Erector Spinae Plane Block (ESPB): A New Technique for Perioperative Pain Control in Patients Undergoing Surgery Through a Flank or Anterior Subcostal Incision.
Phase: PHASE4
Conditions: Nephrectomy, Partial Nephrectomy, Incision Site Discomfort
Sponsor: Milton S. Hershey Medical Center

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HRP-592 - Protocol for Human Subject 
Research with Use of Test Article(s)
IRB 8663
Protocol Title:
Erector spinae plane block (ESPB): A new technique for perioperative pain control in patients undergoing surgery 
through a flank or anterior subcostal incision.
Principal Investigator:
Name:  Alireza Aminsharifi, M.D.
Department:  Surgery/Urology
Telephone:  1131
E-mail Address:   aaminsharifi@pennstatehealth.psu.edu
Version Date:
06/14/2023
Clinicaltrials.gov Registration #:
NCT03691935
Table of Contents
1.0
Objectives
2.0
Background
3.0
Inclusion and Exclusion Criteria
4.0
Recruitment Methods
5.0
Consent Process and Documentation
6.0
HIPAA Research Authorization and/or Waiver or Alteration of Authorization
7.0
Study Design and Procedures
8.0
Subject Numbers and Statistical Plan
9.0
Confidentiality, Privacy and Data Management
10.0
Data and Safety Monitoring Plan
11.0
Risks
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12.0
Potential Benefits to Subjects and Others
13.0
Sharing Results with Subjects
14.0
Subject Stipend (Compensation) and/or Travel Reimbursements
15.0
Economic Burden to Subjects
16.0
Resources Available
17.0
Other Approvals
18.0
Multi-Site Research
19.0
Adverse Event Reporting
20.0
Study Monitoring, Auditing and Inspecting
21.0
Future Undetermined Research: Data and Specimen Banking
22.0
References
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1.0
Objectives
1.1
Study Objectives
Using a randomized double-blinded study design, our goal is to evaluate the superiority of Erector 
Spinae Plane block (ESPB) in the peri-operative pain management in patients undergoing surgery 
through flank or anterior subcostal incisions as compared to the standard of care of using IV and oral 
opiates.
1.2
Primary Study Endpoints
1. Pain scores using the Visual analogue scale (VAS) 0-10 on postoperative day 1. (VAS scale document 
attached)
1.3
Secondary Study Endpoints
1.
Pain scores using the Visual analogue scale (VAS) 0-10 on postoperative day (POD) 2 and 3.
2.
Total dose of IV and oral opiate and study drug use at the completion of POD 1, 2 and 3. 
3.
Length of hospital stay
4.
Patient satisfaction survey of pain control given on POD 1, at discharge and at time of postoperative 
visit (within 14 days of discharge)—(survey document attached)
5.
Amount of oral opiates used from discharge to postoperative visit
6.
Total cost of hospital stay
2.0
Background
2.1
Scientific Background and Gaps
Despite the advances in less invasive surgical techniques, the flank or anterior subcostal incision remains 
a widely used surgical approach for surgeries performed on upper urinary tract.(1) Post-operative pain 
control is a fundamental part of care for any patient undergoing surgery and is often challenging. These 
incisions, in particular, are known to lead to increased postoperative pain due to the multiple layers of 
abdominal musculature incised.  It has been shown that inadequate peri-operative pain control can lead 
to chronic pain in postoperative patients.(2,3) Whereas, proper management of post-operative pain has 
shown benefits such as improved patient satisfaction, earlier mobilization, decreased length of hospital 
stay and even decreased hospital costs.(4,5,6) 
Opioids are the most commonly used agents for peri-operative pain control. Despite being effective, 
opioid use is associated with a long list of side effects and its overuse may be a driver for chronic 
addiction. The use of neuro-axial techniques, especially epidural-analgesia, offered a successful 
alternative to opioid narcotic use. Yet, its use can be limited by coagulopathy, infection and anatomical 
abnormalities. Additionally, the use of an epidural, at times, can delay a patient’s progress to hospital 
discharge.  Thus, the need for developing alternative safe and effective opioid sparing pain management 
techniques has grown. 
The goals of reducing postoperative narcotic requirements, in addition to the availability and high safety 
profile of the US-guided peripheral nerve block techniques, has provided a fertile landscape for studying 
new alternatives to epidural analgesia.(7)  It is promising that the exploration of new techniques for 
perioperative pain management may improve patient satisfaction and outcomes through avoiding 
deleterious side effects, decreasing length of hospital stay and may overall decrease total costs. 
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2.2
Previous Data
Recently, the erector spinae plane block (ESPB) has been described in multiple case studies. In 2016, 
Mauricio and colleagues presented ESPB as a novel analgesic technique in thoracic neuropathic pain. 
The authors used the proposed block successfully to manage thoracic pain in 4 patients presenting with 
chronic thoracic pain (2 cases) and postoperative pain control following video assisted thoracoscopic 
procedures (2 cases).(8) The same group has also utilized the same technique for postoperative pain 
control following ventral hernia repair and thoracotomy.(9,10)
2.3
Study Rationale
Opioid analgesia is associated with multiple side effects and its overuse may be a driver of chronic 
addiction. Establishing opioid sparing techniques for perioperative pain control is crucial for providing 
effective and safe patient care after surgery.
3.0
Inclusion and Exclusion Criteria
3.1
Inclusion Criteria
1.
Subjects undergoing open nephrectomy using a flank or anterior subcostal incision.
2.
Consenting adults age 18-85
3.
Patients weighing over 60 kg.
4.
American Society of Anesthesiologists (ASA) Physical Status classification I to III
5.
Planned to be hospitalized for at least 24 hours post-op
6.
Cognitive capacity to use the visual analogic scale (VAS) and complete the patient satisfaction 
survey 
3.2
Exclusion Criteria
1.
Patient refusal
2.
Patients with allergies to ropivacaine, local anesthetics, specifically amide anesthetics, or opiates 
(hydromorphone or oxycodone)
3.
Scoliosis
4.
Patients with chronic pain syndromes or who are on chronic pain medications/other neurologics of 
more than 3 months or whom have neuromodulators/stimulators 
5.
Concurrent surgeries requiring additional incisions on the body
6.
Pregnant females (pregnancy testing included in study procedures)
7.
Individuals with any clinically relevant history or the presence of neurological deficits or 
cardiovascular disease
8.
Patients with a history of liver dysfunction
3.3
Early Withdrawal of Subjects
3.3.1
Criteria for removal from study
1.
If the block cannot be placed/technically performed in the patient
2.
If the subject does not follow protocol
3.
If they are unable to participate cognitively after the surgery.
4.
Any inpatient Clavian III or greater surgical complication
5.
If surgery needs to be carried out via an incision other than flank or anterior subcostal
6.
If the subject has an adverse event, such an allergic reaction attributed to the study drug, causing 
the patient to become unblinded
7.
If the patient has pain requirements which exceed all options available in this protocol.
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3.3.2
Follow-up for withdrawn subjects
If subjects need to be withdrawn from the study based on the above reasons, they will transition 
to following the clinical standard of care that is medically required for their particular situation.  
The block that is in place will be unblinded to the physician and patient. Unblinding will help the 
physician and patient understand if it may be worth trying to continue with the block in such 
circumstances as a means of pain control.  Continuation with the blinding procedures could only 
delay achievement of adequate pain control and removal of unnecessary hardware, if the block 
ends up containing the control—normal saline.  The remainder of the hospital course for these 
withdrawn subjects will continue according to standard medical practice.  Their course will 
continue to be tracked for research purposes and they will be included and reported in the 
study results.
4.0
Recruitment Methods
4.1
Identification of subjects
The urology surgeons and members of the research team will identify potential study candidates as they 
present to the urology clinic to discuss their upcoming surgery.  Identification of potential subjects can 
occur both prior to clinic by using the patient medical record, as well as at the patient clinical encounter.
4.2
Recruitment process
After identification of potential subjects, at their clinic visit, the urology surgeons will confirm their 
eligibility and interest in participating.  Study information and a copy of the consent form will be 
provided to the patient to review.  Official enrollment of eligible and interested patients will occur in the 
urology clinic by the end of their preop visit.  Consent to participate in the study will formally be 
obtained during this visit by a member of the research team.  Attestation of the subject 
enrollment/consent will be signed by the principal investigator.
4.3
Recruitment materials
Patient consent form
4.4
Eligibility/screening of subjects
All potential subjects will be screened for initial study eligibility according to the inclusion and exclusion 
criteria, listed above—3.1,.3.2, during their urology clinic visit prior to their scheduled surgery.
5.0
Consent Process and Documentation
5.1
Consent Process 
 
5.1.1
Obtaining Informed Consent
5.1.1.1
Timing and Location of Consent
Written consent will take place in the urology clinic following confirmation of 
patient eligibility and agreement to participate in the research study. 
5.1.1.2
Coercion or Undue Influence during Consent
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It will be explained to the patient that research is voluntary. The patient will be 
encouraged to ask questions and it will be explained to the patient that their 
decision to participate or not participate will have no effect on their level of 
care.
5.1.2
Waiver or alteration of the informed consent requirement
Not applicable
5.2
Consent Documentation
5.2.1
Written Documentation of Consent
Written consent will be obtained. The patient will retain a signed and dated copy. A signed and 
dated copy will also be stored in the locked office of the research team and stored in the 
patient’s medical record. 
5.2.2
Waiver of Documentation of Consent (Implied consent, Verbal consent, etc.)
Partial waiver requested for review of schedules/charts for recruitment purposes.
5.3
Consent – Other Considerations 
5.3.1
Non-English Speaking Subjects
Not applicable
5.3.2
Cognitively Impaired Adults
5.3.2.1 Capability of Providing Consent
Not applicable
5.3.2.2
Adults Unable To Consent
Not applicable
5.3.2.3 Assent of Adults Unable to Consent
Not applicable
5.3.3
Subjects who are not yet adults (infants, children, teenagers) 
5.3.3.1 Parental Permission
Not applicable
5.3.3.2 Assent of subjects who are not yet adults
Not applicable
6.0
HIPAA Research Authorization and/or Waiver or Alteration of Authorization
6.1
Authorization and/or Waiver or Alteration of Authorization for the Uses and Disclosures of PHI
Check all that apply:
 
Not applicable, no identifiable protected health information (PHI) is accessed, used or 
disclosed in this study. [Mark all parts of sections 6.2 and 6.3 as not applicable]
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Authorization will be obtained and documented as part of the consent process. [If this is the 
only box checked, mark sections 6.2 and 6.3 as not applicable]
Partial waiver is requested for recruitment purposes only (Check this box if patients’ medical 
records will be accessed to determine eligibility before consent/authorization has been 
obtained). [Complete all parts of sections 6.2 and 6.3]
Full waiver is requested for entire research study (e.g., medical record review studies). 
[Complete all parts of sections 6.2 and 6.3]
Alteration is requested to waive requirement for written documentation of authorization 
(verbal authorization will be obtained). [Complete all parts of sections 6.2 and 6.3]
6.2
Waiver or Alteration of Authorization for the Uses and Disclosures of PHI
6.2.1
Access, use or disclosure of PHI representing no more than a minimal risk to the privacy of 
the individual
6.2.1.1 Plan to protect PHI from improper use or disclosure
Information is included in the “Confidentiality, Privacy and Data Management” 
section of this protocol.
6.2.1.2 Plan to destroy identifiers or a justification for retaining identifiers 
Identifiers will be destroyed by unlinking the subject ID code numbers from their 
MRNs and deleting this information from the database.  This will occur following 
full analysis and publication.
6.2.2
Explanation for why the research could not practicably be conducted without access to and 
use of PHI
Use of PHI is necessary to identify eligible patients and link them to their clinical data.
6.2.3
Explanation for why the research could not practicably be conducted without the waiver or 
alteration of authorization
Waiver of Authorization is requested for assessing patient eligibility prior to review of the 
consent document and enrollment in the research study.
6.3
Waiver or alteration of authorization statements of agreement
Protected health information obtained as part of this research will not be reused or disclosed to any 
other person or entity, except as required by law, for authorized oversight of the research study, or for 
other permitted uses and disclosures according to federal regulations. 
The research team will collect only information essential to the study and in accord with the ‘Minimum 
Necessary’ standard (information reasonably necessary to accomplish the objectives of the research) 
per federal regulations. 
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Access to the information will be limited, to the greatest extent possible, within the research team. All 
disclosures or releases of identifiable information granted under this waiver will be accounted for and 
documented.
7.0
Study Design and Procedures
7.1
Study Design
The study will be prospective, randomized, controlled, and double blinded.  
7.2
Study Procedures
After study approval and prior to study start, Kathy Lehman will be responsible for educating the clinical 
head nursing staff of the inpatient wards, Same Day Unit (SDU) and Post Anesthesia Care Unit (PACU) of 
this study and its protocol requirements. She will also provide an educational session to both the 
division of Urology as well as to the department of Anesthesiology on the study and protocol 
requirements.
7.2.1
Day 1 –Screening and Consent
The urology surgeon and/or study coordinator will identify potential patients according to the 
inclusion/exclusion criteria (3.1-3.2) prior to or on the day of clinic.  These will be patients 
scheduled for surgery using a flank or anterior subcostal incision.  A copy of the consent form 
will be provided to the subject at the time of their clinic visit.  Patient eligibility and interest in 
participation will be confirmed by the urology surgeon at the clinic visit prior to surgery. If they 
meet the criteria to be included into the study, a member of the research team will obtain 
written consent from the patient during this preop clinic visit. 
 
7.2.2
Working Day prior to surgery
A member of the research team will call the patient to ensure that they are planning on coming 
in for their scheduled surgery (i.e.: not sick, running a fever, has transportation). Members of 
the research team who will perform the block will be notified to confirm coordination of this 
procedure in the Same Day Unit (SDU). 
The subject will then be randomized by the study statistician using a computer-generated 
randomization list using SAS software (SAS Institute, Cary, NC) into two groups:

Group 1. Erector spinae plane block (ESPB)

Group 2. Sham Erector spinae plane block. (SESPB)
7.2.3
Day of Surgery - Pre-op
In the SDU, Kathy Lehman will be present to ensure the current surgery and anesthesia team for 
the study patient are sufficiently educated on the protocol requirements and to ensure safety 
and protocol adherence. The patient will receive a study bracelet with the study ID and patient’s 
specific randomization ID.  The block procedure will be performed in the SDU by a member of 
the anesthesia block team, who is also part of the research team.  The placement of the erector 
spinae catheter will occur according to standard practice guidelines using strict sterile conditions 
and is similar regardless of type of study medication that the patient will be randomly receiving.  
After the block catheter is placed, a member of the research team will pick up the study drug 
from the pharmacy, deliver it to the SDU and ensure the correct coordination of study drug to 
the patient using the patient’s study ID bracelet. The ESP catheters will be bolused with 20 ml of 
Ropivacaine 0.5% vs 20ml of normal saline (placebo).  Following this initial bolus, the ESP 
catheter will be connected to a pump containing Ropivacaine 0.2% or normal saline which will 
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deliver automatic boluses of 15ml of either study medication or normal saline every 3 hours.  
The automatic bolus dosing of 0.2% Ropivacaine is based on the standard dosing for all adults 
weighing between 50-120kg.  
7.2.4
Day of Surgery -Operating Room
Once in the operating room, general anesthesia will be induced according to the standard of 
care for the patient and surgery.  The ESPB pump will continue to deliver automatic boluses of 
15ml of either study medication or normal saline every 3 hours throughout the duration of 
surgery.  Intraoperatively, anesthesia is required to use only Fentanyl, a short acting opioid, for 
additional pain control and requested to refrain from using hydromorphone or morphine. At the 
completion of the case, Ondansetron will be administered for postoperative nausea.  
Dexamethasone will not be routinely administered as this can also have analgesic effects.   All 
medications administered by the anesthesia team during the operative case will be recorded in 
the anesthesia record and reviewed and documented by a member of the research team.
7.2.5
Postoperative hospital stay
As per standard of care, the patient will be taken to the post anesthesia care unit (PACU).  Here, 
Kathy Lehman will be present to ensure the PACU team for the study patient are sufficiently 
educated on the protocol requirements and to ensure safety and protocol adherence. The ESPB 
pump will be delivering the automatic boluses of study drug (15ml every 3 hours) and 
additionally allow the patient to self-administer an on demand dose of study drug (0.2% 
Ropivacaine vs. normal saline) 5ml every 30 minutes throughout their hospital stay.  The pump 
will permanently lock out and cease administration of both the automatic and self-administered 
boluses if the total dose of study drug reaches 770mg.  The patient will still be able to initiate a 
demand dose, but no medication will be provided.  If a lock out occurs prior to POD3, when the 
pump is scheduled to be removed, it will remain in place until the schedule day of removal. In 
the PACU, if the patient has additional pain requirements beyond the patient’s previously 
determined acceptable pain score (asked pre-operatively per hospital standard) the PACU team 
may start a patient controlled analgesia (PCA) containing a set demand dose of hydromorphone 
0.2mg every 6 mins.  The pump will lock out if the maximum dose of 2mg per hour is reached.  
Bolus IV dosing of hydromorphone may be administered at the start of the PCA and throughout 
the hospital stay if deemed necessary by the treating physician team to control patient pain 
needs.  One gram of acetaminophen IV every 8hrs will also be started in the PACU and 
continued through the patient’s hospital stay.  Acetaminophen will be converted over to oral 
regimen on POD 1.  When transferred to the inpatient wards, Kathy Lehman will ensure the 
nurse assigned to the study patient is aware and properly educated on the protocol 
requirements on a daily basis.  She will also monitor for subject safety and protocol adherence 
while the study patient remains in the hospital by both identifying the patient room as on a 
research study as well as through daily interaction with the nursing team. While on the inpatient 
wards, additional pain control adjuncts will be provided using oral oxycodone 5-10mg every 4 
hours administered based on a pain scale: pain 3-6 translates to 5mg tab and pain 7-10 
translates to a 10mg tab.  The PCA, as outlined above, may be started later in the hospital 
course, if needed, based on the patient’s needs. The ESP block will be discontinued between 
6AM-9AM on POD 3. Specific research order sets for this study will be created by the principal 
investigator for use of the study drug/placebo, narcotics and acetaminophen.   All medications 
and dosages administered during the hospital stay (PACU and inpatient ward) will be reviewed 
and documented by a member of the research team to tabulate the total IV and oral opioid and 
study drug requirement of all study patients.  Daily pain scales using the Visual analogue scale 
(VAS) 0-10 will be provided to the patient by a member of the research team, each morning 
between 9AM-12PM, on POD 1, 2 and 3 (scale attached).  Additionally, on POD 1, between 
9AM-12PM, a brief patient satisfaction survey (which has been previously validated (11)) will be 
provided to the patient to complete by a member of the research team (document attached). 
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On day of discharge, the same brief patient satisfaction survey will be provided again for the 
patient to complete prior to leaving the hospital.  Each patient will be provided with a standard 
home pain regimen which will include use of acetaminophen 500mg oral tabs every 6 hours as 
needed, oxycodone 5mg oral tabs every 4 hours as needed with a quantity of 30 tabs dispensed.
7.2.6
Postoperative clinic visit
Due to the COVID pandemic, a member of the research team will perform a telephone visit at 14 
days postoperatively to determine and document the number of oral oxycodone tablets 
remaining out of a total of 30 tabs dispensed.  Additionally, this member of the research team 
will also have the study patient fill out the same brief patient satisfaction survey (document 
attached).  It is at this time that the patient’s participation in this study will be concluded.
7.3
Duration of Participation
The patient will remain in the study until their telephone postoperative visit occurring within 14 days 
from discharge from the hospital.
7.4
Test Article(s) (Study Drug(s) and/or Study Device(s))
7.4.1
Description
Ropivacaine Hydrochloride injection 0.2% is FDA approved for use in surgery as a field block 
(infiltration) regional anesthesia.  We will use the Penn State Health standard of care 
ambulatory pump to provide the automatic and demand boluses of the study drug through the 
ESP catheters.
7.4.2
Treatment Regimen
Group 
Drug mixture
ESPB 
Ropivacaine 0.2%
SESPB 
Normal saline
7.4.3
Method for Assigning Subject to Treatment Groups
On the working day prior to surgery, subjects consented for the study will be randomized from a 
computer-generated randomization list using SAS software (SAS Institute, Cary, NC) and using 
block stratification with block sizes of two and four to allow an equal number of participants in 
each of the study groups.
7.4.4
Subject Compliance Monitoring
Members of the research team will verify that the label on the study drug that they receive in 
the SDU matches the study ID and patient’s specific randomization ID on their study bracelet.
7.4.5
Blinding of the Test Article
The study drugs will be prepared and provided by the investigational pharmacy who will be 
unblinded in this study.  Post randomization of study patients (randomization will occur the 
working day prior to scheduled operative date), the study drug will be packaged in a cartridge 
which will be nonspecific to the medication type (Ropivacaine or Normal saline). The cartridge 
will be labeled both with the study ID and the patient’s specific randomization number.  
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7.4.6
Receiving, Storage, Dispensing and Return 
7.4.6.1
Receipt of Test Article 
The Investigational Drug Service Pharmacy will maintain a study-specific supply 
of ropivacaine and normal saline for this study.
7.4.6.2
Storage
The investigational pharmacy will handle storage and distribution of study drugs 
according to their approved handling protocols.
7.4.6.3
Preparation and Dispensing
Following randomization of study patients (randomization will occur the 
working day prior to scheduled operative date), the study drug will be packaged 
both in a syringe which will contain the initial bolus dose and also in a cartridge 
which will contain the automatic pump boluses.  Both the syringe and cartridge 
which will be nonspecific to the medication type (Ropivacaine or Normal saline). 
The syringe and cartridge will be labeled both with the study ID and the 
patient’s specific randomization number.  The ESPB syringe and cartridge will 
contain Ropivacaine 0.2% and the SESPB syringe and cartridge will contain 
normal saline.  All preparation, dispensing of drug into cartridges and cartridge 
labeling will occur by the investigational pharmacy, who will remain unblinded. 
The day of surgery, a member of the research team will pick up both the syringe 
and cartridge and deliver it to the SDU.  Here, the syringe followed by the 
cartridge will be connected to the block catheters allowing administration to 
begin in the SDU.
7.4.6.4
Return or Destruction of the Test Article
Study drug will be discarded as per standard procedures.
7.4.6.5
 Prior and Concomitant Therapy
See section 7.2 Study Procedures for full details on concomitant medical therapy 
administered both during the operation, perioperative period and at hospital 
discharge.
.
8.0
Subject Numbers and Statistical Plan
8.1
Number of Subjects
40 patients, 20 per group.
8.2
Sample size determination
A total of N=17 patients in each group (N=34 total) yields 80% power to detect a 2-point mean decrease 
in pain scores using a 2-sided t-test conducted at a significance level of 0.05 and assuming that the 
standard deviation (in each group) is 2.  The standard deviation was selected to be slightly smaller than 
the standard deviation (2.5) under the assumption that all pain scores are equally likely (uniform 
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distribution).  In order to account for potential patient withdrawals from the study (see section), we 
have expanded the number to 20 patients randomized in each group.  
8.3
Statistical methods
For the primary endpoint, a 2-sided t-test will be used.  T-tests will also be used for all secondary 
endpoints, unless the assumption of normality does not hold, in which case a Wilcoxon Rank Sum Test 
will be used.  
9.0
Confidentiality, Privacy and Data Management 
See the Research Data Plan Review Form
9.1
Confidentiality
9.1.1
Identifiers associated with data and/or specimens
9.1.1.1 Use of Codes, Master List
9.1.2
Storage of Data and/or Specimens
9.1.3
Access to Data and/or Specimens
9.1.4
Transferring Data and/or Specimens
9.2
Subject Privacy
10.0 Data and Safety Monitoring Plan
10.1
Periodic evaluation of data
The PI and research coordinator will review cumulative adverse events, early termination of study 
participation, and accrual every six months and report any issues requiring modification of the study or 
alteration of the risk: benefit ratio to the IRB immediately.  A summary of adverse events, study progress 
and protocol modifications will be included for IRB review in the continuing review.
10.2
Data that are reviewed
The data to be reviewed will be:

Safety data

Untoward events

Efficacy data
10.3
Method of collection of safety information
Safety information will be collected by the research staff preoperatively and post operatively as 
described in Section 7.2.
10.4
Frequency of data collection
Data will be collected via the electronic medical record and begin following patient randomization.  Total 
IV and oral opiate during the hospitalization will be collected post discharge.  The VAS pain scales will be 
administered between 9AM-12AM on POD 1, 2 and 3 and collected daily.  The patient satisfaction 
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survey will be collected on POD 1, day of discharge and at the telephone post operative visit, within 14 
days from discharge.
10.5
Individuals reviewing the data
The PI will provide oversight for the conduct of the study, and the research coordinator will monitor the 
data. They will ensure that all eligible criteria and consent requirements are met prior to a subject’s 
participation in the study and that the procedures and adverse event reporting occur according to the 
IRB approved protocol.
10.6
Frequency of review of cumulative data
The PI and research coordinator will review cumulative adverse events, early termination of study 
participation, and accrual every six months and report any issues requiring modification of the study or 
alteration of the risk: benefit ratio to the IRB immediately.  A summary of adverse events, study progress 
and protocol modifications will be included for IRB review in the continuing review.
10.7
Statistical tests
Not applicable.
10.8
Suspension of research
Not applicable.
11.0 Risks
Risks specific to this study include:

Risk of randomization - patient will be assigned to a treatment program by chance. The treatment 
received may prove to be less effective than the other research treatment(s) or other available 
treatments.

Loss of confidentiality associated with being part of a research study collecting personal health 
information.

Complications of ESPB: local hematoma, local infection, pneumothorax, local anesthetic toxicity.

Adverse effects related to the study medications at proposed dosing are uncommon. Most adverse 
effects noted were at higher dosing; there is limited literature noting adverse effects at proposed 
dosing.
12.0 Potential Benefits to Subjects and Others
12.1
Potential Benefits to Subjects
Potential benefits of being a subject in the study include improved pain control, less nausea/vomiting, 
less sedation, fewer side effects from opiates, and decreased length of hospital stay.
12.2
Potential Benefits to Others
This study will provide data that may potentially create improved pain management protocols in 
patients undergoing general anesthesia for surgery using a flank or anterior subcostal incision.  
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13.0 Sharing Results with Subjects
not applicable
14.0 Subject Stipend (Compensation) and/or Travel Reimbursements
not applicable
15.0 Economic Burden to Subjects
15.1
Costs 
There will be no costs to the subject associated with their participation in the study other than those 
associated with normal standard of care. The study drugs will be provided by Hershey Medical Center.
15.2
Compensation for research-related injury
It is the policy of the institution to provide neither financial compensation nor free medical treatment 
for research-related injury. In the event of injury resulting from this research, medical treatment is 
available but will be provided at the usual charge. Such charges may be paid by the study sponsor as 
outlined in the research agreement and explained in the consent form.
16.0 Resources Available
16.1
Facilities and locations
This study will be completed at Penn State Hershey Medical Center.  This is a large university based 
tertiary care center where kidney surgery is frequently completed.
16.2
Feasibility of recruiting the required number of subjects
The required number of patients (see Section 9) needed should be attainable in 18-24 months according 
to current numbers being operated on at Hershey Medical Center. The project will continue until this 
number is obtained.  The access to these patients will not be limited by the surgical team.
16.3
PI Time devoted to conducting the research
The PI enjoys protected academic time as well as access to urology-specific research infrastructure for 
full support.  
16.4
Availability of medical or psychological resources
All resources needed for the protocol, as well as for any possible adverse event, are available at Penn 
State Hershey Medical Center.
16.5
Process for informing Study Team
Meetings will be held periodically as needed to ensure all research team members are informed about 
the protocol and their duties. Team emails will also be used to keep team members updated.
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17.0 Other Approvals
17.1
Other Approvals from External Entities
Not applicable
17.2
Internal PSU Committee Approvals
Check all that apply:
  Anatomic Pathology – Hershey only – Research involves the collection of tissues or use of pathologic 
specimens. Upload a copy of HRP-902 - Human Tissue For Research Form on the “Supporting 
Documents” page in CATS IRB. This form is available in the CATS IRB Library.
  Animal Care and Use – All campuses – Human research involves animals and humans or the use of 
human tissues in animals
  Biosafety – All campuses – Research involves biohazardous materials (human biological specimens 
in a PSU research lab, biological toxins, carcinogens, infectious agents, recombinant viruses or DNA or 
gene therapy). 
  Clinical Laboratories – Hershey only – Collection, processing and/or storage of extra tubes of body 
fluid specimens for research purposes by the Clinical Laboratories; and/or use of body fluids that had 
been collected for clinical purposes, but are no longer needed for clinical use. Upload a copy of HRP-901 
- Human Body Fluids for Research Form on the “Supporting Documents” page in CATS IRB. This form is 
available in the CATS IRB Library.
  Clinical Research Center (CRC) Advisory Committee– All campuses – Research involves the use of 
CRC services in any way.  
  Conflict of Interest Review – All campuses – Research has one or more of study team members 
indicated as having a financial interest.
  Radiation Safety – Hershey only – Research involves research-related radiation procedures. All 
research involving radiation procedures (standard of care and/or research-related) must upload a copy 
of HRP-903 - Radiation Review Form on the “Supporting Documents” page in CATS IRB. This form is 
available in the CATS IRB Library.
  IND/IDE Audit – All campuses – Research in which the PSU researcher holds the IND or IDE or 
intends to hold the IND or IDE.
  Scientific Review – Hershey only – All investigator-written research studies requiring review by the 
convened IRB must provide documentation of scientific review with the IRB submission. The scientific 
review requirement may be fulfilled by one of the following: (1) external peer-review process; (2) 
department/institute scientific review committee; or (3) scientific review by the Clinical Research Center 
Advisory committee.  NOTE: Review by the Penn State Hershey Cancer Institute Scientific Review 
Committee is required if the study involves cancer prevention studies or cancer patients, records and/or 
tissues. For more information about this requirement see the IRB website at: 
http://www.pennstatehershey.org/web/irb/home/resources/investigator 
18.0 Multi-Site Research
Not applicable 
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19.0 Adverse Event Reporting
19.1
Adverse Event Definitions
For drug studies, incorporate the following definitions into the below responses, as written:
Adverse event
Any untoward medical occurrence associated with the use of the drug in 
humans, whether or not considered drug related
Adverse reaction
Any adverse event caused by a drug
Suspected adverse 
reaction
Any adverse event for which there is a reasonable possibility that the drug 
caused the adverse event.  Suspected adverse reaction implies a lesser degree 
of certainty about causality than “adverse reaction”.

Reasonable possibility.  For the purpose of IND safety reporting, 
“reasonable possibility” means there is evidence to suggest a causal 
relationship between the drug and the adverse event.
Serious adverse 
event or Serious 
suspected adverse 
reaction
Serious adverse event or Serious suspected adverse reaction: An adverse event 
or suspected adverse reaction that in the view of either the investigator or 
sponsor, it results in any of the following outcomes: Death, a life-threatening 
adverse event, inpatient hospitalization or prolongation of existing 
hospitalization, a persistent or significant incapacity or substantial disruption 
of the ability to conduct normal life functions, or a congenital anomaly/birth 
defect. Important medical events that may not result in death, be life-
threatening, or require hospitalization may be considered serious when, based 
upon appropriate medical judgment, they may jeopardize the patient or 
subject and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition. 
Life-threatening 
adverse event or 
life-threatening 
suspected adverse 
reaction
An adverse event or suspected adverse reaction is considered “life-
threatening” if, in the view of either the Investigator (i.e., the study site 
principal investigator) or Sponsor, its occurrence places the patient or research 
subject at immediate risk of death.  It does not include an adverse event or 
suspected adverse reaction that had it occurred in a more severe form, might 
have caused death.
Unexpected 
adverse event or 
Unexpected 
suspected adverse 
reaction.  
An adverse event or suspected adverse reaction is considered “unexpected” if 
it is not listed in the investigator brochure, general investigational plan, clinical 
protocol, or elsewhere in the current IND application; or is not listed at the 
specificity or severity that has been previously observed and/or specified.
For device studies, incorporate the following definitions into the below responses, as written:
Unanticipated 
adverse device 
effect
Any serious adverse effect on health or safety or any life-threatening problem 
or death caused by, or associated with, a device, if that effect, problem, or 
death was not previously identified in nature, severity, or degree of incidence 
in the investigational plan or IDE application (including a supplementary plan 
or application), or any other unanticipated serious problem associated with a 
device that relates to the rights, safety, or welfare of subjects.
19.2
Recording of Adverse Events
Research subjects will be routinely questioned about adverse events at study visits.
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All adverse events (serious or non-serious) and abnormal test findings observed or reported to study 
team believed to be associated with the study drug(s) or device(s) will be followed until the event (or its 
sequelae) or the abnormal test finding resolves or stabilizes at a level acceptable to the investigator.
An abnormal test finding will be classified as an adverse event if one or more of the following criteria are 
met:

The test finding is accompanied by clinical symptoms

The test finding necessitates additional diagnostic evaluation(s) or medical/surgical intervention; 
including significant additional concomitant drug treatment or other therapy
NOTE: Simply repeating a test finding, in the absence of any of the other listed criteria, does not 
constitute an adverse event.

The test finding leads to a change in study drug dosing or discontinuation of subject 
participation in the clinical research study
The test finding is considered an adverse event by the investigator.
19.3
Causality and Severity Assessments
The investigator will promptly review documented adverse events and abnormal test findings to 
determine 1) if the abnormal test finding should be classified as an adverse event; 2) if there is a 
reasonable possibility that the adverse event was caused by the study drug(s) or device(s); and 3) if the 
adverse event meets the criteria for a serious adverse event.
If the investigator’s final determination of causality is “unknown and of questionable relationship to the 
study drug(s) or device(s)”, the adverse event will be classified as associated with the use of the study 
drug(s) or device(s) for reporting purposes.  If the investigator’s final determination of causality is 
“unknown but not related to the study drug(s) or device(s)”, this determination and the rationale for the 
determination will be documented in the respective subject’s case history.
19.4
Reporting of Adverse Reactions and Unanticipated Problems to the FDA  
19.4.1
Written IND/IDE Safety Reports
The Sponsor-Investigator will submit a written IND Safety Report (i.e., completed FDA Form 
3500A) to the responsible new drug review division of the FDA for any observed or volunteered 
adverse event that is determined to be a serious and unexpected, suspected adverse reaction.  
Each IND Safety Report will be prominently labeled, “IND Safety Report”, and a copy will be 
provided to all participating investigators (if applicable) and sub-investigators.
Written IND Safety Reports will be submitted to the FDA as soon as possible and, in no event, 
later than 15 calendar days following the Sponsor-Investigator’s receipt of the respective 
adverse event information and determination that it meets the respective criteria for reporting.
For each written IND Safety Report, the Sponsor-Investigator will identify all previously 
submitted IND Safety Reports that addressed a similar suspected adverse reaction experience 
and will provide an analysis of the significance of newly reported, suspected adverse reaction in 
light of the previous, similar report(s) or any other relevant information.
Relevant follow-up information to an IND Safety Report will be submitted to the applicable 
review division of the FDA as soon as the information is available and will be identified as such 
(i.e., “Follow-up IND Safety Report”).
If the results of the Sponsor-Investigator’s follow-up investigation show that an 
adverse event that was initially determined to not require a written IND Safety Report 
does, in fact, meet the requirements for reporting; the Sponsor-Investigator will 
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submit a written IND Safety Report as soon as possible, but in no event later than 15 
calendar days, after the determination was made.
19.4.2
Telephoned IND Safety Reports – Fatal or Life-threatening Suspected Adverse Reactions
**UNDER REVIEW**
In addition to the subsequent submission of a written IND Safety Report (i.e., completed FDA 
Form 3500A), the Sponsor-Investigator will notify the responsible review division of the FDA by 
telephone or facsimile transmission of any unexpected, fatal or life-threatening suspected 
adverse reaction. 
The telephone or facsimile transmission of applicable IND Safety Reports will be made as soon 
as possible but in no event later than 7 calendar days after the Sponsor-Investigator’s receipt of 
the respective adverse event information and determination that it meets the respective criteria 
for reporting
19.5
Reporting Adverse Reactions and Unanticipated Problems to the Responsible IRB
In accordance with applicable policies of The Pennsylvania State University Institutional Review Board 
(IRB), the investigator will report, to the IRB, any observed or reported harm (adverse event) 
experienced by a subject or other individual, which in the opinion of the investigator is determined to be 
(1) unexpected; and (2) probably related to the research procedures. Harms (adverse events) will be 
submitted to the IRB in accordance with the IRB policies and procedures.
19.6
Unblinding Procedures
Unblinding of the study drug would occur if a patient developed an adverse reaction, such as an allergic 
reaction, attributed to the study drug.  Documentation of the adverse reaction would ensue and the 
patient would be unblinded and then withdrawn from the study.  Such a patient would then be cared for 
in context of standard medical practice and their remainder of their medical course would continue to 
be tracked for research purposes and reported in final study results. Additionally, in any instance that 
the subject is being withdrawn from the study, as listed in section 3.3.1, the subject will also be 
unblinded.  Unblinding will help the physician and patient engage in a more meaningful and effective 
clinical interaction for pain control.  There will be no confusion as to if the block may or may not contain 
active medication, Ropivacaine, and thus could be effective for the clinical scenario.
19.7
Stopping Rules
Not applicable.
20.0 Study Monitoring, Auditing and Inspecting
20.1
Study Monitoring Plan
20.1.1 Quality Assurance and Quality Control
This is a low risk therapeutic study using techniques and agents with a known safety profile.
The PI will ensure that this study is conducted, and that the data are generated, documented 
(recorded), and reported, in compliance with this protocol, with institutional and IRB policies, 
with Good Clinical Practice guidelines and any other applicable regulatory requirements.
20.1.2 Safety Monitoring
The Principal Investigator will confirm that all adverse events (AE) are correctly entered into the 
AE case report forms by the coordinator; be available to answer any questions that the 
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coordinators may have concerning AEs; and will notify the IRB, FDA, sponsor and/or DSMB of all 
applicable AEs as appropriate. All assessments of AEs will be made by a licensed medical 
professional who is an investigator on the research. 
The Research Coordinator will complete the appropriate report forms and logs; assist the PI to 
prepare reports and notify the IRB, FDA, and/or DSMB of all Unanticipated Problems/SAE’s.
21.0 Future Undetermined Research: Data and Specimen Banking
Not applicable 
21.1
Data and/or specimens being stored
not applicable
21.2
Location of storage
not applicable
21.3
Duration of storage
not applicable
21.4
Access to data and/or specimens
not applicable
21.5
Procedures to release data or specimens
not applicable
21.6
Process for returning results
not applicable
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22.0 References
1.
Sharma V, Margreiter M. Partial nephrectomy: is there still a need for open surgery? Curr Urol Rep. 
2013;14:1–4. 
2.
Gerbershagen HJ, Aduckathil S, van Wijck AJ, Peelen LM, Kalkman CJ, Meissner W. Pain intensity on the 
first day after surgery: a prospective cohort study comparing 179 surgical procedures. Anesthesiology. 
2013;118:934–44.
3.
Gerbershagen HJ, Pogatzki-Zahn E, Aduckathil S, et al. Procedure-specific risk factor analysis for the 
development of severe postoperative pain. Anesthesiology. 2014;120:1237–1245. 
4.
De Beer Jde V, Winemaker MJ, Donnelly GA, Miceli PC, Reiz JL, Harsanyi Z, Payne LW, Darke A. Efficacy 
and safety of controlled-release oxycodone and standard therapies for postoperative pain after knee or hip 
replacement. Can J Surg. 2005;48:277
5.
Recart A, Duchene D, White PF, Thomas T, Johnson DB, Cadeddu JA. Efficacy and safety of fast-track 
recovery strategy for patients undergoing laparoscopic nephrectomy. Journal of Endourology. 2005;19:1165.
6.
Watcha MF, Issioui T, Klein KW, White PF. Costs and effectiveness of rofecoxib, celecoxib, and 
acetaminophen for preventing pain after ambulatory otolaryngologic surgery. Anesth Analg. 2003;96):987
7.
Huseyin Yuce Bircan, Dilek Altun, Ismail Caymaz, Alp Demirag, Ayda Turkoz, Anesthesia management 
with ultrasound-guided thoracic paravertebral block for donor nephrectomy: A prospective randomized study. J 
Clin. Anesth. 2017 Feb;37:1-6. doi:10.1016/j.jclinane.2016.10.038. Epub 2016 Dec 15.
8.
Mauricio Forereo, Sanjib D. Adhikary, Hector Lopez, Calvin Tsui and ki Jinn Chin. The erector spinae 
plane block; A novel analgesic technique in thoracic neuropathic pain. J of chronic and interventional pain. 2016 
Sep-Oct;41(5):621-7. doi: 10.1097/AAP.0000000000000451.
9.
Mauricio Forereo, Rajarathinam M, Sanjib D. Adhikary, ki Jinn Chin. Continuous erector spinae plane 
block for rescue analgesia in thoracotomy after epidural failure: A case report. A. A. Case Rep. 2017 May 
15;8(10):254-256. doi: 10.1213/XAA.0000000000000478
10.
Ki Jinn Chin, Sanjib D. Adhikary, Sarwani N., Mauricio Forereo. The analgesic efficacy of pre-operative 
bilateral erector spinae plane (ESP) blocks in patients having ventral hernia repair. Anaesthesia. 2017 
Apr;72(4):452-460. doi: 10.1111/anae.13814. Epub 2017 Feb 11.
11. 
Gordon DB, Polomano RC, Pellino TA, Turk DC, McCracken LM, Sherwood G, Paice JA, Wallace MS, 
Strasseis SA, Farrar JT. Revised American Pain Society Patient Outcome Questionnaire (APS-POQ-R) for quality 
improvement of pain management in hospitalized adults: preliminary psychometric evaluation. J Pain. 2010 
Nov;11(11):1172-86.
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