Conditions: Pain Management
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 46
Healthy volunteers: no

Brief summary:
Opioids are prescribed for moderate to severe pain disorders; however, there are contraindications and side effects that are common to all opioids. The investigators hypothesize using regional anesthetic during sinus surgery will reduce surgical pain, therefore decreasing the need for post-operative opioid medication. The primary of objective is to determine if a long-acting local regional anesthetic applied during a surgery will reduce post-operative oral opioid usage.

Detailed description:
Opioid analgesics are prescribed for moderate to severe acute pain; however, there are contraindications, cautions, and side effects that are common with all opioids. Dependence and tolerance are also likely with regular opioid use, resulting in the current nationwide opioid epidemic. In Alabama alone, there were 343 opioid-related overdose deaths in 2016, 124 of which were related to prescription opioids. Alabama providers have the highest prescribing rate in the country, nearly twice the national rate, per the NIH/NIDA website. In 2015, the Centers for Disease Control (CDC) released prescribing guidelines relating to chronic pain, and in 2018 Alabama's Blue Cross/Blue Shield insurance group limited the supply of opioids allowed to their members to 7 days.

There is currently no clinical guideline for prescribing post operative opioid medications for functional endoscopic sinus surgery (FESS). A 2018 survey documenting prescribing patterns by 168 members of the American Rhinologic Society found that most physicians who participated prescribed, on average, 27 opioid pain pills for patients after surgery. Prior studies have been performed to help decrease the pain patient's feel after sinus surgery. Haytoglu in 2016 revealed that adding non-absorbable sinus packs loaded with local anesthetics such as bupivacaine achieved less pain values and improved patient satisfaction scores.

Given this current data the investigators believe injecting patients with a long acting analgesic during the procedure will help reduce post-operative pain. If the investigators can decrease the amount of pain patients have in the post-operative period, they can theoretically decrease the number of opioid pain pills prescribed. The investigators plan to also track the number of opioid pills consumed by patients in the post-operative period to obtain a somewhat uniform prescribing pattern within surgeons.

Arms:
arm 1: 20 mL of 1.3% bupivacaine with 2 mg dexamethasone injected locally in the location for sensory nerves of the sinus cavities and face during the functional endoscopic sinus surgery (FESS) procedure arm 2: No regional anesthetic of any kind during the functional endoscopic sinus surgery (FESS) procedure

Interventions: intervention 1: Bupivacaine intervention 2: Dexamethasone
Intervention descriptions: intervention 1: 20 mL of 1.3% bupivacaine intervention 2: 2 mg dexamethasone

Protocol document:
Prot_ICF_004.pdf: 
The Role of Regional Anesthesia to Reduce Opioid 
Requirements Following Functional Endoscopic Sinus 
Surgery (FESS) 
 
National Clinical Trial (NCT) Identified Number:  NCT03757715 
Principal Investigator: Bradford Woodworth, MD 
Sponsor: University of Alabama at Birmingham 
 
Version Number:  v.1.0 
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Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................................................. 1 
1 
PROTOCOL SUMMARY ............................................................................................................................... 1 
1.1 
Synopsis ................................................................................................................................................ 1 
1.2 
Schedule of Activities (SoA) ............................................................................................................... 2 
2 
INTRODUCTION ............................................................................................................................................ 2 
2.1 
Study Rationale .................................................................................................................................... 2 
2.2 
Background........................................................................................................................................... 2 
2.3 
Risk/Benefit Assessment .................................................................................................................... 3 
2.3.1 
Known Potential Risks ..................................................................................................... 3 
2.3.2 
Known Potential Benefits ................................................................................................ 4 
2.3.3 
Assessment of Potential Risks and Benefits ................................................................ 4 
3 
OBJECTIVES AND ENDPOINTS ................................................................................................................ 5 
4 
STUDY DESIGN ............................................................................................................................................. 5 
4.1 
Overall Design ...................................................................................................................................... 5 
4.2 
Scientific Rationale for Study Design................................................................................................ 7 
4.3 
Justification for Dose ........................................................................................................................... 7 
4.4 
End of Study Definition ....................................................................................................................... 7 
5 
STUDY POPULATION .................................................................................................................................. 7 
5.1 
Inclusion Criteria .................................................................................................................................. 7 
5.2 
Exclusion Criteria ................................................................................................................................. 7 
5.3 
Screen Failures .................................................................................................................................... 8 
5.4 
Strategies for Recruitment and Retention ........................................................................................ 8 
6 
STUDY INTERVENTION .............................................................................................................................. 8 
6.1 
Study Intervention(s) Administration ................................................................................................. 8 
6.1.1 
Study Intervention Description ....................................................................................... 8 
6.1.2 
Dosing and Administration .............................................................................................. 8 
6.2 
Measures to Minimize Bias: Randomization .................................................................................... 8 
6.3 
Study Intervention Compliance .......................................................................................................... 9 
6.4 
Concomitant Therapy .......................................................................................................................... 9 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ...................................................................................................................... 9 
7.1 
Discontinuation of Study Intervention ............................................................................................... 9 
7.2 
Participant Discontinuation/Withdrawal from the Study ................................................................. 9 
7.3 
Lost to Follow-Up ................................................................................................................................. 9 
8 
STUDY ASSESSMENTS AND PROCEDURES ..................................................................................... 10 
8.1 
STUDY Assessments ........................................................................................................................ 10 
8.2 
Adverse Events and Serious Adverse Events ............................................................................... 11 
8.2.1 
Definition of Adverse Events (AE) ............................................................................... 11 
8.2.2 
Definition of Serious Adverse Events (SAE) .............................................................. 11 
8.2.3 
Classification of an Adverse Event .............................................................................. 11 
8.2.4 
Time Period and Frequency for Event Assessment and Follow-Up ....................... 12 
8.2.5 
Adverse AND SERIOUS Event Reporting.................................................................. 12 
8.3 
Unanticipated Problems .................................................................................................................... 13 
8.3.1 
Definition of Unanticipated Problems (UP) ................................................................. 13 
8.3.2 
Unanticipated Problem Reporting ................................................................................ 13 


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9 
STATISTICAL CONSIDERATIONS .......................................................................................................... 14 
9.1 
Statistical Hypotheses ....................................................................................................................... 14 
9.2 
Sample Size Determination .............................................................................................................. 14 
9.3 
Populations for Analyses .................................................................................................................. 15 
9.4 
Statistical Analyses............................................................................................................................ 15 
9.4.1 
General Approach .......................................................................................................... 15 
9.4.2 
Analysis of the Primary Efficacy Endpoint(s) ............................................................. 16 
9.4.3 
Analysis of the Secondary Endpoint(s) ....................................................................... 16 
9.4.4 
Safety Analyses .............................................................................................................. 17 
9.4.5 
Baseline Descriptive Statistics ..................................................................................... 17 
9.4.6 
Planned Interim Analyses ............................................................................................. 17 
9.4.7 
Sub-Group Analyses ..................................................................................................... 18 
9.4.8 
Tabulation of Individual participant Data .................................................................... 18 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 19 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ........................................................... 19 
10.1.1 
Informed Consent Process ........................................................................................... 19 
10.1.2 
Study Discontinuation and Closure ............................................................................. 19 
10.1.3 
Confidentiality and Privacy ........................................................................................... 20 
10.1.4 
Quality Assurance and Quality Control ....................................................................... 20 
10.1.5 
Data Handling and Record Keeping ............................................................................ 21 
10.1.6 
Protocol Deviations ........................................................................................................ 21 
10.1.7 
Publication and Data Sharing Policy ........................................................................... 21 
10.1.8 
Conflict of Interest Policy .............................................................................................. 22 
10.2 
Abbreviations ...................................................................................................................................... 22 
10.3 
Protocol Amendment History ........................................................................................................... 23 
11 
REFERENCES ............................................................................................................................................. 24 
 


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STATEMENT OF COMPLIANCE 
The trial will be conducted in accordance with International Conference on Harmonisation Good Clinical 
Practice (ICH GCP) and applicable United States (US) Code of Federal Regulations (CFR). The Principal 
Investigator will assure that no deviation from, or changes to the protocol will take place without prior 
documented approval from the Institutional Review Board (IRB), except where necessary to eliminate an 
immediate hazard(s) to the trial participants. All personnel involved in the conduct of this study have 
completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the local Institutional Review Board (IRB) for review and approval.  Approval of both the 
protocol and the consent form must be obtained before any participant is enrolled.  Any amendment to 
the protocol will require review and approval by the IRB before the changes are implemented to the 
study.  All changes to the consent form will be IRB approved; a determination will be made regarding 
whether a new consent needs to be obtained from participants who provided consent, using a 
previously approved consent form. 
1 
 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
Title: 
The Role of Regional Anesthesia to Reduce Opioid Requirements Following 
Functional Endoscopic Sinus Surgery (FESS) 
Study Description: 
Opioid analgesics are prescribed for moderate to severe pain disorders, 
however there are contraindications and side effects that are common to 
all opioids. We hypothesize using local regional anesthetic during sinus 
surgery will reduce pain, therefore decreasing the need for post-operative 
opioid medication. The primary objective is to determine if a long-acting 
regional anesthetic applied during a surgery will reduce post-operative 
oral opioid usage.  
Objectives: 
 
Primary Objective:  The primary of objective is to determine if a long-acting 
regional anesthetic applied after a surgery will reduce post-operative oral 
opioid usage. 
 
Secondary Objective: The secondary objective is to measure the level of 
each patient’s pain. 
Endpoints: 
• 
Primary Endpoint: The amount of post-operative pain after FESS.  
Participants will self-report a pain score on a scale of 0-10, with 0 
being “no pain” and 10 being “worst pain imaginable” on the 
provided questionnaire (see Appendix 1).   
 
• 
Secondary Endpoint: Patient’s daily pain medication usage. 
The amount of opioid medication used post-procedure will be 
determined by a pill count at the first post-operative clinic visit. 
Study Population: 
It is anticipated that 30 subjects will be enrolled in this protocol. Potential 
subjects will be male or female adults over the age of 18 from the United 
States who undergo functional endoscopic sinus surgery under the 
supervision of one surgeon. 
Phase: 
4 


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Description of Study 
Intervention: 
Treatment group: 20 mL of 1.3% bupivacaine with 2 mg dexamethasone 
injected locally in the location for sensory nerves of the sinus cavities and 
face during the FESS.  
 
Control group: No long-acting regional anesthetic will be used during the 
FESS.  
Study Duration: 
12 months 
Participant Duration: 
Up to 21 days (dependent on standard of care scheduling for first post-
operative clinic visit) 
1.2 
SCHEDULE OF ACTIVITIES (SOA) 
 
Procedures 
Screening/
Baseline 
Day of 
Surgery 
Day 10-21 
Informed consent 
X 
 
 
Demographics 
X 
 
 
Medical history 
X 
 
 
Physical exam 
X 
 
 
Vital signs 
X 
 
 
Height & weight 
X 
 
 
Nasal endoscopy 
X 
 
X 
CT scans 
X 
 
 
Randomization 
 
X 
 
Administer study intervention 
 
X 
 
Concomitant medication review 
X 
X 
X 
Adverse event review and evaluation 
X 
X 
X 
Pain diary 
 
X 
X 
Visual analog scale 
X 
X 
X 
Pain medication reconciliation 
 
 
X 
 
 
2 
 
INTRODUCTION 
 
2.1 
STUDY RATIONALE  
Opioid analgesics are still being prescribed to help control moderate to severe pain, however these 
medications are not without risks. Patients are at an increased risk of dependence which is a growing 
national concern. We plan to conduct a clinical trial to evaluate the use of regional anesthesia after 
routine sinus surgery to help decrease the need for post-operative opioid use. 
 
2.2 
BACKGROUND  
Opioid analgesics are prescribed for moderate to severe acute pain; however, there are 
contraindications, cautions, and side effects that are common with all opioids. Dependence and 
tolerance are also likely with regular opioid use, resulting in the current nationwide opioid epidemic. In 


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Alabama alone, there were 343 opioid-related overdose deaths in 2016, 124 of which were related to 
prescription opioids. Alabama providers have the highest prescribing rate in the country, nearly twice 
the national rate, per the NIH/NIDA website (https://www.drugabuse.gov/drugs-abuse/opioids/opioid-
summaries-by-state/alabama-opioid-summary). In 2015, the Centers for Disease Control (CDC) released 
prescribing guidelines relating to chronic pain, and in 2018 Alabama’s Blue Cross/Blue Shield insurance 
group limited the supply of opioids allowed to their members to 7 days 
(https://www.al.com/news/index.ssf/2018/03/bluecross_blueshield_changing.html).  
 
There is currently no clinical guideline for prescribing post-operative opioid medications for functional 
endoscopic sinus surgery (FESS). A 2018 survey documenting prescribing patterns by 168 members of 
the American Rhinologic Society found that most physicians who participated prescribed, on average, 27 
opioid pain pills for patients after surgery. Prior studies have been performed to help decrease the pain 
patient’s feel after sinus surgery.  Haytoglu (2016) revealed that adding non absorbable sinus packs 
loaded with local anesthetics such as bupivacaine achieved less pain values and improved patient 
satisfaction scores.   
 
Given this current data we believe injecting patients with a long acting analgesic during the procedure 
will help reduce post-operative pain. If we can decrease the amount of pain patients have in the post-
operative period we can theoretically decrease the number of opioid pain pills prescribed. We plan to 
also track the number of opioid pills consumed by patients in the post-operative period to obtain a 
somewhat uniform prescribing pattern within surgeons.  
 
2.3 
RISK/BENEFIT ASSESSMENT   
 
2.3.1 KNOWN POTENTIAL RISKS  
All of the drugs to be used in this study are FDA-approved, commonly-used, widely available, generic 
medications. These drugs will be prescribed at their standard dosing for their approved indications. 
 
As outlined in the package inserts for the medications under study in this protocol, the following adverse 
reactions have been identified during post approval use. Because these reactions are reported 
voluntarily from a population of uncertain size, it is not always possible to reliably estimate their 
frequency or establish a causal relationship to drug exposure. 
 
• 
Risks associated with bupivacaine hydrochloride (MarcaineTM): The most frequently reported 
adverse reactions are restlessness, anxiety, dizziness, tinnitus, blurred vision, tremors, nausea, 
vomiting, chills, and constriction of pupils (central nervous system reactions) and depression of 
the myocardium, decreased cardiac output, heartblock, hypotension, bradycardia, ventricular 
arrhythmias, including ventricular tachycardia and ventricular fibrillation, and cardiac arrest 
(cardiovascular system reactions). Other reported reactions include persistent anesthesia, 
paresthesia, weakness, or paralysis. Allergic reactions are characterized by signs such as 
urticaria, pruritus, erythema, angioneurotic edema (including laryngeal edema), tachycardia, 
sneezing, nausea, vomiting, dizziness, syncope, excessive sweating, elevated temperature, and 
possibly, anaphylactoid-like symptomatology (including severe hypotension). Reactions to 
MARCAINE are characteristic of those associated with other amide-type local anesthetics. A 
major cause of adverse reactions to this group of drugs is excessive plasma levels, which may be 
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addition to systemic dose-related toxicity, unintentional subarachnoid injection of drug during 
the intended performance of caudal or lumbar epidural block or nerve blocks near the vertebral 
column (especially in the head and neck region) may result in underventilation or apnea (“Total 
or High Spinal”). Also, hypotension due to loss of sympathetic tone and respiratory paralysis or 
underventilation due to cephalad extension of the motor level of anesthesia may occur. This 
may lead to secondary cardiac arrest if untreated. Patients over 65 years, particularly those with 
hypertension, may be at increased risk for experiencing the hypotensive effects of bupivacaine 
hydrochloride. Factors influencing plasma protein binding, such as acidosis, systemic diseases 
which alter protein production, or competition of other drugs for protein binding sites, may 
diminish individual tolerance.  Bupivacaine hydrochloride carries a black box warning for cardiac 
arrest with difficult resuscitation or death during use for epidural anesthesia in obstetrical 
patients. 
• 
Risks associated with dexamethasone sodium phosphate injection: The most frequently reported 
adverse reactions are anaphylaxis, infection, seizures, hypertension, erythema, rash, urticarial, 
nausea, vomiting, edema, petechial, ecchymosis, skin pigmentation abnormality, acne, 
headache, dizziness, vertigo, insomnia, anxiety, and depression. 
• 
Risks associated with protocol-mandated procedures: 
o Surgical procedures: All surgical procedures will be performed in the routine manner. 
There will be no additional clinical or surgical risks, other than the normal risks for 
patients undergoing this type of treatment. 
o Questionnaires: Completion of a questionnaire and the questions might make the 
subject feel uncomfortable or upset. Subjects will have the choice to not answer any 
such questions.  
 
2.3.2 KNOWN POTENTIAL BENEFITS  
An article published in 2015 by Knezevic evaluated 14 studies in which physicians added  
dexamethasone into the local anesthetic used for brachial plexus block. They concluded patients 
injected with local anesthetic plus dexamethasone had improved post-operative pain when compared to 
a control group. Our goal is to apply this to sinus surgery in providing analgesia to the sensory nerves of 
the face/sinus.  The immediate potential benefit for the patient is reduced discomfort and pain in the 
post-operative period. Potential long term benefits would include decrease need for post-operative 
opioid consumption therefore potentially decreasing the possible addictive habit of using opioids.  
 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
Routinely dexamethasone is used for general anesthesia to help decrease inflammation and post-
operative swelling.  All patients will be screened for any previous reactions to the medications being 
used in our study. Patient medical records will also be reviewed for past drug allergies.  As our study 
plans to evaluate the local effects of bupivacaine with dexamethasone, we anticipate only mild local 
reactions, as we will not systemically inject the drugs being used The risks to participants will likely 
encounter only local skin reactions to the medications. The information gained will help to possibly 
standardize how we treat post-operative pain after sinus surgery.  
 
 
 
 


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3 
OBJECTIVES AND ENDPOINTS 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Primary 
Primary 
Primary 
The primary objective is to 
determine if a long-acting regional 
anesthetic applied after a surgery 
will reduce post-operative oral 
opioid usage. 
 
 
The amount of post-operative pain 
after FESS. Participants will self- 
report a pain score on a scale of 0-10, 
with 0 being “no pain” and 10 being 
“worst pain imaginable.”  
 
   
 
The use of narcotics 
post-operatively is to 
control pain; if we can 
reduce post-operative 
pain, essentially we can 
decrease post-
operative opioid use. 
Secondary 
Secondary 
Secondary 
The secondary objective is to 
measure the level of each patient’s 
pain. 
 
Patients’ daily pain medication usage. 
The amount of opioid medication 
used post-procedure will be 
determined by a pill count at the first 
post-operative clinic visit. 
 
Pain is a subjectively 
based outcome that 
can be difficult to 
determine prior to a 
surgery. We believe if 
we are able to reduce 
pain in the majority of 
our patients tested 
then, we can apply this 
on a global scale to 
create a uniform 
number of opioid pain 
medications prescribed 
after surgery. 
 
 
4 
STUDY DESIGN  
 
4.1 
OVERALL DESIGN 
Opioid analgesics are prescribed for moderate to severe pain disorders; however, there are 
contraindications and side effects that are common to all opioids. We hypothesize using local regional 
anesthetic after sinus surgery will reduce pain, therefore decreasing the need for post-operative opioid 
consumption. 
 
This is a Phase 4, randomized, single-blinded, single-site, parallel-assignment intervention with a primary 
purpose of supportive care after functional endoscopic sinus surgery (FESS). It is anticipated that 30 
subjects will be enrolled in this protocol. Potential subjects will be male or female adults over the age of 
18 from the United States who undergo functional endoscopic sinus surgery (FESS) under the 
supervision of one surgeon. 
 


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Potential participants will be approached during their regularly-scheduled clinic visit about participation 
in the study. If they agree to participate, they will sign an informed consent form. During the baseline 
visit, demographic information, medical history, concomitant medications, vital signs, height, and weight 
will be collected. A routine nasal endoscopy will be performed to assess the need for surgical 
intervention, and routine CT sinus scans will be obtained and/or reviewed. 
 
Participants will be randomized to one of the two following groups: 
• 
Treatment Group (n = 15): participants will receive 20 mL of 1.3% bupivacaine with 2 mg 
dexamethasone injected locally in the location for sensory nerves of the sinus cavities and face 
during the FESS procedure 
• 
Control Group (n = 15): participants will not receive regional anesthetic during the FESS 
procedure 
 
Participants will have their scheduled functional endoscopic sinus surgery procedure. After surgery, 
participants will be given a pain diary to record their pain score on a scale of 1-10, and a place to record 
their use of opioids, as well as over-the-counter non-steroid anti-inflammatories such as acetaminophen 
and ibuprofen. Participants will record their scores and drug use daily for 10 days post-surgery. At their 
first post-operative clinic visit, the diary will be reviewed, and their opioid use will also be evaluated by 
counting the pills left on their prescription. 
 
Data points/variables to be collected during the study could include the following, to be ascertained 
from the medical record and/or patient report:  
• 
Name 
• 
Medical Record Number 
• 
Age 
• 
Gender 
• 
Type of surgery 
• 
Duration of surgery  
• 
Medications given by anesthesia intra- and post-operatively 
• 
Post-operative pain medication used prior to and after discharge 
• 
Post-operative complications 
• 
Post-discharge/post-operative pain evaluation by patient diary 
 
Participant duration will be up to 21 days, dependent on standard-of-care scheduling of the first post-
operative clinic visit. It is anticipated that the study will be open to enrollment for 12 months.  
 
Primary Objective:  The primary of objective is to determine if a long-acting local regional anesthetic 
applied after a surgery will reduce post-operative oral opioid usage. 
• 
Primary Endpoint: The amount of post-operative pain after FESS, as determined by patient self-
report of pain on a scale of 0-10. 
 
Secondary Objective: The secondary objective is to measure the level of each patient’s pain. 
• 
Secondary Endpoint: Patient’s daily pain medication usage. 
 
 


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4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
The rationale for our study deals with anesthetizing the sensory nerves of the face. The nerve 
distribution of the face deals with the trigeminal nerve. We plan to inject a long acting local analgesic at 
the infraorbital, infatrochlear, external nasal, supraorbital, supratrochlear nerves of the face after 
functional endoscopic sinus surgery. The control arm will be randomly chosen for which patient will not 
be injected. A potential problem with the control group is that patients in the PACU will have intact 
facial sensation. This could alert them to the fact that they were not injected with a local analgesic and 
thus reinforce the need for post-operative narcotic usage. 
 
4.3 
JUSTIFICATION FOR DOSE 
The nasal cavity is innervated by sensory nerves via the trigeminal nerve. We believe using a 
standardized dose of bupivacaine 1.3% combined with 2mg preservative-free dexamethasone to areas 
on around the nasal cavity that are innervated with sensory nerves will improve post-operative pain 
control results. A max amount of 20 mL will be injected into each study participant. The control group 
will receive no injection. 
 
4.4 
END OF STUDY DEFINITION 
A participant is considered to have completed the study if he or she has completed all phases of the 
study including the last visit or the last scheduled procedure shown in the Schedule of Activities (SoA), 
Section 1.2. 
 
The end of the study is defined as completion of the last visit or procedure shown in the SoA in the trial. 
 
 
5 
STUDY POPULATION 
 
5.1 
INCLUSION CRITERIA 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
1. Age 18 years or older 
2. Ability to speak English 
3. Ability to sign informed consent form 
4. Ability to comply with all study procedures 
5. Diagnosis of chronic rhinosinusitis 
6. Scheduled to receive functional endoscopic sinus surgery (FESS) at UAB 
 
5.2 
EXCLUSION CRITERIA 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
1. Current use of opioid medication 
2. Known allergic reactions to components of the study intervention 
3. History of IV drug use or abuse 
4. History of opioid abuse 
5. History of chronic pain disorder 
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5.3 
SCREEN FAILURES 
Screen failures are defined as participants who consent to participate in the clinical trial but are not 
subsequently randomly assigned to the study intervention or 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 authorities. Minimal information includes demography, screen 
failure details, eligibility criteria, and any serious adverse event (SAE). 
 
5.4 
STRATEGIES FOR RECRUITMENT AND RETENTION 
Patients who have presented to the UAB Department of Otolaryngology for evaluation and treatment of 
chronic sinusitis requiring surgery. The Principal Investigator has a practices specifically designated for 
treating rhinologic disorders, with potential for enrollment. Subjects will be identified from individuals 
treatment by the investigators in their clinics. Potential subjects will be approached by the Principal 
Investigator or qualified research staff authorized to conduct the informed consent discussion during 
their regularly-scheduled clinic visit about participation in the study. 
 
 
6 
STUDY INTERVENTION 
 
6.1 
STUDY INTERVENTION(S) ADMINISTRATION 
 
6.1.1 STUDY INTERVENTION DESCRIPTION 
 
Bupivacaine hydrochloride (MarcaineTM) is 2-Piperidinecarboxamide, 1-butyl-N-(2,6-dimethylphenyl)- 
monohydrochloride monohydrate. The molecular formula is C18H28N2O with a molecular weight of 
288.43. 
 
Dexamethasone sodium phosphate is 9-Fluoro-11β,17,21-trihydroxy-16∝-methylpregna-1,4-diene-3,20-
dione 21-(dihydrogen phosphate) disodium salt. The molecular formula is C22H28FNa2O8P with a 
molecular weight of 516.41. 
6.1.2 DOSING AND ADMINISTRATION 
Treatment Group: 20 mL of 1.3% bupivacaine with 2 mg dexamethasone injected locally in the location 
for sensory nerves of the sinus cavities and face during the FESS. 
 
Control Group: No local regional anesthetic will be used during the FESS.. 
 
6.2 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION  
Subjects will be randomized 1:1 (parallel assignment) into the two treatment groups. The next subject to 
be randomized into a trial will receive the treatment corresponding to the next free number in the 
randomization schedule. The appropriate number and associated treatment for the next subject will 
only be allocated when entry of that subject to the randomized part of the trial has been confirmed. 
 


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6.3 
STUDY INTERVENTION COMPLIANCE 
Subjects will complete a paper medication diary during the treatment period, recording the dates and 
times when post-operative pain medication is taken. Subjects will bring their bottles of post-operative 
medication to their Post-Op Day 14 clinic visit, at which time any remaining pills will be counted and 
recorded on the visit source document. This count will be reconciled with the medication log to 
calculate compliance. 
 
6.4 
CONCOMITANT THERAPY 
For this protocol, a prescription medication is defined as a medication that can be prescribed only by a 
properly authorized/licensed clinician. Medications to be reported in the Case Report Form (CRF) are 
concomitant prescription medications, over-the-counter medications and supplements. 
 
 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
Discontinuation from  study intervention will mean discontinuation from the study, and those subjects 
will be considered screen failures and will be removed from the dataset. No further data will be 
collected from those who are determined to be screen failures. 
 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Participants are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue or withdraw a participant from the study for the following reasons: 
 
• 
If any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest of the 
participant 
• 
Disease progression which requires discontinuation of the study intervention 
• 
If the participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
• 
Non-compliance with follow-up activities 
Subjects who sign the informed consent form and are randomized but do not receive the study 
intervention may be replaced.  Subjects who sign the informed consent form, and are randomized and 
receive the study intervention, and subsequently withdraw, or are withdrawn or discontinued from the 
study, will be replaced. 
7.3 
LOST TO FOLLOW-UP 
A participant will be considered lost to follow-up if he or she fails to return for the post-operative 
scheduled visit within 21 days and is unable to be contacted by the study site staff.  
 
The following actions must be taken if a participant fails to return to the clinic for a required study visit: 


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• 
The site will attempt to contact the participant and ascertain if the participant wishes to and/or 
should continue in the study. 
• 
The investigator or his clinic staff will make every effort to regain contact with the participant 
(where possible, 3 telephone calls/portal messages/emails, and if necessary, a certified letter to 
the participant’s last known mailing address or local equivalent methods). These contact 
attempts should be documented in the participant’s medical record.  
• 
Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
 
  
8 
STUDY ASSESSMENTS AND PROCEDURES 
 
8.1 
STUDY ASSESSMENTS  
Subjects over the age of 18 who are undergoing functional endoscopic sinus surgery for chronic sinusitis 
as part of routine clinical care will be approached to participate in the study. Subjects screened and 
enrolled will following the schedule of events provided in Section 1.2. The following evaluations will be 
performed: 
 
Screening/Baseline: 
• 
Obtain written informed consent 
• 
Obtain demographic information 
• 
Obtain medical history  
• 
Obtain concomitant medication information 
• 
Obtain routine vital signs, including height and weight  
• 
Obtain routine nasal endoscopy 
• 
Obtain/review routine CT scans of the sinus. This information may be obtained through review 
of existing data 
 
 
Day of Surgery 
• 
Randomization into the Treatment Group or the Control Group, as per measures outlined in 
Section 6.2 
• 
Scheduled routine surgical procedure previously planned, based on subject’s condition 
• 
Study intervention administration to all subjects 
• 
Post-operative medication diary will be given to all subjects 
• 
Post-operative visual analog pain scale will be given to all subjects 
• 
Assessment of adverse events 
• 
Assessment of concomitant medications 
 
Post-Operative Clinic Visit #1 (Day 10-21) 
• 
Obtain routine nasal endoscopy 
• 
Review of medication diary 
• 
Review of visual analog pain scale 
• 
Pain medication reconciliation via pill count 


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• 
Assessment of adverse events 
• 
Assessment of concomitant medication 
 
 
   
8.2 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 
8.2.1 DEFINITION OF ADVERSE EVENTS (AE) 
Adverse event means any untoward medical occurrence associated with the use of an intervention in 
humans, whether or not considered intervention-related (21 CFR 312.32 (a)). 
 
8.2.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE)  
An adverse event (AE) is considered “serious” if, in the view of either the investigator or sponsor, it 
results in any of the following outcomes: 
 
• 
Death 
• 
A life-threatening adverse event (of note, the term “life-threatening” refers to an event in which 
the subject was at risk of death at the time of the event, rather than to an event which 
hypothetically might have caused death if it were more severe) 
• 
inpatient hospitalization or prolongation of existing hospitalization 
• 
a persistent or significant incapacity or substantial disruption of the ability to conduct normal 
life functions 
• 
or a congenital anomaly/birth defect. 
 
Important medical events that may not result in death, be life-threatening, or require hospitalization 
may be considered serious when, based upon appropriate medical judgment, they may jeopardize the 
subject and may require medical or surgical intervention to prevent one of the outcomes listed in this 
definition. Examples of such medical events include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse. 
 
8.2.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.2.3.1 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”. 
 


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8.2.3.2 RELATIONSHIP TO STUDY INTERVENTION 
All adverse events (AEs) must have their relationship to study intervention 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 suspect.  
 
• 
Related – The AE is known to occur with the study intervention, there is a reasonable possibility 
that the study intervention caused the AE, or there is a temporal relationship between the study 
intervention and event. Reasonable possibility means that there is evidence to suggest a causal 
relationship between the study intervention and the AE. 
• 
Not Related – There is not a reasonable possibility that the administration of the study 
intervention caused the event, there is no temporal relationship between the study intervention 
and event onset, or an alternate etiology has been established. 
 
8.2.3.3 EXPECTEDNESS  
The Principal Investigator 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 study intervention. 
8.2.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to the attention of 
study personnel during study visits and interviews of a study participant presenting for medical care, or 
upon review by a study monitor. 
 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be captured on the 
appropriate case report form (CRF). Information to be collected includes event description, time of 
onset, clinician’s assessment of severity, relationship to study product (assessed only by those with the 
training and authority to make a diagnosis), and time of resolution/stabilization of the event. All AEs 
occurring while on study must be documented appropriately regardless of relationship. All AEs will be 
followed to adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an AE. However, if the study participant’s condition deteriorates at any 
time during the study, it will be recorded as an AE.  
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. AEs characterized as intermittent require documentation of 
onset and duration of each episode. 
 
The Study Coordinator will record all reportable events with start dates occurring any time after 
informed consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of 
study participation.  At each study visit, the investigator will inquire about the occurrence of AE/SAEs 
since the last visit.  Events will be followed for outcome information until resolution or stabilization. 
 
8.2.5 ADVERSE AND SERIOUS EVENT REPORTING  


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All serious adverse events must be reported to the IRB according to regulatory requirements. The 
Principal Investigator will immediately report to the sponsor any serious adverse event, whether or not 
considered study intervention related, including those listed in the protocol or package insert and must 
include an assessment of whether there is a reasonable possibility that the study intervention 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 
study intervention and the event (e.g., death from anaphylaxis). In that case, the investigator must 
immediately report the event to the sponsor. 
 
All serious adverse events (SAEs) will be followed until satisfactory resolution or until the Principal 
Investigator deems the event to be chronic or the subject is stable. Other supporting documentation of 
the event may be requested and should be provided as soon as possible. 
 
8.3 
UNANTICIPATED PROBLEMS 
 
8.3.1 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 of 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. 
 
8.3.2  UNANTICIPATED PROBLEM REPORTING  
The investigator will report unanticipated problems (UPs) to the reviewing Institutional Review Board 
(IRB). 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 to the IRB within 24 hours of the 
investigator becoming aware of the event.  


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• 
Any other UP will be reported to the IRB within 10 working days 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) and the Office for Human Research Protections (OHRP) within the 
timeline in accordance with the policy of the IRB’s receipt of the report of the problem from the 
investigator. 
 
9 
STATISTICAL CONSIDERATIONS  
The following subsections should describe the statistical tests and analysis plans for the protocol. They 
should indicate how the study will answer the most important questions with precision and a minimum 
of bias, while remaining feasible.  Many elements below can be found in ICH Guidance for Industry E9 
Statistical Principles for Clinical Trials and the CONSORT statement which describes standards for 
improving the quality of reporting randomized controlled trials.  
 
State whether there will be a formal Statistical Analysis Plan (SAP).  The SAP generally includes additional 
statistical analysis detail (e.g., more detail of analysis populations, summary of statistical strategies). If a 
separate SAP will be developed, subsections below can be summarized.  
 
9.1 
STATISTICAL HYPOTHESES 
State the formal and testable null and alternative hypotheses for primary and key secondary endpoints, 
specifying the type of comparison (e.g., superiority, equivalence or non-inferiority, dose response) and 
time period for which each endpoint will be analyzed. 
 
• 
Primary Efficacy Endpoint(s):  
 
<Insert text> 
 
• 
Secondary Efficacy Endpoint(s): 
 
<Insert text> 
 
9.2 
SAMPLE SIZE DETERMINATION 
Include number of participants to recruit, screen, and enroll to have adequate power to test the key 
hypotheses for the study.  Provide all information needed to validate your calculations and judge the 
feasibility of enrolling and following the necessary number of participants. In particular, specify all of the 
following: 
 
• 
Outcome measure used for calculations (almost always the primary variable) 
• 
Test statistic 
• 
Null and alternative hypotheses 
• 
Type I error rate (alpha) 
• 
Power level (e.g., 80% power) 
• 
Assumed event rate for dichotomous outcome (or mean and variance of continuous outcome) 
for each study arm, justified and referenced by historical data as much as possible 


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• 
Statistical method used to calculate the sample size, with a reference for it and for any software 
utilized  
• 
Anticipated impact of dropout rates, withdrawal, cross-over to other study arms, missing data, 
etc. on study power (see also 9.4.2 Analysis of the Primary Efficacy Endpoint(s) and 9.4.3 
Analysis of the Secondary Endpoint(s)) 
• 
Method for adjusting calculations for planned interim analyses, if any (Section 9.4.6, Planned 
Interim Analyses). 
 
Further, present calculations from a suitable range of assumptions to gauge the robustness of the 
proposed sample size. 
 
Discuss whether the sample size provides sufficient power for addressing secondary endpoints or 
exploratory analyses (e.g., subgroup analyses or moderator analyses involving an interaction term, 
Section 9.4.9, Exploratory Analyses). 
 
<Insert text> 
 
9.3 
POPULATIONS FOR ANALYSES 
Clearly identify and describe the analysis datasets (e.g., which participants will be included in each). As a 
guide, this may include, but is not limited to, any or all of the following: 
 
• 
Intention-to-Treat (ITT) Analysis Dataset (i.e., all randomized participants) 
• 
Modified Intention-to-Treat Analysis Dataset (e.g., participants who took at least one dose of 
study intervention and/or have some particular amount of follow-up outcome data) 
• 
Safety Analysis Dataset: defines the subset of participants for whom safety analyses will be 
conducted (e.g., participants who took at least one dose of study intervention) 
• 
Per-Protocol Analysis Dataset: defines a subset of the participants in the full analysis (ITT) set 
who complied with the protocol sufficiently to ensure that these data would be likely to 
represent the effects of study intervention according to the underlying scientific model (e.g., 
participants who took at least 80% of study intervention for 80% of the days within the 
maintenance period) 
• 
Other Datasets that may be used for sensitivity analyses 
 
<Insert text> 
 
9.4 
STATISTICAL ANALYSES 
The following subsections should include a description of the planned statistical methods. 
 
9.4.1 GENERAL APPROACH 
As a guide, the following should be addressed, as appropriate: 
 
• 
For descriptive statistics, describe how categorical and continuous data will be presented (e.g., 
percentages, means with standard deviations, median, range).  
• 
For inferential tests, indicate the p-value and confidence intervals for statistical significance 
(Type I error) and whether one or two-tailed. 


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• 
Indicate whether covariates will be pre-specified in the sections below or later in a SAP. 
• 
State whether checks of assumptions (e.g., normality) underlying statistical procedures will be 
performed and whether any corrective procedures will be applied (e.g., transformation or 
nonparametric tests). 
 
<Insert text> 
 
9.4.2 ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
For each primary endpoint: 
• 
Define the measurement or observation and describe how it is calculated, if not readily apparent 
• 
Describe the scale (nominal/binary/categorical, ordinal, interval); state if it is measured as a 
single endpoint/summary measure or repeated measure 
• 
Describe the statistical procedure(s) that will be used to analyze the primary endpoint (e.g., 
multiple regression, repeated measures mixed models, logistic regression, Analysis of Covariance 
(ANCOVA)). Describe the covariates and factors in the model. Provide your rationale for 
covariates and how they will be selected to achieve a parsimonious model. If the decision to 
specify covariates is deferred for the SAP, indicate here.  
• 
Describe how results of statistical procedure(s) will be presented (e.g., adjusted means (Least-
squares means (LSMEANS)) with standard errors, odds ratios with 95% confidence intervals, 
prevalence rates, number-needed-to-treat) 
• 
Describe details to check assumptions required for certain types of analyses (e.g., proportional 
hazards, transformations or, when appropriate, nonparametric tests) 
• 
Describe the Populations for which the analysis will be conducted, as discussed in Section 9.3, 
Populations for Analyses 
• 
Describe how missing data will be handled (e.g., type of imputation technique, if any, and 
provide justification), and approach to handling outliers, nonadherence and lost to follow-up  
• 
If there is more than one primary endpoint or more than one analysis of a particular endpoint, 
state the statistical adjustment used for Type I error criteria or give reasons why it was 
considered unnecessary. 
 
Note if more than one endpoint: the statistical approach for endpoints with the same analytic issues can 
be described as a group. 
 
<Insert text> 
 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
For each secondary endpoint: 
 
• 
Note if analysis of secondary endpoint(s) are dependent on findings of primary endpoint  
• 
Define the measurement or observation and describe how it is calculated, if not readily apparent 
• 
Describe the scale (nominal/binary/categorical, ordinal, and interval); state if it is measured as a 
single endpoint/summary measure or repeated measure. 
• 
Describe the statistical procedure(s) that will be used to analyze the secondary endpoint (e.g., 
multiple regression, repeated measures mixed models, logistic regression, ANCOVA). Describe 
the covariates and factors in the model. Provide rationale for covariates and how they will be 


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selected to achieve a parsimonious model. If decision to specify covariates is deferred for the 
SAP, indicate here.  
• 
Describe how results of statistical procedure(s) will be presented (e.g., adjusted means 
(LSMEANS) with standard errors, odds ratios with 95% confidence intervals, prevalence rates, 
and number-needed-to-treat). 
• 
Describe details to check assumptions required for certain types of analyses (e.g., proportional 
hazards, transformations or, when appropriate, nonparametric tests). 
• 
Describe the Populations for which the analysis will be conducted as discussed in Section 9.3, 
Populations for Analyses. 
• 
Describe how missing data will be handled (e.g., type of imputation technique, if any, and 
provide justification), and approach to handling outliers, nonadherence and lost to follow-up.  
• 
If there is more than one primary endpoint or more than one analysis of a particular endpoint, 
state the statistical adjustment used for Type I error criteria or give reasons why it was 
considered unnecessary. 
 
Note if more than one endpoint: the statistical approach for endpoints with the same analytic issues can 
be described as a group. 
 
<Insert text> 
 
9.4.4 SAFETY ANALYSES 
Describe how safety endpoints will be analyzed (e.g., as summary statistics during treatment and/or as 
change scores from baselines such as shift tables).  If your study is evaluating a formal safety endpoint, 
all of the factors to be included in Section 9.4.2, Analysis of the Primary Efficacy Endpoint(s) should be 
included here. Describe how AEs will be coded (e.g., Medical Dictionary for Regulatory Activities 
(MedDRA)), calculated (e.g., each AE will be counted once only for a given participant), presented (e.g., 
severity, frequency, and relationship of AEs to study intervention will be presented by System Organ Class 
(SOC) and preferred term groupings) and what information will be reported about each AE (e.g., start 
date, stop date, severity, relationship, expectedness, outcome, and duration).  Adverse events leading to 
premature discontinuation from the study intervention and serious treatment-emergent AEs should be 
presented either in a table or a listing.  The information included here should be consistent with the 
information contained within Section 8.2, Safety and Other Assessments. 
 
<Insert text> 
 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
Include content in this section if applicable, otherwise note as not-applicable. 
 
Intervention groups should be compared on baseline characteristics, including demographics and 
laboratory measurements, using descriptive statistics. Discuss planned baseline descriptive statistics, 
indicate whether inferential statistics will be used. 
 
<Insert text> 
 
9.4.6 PLANNED INTERIM ANALYSES  
Include content in this section if applicable, otherwise note as not-applicable. 


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This section should describe the types of statistical interim analyses and halting guidelines (if any) that 
are proposed, including their timing and who reviews the interim analyses.  In addition, if the interim 
analyses could result in an adjusted sample size, discuss the statistical algorithm to be used when 
evaluating results.  Pre-specify, to the extent possible, the criteria that would prompt an interim review 
of safety and efficacy data and trial futility. Describe who performs the statistical analysis and who 
reviews the analysis.  In addition, discuss whether they are unblinded and how the blinding will be 
preserved.  
 
If statistical rules will be used to halt enrollment into all or a portion of the study (e.g., for safety or 
futility), describe the statistical techniques and their operating characteristics.  If formal interim analyses 
will be performed, provide unambiguous and complete instructions so that an independent statistician 
could perform the analyses. 
 
Describe safety findings that would prompt temporary suspension of enrollment and/or study 
intervention use until a safety review is convened (either routine or ad hoc). Provide details of the 
proposed rules for halting study enrollment or study intervention/administration of study product for 
safety, including whether they pertain to the entire study, specific study arms or participant subgroups, 
or other components of the study.   
 
State how endpoints will be monitored, the frequency of monitoring, and the specific definitions of 
proposed halting guidelines.  Examples of findings that might trigger a safety review are the number of 
SAEs overall, the number of occurrences of a particular type of SAE, severe AEs/reactions, or increased 
frequency of events. 
 
Also, discuss the impact of the interim analysis (if being done) on the final efficacy analyses, particularly 
on Type I error.   
 
This section should be consistent with Section 7, Study Intervention Discontinuation and Participant 
Discontinuation/Withdrawal. 
 
<Insert text> 
 
9.4.7 SUB-GROUP ANALYSES 
Describe how the primary endpoint will be analyzed based on age, sex, race/ethnicity or other 
demographic characteristic(s) or provide justification for why such analyses are not warranted (e.g., 
study intervention only for use in men or children). 
 
Describe how the secondary endpoint(s) will be analyzed based on age, sex, race/ethnicity or other 
demographic characteristic(s) or provide justification for why such analyses are not warranted (e.g., 
study intervention only for use in men or children). 
 
<Insert text> 
 
9.4.8 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
State whether individual participant data will be listed by measure and time point. 


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<Insert text> 
 
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 
Consent forms describing in detail the study intervention, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to starting any study 
procedures. A separate screening consent form will not be used.  
 
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 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 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 regulatory authorities.  If the study is prematurely 
terminated or suspended, the Principal Investigator (PI) will promptly inform study participants and the 
Institutional Review Board (IRB), and will provide the reason(s) for the termination or suspension.  Study 
participants will be contacted, as applicable, and be informed of changes to study visit schedule. 
  
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 


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• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination that the primary endpoint has been met 
• 
Determination of futility 
 
Study may resume once concerns about safety, protocol compliance, and data quality are addressed, 
and satisfy the IRB. 
 
10.1.3 CONFIDENTIALITY AND PRIVACY  
Participant confidentiality and privacy is strictly held in trust by the participating investigators and their 
staff. 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.  
 
All research activities will be conducted in as private a setting as possible. 
 
Representatives of the Institutional Review Board (IRB) or other 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) for the participants in this study. The clinical study site will 
permit access to such records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by the reviewing IRB or Institutional policies. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
be stored in the UAB Department of Otolaryngology Research Office. 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 research staff will be secured and password protected. At the end of the 
study, all study databases will be de-identified and archived in the UAB Department of Otolaryngology 
Research Office. 
 
10.1.4 QUALITY ASSURANCE AND QUALITY CONTROL 
Each clinical site will perform internal quality management of study conduct, data collection, 
documentation and completion.  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 study coordinator for 
clarification/resolution. 
 
Following written Standard Operating Procedures (SOPs), the monitors will verify that the clinical trial is 
conducted and data are generated and collected, documented (recorded), and reported in compliance 
with the protocol, International Conference on Harmonisation Good Clinical Practice (ICH GCP.  
 
The investigational site will provide direct access to all trial related source data/documents, and reports 
for the purpose of inspection by local and regulatory authorities. 


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10.1.5 DATA HANDLING AND RECORD KEEPING  
 
10.1.5.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the 
Principal Investigator. The PI is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. 
 
All source documents should be completed in a neat, legible manner to ensure accurate interpretation 
of data.   
 
Hardcopies of the source document worksheets will be provided for recording data for each participant 
enrolled in the study.  Data recorded in the case report form (CRF) derived from source documents 
should be consistent with the data recorded on the source documents.  
 
10.1.5.2 STUDY RECORDS RETENTION  
Study documents should be retained for a minimum of 3 years after the completion of the trial. Records 
will be retained in accordance with the Department’s SOP on Research Records Retention. 
 
10.1.6 PROTOCOL DEVIATIONS  
A protocol deviation is any noncompliance with the clinical trial protocol or International Conference on 
Harmonisation Good Clinical Practice (ICH GCP) requirements. The noncompliance may be either on the 
part of the participant, the investigator, or the study site staff. As a result of deviations, corrective 
actions are to be developed by the site and implemented promptly.  
 
These practices are consistent with ICH GCP:  
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3  
• 
5.1 Quality Assurance and Quality Control, section 5.1.1  
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2.  
 
It is the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations within 10 working days of identification of the protocol deviation, or within 10 working days 
of the scheduled protocol-required activity.  Protocol deviations must be sent to the reviewing 
Institutional Review Board (IRB) per their policies. The Principal Investigator is responsible for knowing 
and adhering to the reviewing IRB requirements.  
 
10.1.7 PUBLICATION AND DATA SHARING POLICY 
This study will comply with the Clinical Trials Registration and Results Information Submission rule. As 
such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be 
submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-
reviewed journals.  Data from this study may be requested from other researchers x years after the 
completion of the primary endpoint by contacting <specify person or awardee institution, or name of 
data repository>.  
 
5 years? UAB Department of Otolaryngology? 


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10.1.8 CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical.  Therefore, any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a 
way that is appropriate to their participation in the design and conduct of this trial.  The study 
leadership in conjunction with the UAB Office of the Conflict of Interest Review Board has established 
policies and procedures for all study group members to disclose all conflicts of interest and will establish 
a mechanism for the management of all reported dualities of interest. 
10.2 ABBREVIATIONS 
 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
CFR 
Code of Federal Regulations 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act  
ICH 
International Conference on Harmonisation  
ICMJE 
International Committee of Medical Journal Editors 
IRB 
Institutional Review Board 
LSMEANS 
Least-squares Means 
NCT 
National Clinical Trial 
NIH  
National Institutes of Health 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SOA 
Schedule of Activities 
SOP 
Standard Operating Procedure 
UP 
Unanticipated Problem 
US 
United States 
 
 
 


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10.3 PROTOCOL AMENDMENT HISTORY 
The table below is intended to capture changes of IRB-approved versions of the protocol, including a 
description of the change and rationale. A Summary of Changes table for the current amendment is 
located in the Protocol Title Page.  
 
Version 
Date 
Description of Change  
Brief Rationale 
 
 
 
 
 
 
 


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11 REFERENCES  
Include a list of relevant literature and citations for all publications referenced in the text of the protocol.  
Use a consistent, standard, modern format, which might be dependent upon the required format for the 
anticipated journal for publication (e.g., N Engl J Med, JAMA, etc.).  The preferred format is International 
Committee of Medical Journal Editors (ICMJE). Include citations to product information such as 
manufacturer’s IB, package insert, and device labeling.  
 
Examples: 
 
• 
Journal citation 
Veronesi U, Maisonneuve P, Decensi A. Tamoxifen: an enduring star. J Natl Cancer Inst. 2007 Feb 
21;99(4):258-60. 
• 
Whole book citation 
Belitz HD, Grosch W, Schieberle P. Food chemistry. 3rd rev. ed. Burghagen MM, translator. Berlin: 
Springer; 2004. 1070 p. 
• 
Chapter in a book citation 
Riffenburgh RH. Statistics in medicine. 2nd ed. Amsterdam (Netherlands): Elsevier Academic 
Press; c2006. Chapter 24, Regression and correlation methods; p. 447-86. 
• 
Web Site citation 
Complementary/Integrative Medicine [Internet]. Houston: University of Texas, M.D. Anderson 
Cancer Center; c2007 [cited 2007 Feb 21]. Available from: 
http://www.manderson.org/departments/CIMER/. 
• 
Electronic Mail citation 
Backus, Joyce. Physician Internet search behavior: detailed study [Internet]. Message to: Karen 
Patrias. 2007 Mar 27 [cited 2007 Mar 28]. [2 paragraphs] 
• 
References to package insert, device labeling or investigational brochure 
Cite date accessed, version number, and source of product information. 
 
 


The Role of Regional Anesthesia to Reduce Opioid Requirements Following Functional Endoscopic Sinus 
Surgery (FESS): A Pilot Study 
 
Study Protocol & Statistical Analysis Plan 
 
NCT03757715 
 
 
UAB IRB Approved 16-Feb 2021 through 19-Jan 2022 
 
Bradford A. Woodworth, MD -Principal Investigator 
University of Alabama at Birmingham 
Birmingham, AL 35294 
 


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CONSENT FORM TO BE PART OF A RESEARCH STUDY
Title of Research:
The Role of Regional Anesthesia to Reduce Opioid Requirements Following 
Functional Endoscopic Sinus Surgery (FESS): A Pilot Study
UAB IRB Protocol #:
IRB-300000567
Principal Investigator:
Bradford Woodworth, M.D.
Sponsor:
UAB Department of Otolaryngology
General Information
You are being asked to take part in a research study. This research study is 
voluntary, meaning you do not have to take part in it. The procedures, risks, and 
benefits are fully described further in the consent form.
Purpose
The purpose of the study is to determine if receiving extra pain medication during 
your sinus procedure affects the amount and kind of pain medication that is taken 
after surgery.
Duration & Visits
You will be in this study for up to 21 days.
Overview of Procedures
If you decide to take part in this study, you will assigned by chance to one of the 
treatment groups. This is called randomization. 

If you are picked for the Treatment Group, you will receive 10-12 mL of 
0.5% bupivacaine with 1:200,000 epinephrine and 2 mg dexamethasone 
injected locally in the location for sensory nerves of the sinus cavities and 
face intraoperatively, or during the FESS procedure.

If you are picked for the Control Group, you will not receive any local 
anesthetic during the FESS procedure.
Both groups will receive the same post-operative prescription pain medication 
(Norco), will complete a daily pain diary (recording pain score and medications 
taken), and will have a prescription pain medication pill count at the first post-
operative clinic visit.
Risks
You will be assigned to a group by chance, which may prove to be less effective or 
to have more side effects than the other study group or alternatives. 
The most common side effects of the medications include nausea/vomiting, 
restlessness, anxiety, dizziness, rash, and headache.
Benefits
You may not benefit directly from taking part in this study. However, this study 
may help us better understand how to treat post-surgical pain in the future.
Alternatives
You do not have to participate in this study to receive standard of care treatment 
for your sinus disorder. Your doctor will tell you more about other treatments that 
may be available to you. You may choose to have no treatment at all. One 
alternative may be to not to participate in this study.
Purpose of the Research Study
We are asking you to take part in a research study because you are scheduled to have a functional endoscopic 
sinus surgery (FESS) procedure for your sinus issue. You will be given a prescription for opioid pain medication 
UAB IRB
Approved
16-Feb-2021
until
19-Jan-2022


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as part of your routine care after your surgery. The purpose of this pilot research study is to assess whether 
injecting a local anesthetic during FESS is feasible and whether it may affect the amount and kind of pain 
medication that you will use after surgery.
There will be 30 participants enrolled at UAB.
Study Participation & Procedures
If you agree to join the study, your medical record will be reviewed to obtain information regarding your 
medical condition and diagnosis, as well as demographic information, such as your age and gender. During 
your pre-surgery clinic visit, you will have a routine nasal endoscopy, and your sinus CT scans will be obtained 
and/or reviewed. 
You will be randomly picked (like the flip of a coin) to either receive the study intervention, or to receive the 
standard of care treatment during your surgery:

If you are picked for the Treatment Group, you will receive 10-12 mL of 0.5% bupivacaine with 
1:200,000 epinephrine and 2 mg dexamethasone injected locally in the location for sensory nerves of 
the sinus cavities and face intraoperatively, during the FESS procedure.

If you are picked for the Control Group, you will not receive any local anesthetic during the FESS 
procedure.
You will then have your surgery. This surgery will be performed in the routine manner that was planned for 
you, based on your condition.  If you are picked for the Treatment Group, you will receive the extra 
medication during the procedure. If you are picked for the Control Group, you will not receive any extra 
medication during the procedure.
After your surgery, you will be prescribed pain medication in the routine manner. These are the same 
medications that you would have whether you were participating in this study or not.
For study purposes, you will be given a study diary to complete for the first ten days following your surgery. 
This will consist of a pain scale, graded on a scale of 1-10, as well as a medication diary. You will be asked to 
record all of the medications you take for the pain you experience after your surgery, both the prescribed 
opioid as well as over-the-counter medications such as Tylenol or Advil. 
At your first post-operative clinic visit, you will bring in your study diary and your medicine bottles so that we 
can count the number of pills you have left on your prescription. We will record these amounts for our 
research data only. 
The daily study diary will take approximately 5 minutes per day to complete. The total amount of time you will 
be in the study is up to 21 days, depending on when your first post-operative clinic visit is scheduled.
Risks and Discomforts
All of the drugs to be used in this study are FDA-approved, commonly-used, widely available, generic 
medications. These drugs will be used at their standard dosing for their approved indications.
If you are picked for the Treatment Group, you will receive extra pain medication during the FESS procedure.
The most common side effects of bupivacaine with epinephrine (MarcaineTM) are:

restlessness


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
anxiety

dizziness

tinnitus

blurred vision

tremors

nausea/vomiting

chills

central nervous system reactions, such as constriction of the pupils

heart block

hypotension (low blood pressure)

bradycardia (slow pulse)

irregular heart beat

rapid, life-threatening heart rhythms
The most common side effects of dexamethasone are:

allergic reaction

seizure

hypertension (high blood pressure)

skin irritation or rash

nausea/vomiting

edema (fluid collection under the skin)

bruising

acne

headache

dizziness

insomnia

anxiety

depression 
Save for the above-mentioned risks of side effects, there is no additional risk to taking bupivacaine with 
epinephrine and dexamethasone as part of this study. There aren’t any known increased risks for taking these 
medications in combination. They do not have cross reactions with each other or other known interactions 
that may lead to increased risks, other than those listed above.
No matter what group you are assigned to, you will receive a prescription for hydrocodone-acetaminophen 
(commonly known as Norco) for any post-operative surgical pain you may have. There is a chance that those 
assigned to Control Group (who will not receive any local anesthetic during the FESS procedure) will have an 
increase use of this post-operative pain medication. Risks associated with opioid use include:

respiratory depression

nausea/vomiting

allergic reaction

constipation

dizziness

headache

weakness

dry mouth


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There is a risk of a loss of confidentiality for patients involved in research studies. All of your personal and 
medical information will be stored in a locked area. Only qualified research staff will have access to this 
information. Once your research data has been collected, all information that could link your personal identity 
to your medical information will be deleted. There will be no personally identifying information used to report 
any findings from this study.
You will be assigned to a group by chance, which may prove to be less effective or to have more side effects 
than the other study group or alternatives.
Confidentiality and Authorization to Use and Disclose Information for Research Purposes
Federal regulations give you certain rights related to your health information. These include the right to know 
who will be able to get the information and why they may be able to get it. The study doctor must get your 
authorization (permission) to use or give out any health information that might identify you.
What protected health information may be used and/or given to others?
All medical information, including but not limited to information and/or records of any diagnosis or treatment 
of disease or condition, which may include sexually transmitted diseases (e.g., HIV, etc.) or communicable 
diseases, drug/alcohol dependency, etc.; all personal identifiers, including but not limited to your name, social 
security number, medical record number, date of birth, dates of service, etc.; any past, present, and future 
history, examinations, laboratory results, imaging studies and reports and treatments of any kind, including but 
not limited to drug/alcohol treatment, psychiatric/psychological treatment; financial/billing information, 
including but not limited to copies of your medical bills; any other information related to or collected for use in 
the research study, regardless of whether the information was collected for research or non-research (e.g., 
treatment) purposes; records about any study drug you received or about study devices used; and consent 
forms from past studies that might be in your medical record.
Your consent form will be placed in your medical record at UAB Health System. This may include either a paper 
medical record or electronic medical record (EMR). An EMR is an electronic version of a paper medical record 
of your care within this health system. Your EMR may indicate that you are on a clinical trial and provide the 
name and contact information for the principal investigator.
If you are receiving care or have received care within this health system (outpatient or inpatient), results of 
research tests or procedures (i.e. laboratory tests, imaging studies and clinical procedures) may be placed in 
your existing medical record.
If you have never received care within this health system (outpatient or inpatient), a medical record will be 
created for you to maintain results of research tests or procedures.
Results of research tests or procedures may be placed in your medical record. All information within your 
medical record can be viewed by individuals authorized to access the record.
A description of this clinical trial will be available on www.ClinicalTrials.gov, as required by U.S. Law. This 
website will not include information that can identify you. At most, the website will include a summary of the 
results. You can search this website at any time. The National Clinical Trial (NCT) identifier for this protocol is 
NCT03757715.
Who may use and give out information about you?


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Information about your health may be used and given to others by the study doctor and staff. They might see 
the research information during and after the study.
Who might get this information?
All Individuals/entities listed in the informed consent document(s), including but not limited to, the physicians, 
nurses and staff and others performing services related to the research (whether at UAB or elsewhere). Your 
information may also be given to the sponsor of this research. “Sponsor” includes any persons or companies 
that are working for or with the sponsor, or are owned by the sponsor, or are providing support to the sponsor 
(e.g., contract research organization).
Information about you and your health which might identify you may be given to:

the Office for Human Research Protections (OHRP)

the U.S. Food and Drug Administration (FDA)

Department of Health and Human Services (DHHS) agencies

Governmental agencies in other countries

Governmental agencies to whom certain diseases (reportable diseases) must be reported

the University of Alabama at Birmingham - the physicians, nurses and staff working on the research study 
(whether at UAB or elsewhere); other operating units of UAB, UAB Hospital, UAB Highlands Hospital, 
University of Alabama Health Services Foundation, Children’s of Alabama, Eye Foundation Hospital, and 
the Jefferson County Department of Health, as necessary for their operations; the UAB IRB and its staff

the billing offices of UAB and UAB Health Systems affiliates and/or Children’s of Alabama and its billing 
agents
Why will this information be used and/or given to others?
Information about you and your health that might identify you may be given to others to carry out the 
research study. The sponsor will analyze and evaluate the results of the study. In addition, people from the 
sponsor and its consultants will be visiting the research site. They will follow how the study is done, and they 
will be reviewing your information for this purpose.
What if I decide not to give permission to use and give out my health information?
By signing this consent form, you are giving permission to use and give out the health information listed above 
for the purposes described above. If you refuse to give permission, you will not be able to be in this research.
May I review or copy the information obtained from me or created about me?
You have the right to review and copy your health information. However, if you decide to be in this study and 
sign this permission form, you will not be allowed to look at or copy your information until after the research is 
completed.
May I withdraw or revoke (cancel) my permission?
Yes, but this permission will not stop automatically. The use of your personal health information will continue 
until you cancel your permission.
You may withdraw or take away your permission to use and disclose your health information at any time. You 
do this by sending written notice to the study doctor. If you withdraw your permission, you will not be able to 
continue being in this study.
When you withdraw your permission, no new health information which might identify you will be gathered 
after that date. Information that has already been gathered may still be used and given to others. This would 
be done if it were necessary for the research to be reliable.


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Is my health information protected after it has been given to others?
If you give permission to give your identifiable health information to a person or business, the information may 
no longer be protected. There is a risk that your information will be released to others. Including others 
outside of UAB, without your permission.
Voluntary Participation and Withdrawal
Whether or not you take part in this study is your choice. There will be no penalty if you decide not to be in it. 
If you decide not to be in the study, you will not lose any benefits you are otherwise owed.
You are free to withdraw from this study at any time. Your choice to leave the study will not affect your 
relationship with this institution. Contact the study doctor if you want to withdraw from the study.
You may be removed from the study without your consent if the sponsor ends the study, if the study doctor 
decides it is not in the best interest of your health, or if you are not following the study rules.
If you are a UAB student or employee, taking part in this research is not a part of your UAB class work or 
duties. You can refuse to enroll, or withdraw after enrolling at any time before the study is over, with no effect 
on your class standing, grades, or job at UAB. You will not be offered or receive any special consideration if you 
take part in this research.
Cost of Participation
There will be no cost to you for taking part in this study. The costs of your standard medical care will be billed 
to you and/or your insurance company in the usual manner.
Payment for Participation
You will be not be paid to participate in this study.
Payment for Research-Related Injuries
UAB has not provided for any payment if you are harmed as a result of taking part in this study. If such harm 
occurs, treatment will be provided. However, this treatment will not be provided free of charge.
New Findings
You will be told by the study doctor or the study staff if new information becomes available that might affect 
your choice to stay in the study.
Questions
If you have any questions, concerns, or complaints about the research or a research-related injury including 
available treatments, please contact the study doctor. You may contact Dr. Woodworth at (205) 937-9777.
If you have questions about your rights as a research participant, or concerns or complaints about the 
research, you may contact the UAB Office of the IRB (OIRB) at (205) 934-3789 or toll free at 1-855-860-3789. 
Regular hours for the OIRB are 8:00 a.m. to 5:00 p.m. CT, Monday through Friday.
Legal Rights
You are not waiving any of your legal rights by signing this consent form.


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Signatures
Your signature below indicates that you have read (or been read) the information provided above, and that 
you agree to participate in this study. You will receive a copy of this signed consent form.
Signature of Participant
Date
Signature of Person Obtaining Consent
Date