Efficacy of the Erector Spinae Plane Block for Abdominal Pain From Gastrointestinal Malignancies
Phase: NA
Conditions: Gastrointestinal Malignancy, Pain Control
Sponsor: Abramson Cancer Center at Penn Medicine

 
 
 
 
Protocol UPCC 27224- ESPB for GI Malignancy Pain 
 
 
 
 
Protocol Template V3.0 (09Nov2020) 
 
 

 
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CLINICAL RESEARCH PROTOCOL 
 
INVESTIGATIONAL 
PRODUCT(S): 
 
None 
STUDY 
NUMBER(S): 
IRB 
Number 
Pending  
Other 
Protocol 
Identifiers  
 
UPCC 27224 
PROTOCOL(S) TITLE: 
Efficacy of the Erector Spinae Plane Block for Abdominal Pain 
from Gastrointestinal Malignancies 
REGULATORY 
SPONSOR: 
None 
FUNDING SPONSOR(S): 
None 
MEDICAL DIRECTOR 
Michael Shalaby, MD 
ORIGINAL PROTOCOL 
DATE: 
7/24/2025 
VERSION NUMBER: 
v 1.0  
VERSION DATE: 
7/24/2025 
 
 

 
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1 
Study Summary .......................................................................................................... 9 
1.1 
Synopsis .................................................................................................................. 9 
1.2 
Key Roles and Study Governance ..................................................................... 13 
1.3 Schema ....................................................................................................................... 14 
2 
Introduction and RationalE .................................................................................... 15 
2.1 
Study Rationale ................................................................................................... 15 
2.2 
Background .......................................................................................................... 15 
2.2.1 
Pharmacokinetics, Pharmacodynamics and Toxicology ........................... 19 
2.2.2 
Assessment for Potential Study Products Drug-Drug, Drug-Device, 
Device-Device Interactions ........................................................................... 20 
2.2.3 
Clinical Adverse Event Profile ..................................................................... 20 
2.2.4 
Dosing Rationale ........................................................................................... 20 
2.3 
Risk/Benefit Assessment ..................................................................................... 20 
2.3.1 
Known Potential Risks .................................................................................. 20 
2.3.2 
Known Potential Benefits ............................................................................. 20 
2.3.3 
Assessment of Potential Risks and Benefits ................................................ 20 
3 
Study Objectives and Endpoints............................................................................. 22 
4 
Study Plan ................................................................................................................. 24 
4.1 
Study Design ........................................................................................................ 24 
4.2 
Scientific Rationale for Study Design ................................................................ 26 
4.3 
Justification for Dose .......................................................................................... 26 
4.4 
End of Study Definition ...................................................................................... 26 
5 
Study Population ...................................................................................................... 27 
5.1 
Inclusion Criteria ................................................................................................ 27 
5.2 
Exclusion Criteria ............................................................................................... 27 
5.3 
Lifestyle Considerations ..................................................................................... 27 
5.4 
Screen Failures .................................................................................................... 27 
5.5 
Strategies for Recruitment and Retention ........................................................ 28 
6 
Study Intervention ................................................................................................... 30 
6.1 
Study Intervention(s) Administration ............................................................... 30 
6.1.1 
Study Intervention Description .................................................................... 30 
6.1.2 
Dosing and Administration .......................................................................... 30 
6.2 
Preparation/Handling/Storage/Accountability ................................................ 30 
6.2.1 
Acquisition and accountability .................................................................... 30 
6.2.2 
Formulation, Appearance, Packaging, and Labeling ................................ 30 
6.2.3 
Product Storage and Stability ...................................................................... 30 
6.2.4 
Preparation .................................................................................................... 30 
6.3 
Measures to Minimize Bias: Randomization and Blinding ............................. 30 
6.4 
Study Intervention Compliance ......................................................................... 31 
6.5 
Concomitant Therapy ......................................................................................... 31 
6.5.1 
Rescue Medicine ............................................................................................ 31 
 

 
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7 
Study Intervention Discontinuation and Participant 
Discontinuation/Withdrawal ................................................................................... 32 
7.1 
Discontinuation of Study Intervention .............................................................. 32 
7.2 
Participant Discontinuation/Withdrawal from the Study ............................... 32 
7.3 
Lost To Follow-Up .............................................................................................. 32 
8 
Study Assessment and Procedures ......................................................................... 33 
8.1 
Efficacy Assessments ........................................................................................... 33 
8.2 
Safety and Other Assessments ........................................................................... 34 
8.3 
Adverse Events and Serious Adverse Events ................................................... 35 
8.3.1 
Definition of Adverse Events (AE) .............................................................. 35 
8.3.2 
Definition of Serious Adverse Events (SAE) ............................................... 35 
8.3.3 
Unanticipated Adverse Device Effect (UADE) ........................................... 47 
8.3.4 
Classification of an Adverse Event .............................................................. 36 
8.3.5 
Time Period and Frequency for Event Assessment and Follow-Up ......... 36 
8.3.6 
Adverse Event Reporting ............................................................................. 37 
8.3.7 
Serious Adverse Event Reporting ................................................................ 38 
8.3.8 
Reporting Events to Participants ................................................................. 38 
8.3.9 
Events of Special Interest ............................................................................. 39 
8.3.10 
Reporting of Pregnancy ................................................................................ 39 
8.4 
Unanticipated Problems ..................................................................................... 39 
8.4.1 
Definition of Unanticipated Problems (UP) ................................................ 39 
8.4.2 
Unanticipated Problem Reporting .............................................................. 39 
8.4.3 
Reporting Unanticipated Problems To Participants ................................. 40 
8.5 
Device Reporting ................................................................................................. 59 
9 
Statistical Considerations ........................................................................................ 40 
9.1 
Statistical Hypotheses ......................................................................................... 40 
9.2 
Sample Size Determination ................................................................................ 40 
9.3 
Populations for Analyses .................................................................................... 41 
9.4 
Statistical Analyses .............................................................................................. 41 
9.4.1 
General Approach ......................................................................................... 41 
9.4.2 
Analysis of the Primary Efficacy Endpoint(s) ............................................ 42 
9.4.3 
Analysis of the Secondary Endpoint(s) ....................................................... 42 
9.4.4 
Safety Analyses .............................................................................................. 42 
9.4.5 
Baseline Descriptive Statistics ...................................................................... 42 
9.4.6 
Planned Interim Analyses ............................................................................ 43 
9.4.7 
Sub-Group Analyses ..................................................................................... 43 
9.4.8 
Tabulation of Individual Participant Data ................................................. 44 
9.4.9 
Exploratory Analyses .................................................................................... 44 
10 Supporting Documentation and Operational Considerations ............................. 44 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ............................. 44 
10.1.1 
Informed Consent Process ............................................................................ 44 

 
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10.1.2 
Study Discontinuation and Closure ............................................................. 45 
10.1.3 
Confidentiality and Privacy ......................................................................... 45 
10.1.4 
Future Use of Stored Specimens and Data ................................................. 45 
10.1.5 
Safety Oversight ............................................................................................ 46 
10.1.6 
Clinical Monitoring ....................................................................................... 46 
10.1.7 
Quality Assurance and Quality Control ..................................................... 47 
10.1.8 
Data Handling and Record Keeping ........................................................... 47 
10.1.9 
Protocol Deviations ....................................................................................... 48 
10.1.10 
Publication and Data Sharing Policy .......................................................... 49 
10.1.11 
Conflict of Interest Policy ............................................................................. 49 
10.2 
Additional Considerations .................................................................................. 78 
10.3 
Protocol Amendment History ............................................................................ 49 
11 References ................................................................................................................. 50 
12 APPENDIX ............................................................................................................... 56 
12.1 
Schedule of Activities (SoA) ............................................................................... 56 
 
 
 
 
 

 
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PRINCIPAL INVESTIGATOR SIGNATURE 
 
STUDY 
SPONSOR: 
Department of Emergency Medicine 
STUDY TITLE: 
Efficacy of the Erector Spinae Plane Block for Abdominal Pain from 
Gastrointestinal Malignancies 
STUDY ID 
PROTOCOL 
VERSION 
pending 
v 1.0  
I have read the referenced protocol. I agree to conduct the study in accordance to this protocol, in 
compliance with the Declaration of Helsinki, Good Clinical Practices (GCP), and all applicable 
regulatory requirements and guidelines. 
Principal 
Investigator Name  
Michael Shalaby, MD 
 
Signature 
 
Affiliation: 
Department of Emergency 
Medicine 
 
Date 
7/24/2025 
 
 
 
 
 
 
 
 

 
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Abbreviations 
APS-POQ-R 
Revised American Pain Society Patient Outcome Questionnaire  
BMI 
Body Mass Index 
Cedar 
Hospital of the University of Pennsylvania Cedar 
CFR 
Code of Federal Regulations 
CRC 
Clinical Research Coordinator 
ED 
Emergency Department  
EDC 
Electronic Data Capture 
EMR 
Electronic Medical Record 
ESPB 
Erector Spinae Plane Block 
GI 
Gastrointestinal  
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
HUP 
Hospital of the University of Pennsylvania 
ICH 
International Conference on Harmonization 
ICH GCP 
International Conference on Harmonization Good Clinical Practice 
IQR 
Interquartile Range 
LAST 
Local Anesthetic Systemic Toxicity 
LOS 
Length of Stay 
MME 
Milligram Morphine Equivalent 
MRN 
Medical Record Number  
NRS 
Numeric Rating Scale  
PAH 
Pennsylvania Hospital 
PI 
Principal Investigator 
PPMC 
Penn Presbyterian Medical Center  
QC 
Quality Control 
RA 
Research Assistant 
SOP 
Standard Operating Procedures 
SSN  
Social Security Number 

 
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UGRA 
Ultrasound-Guided Regional Anesthesia 
UPHS 
University of Pennsylvania Health System 
WHO 
World Health Organization 
 
 
 

 
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1 STUDY SUMMARY 
1.1 
Synopsis 
Title:  
Efficacy of the Erector Spinae Plane Block for Abdominal Pain from 
Gastrointestinal Malignancies 
Short Title: 
ESPB for GI Malignancy Pain 
Study 
Description:  
This study will target patients with gastrointestinal (GI) malignancy who 
present to any of 4 Penn Medicine emergency departments (EDs) with 
intractable abdominal pain. We will offer eligible patients an erector 
spinae plane block (ESPB), a regional anesthesia technique which is 
already offered to such patients in the ED at the University of 
Pennsylvania Healthy System (UPHS), for their intractable abdominal 
pain. We will compare the outcomes of this prospective cohort of patients 
to a matched historical control of patients with GI malignancy who were 
treated in the ED during the same time period as recruitment, but who 
were not recruited to partake in the study and who were managed with 
standard of care. Opioid consumption as measured by total milligram 
morphine equivalents (MMEs) over a 24-hour period and hospital length 
of stay (LOS) will be compared between cohorts. Additionally, for the 
ESPB cohort, pain level pre/post ESPB, and functionality and satisfaction 
with pain management at 24 hours will also be examined. 
Given that the ESPB is currently offered to patients with GI malignancy 
as part of standard of care in the ED within UPHS, this protocol is being 
submitted for expedited review because we are consenting participants to 
provide and to allow the research team to abstract the following data: pain 
levels and satisfaction scores, data on total LOS (ED + hospital) and their 
opioid consumption. Patients who wish not to provide this information, 
and therefore not to participate in the study, will still be offered the ESPB 
for their abdominal pain.  
 
Objectives:  
Primary objective: To determine whether patients with GI malignancy 
receiving an ESPB for intractable abdominal pain consume less opioids 
(measured in MMEs) in a 24-hour period compared to standard of care 
analgesia. 
Secondary objectives:  

 
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• To determine whether patients who receive an ESPB have shorter 
hospital LOS compared to standard of care analgesia.  
• Within the cohort receiving the ESPB, to determine whether there 
was a change in pain level as measured by the numeric rating 
scale (NRS) pre/post block.  
Exploratory: Within cohort receiving the ESPB, to determine level of 
patient satisfaction and functionality as measured by the Revised 
American Pain Society Patient Outcome Questionnaire (APS-POQ-R) 
Primary 
Endpoint:  
Difference in MMEs consumed in 24-hour period between the 
prospective cohort who received the ESPB and historical controls.  
 
Secondary 
Endpoints: 
1. Difference in hospital LOS between cohorts, as determined by time 
from enrollment to hospital discharge. Enrollment for the ESPB 
cohort will be from the time of the intervention. Enrollment for the 
standard of care cohort will be from the time of administration of the 
first analgesic in the ED under the care of a treating physician (ie, not 
in the waiting room).   
2. In the ESPB cohort, difference in pain level as measured by NRS at 
pre-ESPB and 30 minutes post block.   
3. In the ESPB cohort, scores on APS-POQ-R administered at 24 hours 
after the ESPB (see Appendix) 
Study 
Population: 
Patients with a GI malignancy presenting with intractable abdominal pain.  
To any of 4 EDs, (1) Hospital of the University of Pennsylvania (HUP), 
(2) Penn Presbyterian Medical Center (PPMC), (3) Pennsylvania Hospital 
(PAH), and (4) HUP Cedar (Cedar)   
Exclusion criteria: pregnant, incarcerated, admissions for serial 
abdominal examinations, small bowel obstruction, sepsis, altered mental 
status, hemodynamic instability. 
Sample size:  
• Prospective ESPB cohort: n=25 
• Historical controls: n = 25  
Phase: 
N/A 
 

 
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Description of 
Sites/Facilities  
(1) Hospital of the University of Pennsylvania 
(2) Penn Presbyterian Medical Center  
(3) Pennsylvania Hospital  
(4) HUP Cedar 
Enrolling Sites: 
EDs of the aforementioned sites.  
Currently, emergency physicians who are capable of performing the 
ESPB see patients at all 4 sites.  
Description of 
Study 
Intervention: 
Participants will receive an ESPB, a nerve block performed by injecting 
anesthetic between a single spinal transverse process and the erector 
spinae muscle complex (Forero et al). Anesthetic reaches the dorsal nerve 
root ganglia but also diffuses anteriorly to the paravertebral space which 
contains the thoracic sympathetic ganglia (Chin et al). Visceral afferent 
fibers transmit pain signals arising from the stomach to midway through 
the sigmoid colon utilizing the same anatomical conduit as sympathetic 
efferent fibers (Moore et al). While physically associated, they travel in 
the reverse direction of the sympathetic efferents and are functionally 
distinct. From the abdominal viscera to spinal cord, visceral afferents 
transmit pain signals first through the peri-aortic autonomic plexuses and 
prevertebral ganglia, then along the splanchnic nerves to reach the 
sympathetic trunk, where they travel via the white rami communicantes to 
reach the spinal nerves of T5 to L2, before finally being conducted 
centrally. Thus, anesthetizing the thoracolumbar spinal nerves and 
sympathetic chain, via an ESPB performed between the levels of T5 and 
L2, should block abdominal visceral pain signaling, and may provide 
significant analgesia for patients with abdominal pain from GI 
malignancy.  
The ESPB is considered a part of standard of care treatment in the ED and 
thus patients are eligible to receive it regardless of enrollment in the 
study. Participants will be consented to assess their pain levels 
immediately before, 30 minutes after, and 24 hours after the ESPB is 
administered; and to take the APS-POQ-R survey at 24 hours after the 
ESPB is administered.  
 
Study Duration: 
12 months  

 
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Participant 
Duration: 
 
Resources 
Necessary for 
Human Research 
Protection: 
 
24 hours. Patients who receive the ESPB will receive a final assessment 
at 24 hours after administration of the ESPB via the APS-POQ-R. 
 
This study is being conducted by the Division of Ultrasound within the 
Department of Emergency Medicine. The Principal Investigator (PI) is an 
ultrasound faculty member and the Director of Ultrasound Research. 
Other research staff include a biostatistician, the ultrasound division’s 
clinical research coordinator (CRC), and the research assistants (RAs) 
within the Emergency Medicine Academic Associates program.  
Prior to the initiation of enrollment, the PI will meet with the Academic 
Associates team to discuss recruitment including establishing an EPIC 
Haiku notification system, as well as inclusion and exclusion criteria. The 
CRC is trained on data storage in REDCap. All resources required to 
complete this controlled trial are provided by the Department of 
Emergency Medicine and the Division of Ultrasound, including the RAs, 
the CRC, and the biostatistician. Progress of the trial will be discussed at 
least every other week at the research meetings within the Division of 
Ultrasound.  
  
 
 
 
 
 
 

 
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1.2 
Key Roles and Study Governance 
Medical Director 
Michael Shalaby, MD, Director of Ultrasound 
Research 
Department of Emergency Medicine 
University of Pennsylvania  
3400 Spruce Street, Philadelphia, PA 19104 
504-417-0249 (personal); 267-624-4394 
(work) 
Michael.shalaby@pennmedicine.upenn.edu 
 
 

 
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1.3 Schema 
Prior to  
Enrollment 
 
Time Point 1 
 
 
  
Time Point 2 
30 minutes 
Post intervention  
 
 
Time Point 3 
24 hours  
post intervention   
 
 
Total n=25:  Screen potential participants by inclusion and exclusion 
criteria. Obtain informed consent, obtain history, document. 
Follow-up assessments of study endpoints and safety 
Refer to Appendix Section 12.1, Schedule of Activities 
Perform baseline assessments. 
Administer study intervention. 
Refer to Appendix Section 12.1, Schedule of Activities 
Follow-up phone call 
Refer to Appendix Section 12.1, Schedule of Activities 

 
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2 INTRODUCTION AND RATIONALE 
2.1 
Study Rationale 
In 2024 there were greater than 2 million new cases of cancer in the United States, more than any 
year prior (Siegel et al). The incidence of new GI malignancies also broke previous records, with 
more than 350,000 new cases in 2024 (Siegel et al). Over 4 million patients with cancer seek 
care in EDs for oncologic emergencies annually, with breakthrough pain commonly requiring 
management with higher-dose opioids and hospital admission (Gould Rothberg et al). Among 
these patients, those with GI malignancies are the second most prevalent group, and patients’ 
primary presenting complaint is abdominal pain (Siregar et al). The high levels of poorly 
controlled background pain from which patients with GI malignancy suffer arise from a variety 
of sources, including local tumor invasion of organs, the omentum, retroperitoneal tissues, and 
neural tissue (Mercadante et al) (van den Beuken-van Everdingen et al). As tumor burden 
progresses so do patients’ pain and their use of opioids for pain control (Whitney et al). 
Meanwhile, oncologic treatments, including neurotoxic chemotherapeutics, radiation, and 
palliative or curative surgical procedures can paradoxically worsen pain (Mercadante et al). 
Opioids have been the mainstay of treating cancer pain since their recommendation by the World 
Health Organization (WHO) in 1996 as part of the “analgesic ladder,” and most patients with GI 
malignancy manage their background pain with high-dose home opiate regimens (> 90 mg 
equivalent dose of oral morphine daily) (Bennett et al) (World Health Organization). Despite 
this, nearly 90% of patients with GI malignancy experience at least one severe breakthrough pain 
episode, which is a sudden increase in pain intensity that often leaves patients unable to perform 
even basic activities of daily living such as walking (Caraceni et al). Therefore, there is a critical 
need for more effective analgesia for this growing population of patients with GI malignancy 
presenting to an ED with breakthrough pain.  
 
Breakthrough abdominal pain from GI malignancy is usually treated with high-dose opioids, 
which have significant short- and long-term side effects. Symptoms of acute opioid overdose 
include nausea, vomiting, delirium, and hypoxia, and can occur even at normal doses (Wei et al). 
This, in turn, increases ED presentations, complicates hospital courses, and contributes to longer 
hospital stays (Oderda et al). Patients with GI malignancies who are on prolonged high-dose 
home opioid regimens face an increased risk of adverse outcomes related to chronic opioid use. 
For example, physiologic dependence on and tolerance to opioids forces GI malignancy patients 
to use increasing doses of opioids to achieve the same or lesser levels of analgesia, which then 
lowers the threshold for acute overdose (Benyamin et al). Chronic opioid use also precipitates 
opiate-induced hyperalgesia, a paradoxical phenomenon in which opioid metabolites lead to 
worsening pain (Benyamin et al). Elevated opioid use among cancer patients, even after 
accounting for prognosis, is associated with more frequent hospitalizations and an earlier risk of 
death (Doshi et al). Patients with cancer pain are therefore more susceptible to the adverse effects 
of opioids, which continue to be the mainstay of treatment for breakthrough cancer pain 
(Mercadante et al). Additionally, hospitalized patients with cancer pain feel that opioids give 

 
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them little control over their level of analgesia, cause them to have trouble sleeping most of their 
nights in the hospital, and are addictive (Eyigor et al). Unlike the United States, the European 
Society for Medical Oncology supports the use of regional anesthesia as an adjunct for the 
treatment of cancer pain, especially for its opioid-sparing effects (Fallon et al). As the number of 
cancer patients continues to grow yearly, there is a vital need to address non-opioid analgesia for 
these patients.  
 
The abdominal viscera, from the stomach to midway through the sigmoid colon, derives its 
sensory innervation from afferent fibers that travel with, but are distinct from, the sympathetic 
nerve fibers from the 5th thoracic (T5) to the 2nd lumbar (L2) spinal levels (Moore et al). These 
fibers converge at the celiac plexus, located near the celiac artery and the aorta. From there, they 
bifurcate into the paravertebral sympathetic chain and subsequently ascend to the spinal cord and 
integrate into the central nervous system (Lohse et al). The celiac plexus block is an invasive 
procedure performed by an interventional anesthesiologist or palliative care specialist to lyse the 
celiac plexus and has been shown to reduce pain and opiate use in patients suffering from GI 
malignancy (Ashlock et al). While there are multiple methods to perform a celiac plexus block, it 
involves a steep needle trajectory either posteriorly through the retroperitoneum or anteriorly 
through the abdominal wall close to or even through the abdominal aorta (Nagels et al). Due to 
its technical complexity, the availability of the celiac plexus block for patients with acute 
abdominal pain from GI malignancy is limited, and it carries a risk of serious complications. 
These complications include GI bleeding from viscus perforation (Pello et al), pneumothorax 
(Rathmell et al), paraplegia (De Conno et al), aortic dissection, and death (Kaplan et al). 
Conversely, the ESPB is a novel ultrasound-guided regional anesthesia (UGRA) technique that 
has gained popularity in emergency medicine due to its effective analgesic properties and low 
complication rates (Abdelhamid et al). During this procedure, anesthetic injected deep to the 
erector spinae muscle complex at the thoracic spine level diffuses anteriorly to reach the 
paravertebral sympathetic chain. Consequently, the ESPB effectively targets the same neural 
pathways as the celiac plexus block without the same risks of complications and demonstrates 
promise as a simpler and safer alternative to the celiac plexus block (Abdelhamid et al). 
However, as yet there are no large, well-designed trials assessing the efficacy of the ESPB for 
managing abdominal pain associated with GI malignancies in an ED setting. Therefore, this 
presents a unique opportunity for a rigorously designed trial to investigate the efficacy of the 
ESPB in managing abdominal pain associated with GI malignancies.  
 
UGRA has become established as an effective adjunct to acute pain management in the ED. Both 
the American College of Emergency Physicians and the American Academy of Emergency 
Medicine endorse its integration into multimodal analgesia in the ED (American Academy of 
Emergency Medicine) (American College of Emergency Physicians). Despite its novelty, the 
ESPB has already gained traction in emergency care owing to its safety and efficacy 
(Abdelhamid et al). The ESPB’s straightforward needle trajectory requires no redirection and 
passes through back muscles, avoiding vital structures. For visceral structures, the ESPB  is a 

 
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potent analgesic: it surpasses ketorolac for renal colic and matches epidural anesthesia for acute 
pancreatitis (Aydin et al) (Shapkin et al). The thoracic paravertebral sympathetic chain, which 
innervates the kidneys and pancreas, also innervates the rest of the GI tract. Therefore, in this 
cohort study we plan to explore the ESPB as a potential tool for managing acute abdominal pain 
from GI malignancy. 
2.2 
Background 
While there have not been any previously published large-scale trials on the use of the ESPB for 
treating abdominal pain from GI malignancy, there have been some published cases, including 
our own (Gawel et al). Ashworth et al utilized an ESPB to resolve intractable abdominal pain for 
a patient in the ED with colon cancer with metastasis to the liver (Ashworth et al). Similarly, 
Gopinath and colleagues performed an ESPB on a patient in the ED with intractable abdominal 
pain from cholangiocarcinoma, who did not require analgesics for 18 hours after blockade 
(Gopinath et al). In the EASIER trial, a randomized controlled trial exploring the use of the 
ESPB for treating intractable abdominal pain from hepatic, liver, and biliary sources, David et al 
performed the ESPB on two patients with cholangiocarcinoma (David et al). Of all patients in the 
EASIER trial who received the ESPB, the average improvement in pain relief was nearly 90% 
from baseline, and all patients who received the ESPB reported high satisfaction with the 
procedure. Bugada et al performed the ESPB on a patient with colon cancer with metastases to 
the vertebra and retroperitoneal tissues, who subsequently did not require rescue analgesics for 
three days (Bugada et al). In our publication, we demonstrated that the ESPB successfully treated 
intractable abdominal pain for patients with hepatic, biliary, and pancreatic cancer (Gawel et al). 
Two patients with pancreatic cancer opted to be discharged home instead of being admitted for 
pain control. We have also utilized the ESPB to treat intractable abdominal pain from gastritis 
and gastroparesis (Gawel et al), acute cholecystitis, acute pancreatitis, and for patients in opiate 
withdrawal (Gawel et al). All of our patients have reported great satisfaction with the ESPB. 
There have been no documented adverse effects of the ESPB in the included trials and in our 
experience. The strength of the prior research and of our experience has been that the ESPB has 
shown benefit in treating abdominal pain from a variety of sources, but the results are mostly 
confined to case reports and to our anecdotal experience. In the case reports listed above, all 
patients consumed fewer opiates after receiving the ESPB. In the EASIER trial, patients who 
were randomized to the ESPB required a lower dosage of opioids compared to those who were in 
the standard of care group. Similarly, Hacıbeyoğlu et al demonstrated that patients undergoing 
hepatectomy who were randomized to receive an ESPB demonstrated significantly lower opioid 
use than those who were managed with patient-controlled analgesia (Hacıbeyoğlu et al). 
Additionally, Dubilet et al demonstrated that patients who received a pre-operative ESPB for 
oncologic surgery used fewer opioids than those who received traditional postoperative analgesia 
(Dubilet et al). In our practice, all patients who received an ESPB for abdominal pain from GI 
malignancy were already on home opioid regimens. Both patients with pancreatic cancer who 
received the ESPB did not receive any more analgesics in the ED. The patients with hepatic 
cancer, biliary cancer, gastritis, pancreatitis, and acute cholecystitis did not request analgesics for 

 
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at least 14 hours after receiving the ESPB. Two of the patients with abdominal pain, vomiting, 
and diarrhea who were in opiate withdrawal also did not request any symptomatic relief for three 
hours after receiving the ESPB and stayed for placement in rehab. One of the patients in opiate 
withdrawal did not request any opiate analgesics at all during his 9-hour stay in the ED.  
A meta-analysis of 11 studies by Pepper et al demonstrated that patients who received a single 
ESPB postoperatively for noncardiac surgery demonstrated reductions in pain and opioid use 
even up to 24 hours after injection, compared to those who were managed without one (Pepper et 
al). Similarly, Rambhia et al demonstrated that patients who received a single genicular block 
had improvements in pain scores and opioid use even at 48 hours post knee surgery (Rambhia et 
al). A meta-analysis of 16 studies of patients who received a single ESPB after lumbar surgery 
compared to those who were managed with standard of care also demonstrated a reduction in 
pain and decrease in opioid use at 48 hours in those who received the ESPB compared to 
standard of care (Cao et al). Multiple studies have demonstrated that patients who receive UGRA 
in the ED are more satisfied with their care (Tekin et al) (Nejati et al). Other studies have 
demonstrated improved functional outcomes in patients who are managed with UGRA, such as 
mobility after hip surgery for patients receiving a pericapsular nerve group (PENG) block 
(Kimachi et al). Therefore, even a single ESPB could significantly reduce pain for prolonged 
periods, improve functional status, and increase satisfaction when used to treat abdominal pain 
from GI malignancy.  
 
Inpatient opioid use, even at physiologic doses, is known to lead to adverse events and to 
increase hospital LOS and even mortality (Wei et al). Conversely, by reducing opiate use and 
their associated complications, UGRA can reduce hospital LOS. Vaughan et al conducted a 
retrospective examination which revealed that patients who received an ESPB for open cardiac 
surgery used fewer opioids postoperatively and had a shorter hospital LOS compared to those 
who did not (Vaughan et al). Similarly, Amoroso et al also demonstrated reduced opioid use and 
hospital LOS for patients who received an ESPB after lumbar surgery (Amoroso et al). In a 
prospective cohort trial, Kolodychuk et al demonstrated that hip fracture patients who received a 
single fascia iliaca plane block in the ED had a shorter hospital LOS compared to those who did 
not (Kolodychuk et al). In our own practice, the use of the ESPB for abdominal pain from GI 
malignancy has precluded hospital admission for two patients. Therefore, the ESPB may prevent 
admission or reduce hospital LOS for patients with GI malignancy.  
 
This project is the first proposed project for specifically treating abdominal pain from GI 
malignancy with UGRA, and thus for taking one step closer towards replacing opioids as a 
treatment for breakthrough cancer pain in the ED. The current treatment paradigm as it pertains 
to abdominal pain from GI malignancy is to utilize intravenous opioids for breakthrough pain 
control. However, this approach is unsatisfactory because it leaves patients subject to subpar pain 
relief and to the undesirable effects of opioids, including dependence, tolerance, delirium, 
hypoxia, increased hospital LOS, and increased mortality rates. The proposed research is 

 
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innovative, in our opinion, because it will establish UGRA as a new modality for treating 
abdominal pain from GI malignancy, not only in the ED but also in other inpatient settings. 
 
The PI, Michael Shalaby, has an extensive background in UGRA in the ED. He has authored 
over 35 publications on regional anesthesia, with more accepted and in press and others 
submitted and under review. Dr Shalaby currently serves as the editor-in-chief of the first 
textbook on emergency regional anesthesia, titled Regional Anesthesia for the Emergency 
Physician, which is in progress and will be published by Taylor and Francis, an esteemed 
publishing house. In addition to the clinical practice of UGRA, Dr. Shalaby has been teaching it 
to residents, fellows, and attending physicians since he was a 2nd year emergency medicine 
resident. In his ultrasound fellowship year alone, Dr Shalaby completed over 100 ultrasound-
guided nerve blocks, and he has achieved proficiency and published in regional anesthesia of all 
areas of the human body that have been performed in the ED setting. Dr. Shalaby leads a year-
long didactic curriculum on regional anesthesia for the emergency medicine residency, and he is 
leading a multi-state “Regional Anesthesia Day” with the Department of Anatomy at the 
Perelman School of Medicine which will employ fresh cadavers to teach regional anesthesia to 
medical students, residents, and attending physicians. Specific to the ESPB, Dr Shalaby has 
published three articles, and two more articles are currently under review. Dr. Shalaby has 
performed over 40 ESPB’s. Dr. Shalaby published a large retrospective cohort study in the 
Annals of Emergency Medicine which demonstrated that nearly 300 ultrasound-guided nerve 
blocks performed in his community ED (Dr. Shalaby had been faculty at Mount Sinai Medical 
Center Miami Beach) at that time resulted in no adverse events. Dr. Shalaby authored another 
review article on the prevention and management of local anesthetic systemic toxicity (LAST). 
Dr. Shalaby’s bibliography can be accessed at 
https://www.ncbi.nlm.nih.gov/myncbi/michael.shalaby.1/bibliography/public/. 
 
The ESPB is already offered as part of usual care for abdominal pain from GI malignancy in the 
ED within UPHS. Patients can receive the ESPB for their abdominal pain outside the scope of 
this trial. In the ED, patients provide written consent before receiving any form of UGRA as part 
of their care, including the ESPB. Thus, in this trial we will specifically consent patients to 
document data on their length of stay, 24-hour opiate consumption, and pain / functionality 
levels (see Primary and Secondary Endpoints in Section 1.1 above). However, any patient who 
receives the ESPB as part of their analgesic regimen for abdominal pain from GI malignancy in 
the ED, but who does not consent to partake in this study, will not be included in the primary or 
secondary analysis. Furthermore, they will not be included as part of the historical control group 
either. For authorization of the use of data for the historical control group, please see the separate 
“Request for Waiver of HIPAA Authorization” form submitted through HSERA.  
 
2.2.1 
Pharmacokinetics, Pharmacodynamics and Toxicology 
N/A 

 
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2.2.2 
Assessment for Potential Study Products Drug-Drug, Drug-Device, 
Device-Device Interactions 
N/A 
2.2.3 
Clinical Adverse Event Profile 
N/A 
2.2.4 
Dosing Rationale 
N/A 
2.3 
Risk/Benefit Assessment 
2.3.1 
Known Potential Risks 
We anticipate no immediate or long-term risks of patient participation in this study. We will not 
collect the following sensitive data: social security number (SSN), home address, or bank 
information. The CRC or academic associates will collect the following data:  
• Pain level on NRS immediately before the ESPB. 
• Pain level on NRS 30 minutes after the ESPB.  
• APS-POQ-R at 24 hours after the ESPB.  
• Total length of stay (ED + hospital)  
• Opioid use while in the ED / hospital 
If patients choose not to participate in this study, they will still be offered the ESPB for their 
pain.  
2.3.2 
Known Potential Benefits 
Patients with GI malignancy often have significant background abdominal pain. By the time they 
present to the ED, they are in significant pain which requires admission, sometimes with patient-
controlled analgesia. Previous anecdotal experience for patients with GI malignancy who receive 
an ESPB has demonstrated that they achieve significant pain control with even a single nerve 
block.  
 
2.3.3 
Assessment of Potential Risks and Benefits 
There are few potential risks of this project. Patients will only be approached by members of the 
study team, their data will be recorded and stored via REDCap, and best clinical practices will be 
maintained. For patients who are discharged home from the ED, the CRC will obtain a method of 

 
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follow-up at 24 hours which the patient consents to provide. At no time will patients be coerced 
to provide protected health information (PHI) or answers to assessments to which they are not 
comfortable. Prior to participation, patients will sign informed consent which will outline the 
risks and benefits of participating in the study, the assessments which will be performed, and the 
method of follow-up which will be used at 24 hours. Patients will be given enough time to read 
and comprehend the informed consent form and ask their provider any questions about 
participation. Patients will also be made aware that they may withdraw from the study at any 
time.  

 
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3 STUDY OBJECTIVES AND ENDPOINTS 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION 
FOR ENDPOINTS 
Primary 
 
 
Reduction in Opiate Use 
To determine whether patients 
with GI malignancy receiving an 
ESPB for intractable abdominal 
pain consume less opioids 
(measured in MMEs) in a 24 
hour period compared to 
standard of care analgesia. 
  
 
Difference in MMEs consumed in 
24 hour period between the 
prospective cohort and historical 
controls 
 
 
Since we will not be 
able to interview historic 
controls about their pain 
levels, we will use 
opiate consumption as a 
marker of efficacy of the 
ESPB in relieving 
abdominal pain.  
Secondary 
 
 
LOS 
To determine whether patients 
who receive an ESPB have 
shorter hospital LOS compared 
to standard of care analgesia.  
Difference in hospital LOS 
between the prospective cohort 
and historical controls, as 
determined by time from 
enrollment to hospital discharge. 
LOS for the ESPB cohort will 
defined as time of the block to 
hospital discharge whereas the 
standard of care historical control 
group will be from the time of 
administration of the first 
analgesic in the ED under the care 
of a treating physician (ie, not in 
the waiting room).   
This endpoint will 
evaluate whether 
treatment with the ESPB 
can shorten ED LOS 
compared to standard of 
care analgesia.   
 
Pain 
Within the cohort receiving the 
ESPB, to determine whether 
there was a change in pain level 
as measured by the NRS pre/post 
block.  
In the ESPB cohort, difference in 
pain level as measured by NRS at 
pre-ESPB and 30 minutes post 
block 
This endpoint will 
evaluate whether the 
ESPB provides a 
clinically meaningful 
reduction in pain 
pre/post block. 

 
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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION 
FOR ENDPOINTS 
Exploratory 
 
 
Functionality and satisfaction 
Within cohort receiving the 
ESPB, to determine level of 
patient satisfaction and 
functionality as measured by the 
Revised American Pain Society 
Patient Outcome Questionnaire 
(APS-POQ-R) 
In the ESPB cohort, scores on 
APS-POQ-R administered at 24 
hours after the ESPB (see 
Appendix) 
This endpoint will 
evaluate whether 
patients will have 
improved satisfaction 
with treatment when 
receiving the ESBP 
using a modified version 
of the APS-POQ  
 
 

 
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4 STUDY PLAN 
4.1 
Study Design 
This is a prospective trial of patients with breakthrough abdominal pain from GI malignancy 
presenting to the ED for which a prospectively collected cohort of patients will receive the 
ESPB for pain control and compared to a matched group of historical controls who received 
current ED standard of care (ie, opioid analgesia) for their abdominal pain who were treated 
in the ED at the same time frame as the prospective cohort was recruited.  
The matched group of historical controls will equal the interventional group in number 
(n=25) and we will match as closely as possible based on oncological diagnosis (eg, an equal 
number of patients with liver cancer, and an equal number with pancreatic cancer). Patients 
who received the ESPB but who were not enrolled to participate in the study will be excluded 
from the historical control group for analysis. 
The data on the historical cohorts will be obtained after study recruitment is completed. At 
that time, the prospectively collected data on all 25 patients will be separated by ICD-10 
diagnosis code of their pre-existing oncologic diagnosis (or new diagnosis obtained during 
the same ED visit during which they were recruited to participate in this study) and a 10-year 
age range and gender (eg, 1 prospectively enrolled patient who is a 45 year old female with 
liver cancer will be matched with 1 retrospective patient who is a female aged 35-55 with 
liver cancer). With the assistance of the HUP Data Analytics Team, the charts of 25 patients 
with matching oncological ICD-10 diagnosis codes, age, and gender who were seen and 
treated at any of the 4 ED sites during the study period (the beginning and end of which will 
be defined by the day the first patient was recruited patient and 24 hours after the last patient 
was recruited, respectively) will be randomly selected. A “Request for Waiver of HIPAA 
Authorization” form has been submitted through HSERA to retrospectively collect the 
following data for the historical controls: ICD-10 diagnosis code, LOS, opiate consumption 
(in MME) over 24 hours starting from the first dose of analgesic administered while roomed 
in the ED. Prospectively and retrospectively collected patient data will be stored in REDCap. 
The CRC is a trained REDCap user and will collect and store all documents and information 
relevant to the study, including protocols, adverse events, informed consent, and the 
abstraction of prospective and retrospective patient data.  
Our hypotheses are: 1) patients who receive the ESPB will consume less opioids and 2) 
therefore have a shorter hospital LOS and/or increase discharges from the ED compared to 
the historical standard of care group; 3) within the ESPB cohort, the ESPB will significantly 
reduce participants’ abdominal pain, improve their functionality, and improve satisfaction 
from before receiving the ESPB to after (at 30 minuets and 24 hours). For the ESPB cohort, 
patients with either previously diagnosed or newly diagnosed GI malignancy who present to 
one of four primary ED sites within UPHS will be eligible for inclusion. After receiving a 
computed tomography (CT) scan of the abdomen / pelvis as part of their normal care 
performed in the ED, which demonstrates a malignant cause of abdominal pain, and who 

 
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otherwise meet inclusion criteria (see section 5.1), they will be approached by a member of 
the study team (physician, academic associate, or CRC) to participate in the study. Additional 
exclusion criteria will include: 1) patients receiving a research CT as part of this study, and 
2) patients admitted for serial abdominal examinations due to unknown surgical planning (ie, 
potentially ruptured viscous, small bowel obstruction, biliary colic) until the time that a 
definite surgical plan is known, if they are still in the ED.  Furthermore, an EPIC Haiku 
notification will be created to notify the research team when potential participants arrive in 
the ED. Participants will be offered an ESPB for pain control after being consented by the 
performing RA, who will ask patients to rate their pain on a 0-10 NRS. The ESPB will be 
performed with the ideal body weight-based dose of ropivacaine 0.2%, mixed with 4 mg 
dexamethasone immediately prior to administration in the ED, by the treating physician. If a 
participant’s body mass index (BMI) is under 25 kg/m2, their actual body weight will be used 
for dosing. Participants will be placed on the cardiopulmonary monitor prior to blockade for 
at least 30 minutes while remaining in the ED, and thereafter should their clinical condition 
or diagnosis require it. 30 minutes after blockade, the RA will ask participants to rate their 
pain on the NRS. 24 hours after blockade participants will be contacted by the CRC, who 
will administer the modified APS-POQ-R (see Appendix) (Gordon et al). The patient’s 
encrypted medical record number (MRN) and NRS and APS-POQ-R responses will be 
recorded by the CRC, who will store all data in REDCap. 
An interim analysis will be performed after 10 patients are recruited to participate, to assess 
progress towards the study’s primary and secondary endpoints. (See section 9.4.6 Planned 
Interim Analyses). For the historical standard of care comparator group, these patients are 
patients with GI malignancy and abdominal pain who will be treated at any of the 4 ED sites 
within UPHS during the time period of recruitment of the prospective cohort, but who do not 
receive the ESPB and who are not enrolled to participate in the study prospectively. These 
patients will have been treated with standard of care analgesia (ie, opioids, non-steroidal anti-
inflammatory drugs (NSAIDs), acetaminophen, and others). We will randomly match 25 
patients from the historical standard of care group based on ICD-10 code for GI malignancy 
(eg, matching an equal number of historical standard of care patients with the same or similar 
oncologic diagnoses as those who are prospectively recruited), gender, and age. Data for 
patients in the “standard of care cohort” will be collected with the assistance of the HUP Data 
Analytics Team. Abstracted data from patients in the standard of care cohort will consist of 
the same data points as that of study participants, including diagnosis, age, gender, ED / 
hospital LOS, opioid consumption in MMEs.  Standard of care group patients will not be 
contacted and their information will be kept confidential, stored, and password-protected on 
REDCap.  
 

 
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4.2 
Scientific Rationale for Study Design 
This study is a first step in determining the efficacy of whether an ESPB can provide superior 
analgesia (both greater relief of pain and longer acting) for patients suffering from GI 
malignancy pain as compared to a matched historical group of patients receiving current standard 
of care (opioid analgesia). For cancer pain management, opioids have been the analgesic 
mainstay since the WHO began supporting their use in this patient population starting in 1996. 
Yet opioids do not provide adequate baseline analgesia for up to 25% of cancer patients. Opioids 
are also associated with a plethora of adverse effects including delirium (especially in the 
elderly), nausea/vomiting, hypotension, constipation, respiratory depression, dependence, and 
tachyphylaxis. Moreover, breakthrough pain is common despite opioid therapy and represents an 
acute driver of ED presentation. A survey study on patients with abdominal cancer pain revealed 
that even among patients with optimized background pain regimens, episodes of breakthrough 
pain occurred frequently (88%) (Mercadante et al). All together, there is a critical need for novel, 
safer, more efficacious, and better tolerated oncologic pain management strategies. In terms of 
abdominal visceral cancer pain, emergency regional anesthesia has the potential to provide long-
acting, potent analgesia. This cohort study design was chosen as this was the next step in proving 
efficacy before moving to a more rigorous study design such as an RCT. 
 
4.3 
Justification for Dose 
N/A 
4.4 
End of Study Definition 
Participants are considered to have completed the study if they have completed all phases of the 
study including the last visit or the last scheduled procedure shown in the Schedule of Activities 
(SoA), Appendix Section 12.1. 
For the ESPB cohort, a participant will have completed this study at 24 hours after the 
intervention, when the CRC or performing physician will contact the patient and administer the 
APS-POQ-R at 24 hours, even if the patient decides to go home (see Appendix). Adverse events 
will be treated, but will not prolong the study duration for participants. Since there is no active 
participation of the standard of care cohort, study end, is when data has been extracted from the 
EMR and deidentified. 
 

 
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5 STUDY POPULATION 
5.1 
Inclusion Criteria 
1. Patients age > 18 years old with GI malignancy presenting to a Penn Medicine ED with 
intractable abdominal pain. 
2. Same-day or recent CT scan of the abdomen / pelvis which demonstrates that the patient’s 
abdominal pain can be reasonably attributed to a malignant source. 
5.2 
Exclusion Criteria 
1. Allergy to ropivacaine or history of local anesthetic systemic toxicity. 
2. Pregnancy 
3. Incarcerated 
4. Patients being admitted for serial abdominal examinations to determine their surgical 
course.  
5. Altered mental status or inability for patient to consent for the procedure 
6. Hemodynamic instability 
7. Previously enrolled in the study 
 
Rationale for selected inclusion/exclusion criteria: 
1. CT scan: oncologic processes quickly evolve so care must be taken not to miss a new 
potentially surgical cause of abdominal pain 
2. Patients being admitted for serial abdominal examinations to determine their surgical 
course: An ESPB may mask a developing surgical pathology. Patients with a known 
surgical course (either definitely going to get surgery or definitely not) will still be included.  
3. Pregnant patients have decreased levels of alpha-1 glycoprotein which places them at 
inherently increased risk for LAST. 
4. Incarcerated: incarcerated patients will be more difficult to contact for the 24-hour APS-
POQ-R if they are discharged before then.  
5. Pediatric patients: GI malignancy is rare in pediatric patients. Furthermore, most pediatric 
oncology patients receive their care CHOP, and will not be encountered in the EDs within 
UPHS.  
5.3 
Lifestyle Considerations 
N/A 
5.4 
Screen Failures 
Screen failures are defined as participants who consent to participate in the case series but are not 
subsequently entered in the study. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure participants, to meet the Consolidated Standards of 
Reporting Trials (CONSORT) publishing requirements and to respond to queries from regulatory 

 
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authorities. Minimal information includes demography, screen failure details, eligibility criteria, 
and any serious adverse event (SAE). 
5.5 
Strategies for Recruitment and Retention 
General strategies for the ESPB cohort: 
• Target sample size: 25 patients in ESPB cohort, 25 patients in the historical standard of 
care group. 
• Anticipated accrual rate: 100% 
• Anticipated number of sites and participants to be enrolled: 4 clinical sites (EDs of HUP, 
PPMC, PAH, or HUP Cedar) 
• Source of participants: ED patients 
• Recruitment venues: ED 
• How potential participants will be identified and approached: Participants in the ESPB 
cohort will be identified via chart screening by either participating physicians or research 
assistants.  For the retrospective standard of care cohort, review of EMR for patients with 
GI malignancy presenting to one of the site EDs and treated with standard analgesia. 
• Justification for exclusion of pregnant patients: pregnant patients have naturally lower 
levels of alpa-1 glycoprotein, which leaves them more susceptible to developing LAST 
(Shalaby et al). 
• Justification for exclusion of prisoners: prisoners may not be available for follow-up, so 
they will be excluded.  
• Justification for exclusion of pediatric patients: rarity of condition in pediatric patients, 
who also receive their care at CHOP.  
Patients with GI malignancy presenting to the ED at HUP, PPMC, PAH, and HUP Cedar with 
abdominal pain will be screened by a member of study team to determine eligibility based on 
inclusion and exclusion criteria described in sections 5.1 and 5.2. If patient is eligible, a member 
of study team (physician or RA) will approach the patient to obtain informed consent for the 
ESPB.    
Although not directly targeted, mentally disabled persons, economically or educationally 
disadvantaged persons, and/or employees or students of the University of Pennsylvania will not 
be denied enrollment and any special protections and/or additional safeguards will be undertaken 
in order to protect the rights and welfare of these subjects from coercion or undue influence as 
appropriate.  
 
 

 
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6 STUDY INTERVENTION 
6.1 
Study Intervention(s) Administration 
6.1.1 
Study Intervention Description 
The study intervention consists of questions about pain levels which the participants will report 
on NRS before and 30 minutes after receiving the ESPB, the APS-POQ-R which will be 
administered to participants at 24 hours after the ESPB, of data collected prospectively on 
participants’ LOS and opioid consumption in MME, and of retrospective data on a matched 
group of historical controls’ LOS and opioid consumption.  
6.1.2 
Dosing and Administration 
N/A 
6.2 
Preparation/Handling/Storage/Accountability 
. 
6.2.1 
Acquisition and accountability 
N/A 
6.2.2 
Formulation, Appearance, Packaging, and Labeling 
N/A 
6.2.3 
Product Storage and Stability 
N/A 
6.2.4 
Preparation 
N/A 
6.3 
Measures to Minimize Bias: Randomization and Blinding 
This study is not blinded. The treating physician, the participant, and all members of the study 
team will be aware that the injectate consisted of ropivacaine 0.2% and dexamethasone. Given 
the exploratory nature of this study, blinding is not desirable.  
 

 
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6.4 
Study Intervention Compliance 
Protocol adherence will require that participants rate their pain on a NRS immediately before and 
30 minutes after receiving the ESPB, and to provide survey responses to the APS-POQ-R at 24 
hours after receiving the ESPB.  
6.5 
Concomitant Therapy 
N/A 
6.5.1 
Rescue Medicine 
N/A 

 
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7 STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of Study Intervention 
The intervention in this study is the recording of participants’ pain levels on the NRS, their 
overall symptoms on the APS-POQ-R, their opioid consumption while in the hospital, and their 
LOS. Patients who do not wish to provide this information will be excluded.  
7.2 
Participant Discontinuation/Withdrawal from the Study 
Participants may voluntarily withdraw from participation in the study at any time upon request.  
7.3 
Lost To Follow-Up 
Participants who do not provide responses to the APS-POQ-R at 24 hours will be considered lost 
to follow-up.  

 
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8 STUDY ASSESSMENT AND PROCEDURES 
8.1 
Efficacy Assessments 
Patients with GI malignancy presenting to any of the ED sites within UPHS with abdominal pain 
will be screened by a member of study team to determine eligibility based on inclusion and 
exclusion criteria described in sections 5.1 and 5.2. For the ESPB cohort, if the patient is eligible, 
the RA will obtain informed consent. Recruitment, consent discussion, and all procedures will be 
performed in a private setting. An EPIC Haiku notification will also be created in which patients 
with a diagnosis of GI malignancy will alert the notification system upon arrival to the ED. The 
Academic Associates program in the Department of Emergency Medicine consists of post-
graduate RAs who are available in the ED at HUP and PPMC from 7 AM to 10 PM daily, 7 days 
a week. Patients will not be recruited outside these hours. The PI will lead a training session with 
the Academic Associates prior to initiation of patient recruitment to establish the process of 
recruitment and of notifying the PI and other physicians when an eligible patient has been 
identified. Although the Academic Associates only staff HUP and PPMC, this project will still 
recruit patients from PAH and HUP Cedar, since physicians who are able to participate in this 
proposal staff the latter two ED sites as well.  
As discussed in section 6, the ESPB cohort will receive a single ESPB with ideal body weight (or 
actual body weight, if BMI <25) ropivacaine 0.2% with dexamethasone 4 mg for abdominal pain 
in patients with GI malignancy. Prior to the block, patients will be placed on the 
cardiopulmonary monitor and will remain monitored for at least 30 minutes after the 
intervention.  
The primary endpoint and determination of efficacy will be the total MMEs consumed of the 
participants enrolled prospectively in the ESPB cohort compared to the retrospective group of 
patients with GI malignancy who were also treated in the ED during the same study period, but 
who were not enrolled and instead were managed with standard of care (excluding patients who 
may have received the ESPB as part of their care). After the enrollment period concludes in the 
ESPB cohort, when all participants have been enrolled prospectively, the CRC will gather data 
from EMR on each participants’ MME. An average MME will be compared to the average of the 
standard of care cohort.  
The secondary endpoints include pain levels and LOS. An exploratory analysis will measure 
functionality and patient satisfaction based on the APS-POQ-R questionnaire. Prior to the 
procedure, pain level measured on the NRS will be recorded by the RA. The ESPB will be 
performed under clean conditions and with ultrasound guidance. The injection site will be 
between the transverse process and the erector spinae muscle group at the appropriate thoracic 
vertebra, on either side. A guide for appropriate injection site based on organ involvement will 
be available to all physicians who partake in the study (see appendix). A mixture of ropivacaine 
0.2% and dexamethasone 4 mg will be injected within this fascial plane.  None of the imaging 
acquired during this procedure will be provided to the patient. At 30 minutes after injection the 
RA will ask patients to rate their pain on the NRS. At 24 hours after blockade the CRC will 

 
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contact the patient to administer the modified APS-POQ-R questionnaire, which will determine 
their levels of functionality during the 24 hours after receiving the block and assess their 
satisfaction with the procedure. Lastly, at the conclusion of the study period the CRC will also 
gather data from the EMR on each participant’s LOS. The HUP Data Analytics team will gather 
datapoints for the retrospective standard of care group. Hospital LOS (in hours) in the ESPB 
cohort will be compared to the LOS of the retrospective standard of care group. 
Additional analgesia will be available to study participants in the ESPB cohort throughout 
participation, and at no time will be withheld from participants, in keeping with the current 
standard of care. This includes any analgesic available within the ED, including opioids, 
NSAIDs, acetaminophen, and others. Administration of standard of care analgesia will not have 
a confounding effect on the primary or secondary endpoints: 
• Primary endpoint: Difference in MME use between the ESPB cohort and usual care 
cohort. 
• Secondary endpoints: 
Pain reduction 30 minutes after ESPB: if participants do not meaningfully achieve 
analgesia after the ESPB, standard of care analgesia will be available, even before the 30-
minute reassessment time point. For each participant, all analgesic medications will be 
documented and will be noted for any participants who receive repeat analgesics prior to 
the 30-minute reassessment period. However, we opted to reassess pain levels at 30 
minutes because anecdotally we have noted that patients who receive the ESPB for 
abdominal pain have achieved analgesia within 30 minutes.  
 
8.2 
Safety and Other Assessments 
Patients will be placed on the cardiorespiratory monitor before the intervention and will remain 
on it during the procedure and for at least 30 minutes after the intervention (thereafter depending 
on their clinical diagnosis and requirements). Cardiopulmonary monitoring allows physicians to 
detect signs of LAST early, such as tachy- or bradyarrhythmias and desaturation (Shalaby M et 
al). Other methods to enhance safety of ultrasound-guided regional anesthesia, as recommended 
by the American Society of Regional Anesthesia, include the use of real-time ultrasound 
guidance, ideal body-weight dosing (unless BMI <25, in which actual body weight dosing will 
be used), aspiration prior to the initiation of injection, and injection in 5-10 ml aliquots followed 
by a pause and a repeat aspiration prior to continued injection (Neal et al). 
The CRC will follow up with patients via phone call 24 hours after the procedure to determine 
the presence of complications. 
In the informed consent, participants will be provided with the PI’s institutional email address 
and contact information to report any complications or concerns which may arise after discharge. 
To help guide participants’ understanding of complications of the ESPB, these will be listed and 

 
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explained, and will include shortness of breath (in the case of undetected or missed 
pneumothorax), neuropathy, and cellulitis at the injection site. The study team will not 
independently contact patients to assess for these risks. 
8.3 
Adverse Events and Serious Adverse Events 
8.3.1 
Definition of Adverse Events (AE) 
An adverse event (AE) is any untoward medical occurrence associated with the use of an 
intervention in humans, whether or not considered intervention related. Intercurrent illnesses or 
injuries should be regarded as adverse events. 
A pre-existing condition should be recorded as an adverse event if the frequency, intensity or the 
character of the condition changes. 
 
8.3.2 
Definition of Serious Adverse Events (SAE)  
Serious Adverse Events (SAE) 
Adverse events are classified as serious or non-serious. A serious adverse event is any AE that, 
in the view of either the investigator or the sponsor, is: 
• fatal 
• life-threatening 
• requires or prolongs hospital stay 
• results in persistent or significant disability or incapacity 
• a congenital anomaly or birth defect 
• an important medical event when the event does not fit the other outcomes, but the event 
may jeopardize the patient and may require medical or surgical intervention (treatment) 
to prevent one of the other outcomes. 
• required intervention to prevent permanent impairment or damage (for devices only) 
Important medical events are those that may not be immediately life threatening but are clearly 
of major clinical significance. They may jeopardize the subject and may require intervention to 
prevent one of the other serious outcomes noted above. For example, drug overdose or abuse, a 
seizure that did not result in in-patient hospitalization, or intensive treatment of bronchospasm in 
an emergency department would typically be considered serious.  
 

 
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8.3.3 
Classification of an Adverse Event 
8.3.3.1 
Severity of Event 
For adverse events (AEs) not included in the protocol defined grading system, the following 
guidelines will be used to describe severity. 
• Mild – Events require minimal or no treatment and do not interfere with the participant’s 
daily activities.  
• Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
• Severe – Events interrupt a participant’s usual daily activity and may require systemic 
drug therapy or other treatment. Severe events are usually potentially life-threatening or 
incapacitating. Of note, the term “severe” does not necessarily equate to “serious”. 
8.3.3.2 
Relationship to Study Intervention 
All adverse events (AEs) must have their relationship to the ESPB assessed by the clinician who 
examines and evaluates the participant based on temporal relationship and his/her clinical 
judgment. The degree of certainty about causality will be graded using the categories below. In a 
clinical trial, the study product must always be considered. 
• Related – The AE is known to occur with the ESPB there is a reasonable possibility that 
the ESPB caused the AE, or there is a temporal relationship between the ESPB and event. 
Reasonable possibility means that there is evidence to suggest a causal relationship 
between the ESPB and the AE. 
• Not Related – There is not a reasonable possibility that the administration the ESPB 
caused the event, there is no temporal relationship between the ESPB and event onset, or 
an alternate etiology has been established. 
 
8.3.3.3 
Expectedness  
The PI, Dr. Michael Shalaby, will be responsible for determining whether an adverse event (AE) 
is expected or unexpected. An AE will be considered unexpected if the nature, severity, or 
frequency of the event is not consistent with the risk information previously described for the 
ESPB. 
 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up 
Safety will be assessed by monitoring and recording potential adverse effects using Common 
Terminology Criteria for Adverse Events (CTCAE) at each study visit. Participants will be 

 
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monitored by medical histories, continuous cardiorespiratory monitoring during and after the 
procedure. If CTCAE grading does not exist for an adverse event, the severity of mild, moderate, 
severe, life-threatening, and death, corresponding to Grades 1-5, will be used whenever possible. 
At each contact with the subject, the investigator will seek information on adverse events by non-
directive questioning and, as appropriate, by examination. Adverse events may also be detected 
when they are volunteered by the subject during the screening process, through physical 
examination, or other assessments. Information on all adverse events will be recorded in the 
source documentation. To the extent possible, adverse events will be recorded as a diagnosis and 
symptoms used to make the diagnosis recorded within the diagnosis event. 
As much as possible, each adverse event or follow-up information will be evaluated to 
determine: 
1. Severity grade (CTCAE Grade 1-5) 
2. Duration (start and end dates) 
3. Relationship to the study treatment or process – [Reasonable possibility that AE is 
related: No (unrelated/ not suspected) or Yes (a suspected adverse reaction)]. If yes 
(suspected) - is the event possibly, probably or definitely related to the investigational 
treatment? 
4. Expectedness to study treatment or process – [Unexpected – if the event severity and/or 
frequency is not described in the investigator brochure (if applicable) or protocol]. 
5. Action taken with respect to study or investigational treatment or process (none, dose 
adjusted, temporarily interrupted, permanently discontinued, unknown, not applicable) 
6. Whether medication or therapy taken (no concomitant medication/non-drug therapy, 
concomitant medication/non-drug therapy) 
7. Whether the event is serious 
Once an adverse event is detected, it should be followed until its resolution or until it is judged to 
be permanent, and assessment should be made at each visit (or more frequently, if necessary) of 
any changes in severity, the suspected relationship to the study treatment, the interventions 
required to treat it, and the outcome. 
 
8.3.5 
Adverse Event Reporting 
Reporting Period 
Adverse events will be reported from the time of informed consent until study completion. 
Investigator Reporting: Notifying the Study Sponsor 

 
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Every SAE, regardless of suspected causality (e.g., relationship to study product(s) or study 
procedure(s) or disease progression) must be reported to the sponsor within 24 hours of learning 
of its occurrence. 
Recurrent episodes, complications, or progression of the initial SAE must be reported to the 
Sponsor as a follow-up to the original episode within 24 hours of the investigator receiving the 
follow-up information. A SAE considered completely unrelated to a previously reported one 
should be reported separately as a new event. 
Send the SAE report to the PI. 
New information regarding the SAE will be reported as it becomes available and in the same 
manner that the initial SAE (i.e. SAE form). The investigator must follow the event to resolution 
or until the event is deemed and documented irreversible, whichever is longer. 
Investigator Reporting: Local Reporting Requirements 
The investigator will report AEs and SAEs to the IRB/EC of record and other local regulatory 
groups per the local requirements. 
 
8.3.6 
Serious Adverse Event Reporting  
The study clinician will immediately report to the PI any serious adverse event, whether or not 
considered the ESPB related, including those listed in the protocol or investigator brochure and 
must include an assessment of whether there is a reasonable possibility that the ESPB caused the 
event. Study endpoints that are serious adverse events (e.g., all-cause mortality) must be reported 
in accordance with the protocol unless there is evidence suggesting a causal relationship between 
the ESPB and the event (e.g., death from anaphylaxis). In that case, the investigator must 
immediately report the event to the sponsor. 
New information regarding the SAE will be reported as it becomes available and in the same 
manner that the initial SAE (i.e. SAE form). All serious adverse events (SAEs) will be followed 
until satisfactory resolution or until the site investigator deems the event to be chronic or the 
participant is stable. Other supporting documentation of the event may be requested by the Data 
Coordinating Center (DCC)/study sponsor and should be provided as soon as possible. 
 
8.3.7 
Reporting Events to Participants  
Participants who experience adverse events or serious adverse events will be immediately 
informed and consented for treatment. The only delayed adverse event which we expect to be a 
possibility is injection site infection, which participants will be educated on both verbally and in 
the informed consent form prior to consenting to partake in the study.   
 

 
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8.3.8 
Events of Special Interest  
N/A 
8.3.9 
Reporting of Pregnancy 
Given that pregnant patients will be excluded from this study, all potential pre-menopausal 
female participants will be screened with a urine or serum hCG pregnancy test.  
 
8.4 
Unanticipated Problems 
8.4.1 
Definition of Unanticipated Problems (UP) 
The Office for Human Research Protections (OHRP) considers unanticipated problems involving 
risks to participants or others to include, in general, any incident, experience, or outcome that 
meets all the following criteria: 
• Unexpected in terms of nature, severity, or frequency given (a) the research procedures 
that are described in the protocol-related documents, such as the Institutional Review 
Board (IRB)-approved research protocol and informed consent document; and (b) the 
characteristics of the participant population being studied; 
• Related or possibly related to participation in the research (“possibly related” means there 
is a reasonable possibility that the incident, experience, or outcome may have been 
caused by the procedures involved in the research); and 
• Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
 
8.4.2 
Unanticipated Problem Reporting 
Unanticipated problems (UPs) such as: 
• 
Post-marketing withdrawal of a drug, device, or biologic used in a research protocol due 
to safety concerns. 
• 
FDA ban of a drug, device, or biologic used in a research protocol due to safety concerns. 
• 
Complaint of a participant when the complaint indicates unexpected risks, or the 
complaint cannot be resolved by the research team 
• 
Breach of confidentiality 
• 
Incarceration of a participant when the research was not previously approved under 
Subpart C and the investigator believes it is in the best interest of the subject to remain on 
the study 

 
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• 
Premature closure of a study (e.g., due safety, lack of efficacy, feasibility, financial 
reasons, etc.) 
should be reported by the investigator to the 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 or other corrective actions that have been 
taken or are proposed in response to the UP. 
To satisfy the requirement for prompt reporting, UPs will be reported using the following 
timeline: 
• UPs that are serious adverse events (SAEs) will be reported as any other SAE. 
• Any other UP will be reported to the IRB and to the DCC within 48 hours of the 
investigator becoming aware of the problem. 
• All UPs should be reported to appropriate institutional officials (as required by an 
institution’s written reporting procedures), the supporting agency head (or designee), and 
the Office for Human Research Protections (OHRP) within 48 hours of the IRB’s receipt 
of the report of the problem from the investigator. 
 
8.4.3 
Reporting Unanticipated Problems To Participants  
N/A 
9 STATISTICAL CONSIDERATIONS 
9.1 
Statistical Hypotheses 
Primary endpoints: 
• H0: Mean/median morphine equivalents in 24 hours in the ESPB group = Mean/median 
morphine equivalents in 24 hours in the standard of care cohort.  
H1: Mean/median morphine equivalents in 24 hours in the ESPB group ≠ Mean/median 
morphine equivalents in 24 hours in the usual care cohort. 
Secondary endpoints: 

 
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• H0: Mean/median hospital LOS in the ESPB group = Mean/median hospital LOS in the 
usual care cohort. 
• H1: Mean/median hospital length of stay in the ESPB group ≠ Mean/median hospital 
length of stay in the usual care cohort. 
• H0: Mean pain difference pre/post ESPB=0.  
• H1: Mean pain difference pre/post ESPB≠0.  
9.2 
Sample Size Determination 
Sample size determination will be based on the primary endpoint, mean difference in MME 
between the ESPB cohort and the historical cohort who received standard of care. The sample 
size was based on the EASIER trial (Ref P), for which the median MMEs at 24 hours was 13 
(IQR:11, 19) and 22 (IQR:17, 32), for ESPB and IV opioids respectively. Assuming the mean 
difference in MMEs between the ESPB and usual care cohort will be at least 9-10, with a 
standard deviation between 10-12, sample sizes between 17-25 for each cohort will achieve 80% 
power to detect a difference in MMEs between ESPB, with alpha set at 0.05 using a two-sided 
two-sample unequal-variance t-test. Although we will only need 25 in the usual care cohort, 
since it is retrospective data and easily obtainable, we will increase this sample size to between 
50-100, which will provide us with a more heterogeneous sample and also reduce the error. 
9.3 
Populations for Analyses 
There will be 2 groups: 1) A prospective cohort of participants with GI malignancy during the 12 
month period compared to 2) a retrospective group of patients with GI malignancy who did not 
receive the ESPB and who instead were treated at our EDs with standard of care during the same 
period of time.  Data from the first cohort will be collected prospectively, whereas the second 
cohort will be retrospective obtained by EMR review. 
 
9.4 
Statistical Analyses 
9.4.1 
General Approach 
Prior to analysis, all primary and secondary outcome measures will be summarized with 
descriptive statistics (mean ± standard deviation (SD) or median and IQR), their distributions 
examined, tested for normality and transformed as needed. Additionally all demographics will be 
summarized using mean ± SD, for continuous variables and frequencies and percentages for 
categorical variables.  
Results from statistical testing for continuous variables, will be presented with p-values and 95% 
confidence intervals for tests using means or medians and IQR if a non-parametric test is used. 
For categorical variables, the chi-square or Fisher’s exact test will be performed to examine 

 
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whether treatment arms differ with regard to demographics and other baseline variables. 
Similarly, for side effects, descriptive statistics and Fisher’s exact tests will be performed for 
possible differences between the treatment arms. Regardless of type statistical test, all will be 
two-sided. 
 
9.4.2 
Analysis of the Primary Efficacy Endpoint(s) 
The primary efficacy endpoint is difference in opioid consumption at 24 hours between the 
ESPB and standard of care cohorts. Opioid consumption will be measured in MMEs and is an 
interval/ratio variable. To assess differences in MMEs between cohorts, either a 2-sample t-test 
(normally distributed) or a Wilcoxon rank-sum test (positively skewed) will be performed. 
Results will be presented as means ± 95% confidence intervals for each cohort, if normally 
distributed or medians with interquartile range (IQR) if study samples are positively skewed. 
 
9.4.3 
Analysis of the Secondary Endpoint(s) 
One secondary endpoint is difference in hospital LOS between cohorts. This endpoint, measured 
in hours, is an interval/ratio variable. To assess differences in LOS between cohorts we will 
perform similar analyses as for the primary endpoint of MMEs. 
The secondary endpoint of change in pain level in the ESPB will be measured using the NRS (0-
10) which is an ordinal variable. To assess differences in NRS pre/post block in the ESPB 
cohort, a paired t-test (normally distributed) or a Wilcoxon signed rank test will be performed.  
The final secondary endpoint is score on the modified APS-POQ-R. For the APS-POQ-R each of 
15 questions are based on an ordinal scale from 0-10. Functionality score on the APS-POQ-R is 
a continuous variable based on 14 questions (does not include satisfaction) with a range of scores 
from 0-140, higher scores indicating worse outcomes.  Results for this endpoint are descriptive 
and will be presented as means ± SD, or median and IQR if distribution of scores positively 
skewed.    
9.4.4 
Safety Analyses 
Safety endpoints are not primary endpoints for analysis for this proposal, but will be documented 
in REDCap for each participant. Adverse events and serious adverse events will be documented 
for each participant.  
 
9.4.5 
Baseline Descriptive Statistics 
Baseline and demographic characteristics will be summarized using descriptive statistics (mean 
± SD or median and IQR) for continuous variables such as age, NRS, total opioids consumed 

 
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( MMEs), hospital LOS and frequencies and percentages for categorical variables such as 
race/ethnicity, insurance, gender. 
 
9.4.6 
Planned Interim Analyses  
An interim analysis will be conducted after the enrollment and completion of data collection for 
the first 10 patients receiving the nerve block intervention. The primary objectives of this interim 
analysis are to review preliminary data on study endpoints and to determine whether continuing 
the study is justified based on the observed data. 
 
Objectives of Interim Analysis: 
• Efficacy and Endpoint Assessment: The interim analysis will include descriptive 
statistics to examine preliminary data on the primary and secondary endpoints, including: 
o Length of hospital stay 
o Post-procedure opioid consumption 
o Pain scores and patient satisfaction levels at 24 hours 
• 
Safety Oversight: 
o Since the ESPB is part of routine standard of care, a DSMB will not be created to 
provide oversight of safety. 
o However, if any safety concerns arise, such as an unexpected pattern of adverse 
events, the methodology will either be modified with a halt in recruitment until 
the IRB approves, or if necessary the study will be halted.  
o Based on the findings, potential protocol modifications or additional monitoring 
measures may be recommended and implemented with IRB approval. 
• 
Confidentiality, Data Integrity, and Best Clinical Practices 
o All analyses will be conducted in accordance with data confidentiality protocols. 
o The PI will ensure adherence to best clinical practices, including storage of signed 
informed consent forms and patient data on Penn Vault.  
o The interim analysis report will be shared only with designated study oversight 
personnel and IRB, and will not be used to make definitive conclusions until the 
full study is completed, unless early termination is otherwise deemed necessary.  
 
The PI and study statistician will review the interim analysis report. 
 
 
9.4.7 
Sub-Group Analyses 
None 

 
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9.4.8 
Tabulation of Individual Participant Data 
Individual patient data will be listed by endpoint of total MMEs at 24 hours, hospital LOS, (both 
cohorts).  For the ESPB cohort, NRS at baseline and 30 minutes post ESPB, as well as APS-
POQ-R at 24 hours.  
 
9.4.9 
Exploratory Analyses 
None. 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 Regulatory, Ethical, and Study Oversight Considerations 
10.1.1 
Informed Consent Process 
10.1.1.1 
Consent/Assent and Other Informational Documents Provided To 
Participants 
Prior to receiving the ESPB, participants will sign the standard procedure consent form available 
at all ED sites. However, their consent for this particular study will entail permission to record 
their responses to NRS pain scale and the APS-POQ-R, and to document their LOS and opioid 
consumption while in the hospital.  
The following consent materials are submitted with this protocol: Informed Consent Form. 
 
10.1.1.2 
Consent Procedures and Documentation 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in 
the study and continues throughout the individual’s study participation. Consent forms will be 
Institutional Review Board (IRB)-approved and the participant will be asked to read and review 
the document. The investigator will explain the research study to the participant and answer any 
questions that may arise. A verbal explanation will be provided in terms suited to the 
participant’s comprehension of the purposes, procedures, and potential risks of the study and of 
their rights as research participants. Participants will have the opportunity to carefully review the 
written consent form and ask questions prior to signing. The participants should have the 
opportunity to discuss the study with their family or surrogates or think about it prior to agreeing 
to participate. The participant will sign the informed consent document prior to any procedures 
being done specifically for the study. Participants must be informed that participation is 
voluntary and that they may withdraw from the study at any time, without prejudice. A copy of 
the informed consent document will be given to the participants for their records. The informed 

 
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consent process will be conducted and documented in the source document (including the date), 
and the form signed, before the participant undergoes any study-specific procedures. The rights 
and welfare of the participants will be protected by emphasizing to them that the quality of their 
medical care will not be adversely affected if they decline to participate in this study. 
 
10.1.2 
Study Discontinuation and Closure 
This study may be temporarily suspended or prematurely terminated by the Sponsor or the PI at 
any site if there is sufficient reasonable cause. Written notification, documenting the reason for 
study suspension or termination, will be provided by the suspending or terminating party to 
investigator. If the study is prematurely terminated or suspended, the PI will promptly inform 
study participants, the Institutional Review Board (IRB), and sponsor and will provide the 
reason(s) for the termination or suspension.  
Circumstances that may warrant termination or suspension include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to participants 
• Insufficient compliance to protocol requirements 
• Data that are not sufficiently complete and/or evaluable 
• Determination of futility 
Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the sponsor, IRB and/or Food and Drug Administration (FDA). 
In terminating the study, the Sponsor and the PI will assure that adequate consideration is given 
to the protection of the subjects’ interests. 
 
10.1.3 
Confidentiality and Privacy 
Participant confidentiality and privacy are strictly held in trust by the participating investigators, 
their staff, and the sponsor(s) and their interventions. This confidentiality is extended to cover 
testing of biological samples and genetic tests in addition to the clinical information relating to 
participants. Therefore, the study protocol, documentation, data, and all other information 
generated will be held in strict confidence. No information concerning the study or the data will 
be released to any unauthorized third party without prior written approval of the sponsor.  
The study monitor, representatives of the Institutional Review Board (IRB), or regulatory 
agencies may inspect all documents and records required to be maintained by the investigator, 
including but not limited to, medical records (office, clinic, or hospital) and pharmacy records 
for the participants in this study. The clinical study site will permit access to such records. 

 
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The study participant’s contact information will be securely stored at each clinical site for 
internal use during the study. At the end of the study, all records will continue to be kept in a 
secure location for as long a period as dictated by the reviewing IRB, Institutional policies, or 
sponsor requirements. 
Study participant research data, which is for purposes of statistical analysis and scientific 
reporting, will be entered and stored on REDCap. This will not include the participant’s contact 
or identifying information. Rather, individual participants and their research data will be 
identified by a unique study identification number. The study data entry and study management 
systems used by clinical sites will be secured and password protected. At the end of the study, all 
study databases will be de-identified and archived on REDCap. 
Throughout participant recruitment, intervention, and during the study period, we will maintain 
patient privacy. Patients will be approached to participate in the study while they are in their 
room in the ED, and not while they are in the waiting room or otherwise in a public area of the 
ED, so as to maintain their privacy and keep their protected health information private. 
Furthermore, all interventions will be performed when the patients are in their room, and again 
not in a space in the ED in which other patients are present. Prior to discussing recruitment and 
participation, if patients are not alone in the room (ie, with their family or other loved ones) they 
will be asked if they would like to discuss participation privately. The CRC will use a hospital-
provided phone to contact patients at follow-up at 24 hours, and their names and phone numbers 
will not be stored in the hospital phone and patients will not be contacted from the private phone 
lines of any member of the team. The patient will only interact with the investigator while in 
their assigned room in the ED.  
10.1.4 
Future Use of Stored Specimens and Data  
Data collected for this study will be analyzed and stored on REDCap. After the study is 
completed, the de-identified, archived data will be on REDCap, for use by other researchers. 
Permission to store data on REDCap will be included in the informed consent. 
When the study is completed, access to study data and/or samples will be provided through 
REDCap. 
10.1.5 
Safety Oversight 
Since this trial is not a trial to determine the safety and efficacy of a novel intervention, a DSMB 
will not be established for safety oversight. Rather, this trial is to determine if an intervention 
which is already offered as standard of care in the ED (the ESPB) results in improved outcomes 
for participants who receive it, compared to patients who do not.  
10.1.6 
Clinical Monitoring 
Clinical site monitoring is conducted to ensure that the rights and well-being of trial participants 
are protected, that the reported trial data are accurate, complete, and verifiable, and that the 

 
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conduct of the trial is in compliance with the currently approved protocol/amendment(s), with 
International Conference on Harmonisation Good Clinical Practice (ICH GCP), and with 
applicable regulatory requirement(s). 
Centralized monitoring of this study will be completed by the Division of Ultrasound in the 
Department of Emergency Medicine, including a biostatistician, five faculty members, five 
fellows, and a research coordinator. The monitoring will occur once every two months and will 
consist of a random review of the data for verification of endpoint and safety.  
Independent audits may be conducted by the Office of Clinical Research at UPHS to ensure 
monitoring practices are performed consistently across all participating sites.  
 
10.1.7 
Quality Assurance and Quality Control 
All monitoring and audits are to be performed according to ICH GCP E6(R2). 
Each clinical site will perform internal quality management of study conduct, data collection, 
documentation and completion. An individualized quality management plan will be developed to 
describe a site’s quality management.  
Quality control (QC) procedures will be implemented beginning with the data entry system and 
data QC checks that will be run on the database will be generated. Any missing data or data 
anomalies will be communicated to the site(s) for clarification/resolution. 
Following written Standard Operating Procedures (SOPs), the monitors will verify that the 
clinical trial is conducted and data are generated, and specimens are collected, documented 
(recorded), and reported in compliance with the protocol, International Conference on 
Harmonisation Good Clinical Practice (ICH GCP), and applicable regulatory requirements (e.g., 
Good Laboratory Practices (GLP), Good Manufacturing Practices (GMP)). 
The investigational site will provide direct access to all trial related sites, source data/documents, 
and reports for the purpose of monitoring and auditing by the sponsor, and inspection by local 
and regulatory authorities. 
10.1.8 
Data Handling and Record Keeping  
10.1.8.1 
Data Collection and Management Responsibilities  
Data collection is the responsibility of the clinical trial staff at the site under the supervision of 
the site investigator. The investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. 
All source documents should be completed in REDCap and follow ALCOAC standards 
(Attributable, Legible, Contemporaneous, Original, Accurate, and Complete). 

 
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Clinical data (including adverse events (AEs), concomitant medications, and expected adverse 
reactions data) and clinical laboratory data will be entered into PennCRMS (Velow) a 21 CFR 
Part 11-compliant data capture system provided by the Perelman School of Medicine (PSoM). 
The data system includes password protection and internal quality checks, such as automatic 
range checks, to identify data that appear inconsistent, incomplete, or inaccurate. Clinical data 
will be entered directly from the source documents. 
Clinical and laboratory data will be entered into a Penn CRMS, 21 CFR Part 11-compliant 
electronic data capture system (EDC) that includes individual user account level password 
protection. This EDC (Velos version 9) supports programmable data entry validation rules and 
edit checks to identify data entry errors. 
 
10.1.8.2 
Study Records Retention  
Study documents should be retained for a minimum of 2 years after the last approval of a 
marketing application in an International Conference on Harmonization (ICH) region and until 
there are no pending or contemplated marketing applications in an ICH region or until at least 2 
years have elapsed since the formal discontinuation of clinical development of the phrenic nerve 
block. These documents should be retained for a longer period, however, if required by local 
regulations. No records will be destroyed without the written consent of the sponsor, if 
applicable. It is the responsibility of the sponsor to inform the investigator when these documents 
no longer need to be retained.  
 
10.1.9 
Protocol Deviations 
 The PI and the study team should document all scenarios where the protocol is not followed and 
provide, in particular: 
• Who deviated from the protocol 
• What was the deviation 
• When did the deviation occur 
• How did the deviation happen 
• What is the impact of the deviation 
• A root cause analysis of why the deviation occurred 
If the assessment results in a determination that any of the following are potentially affected, the 
deviation would be considered of significant impact: 
• having the potential to adversely affect subject safety; OR 

 
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• increases risks to participants; OR 
• adversely affects the integrity of the data; OR 
• violates the rights and welfare of participants, OR 
• affects the subject’s willingness to participate in research.  
• there is a potential for an overall impact on the research that should be shared with the 
IRB for consideration and development of next best steps to address it 
Publication and Data Sharing Policy 
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who have 
a role in the design, conduct, analysis, publication, or any aspect of this trial will be disclosed 
and managed. Furthermore, persons who have a perceived conflict of interest will be required to 
have such conflicts managed in a way that is appropriate to their participation in the design and 
conduct of this trial. 
 
10.1.10 
Conflict of Interest Policy 
10.2 Protocol Amendment History 
 
Version 
Date 
Description of Change  
Brief Rationale 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Protocol UPCC 27224- ESPB for GI Malignancy Pain 
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32. Aydin ME, Tekin E, Ahiskalioglu EO, et al. Erector spinae plane block vs non-
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35. Ashworth H, Sanders N, Mantuani D, Nagdev A. Ultrasound-Guided Erector 
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40. Gawel RJ, Kramer JA, Panebianco N, Gottlieb M, Shofer FS, Shalaby M. Erector 
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12 APPENDIX  
12.1  Schedule of Activities (SoA) 

 
Protocol [Insert Study Number] –  
ESPB for GI Malignancy 
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