: 11/20/2020 
Page 3 of 27 
 
 
3.0 
STUDY SUMMARY  
 Synopsis 
Full Title 
Pecto-Intercostal Fascial Plane Block for Enhanced Recovery After Cardiac Surgery 
Short Title 
PIFB and Recovery After Cardiac Surgery 
Protocol Number 
HS IRB 2021-0111 
ClinicalTrials.gov 
Identifier & 
Summary 
Pending 
 
This study is being done to see if bilateral pecto-intercostal fascial plane blocks with a 
mixture of liposomal and standard bupivacaine decrease pain and opioid requirements in 
patients undergoing cardiac surgery via median sternotomy compared to controls (sham 
blocks with saline). 
Number of 
Site(s) 
1  
Main Inclusion 
Criteria 
• 
The patient is 18-80 years old 
• 
The patient’s ideal body weight (IBW) is >50kg 
• 
The patient is planned to undergo elective coronary artery bypass graft or single valve 
repair/replacement surgery via median sternotomy 
Main Exclusion 
Criteria 
• 
The patient has a preoperative coagulopathy (INR >1.4, platelets <100,000) or ongoing 
anticoagulation or anti-platelet therapy (except aspirin 81mg) 
• 
The patient has an allergy or sensitivity to amide-type local anesthetics, 
dexmedetomidine or ketamine  
• 
The patient has severe left ventricle dysfunction (defined quantitatively as an ejection 
fraction of less than or equal to 35%)  or right ventricle dysfunction (defined qualitatively 
as “severe”) 
• 
The patient uses chronic opioids (meaning at the time of the preoperative screening 
evaluation by the study team, the patient is prescribed and taking any opioid pain 
medication)  
Objective(s) 
Primary Objective  
• 
To evaluate postoperative opioid requirement within 72 hours in patients who received 
local anesthetics via PIFB compared to those control patients who received saline. 
Secondary Objectives  
• 
To evaluate intraoperative opioid consumption in patients who received local anesthetics 
via PIFB compared to those control patients who received saline. 
• 
To evaluate intensity of postoperative pain in patients who received local anesthetics via 
PIFB compared to those control patients who received saline. 
• 
To evaluate duration of mechanical ventilation in patients who received local anesthetics 
via PIFB compared to those control patients who received saline. 
• 
To evaluate return of bowel function in patients who received local anesthetics via PIFB 
compared to those control patients who received saline. 
• 
To evaluate postoperative delirium in patients who received local anesthetics via PIFB 
compared to those control patients who received saline. 
• 
To evaluate length of hospital stay in patients who received local anesthetics via PIFB 
compared to those control patients who received saline. 

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• 
To evaluate chronic opioid use at 90 days postoperatively in patients who received local 
anesthetics via PIFB compared to those control patients who received saline. 
Endpoints 
Primary Endpoint 
• 
Total daily opioid consumption during the initial 72 hours postoperatively will be 
measured in morphine equivalents and compared between groups.   
Secondary Endpoints 
• 
Total intraoperative opioid consumption will be measured in morphine equivalents and 
compared between groups. 
• 
Pain will be assessed, according to standard of care, every 4 hours using the 11-point 
Numerical Rating Scale (NRS), beginning at time 0 (arrival to ICU).  Each patient’s pain 
scores within discrete 8-hour time intervals will be averaged, and the median pain scores 
during each time interval will be compared between the intervention and control groups.  
Pain at 90 days postoperative will be surveyed by phone. 
• 
Duration of mechanical ventilation will be measured by hours of mechanical ventilation 
after admission to the ICU. 
• 
Return of bowel function will be measured in the number of postoperative days until the 
first bowel movement. 
• 
Postoperative delirium will be measured according to standard of care by utilizing the 
Confusion Assessment Method for the ICU (CAM-ICU) assessment every 8-12 hours. 
• 
Intensive care unit length of stay will be measured by the number of hours that the patient 
is in the ICU before an order is placed for transfer to a lower level of care.  
• 
Duration of hospital stay will be measured by the number of post-operative days until the 
patient is discharged. 
• 
Patient use of opioids at 90 days will be obtained by phone call. 
 
Study Design 
This study is a prospective, single-center, randomized, double-blind, controlled trial to 
evaluate whether bilateral pecto-intercostal fascial plane blocks with liposomal and standard 
bupivacaine decrease pain and opioid requirements in patients undergoing cardiac surgery 
via median sternotomy compared to controls (sham blocks with saline). 
Study 
Intervention 
The patients will be randomized to receive bilateral PIFB with a mixture of standard and 
liposomal bupivacaine or bilateral PIFB with saline only. Recovery characteristics, including 
opioid consumption, pain scores, duration of mechanical ventilation, ICU length of stay, 
hospital length of stay, side effects, and chronic opioid use will be evaluated. 
Total Number of 
Subjects 
A total of 100 subjects will be recruited. 
Statistical 
Methodology 
Data analysis will be performed on an intent-to-treat basis based upon assignment to a study 
arm. Continuous data will be compared using student T-test or Wilcoxon-rank sum testing as 
appropriate. Categorical data will be compared using Chi-square or Fisher exact testing as 
appropriate. The data will be presented graphically where possible using scatter plots, profile 
plots, or histograms. For all tests, statistical significance will be defined as a p-value less than 
0.05. 
Estimated 
Subject Duration 
The duration of the study for each subject is approximately 100 days.  
Estimated 
Enrollment 
Period & Study 
Duration 
Study enrollment and follow-up will occur over 3 months with the total expected duration of 
the trial to be 24 months.  

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 Schematic of Study Design 
 
 
Screening –  
Phone/in-person visit 
(Visit 1) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intra-operative Period 
(Visit 2) 
 
 
 
Postoperative Period – 
ICU (Visit 3) 
 
 
 
 
Postoperative Period – 
24, 48, 72 hours 
(Visits 4-6) 
 
 
 
Follow up – 90 days 
after DOS (phone) 
 
 
90-day follow-up assessments of study endpoints and safety  
Pain score and pain questionnaire, opioid use  
Post-ICU assessments of study endpoints and safety (24, 48, 72-hrs postop) 
Opioid consumption, pain scores, and return of bowel function,  
CAM-ICU, hospital length of stay (visits 4,5,and 6) 
Procedure 
Administer initial study intervention (PIFB or saline).  
Total N:  Obtain informed consent. Screen potential participants by inclusion and 
exclusion criteria; obtain history, document. 
Randomize 
Arm 2 (Saline Control) 
N=50  
Arm 1 (PIFB) 
N=50  
ICU assessments of study endpoints and safety 
Opioid consumption, pain scores, time until extubation and return of bowel 
function, CAM-ICU, ICU length of stay 

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4.0 
KEY ROLES 
The following is a list of all key personnel and roles: 
 
Multiple- Investigator 
Patrick Meyer, MD 
Title: Assistant Professor 
Department of Anesthesiology 
University of Wisconsin-Madison 
UW School of Medicine and Public Health 
600 Highland Avenue 
B6/319 CSC 
Madison, WI 53792-3272  
 (608)263-8100 
psmeyer@wisc.edu 
Multiple-Investigator 
Eric R. Simon, MD 
Assistant Professor 
Department of Anesthesiology 
University of Wisconsin-Madison 
UW School of Medicine and Public Health 
600 Highland Avenue 
B6/319 CSC 
Madison, WI 53792-3272  
(608) 263-8100 
esimon2@wisc.edu 
Co-Investigator 
Amy Fiedler, MD 
Assistant Professor 
Division of Cardiothoracic Surgery  
Department of Surgery 
University of Wisconsin-Madison 
UW School of Medicine and Public Health 
600 Highland Ave 
Madison, WI 53792 
(608) 262-3858 
fiedler@surgery.wisc.edu 
Participating Site(s) 
University of Wisconsin-Madison 
UW School of Medicine and Public Health 
 
Biostatistician 
Bryan Krause, PhD Scientist,  
Biostatistician 
University of WI-Madison 600 Highland Ave, B6/319 
Madison WI, 53792  
bmkrause@wisc.edu.  
 
 
 
 

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5.0 
INTRODUCTION 
 Background 
Pain after cardiac surgery via median sternotomy occurs as a direct result of surgical manipulation and 
tissue trauma. Acute pain is typically an inflammatory response and may be related to the surgical incision, 
pericardiotomy, retraction, suturing, and/or chest tube placement, among other causes. Acute pain after 
cardiac surgery has historically been treated with intravenous opioids, however significant side effects may 
limit their use and efficacy. A subset of patients experience severe acute postoperative pain, which may 
increase length of stay, morbidity, mortality, and healthcare costs1. In addition, 30-50% of patients report 
chronic pain (lasting at least 2 months) after coronary bypass surgery2, and the greatest predictor of 
chronic post-surgical pain is poorly controlled acute postoperative pain2.  
Over the past decade, with the emergence of enhanced recovery after surgery (ERAS) for cardiac surgery 
programs, cardiac anesthesiologists have been exploring unique options for maintenance of anesthesia 
and management of postoperative pain in place of high-dose opioids. Neuraxial anesthetic techniques 
have been used and studied extensively in this context, and while they appear safe and may even improve 
outcomes4-6, persistent concern over the rare, yet devastating, risk of spinal or epidural hematoma during 
full heparinization has limited their use in cardiac surgery. In addition, paravertebral blocks have shown 
comparable analgesic effects after cardiac surgery compared to thoracic epidural blockade7, however 
similar concerns over epidural hematoma exist.  
The anteromedial chest wall, including the sternum, is innervated by the anterior cutaneous branches of 
the intercostal nerves. One option to target these nerves is the transversus thoracic plane (TTP) block, 
described by Ueshima et al, where local anesthetic is injected in the fascial plane between the transversus 
thoracic and internal intercostal muscles just lateral to the sternum8. However, the internal mammary artery 
(IMA) is located in the same plane, which could lead to devastating complications if this block is used for 
coronary bypass surgery involving the IMA.  
The pecto-intercostal fascial plane block (PIFB) aims to block the anterior cutaneous branches of the 
intercostal nerves as they ascend in the parasternal region between the pectoralis major and external 
intercostal muscles. This block is superficial to the TTP and therefore should decrease the risk of injury to 
the IMA as well as the risk of pneumothorax. This block has been described by several different names in 
the literature, including the subpectoral interfascial plane block, the parasternal intercostal plane block, and 
the anterior thoracic medial block. Case reports and case series have demonstrated success in using this 
fascial plane block for acute post-sternotomy pain9-10, sternal fractures or anterior rib fractures11-14, and as 
an adjunct for coverage of medial breast procedures15-18. Two recently published randomized controlled 
trials have supported this block as safe and effective for reducing visual analog scale pain scores19 and 
postoperative opioid requirements using standard bupivacaine injection within this fascial plane20. 
In 2011, the Food and Drug Administration (FDA) announced the approval of Exparel© liposomal 
bupivacaine formulation for surgical site infiltration and field blocks. It has been marketed for local nerve 
infiltration, hemorrhoidectomy, bunionectomy and fascial plane blocks. In 2018, the FDA expanded its 
indication to include interscalene brachial plexus blocks following further evidence of its efficacy and safety. 
One downside of single shot peripheral nerve blockade is the duration of analgesia can be relatively short 
lived. Exparel© uses the multivesicular liposomal formulation of bupivacaine to deliver an extended-release 
effect of local anesthetic. This extended-release action may offer the benefit of long-lasting opioid sparing 
effects of regional analgesia without the need for perineural catheters or repeat single-shot injections, 
which may be time-consuming, increase wound infection risk, and place the patient at risk of requiring 
repeat procedures. To that end, the use of liposomal bupivacaine in fascial plane blocks for colorectal 
surgery ERAS protocols has found advantages over single-shot techniques with standard bupivacaine21 

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and similar efficacy with less opioid use compared to a catheter/epidural-based analgesic approach22. The 
use of liposomal bupivacaine for cardiac surgery and median sternotomy has been limited with mixed 
results to date23-24, with no studies to our knowledge evaluating its use in the PIFB. 
This study aims to evaluate the efficacy of bilateral pecto-intercostal fascial plane blocks with liposomal 
bupivacaine in the setting of a multimodal perioperative analgesic regimen in elective cardiac surgery 
patients requiring median sternotomy. 
 Rationale  
Thousands of heart surgeries are performed every day in the United States25. Unattenuated perioperative 
pain has been shown to contribute to increased morbidity, mortality, length of stay, and healthcare costs. 
Practice guidelines from the American Society of Regional Anesthesiologists recommend pre-incision 
techniques to reduce perioperative pain26, however in cardiac surgery, there are no commonly used 
techniques to follow this recommendation. The PIFB is a newly described fascial plane block and existing 
literature supports the safety and efficacy of the PIFB in cardiac surgery patients. However, there are no 
randomized controlled trials evaluating this technique with a long-acting depot local anesthetic.  
The purpose of this study is to determine whether bilateral pecto-intercostal fascial plane blocks with 
liposomal bupivacaine decrease pain and opioid requirements in patients undergoing cardiac surgery via 
median sternotomy compared to controls (sham blocks with saline). Our primary hypothesis is that patients 
receiving effective regional anesthesia with liposomal bupivacaine via PIFB will demonstrate a clinically 
significant (25%) reduction in total daily opioid consumption through 72 hours postoperatively compared to 
patients receiving standard of care without effective regional anesthesia (saline only via PIFB).  
6.0 
STUDY OBJECTIVES AND ENDPOINTS 
 
Objectives 
Endpoints 
Primary 
To evaluate postoperative opioid 
requirement within 72 hours in patients 
who received local anesthetics via PIFB 
compared to those control patients who 
received saline.  
Total opioid consumption during the initial 72 
hours postoperatively will be measured in 
morphine equivalents and compared between 
groups.  
Secondary 
• 
To evaluate intraoperative opioid 
consumption in patients who received 
local anesthetics via PIFB compared 
to those control patients who received 
saline.  
• 
Total intraoperative opioid consumption will 
be measured in morphine equivalents and 
compared between groups. 
• 
To evaluate intensity of postoperative 
pain in patients who received local 
anesthetics via PIFB compared to 
those control patients who received 
saline.   
• 
Pain will be assessed, according to standard 
of care, every 4 hours using the 11-point 
Numerical Rating Scale (NRS), beginning at 
time 0 (arrival to ICU).  Each patient’s pain 
scores within each postoperative day will be 
averaged, and the mean pain scores during 
each day and throughout the first 72 hours 
will be compared between the intervention 
and control groups.  Maximum pain scores 
will also be compared between groups. Pain 

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at 90 days postoperative will be surveyed by 
phone. 
• 
To evaluate daily postoperative opioid 
consumption within 72 hours in 
patients who received local 
anesthetics via PIFB compared to 
those control patients who received 
saline.  
• 
Daily opioid consumption during the initial 72 
hours postoperatively will be measured in 
morphine equivalents and compared between 
groups.  
• 
To evaluate duration of mechanical 
ventilation in patients who received 
local anesthetics via PIFB compared 
to those control patients who received 
saline. 
• 
Duration of mechanical ventilation will be 
measured by hours of mechanical ventilation 
after admission to the ICU. 
• 
To evaluate return of bowel function in 
patients who received local 
anesthetics via PIFB compared to 
those control patients who received 
saline. 
• 
Return of bowel function will be measured in 
the number of postoperative days until the 
first bowel movement. 
• 
To evaluate postoperative delirium in 
patients who received local 
anesthetics via PIFB compared to 
those control patients who received 
saline. 
• 
Postoperative delirium will be measured 
according to standard of care by utilizing the 
Confusion Assessment Method for the ICU 
(CAM-ICU) assessment every 8-12 hours.   
• 
To evaluate ICU length of stay in 
patients who received local 
anesthetics via PIFB compared to 
those control patients who received 
saline. 
• 
Duration of ICU stay will be measured by the 
number of hours that the patient is in the ICU 
until an order is placed for transfer to a lower 
level of care. 
• 
To evaluate length of hospital stay in 
patients who received local 
anesthetics via PIFB compared to 
those control patients who received 
saline. 
• 
Duration of hospital stay will be measured by 
the number of post-operative days until the 
patient is discharged. 
• 
To evaluate chronic opioid use in 
patients who received local 
anesthetics via PIFB compared to 
those control patients who received 
saline. 
• 
Patient use of opioids at 90 days will be 
obtained by phone call. 
 
7.0 
STUDY DESIGN 
This study is a prospective, single-center, randomized, double-blind, controlled trial in which 100 patients will 
be enrolled at the University of Wisconsin Hospitals and Clinics. The patients must satisfy the inclusion and 
exclusion criteria below. The patients will be randomized to receive bilateral PIFB with liposomal bupivacaine 
or bilateral PIFB with saline only. Recovery characteristics, including opioid consumption, pain scores, duration 
of mechanical ventilation, ICU length of stay, hospital length of stay, side effects, and chronic opioid use will be 
evaluated. 

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8.0 
SUBJECT SELECTION 
 Inclusion Criteria   
Each patient must meet all of the following inclusion criteria to be enrolled in the study. 
1. The patient provides consent to participate in study. 
2. The patient is 18-80 years old. 
3. The patient’s ideal body weight (IBW) is >50kg. 
4. The patient is planned to undergo coronary artery bypass graft or single valve repair/replacement 
surgery via median sternotomy. 
5. The patient is undergoing an elective procedure. 
 Exclusion Criteria 
Patients meeting any of the following exclusion criteria are not to be enrolled in the study. 
1. The patient is unable or unwilling to give consent. 
2. The patient is non-English speaking. 
3. The patient is known or believed to be pregnant or is currently breastfeeding. 
4. The patient is a prisoner. 
5. The patient is clinically unstable per discretion of the Investigator. 
6. The patient requires urgent/emergent surgery. 
7. The patient has a history of previous sternotomy. 
8. Preoperative coagulopathy (INR >1.4, platelets <100,000) or ongoing anticoagulation or anti-
platelet therapy (except aspirin 81mg). 
9. The patient has an allergy or sensitivity to amide-type local anesthetics, dexmedetomidine or 
ketamine. 
10. The patient has decompensated heart failure. 
11. The patient has severe left ventricle dysfunction (defined quantitatively as an ejection fraction of 
less than or equal to 35%)  or right ventricle dysfunction (defined qualitatively as “severe”) 
12. The patient has a diagnosis of cirrhosis or end-stage liver disease 
13. The patient requires the use of mechanical circulatory support pre-operatively. 
14. The patient uses chronic opioids (meaning at the time of the preoperative screening evaluation by 
the study team, the patient is prescribed and taking any opioid pain medication). 
 Vulnerable Populations 
Prisoners 
Due to the complexity of state and federal requirements governing the participation of prisoners in 
research, patients who are prisoners will not be considered for participation in this trial. In the unlikely event 
that a subject becomes a prisoner while participating in this trial, study procedures will stop and the subject 
will be returned to the clinical mode used prior to the intervention period or, if desired, an alternative mode 
requested by the clinical care team. 
 
Pregnancy 
Patients who are known to be pregnant will be excluded from participation. 
 Subject Identification 
A member of the research team will review the surgery schedule at least one week in advance and identify 
patients who appear to be candidates for the study. The study team will work with the perioperative care 
team (including the assigned anesthesia staff and surgeon) to confirm eligibility criteria and potential 
participation. All protected health information used during the screening process of a potential subject will 
be the minimum necessary for the conduct of this study. Any protected health information recorded for 

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screening will be destroyed for ineligible patients once they are deemed ineligible by a study team member 
aside from the reason for exclusion. Any protected health information recorded for an eligible patient who 
declines study participation and is not enrolled in the study will immediately be destroyed.  
 Subject Recruitment and Informed Consent 
When potential participants are identified and approved by the teams involved, a member of the study team 
will call the patient prior to the day of surgery and determine their interest in participating. On the day of 
surgery, potential participants will proceed through the usual preoperative process. A member of the study 
team will meet with the patients the morning of surgery. In order to ensure the candidate’s privacy and 
confidentiality, the cubicle’s curtain or room door will be closed. In a tone of voice insufficient for others to 
overhear the conversation and in the presence of only those immediately accompanying the patient and 
those who are directly involved with the patient’s care, the candidate’s eligibility, the study purpose, 
procedures, risks, benefits and alternatives will then be discussed. The written information about the study 
provided to the candidate at the time of their check-in will be reviewed and they will be instructed to take as 
much time as needed to consider their participation. Any questions that the candidate may have will be 
answered. Undue coercion will be prevented by stressing that the potential subject does not have to agree 
to participation and that the future care of the potential subject will not change regardless of the decision to 
participate. If the candidate has no further questions and would like to participate, they will be asked to sign 
the written informed consent document. The research subject will be given a copy of the signed and dated 
informed consent form. The original signed informed consent form is kept in a locked office in the 
Department of Anesthesiology. 
 Enrollment 
A research subject will be defined as “enrolled” in the study when they meet the following criteria: 
• 
The subject has been consented by study staff and has agreed to participate.  
• 
The subject and study staff have completed all screening documentation. 
• 
The PI has verified that the subject meets all of the inclusion criteria. 
• 
The PI has verified that subject meets none of the exclusion criteria. 
• 
The subject has been assigned to the protocol by study staff.  
• 
The subject has been randomized. 
• 
The subject has received the study intervention. 
 Early Termination and Withdrawal 
At any point prior to or during the intervention period, the patient’s clinical care team or a study physician 
may decide that the subject should be withdrawn from the study. In addition, at any point, a patient may 
elect to withdraw themselves from the study. If a patient is withdrawn from the study for any reason, the 
patient will then be followed according to standard of care follow-up. In the event that a subject is 
withdrawn from the study prematurely, the reason for withdrawal will be documented on a case report form. 
9.0 
PROCEDURAL INTERVENTION  
 Study Procedural Intervention(s) Description  
The intervention portion of this study is the randomized assignment (1:1) to receive 25mL of saline or 15mL 
of 0.25% bupivacaine mixed with 10mL of liposomal bupivacaine (133mg) as a single-shot injection into the 
pecto-intercostal fascial plane bilaterally. All studied volumes are well within the acceptable range for 
pecto-intercostal nerve blocks described previously. All patients will be treated intraoperatively according to 
our institutional enhanced recovery after surgery for cardiac patients, including the use of 
dexmedetomidine and ketamine infusions with as-needed fentanyl intravenous dosing. 

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 Method for Assigning to Treatment Groups 
After consent is obtained, participants will be randomized to an intervention group. Randomization will be 
accomplished using an online service (www.randomizer.org) and prefilling sealed envelopes determining 
each subject’s intervention group. Randomization will occur immediately prior to the intervention. All 
subjects will receive the standard of anesthesia care appropriate for their surgery or procedure as 
determined by the primary anesthesia team caring for the subject, regardless of randomization group. Each 
study subject as well as the OR anesthesia team, cardiac surgery team, cardiothoracic ICU team, and 
nursing staff caring for the patient will be blinded to the study drug the patient received. However, the 
anesthesia provider performing the block (separate from the provider caring for the patient in the operating 
room) will not be blinded to the study drug injected and will have access to all monitors deemed 
appropriate by the primary team caring for the subject. In order to maintain blinding during the procedure, 
the medication syringe will be covered by a towel after being drawn up and during injection to prevent the 
intraoperative teams from visualizing the contents being injected. The ultrasound will also be turned such 
that only the anesthesiologist performing the procedure can see, as Exparel has a distinct sonographic 
appearance on injection. Specific individuals who were involved in the block placement will not perform any 
follow-up assessments or evaluations of the study patients for the remainder of the study. 
 Unblinding Procedures 
To minimize the safety risk associated with blinding, the anesthesiologist performing the block will be 
available to be contacted by other caregivers for unblinding in the situation where that becomes necessary 
for patient safety. The anesthesiologists, surgeons, intensivists and nursing staff will be aware that the 
patient is enrolled in a study and may have received bupivacaine with liposomal bupivacaine injections. 
10.0 
STUDY CALENDAR, MEASUREMENTS, AND ACTIVITIES   
 
Study Calendar 
 
 
Screening 
Visit 1 
Phone/ 
inperson 
visit 
 
Procedure 
Visit 2 
ICU 
Visit 3 
24-
hours 
Post-op 
Visit 4 
48-hours  
Post-Op 
Visit 5 
 
72-hours 
Post-op  
Visit 6  
 
3 Months 
or 90 days 
after DOS 
(Phone) 
Window 
Up to 60 
days 
before 
surgery 
Morning of 
Surgery 
Followi
ng 
surgical 
proced
ure 
24 
hours 
post-op 
+/- 6 
hours 
48 hours 
post-op 
+/- 6 
hours 
72 hours 
post-op 
+/- 6 hours 
 
Screening  
X 
 
 
 
 
 
 
Eligibility 
X 
X 
 
 
 
 
 

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1 All medications taken for analgesia at home regularly, prior to arrival on the day of surgery, and perioperatively (until 72 hours 
postoperatively) will be recorded. 
2. EDC will all capture the opioid intake, pain measuresurement and all other relevant study information that is not capture during 
the study procedures. 
 
 
Study Measurements 
10.2.1 Preoperative Period - Screening (Visit 1) 
• Age 
• Sex 
• Height 
• Weight 
• Body mass index 
• Date of surgery 
• Procedure 
• Indication for procedure 
• Baseline creatinine 
Informed 
Consent 
X 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical History 
SOC 
 
 
 
 
 
 
Randomization 
and 
Intervention: 
Pecto-
Intercostal 
Fascial Plane 
Blocks vs Sham 
(control) 
 
X 
 
 
 
 
 
Electronic Data 
Collection 
(EDC) 
 
X 
X 
X 
X 
X 
 
Brief Pain 
Inventory Form  
 
 
 
 
 
 
 
 
 
 
X 
Concomitant 
Medications1 
 
 
SOC 
 
X 
 
X 
 
      X 
 
X 
 
X 
Adverse Events 
 
SOC 
 
SOC 
 
 
 

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• Baseline INR 
• Baseline platelet count 
• Preoperative anticoagulation 
• Baseline left ventricle ejection fraction 
• Baseline qualitative right ventricular function 
• Presence of cirrhosis or end-stage liver disease diagnosis 
• Presence of preoperative opioid use 
• Baseline pain score (Numeric rating scale [NRS]) 
10.2.2 Intra-operative Period (Visit 2) 
• Surgery length 
• Intraoperative opioid consumption 
• ASA Status 
10.2.3 Postoperative Period – ICU (Visit 3) 
• Opioid consumption  
• Pain scores (Critical Care Pain Observation Tool [CPOT], numeric rating scale [NRS]) q 4 hours 
• Time until first rescue opioid analgesia 
• Time until extubation 
• Time until return of bowel function 
• CAM-ICU q 8-12 hours 
• ICU length of stay 
10.2.4 Postoperative Period - 24 hours (Visit 4)  
• Opioid consumption  
• Pain scores (CPOT, NRS) q 4 hours 
• Time until first rescue opioid analgesia 
• Time until return of bowel function, recorded as time to first documented bowel movement 
• CAM-ICU q 8-12 hours 
10.2.5 Postoperative Period - 48 hours (Visit 5) 
• Opioid consumption  
• Pain scores (CPOT, NRS) q 4 hours 
• Time until first rescue opioid analgesia 
• Time until return of bowel function 
• CAM-ICU q 8-12 hours 
10.2.6 Postoperative Period - 72 hours (Visit 6) 
• Opioid consumption  
• Pain scores (CPOT, NRS) q 4 hours 
• Time until first rescue opioid analgesia 
• Time until return of bowel function 
• CAM-ICU q 8-12 hours 

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• Hospital length of stay 
10.2.7 Follow Up - 90 days after DOS (phone) 
• Standardized pain questionnaire (Brief Pain Inventory Short Form)  
 
Study Activities 
1. Surgery clinic education form explaining the study will be provided to the patient. 
2. Anesthesia schedule will be screened by a member of the research team at least one week in advance 
to identify prospective study participants. 
3. One of the study team members will call the patient prior to the day of surgery,  confirm eligibility to 
participate, explain the study,  review the study materials and obtain verbal consent from patient prior to 
the DOS. 
4. Prospective patients will be added to Anesthesia Block List with a note about the study after written 
consent is obtained from the patient. 
5. On the day of surgery, the patient will proceed through the usual preoperative process. A member of 
the study team will meet the patient, evaluate the patient for interval changes in their health, and obtain 
written informed consent to participate in the study. 
6. Randomization will occur the morning of surgery. The patient will be randomized to receive 15mL of 
0.25% bupivacaine with 10mL of liposomal bupivacaine bilaterally vs 25mL saline bilaterally within the 
pecto-intercostal fascial plane.  
7. The block team will perform ultrasound-guided bilateral single-shot PIFBs with 0.25% bupivacaine plus 
liposomal bupivacaine versus saline after induction of general anesthesia in the operating room.  
8. The patient, in-room anesthesia team, surgical team, and ICU team will be blinded to randomization 
status. The block team will not be blinded given the need to draw-up medications immediately prior to 
block placement and the distinct sonographic appearance of liposomal bupivacaine. The medication 
syringe will be covered by a towel after being drawn up and during injection to prevent blinded parties 
from visualizing the contents being injected. The ultrasound will also be turned such that only the 
anesthesiologist performing the procedure can see. 
9. All patients participating in the study will receive wrist bands indicating the possible use of liposomal 
bupivacaine to avoid additional local anesthetic or regional intervention for at least 96 hours following 
the nerve block or sham procedure. 
10. All patients participating in the study will receive a standardized intraoperative analgesic protocol 
according to our local institutional cardiac ERAS protocol. 
11. A member of the anesthesia block team (who was not involved in the block procedure) will see the 
patient on postoperative day (POD) 1 to monitor for any complications of the block. 
12. The remainder of data collection will occur electronically. 
13. A member of the research team will call the patient 90 days after surgery to administer a Brief Pain 
Inventory Short Form. 
14. All medications taken for analgesia at home regularly, prior to arrival on the day of surgery, and 
perioperatively (until 72 hours postoperatively) will be recorded. 
11.0 
DATA HANDLING AND RECORD KEEPING 
 
Data Collection  
11.1.1 Data Collection Forms 
All study data will be collected by a study team member on a standardized case report form (CRF) and 
stored within the university approved data collection site OnCore. Data entry into electronic format will 
take place on a private computer away from potential viewing by non-study personnel. The paper and 
electronic data will be kept in a locked office in the Department of Anesthesiology. The computer will be 
pass-coded and linked to a secure Anesthesia Department server to allow access only to approved 
study personnel. All identifiable data will be destroyed as soon as it is no longer required. De-identified 

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data will be retained for 7 years per UW-Madison best practices. For statistical analysis, de-identified 
data will be sent to biostatistician via email as a password protected encrypted zip file. 
11.1.2 Data Management Software System(s) 
Clinical data (including AEs, concomitant medications, and solicited events data) and clinical laboratory 
data will be entered into the following data management software system(s) to ensure consistent data 
entry and data quality. Clinical data will be entered directly from the source documents. 
 
OnCore  
The Online Collaborative Research Environment (OnCore) Clinical Trial Management Software (CTMS) 
will be used for this study. 
 
OnCore is a web-based data management system that: a) ensures secure, easy data entry at multiple 
sites; b) integrates multiple data sources; c) provides controlled, secure access to sensitive data using 
role-based access control; d) provides workflow automation; and e) allows export and reporting of data 
for Data (and Safety) Monitoring Committee(s) and statisticians. This software provides protocol and 
subject management functions (e.g., subject scheduling; screening; data organization), maintains 
updated forms, addresses budget development, billing and fiscal management, generates summary 
reports, and provides essential links with research administration and electronic medical records 
systems. The OnCore system eases the burden of the individual researcher and unifies protocol 
management within research programs and across research sites, enhancing protocol integrity and 
regulatory compliance efforts. 
 
The OnCore Support Team works with the investigator, statistician, and study team to ensure the 
relevant, applicable study data are collected and managed in a secure web-based system with 
restricted access using the software electronic case report forms (eCRFs). The OnCore Support Team 
will work with the study team to ensure the appropriate data is exported for analysis, but will not 
perform the analysis. 
 
Confidentiality and Privacy 
All study staff engaged in the conduct of this project have completed training on the protection of human 
subjects and the Health Insurance Portability and Accountability (HIPAA) Privacy Rule. In addition, all key 
personnel (i.e., Principal Investigator, individuals involved in identifying/recruiting subjects, obtaining 
informed consent, or interacting and intervening with subjects) have undergone Good Clinical Practice 
(GCP) training. 
 
Information about study subjects will be kept confidential and managed according to HIPAA requirements. 
All subjects will sign an informed consent document and a HIPAA authorization form or a combined 
informed consent and HIPAA authorization form> that includes specific privacy and confidentiality rights. 
Study data will be maintained per federal, state, and institutional data policies. 
 
Confidentiality will be protected to the extent possible by coding subject data and storing electronic data on 
password-protected anesthesiology department network computers and hard copy data in a locked study 
office until destruction. We will also utilize a secure information storage program OnCore. All hard copy 
data (source documents, signed consent forms, CRFs) will be stored in a locked study office. For statistical 
analysis, data will be de-identified on an excel spreadsheet that will be sent via email as a password 
protected encrypted zip file to the statistician. 
 
Authorized representatives of the following groups may need to review this research as part of their 
responsibilities to protect research subjects: representatives of the IRB, DSMB/DSMC, and federal 
oversight agencies. The clinical study site will permit access to such records. 

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Records Retention 
It is the investigator’s responsibility to retain study essential documents for a minimum period of 7 years 
following completion of the study per UW-Madison institutional policy. 
 
Publication and Data Sharing Policies 
This study will be conducted in accordance with the following publication and data sharing policies and 
regulations: 
 
This trial will be registered at ClinicalTrials.gov, and results information from this trial will be submitted to 
ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-reviewed journals.   
12.0 
STUDY ANALYSIS 
 
Statistical Hypotheses 
12.1.1 Primary Efficacy Endpoint(s):  
Patients who receive local anesthetic via PIFB will demonstrate lower total opioid use during the initial 
72 hours postoperatively compared to patients in the sham-control group. 
12.1.2 Secondary Efficacy Endpoint(s): 
• Patients who receive local anesthetic via PIFB will have a decreased intraoperative opioid 
requirement compared to patients in the saline-control group. 
• Patients who receive local anesthetic via PIFB will have lower maximum and mean pain scores 
during the first 72 hours postoperatively and at 90 days postoperatively compared to patients in the 
saline-control group. 
• Patients who receive local anesthetic via PIFB will demonstrate lower daily opioid use during the 
initial 72 hours postoperatively compared to patients in the sham-control group. 
 
• Patients who receive local anesthetic via PIFB will demonstrate a significant reduction in time to 
extubation compared to patients in the saline-control group.  
• Patients who receive local anesthetic via PIFB will demonstrate a significantly decreased time to 
return of bowel function compared to patients in the saline-control group.  
• Patients who receive local anesthetic via PIFB will demonstrate a significantly reduced rate of 
postoperative delirium compared to patients in the saline-control group.  
• Patients who receive local anesthetic via PIFB will demonstrate a significantly decreased ICU length 
of stay compared to patients in the saline-control group. 
• Patients who receive local anesthetic via PIFB will demonstrate a significantly decreased hospital 
length of stay compared to patients in the saline-control group.  
• Patients who receive local anesthetic via PIFB will demonstrate a significantly decreased persistent 
use of opioids at 90 days postoperatively compared to patients in the saline-control group.  
 
Sample Size Justification 
We conducted a retrospective chart review on prior single valve and CABG procedures utilizing a median 
sternotomy over a two-month period at our institution to characterize opioid consumption in our current 
patients. We found the average total opioid consumption in the first 72 hours following sternotomy was 245 

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MME (morphine milligram equivalents) +/- 87mg. We concluded that a 25% reduction in postoperative 
opioid requirements would be clinically significant, which is in line with what prior studies have utilized27. 
Therefore, using a type 1 error rate of 0.05, power of 90%, and a sampling ratio of 1:1 between study arms, 
we calculated a sample size of 86 patients (43 patients per group). To compensate for potential dropouts 
and incomplete data, a total of 100 patients (50 patients in each group) will be targeted for enrollment. 
 
Subject Population(s) for Analysis 
• 
Intention-to-Treat (ITT): all randomized subjects 
• 
Safety Analysis Dataset: all randomized subjects who received the required study intervention. 
• 
Protocol-compliant Population: all randomized subjects who received the required study intervention. 
 
Statistical Methods 
The primary endpoint is total postoperative opioid requirement within 72 hours. Total opioid requirement will be 
measured in morphine equivalents, presented as mean +/- standard deviation, and compared between study groups 
using a two-tailed independent samples t-test. Secondary outcomes (total intraoperative opioid requirement, mean 
and maximum 72-hour postoperative pain scores, and pain score 90 days postoperatively) will also be presented as 
mean +/- standard deviation and compared using independent samples t-tests. Daily postoperative opioid use and 
mean pain scores on POD1, POD2, and POD3 will also be compared separately with Holm-Bonferroni correction. For 
pain scores, we will compare mean VRS and average each patient’s score within each day before averaging across 
days. We recognize the debate in the literature about how to analyze pain scores. In the previously referenced 
randomized controlled trials19,20, the authors used mean scores so we will do so as well. 
 
Continuous secondary outcomes that we expect will not be approximately normally distributed (duration of 
mechanical ventilation, time until return of bowel function, ICU length of stay, hospital length of stay) will be 
presented as median with interquartile range and compared using Mann-Whitney tests. Categorical variables 
(delirium, chronic opioid use) will be presented as counts or as percentages and will be compared using Fisher's 
exact test. For all planned comparisons with parametric tests, non-parametric equivalents will be substituted if the 
assumptions of parametric testing are found to be violated before testing. 
 
Handling of Missing Data 
Guidelines promulgated in the National Research Council report on handling of missing data will be 
followed.28,29. 
13.0 
RISK/BENEFIT ASSESSMENT 
 
Known Potential Benefits to the Subjects 
Possible benefits of participating in this research study include improved postoperative analgesia, 
decreased opioid requirements and related side effects, shorter intensive care unit and hospital length of 
stay, and a decreased risk of developing chronic pain related to the surgery. 
 
Known Potential Risks 
PIFB risks 
Possible risks of a pecto-intercostal fascial plane block include bleeding, infection, failed block, vascular 
injury, or pneumothorax30. However, compared to the transversus thoracic muscle plane block, the PIFB is 
more superficial and thought to be safer due to the increased distance between the fascial plane and the 
pleura and internal thoracic vessels31. No serious block related complications have been reported with the 

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PIFB19,20. Reactions to bupivacaine are characteristic of those associated with other amide-type local 
anesthetics. A major cause of adverse reactions in this group of drugs is related to excessive plasma levels 
due to overdosage, unintentional intravascular injection or slow metabolic degradation. Central nervous 
system reactions as a result of these may include restlessness, anxiety, dizziness, tinnitus, blurred vision, 
or tremors may occur, possibly proceeding to convulsions, drowsiness, unconsciousness and respiratory 
arrest. Other central nervous system effects may be nausea, vomiting, chills, and constriction of the pupils. 
The incidence of convulsions associated with the use of local anesthetics varies with the procedure used 
and the total dose administered. Cardiovascular system reactions from high doses or unintentional 
intravascular injection may lead to high plasma levels and related depression of the myocardium, 
decreased cardiac output, heartblock, hypotension, bradycardia, ventricular arrhythmias, including 
ventricular tachycardia and ventricular fibrillation, and cardiac arrest. Allergic-type reactions are rare and 
may occur as a result of sensitivity to the local anesthetic or to other formulation ingredients, such as the 
antimicrobial preservative methylparaben contained in multiple-dose vials or sulfites in epinephrine-
containing solutions. These reactions are characterized by signs such as urticaria, pruritus, erythema, 
angioneurotic edema (including laryngeal edema), tachycardia, sneezing, nausea, vomiting, dizziness, 
syncope, excessive sweating, elevated temperature, and possibly, anaphylactoid-like symptomatology 
(including severe hypotension). Neurologic effects following procedures may include persistent anesthesia, 
paresthesia, weakness, paralysis, all of which may have slow, incomplete, or no recovery.  
In clinical trials utilized for FDA approval of Exparel (liposomal bupivacaine), the most common adverse 
reactions (incidence greater than or equal to 10%) following EXPAREL administration were nausea, 
constipation, and vomiting. The common adverse reactions (incidence greater than or equal to 2% to less 
than 10%) following EXPAREL administration were pyrexia, dizziness, edema peripheral, anemia, 
hypotension, pruritus, tachycardia, headache, insomnia, anemia postoperative, muscle spasms, 
hemorrhagic anemia, back pain, somnolence, and procedural pain. The less common/rare adverse 
reactions (incidence less than 2%) following EXPAREL administration were chills, erythema, bradycardia, 
anxiety, urinary retention, pain, edema, tremor, dizziness postural, paresthesia, syncope, incision site 
edema, procedural hypertension, procedural hypotension, procedural nausea, muscular weakness, neck 
pain, pruritus generalized, rash pruritic, hyperhidrosis, cold sweat, urticaria, bradycardia, palpitations, sinus 
bradycardia, supraventricular extrasystoles, ventricular extrasystoles, ventricular tachycardia, hypertension, 
pallor, anxiety, confusional state, depression, agitation, restlessness, hypoxia, laryngospasm, apnea, 
respiratory depression, respiratory failure, body temperature increased, blood pressure increased, blood 
pressure decreased, oxygen saturation decreased, urinary incontinence, vision blurred, tinnitus, drug 
hypersensitivity, and hypersensitivity. 
 
Risks associated with loss of confidentiality 
There is a risk that information recorded about subjects will be shared with people who would not normally 
have access to this information.  
 
Unknown risks 
This study may involve risks to the subject which are currently unforeseeable. We will inform subjects as 
soon as possible if we discover any information that may affect the subject's health, welfare, or decision to 
be in this study. 
 
Risk/Benefit Analysis 
PIFB:  
The risk of infection will be minimized by using the standard of care for regional anesthesia including a 
mask and sterile gloves for the provider, sterilizing the field of the block, and using sterile equipment. The 

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risk of bleeding will be minimized by adhering to the American Society of Regional Anesthesia evidenced-
based guidelines for regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy32. 
Despite not being a neuraxial technique, we will use the more conservative guidelines specific for neuraxial 
techniques to further minimize the risk of significant bleeding. Performing the procedure under ultrasound 
guidance allows us to identify all important adjacent structures to avoid injury to surrounding tissues and 
blood vessels. 
Blinding: 
All of the patients enrolled in the study will receive wrist bands indicating the possible use of liposomal 
bupivacaine in order to avoid the use of any additional local anesthetic or regional intervention for 96 hours. 
To minimize the risk associated with blinding, the co-principal investigators will be available to be contacted 
by other caregivers for unblinding in the situation where that becomes necessary for patient safety.      
Failed block:  
The risk of a failed block and inadequate analgesia will be minimized by the availability of supplemental 
oral and intravenous analgesics. 
 
In light of the mitigation strategies described above we believe the risk-to-benefit ratio is acceptable.  
14.0 
DATA AND SAFETY MONITORING  
 
Adverse Event (AE) Definition 
An adverse event (AE) is defined as any untoward or unfavorable medical occurrence in a human subject 
enrolled in this study, including any abnormal sign, symptom, or disease temporally associated with the 
PIFB or other study procedure that appears or worsens during the study or study follow-up period. AEs 
may be anticipated (i.e. redness or soreness at the injection site) or unanticipated (i.e. bleeding, infection, 
allergic reaction). Adverse event information will be collected throughout the entire study, and through 
resolution of the AE if present.  
Study staff will monitor for AEs by following up with the patient on post-operative day (POD) 1 and POD 90, 
electronic chart review, and with additional follow-up as needed related to any concerns for AEs from the 
primary care teams. All AEs will be recorded on a study data sheet and in the electronic database by a 
study investigator or study staff. In the event of an unanticipated AE, the primary anesthesia or intensive 
care unit team caring for the subject will intervene as deemed appropriate.  
 
Serious Adverse Event (SAE) Definition 
A serious adverse event (SAE) is defined as any adverse event that meets one of the following criteria: 
• 
Results in death 
• 
Is life-threatening 
• 
Requires hospitalization or prolongs existing hospitalization 
• 
Results in significant or persistent disability or incapacity 
• 
Results in a congenital anomaly/birth defect 
 
Classification of an Adverse Event 
14.3.1 Severity of Event 
The severity of all adverse events will be assessed according to the following scale: 

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• 
Mild: not requiring treatment or intervention 
• 
Moderate: resolved with treatment/intervention 
• 
Severe: inability to carry on normal activities and required professional medical attention 
14.3.2 Relationship to Study, Study Procedure(s) and/or Study Intervention(s) 
A co-principal investigator will determine the relationship of any adverse events to the research 
intervention using the following scale: 
• 
Definite: AE is clearly related to the study procedures 
• 
Probable: AE is likely related to the study procedures 
• 
Possible: AE is possibly related to the study procedures 
• 
Unlikely: AE is doubtfully related to the study procedures 
• 
Unrelated: AE is clearly not related to the study procedures 
 
Reporting AEs and SAEs  
Non-serious adverse events will be recorded if they occur from the time the study procedure begins to the 
patient’s hospital discharge. All serious adverse events will be recorded if they occur from the time that the 
subject provides informed consent through and including the 90-day follow-up phone call. All adverse 
events will be communicated to and between the co-principal investigators. 
 
Given the minimal risk associated with the use of PIFB, no serious adverse events are anticipated. If a SAE 
occurs, the study co-principal investigators will be immediately notified and further enrollment in the study 
will be halted until a full explanation of the cause of the event and its relationship to the PIFB and/or study 
procedure is understood. The IRB will be notified and re-initiation of study enrollment will not occur until 
approved by the IRB. 
 
Unanticipated Problems 
An unanticipated problem (UP) is defined as an event that meets all of the following criteria: 
• 
Unexpected in severity, nature, or frequency given the research procedures and the characteristics of 
the subject population 
• 
Related or possibly related to participation in the research study: 
 
The investigator will report UPs to the reviewing IRB and lead Principal Investigator (PI). The UP report will 
include the following information: 
• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project number; 
• 
A detailed description of the event, incident, experience, or outcome;  
• 
An explanation of the basis for determining that the event, incident, experience, or outcome represents 
an UP;  
• 
A description of any changes to the protocol, informed consent documents, or other corrective actions 
that have been taken or are proposed in response to the UP. 
 
• 
Report UPs within the timeframe(s) specified by the IRB(s) of record. 
 
 
Other Reportable Events 
Reporting timeframes begin when the site learns of the occurrence of the event.  
 
Event 
Definition 
Reporting  

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Breach of 
confidentiality 
The exposure of any study information or 
communications directly related to a study 
subject to anyone not named as study staff 
or the release of a study subject’s 
identifiable information to study staff who 
were not specified to receive such 
information in the protocol or IRB 
application.  
Treat as major deviation 
(below) 
Protocol 
deviation 
A deviation is an incident involving a 
departure from the IRB-approved protocol in 
the actual conduct of the study. Deviations 
may result from the action of the participant, 
investigator, or staff. 
See below 
Major 
deviations 
Deviations are considered major when the 
unapproved change(s) in previously 
approved research activities, implemented 
without IRB approval, may potentially 
adversely affect subjects’ rights, safety, 
welfare, or willingness to continue 
participation, or affect the scientific design of 
the study and/or the integrity of the resultant 
data. 
Treat as an Unanticipated 
Problem (above) 
Minor 
deviations  
Deviations are considered minor when the 
unapproved change(s) in previously 
approved research activities, implemented 
without IRB approval, do not adversely 
affect subjects or the integrity of the study 
data. 
Sites are to report cumulative 
events to AE Coordinator at 
time of continuing review.  
Protocol 
violation 
An incident involving an intentional deviation 
from the IRB-approved protocol that was not 
implemented in response to an emergency 
situation and that may impact a subject’s 
rights, safety, and/or welfare, makes a 
substantial alteration to risks to subjects, or 
affects the scientific design of the study 
and/or the integrity of the resultant data. 
Violations may also be repeated deviations 
(major or minor) of the same nature. 
Violations can represent serious or 
continuing non-compliance with the federal 
regulations and guidelines for ethical 
conduct of human subject research. 
Treat as an Unanticipated 
Problem (above) 
Protocol 
Exceptions 
A protocol exception is an IRB-approved 
deviation for a single subject or a small 
Protocol exceptions must be 
approved by local IRB prior 
to implementation. 

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group of subjects, but is not a permanent 
revision to the research protocol. 

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Safety Oversight 
After 15 subjects have been recruited, the study data will be reviewed by an independent anesthesiologist, 
blinded to study arm assignment, to ensure that no safety concerns exist. In the unlikely event that there is 
a safety concern, study recruitment will be halted and an independent Data Safety Monitoring Committee 
(DSMC), consisting of a minimum of three qualified practitioners, will be convened to evaluate the safety 
concern and make recommendations regarding changes to the study methods or termination of the study. 
Provided that no safety concerns exist after 10 patients, the independent anesthesiologist will periodically 
monitor the data through the end of the study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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15.0 
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PIFB and Recovery After Cardiac Surgery 
 
Meyer & Simon 
 
 
 
Version #: 1.0 
Version Date: 11/20/2020 
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