Clinical trial NCT03872700
Conditions: Abscess
Sponsor: Montefiore Medical Center
Start date: 2019-08-01; Completion date: 2022-12-31
Enrollment: 49 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This randomized clinical trial aims to compare the analgesic efficacy of intranasal fentanyl to placebo as analgesic adjunct to conventional local anesthesia for the treatment of pain of the overall procedure in adult patients undergoing lidocaine infiltration and subsequent abscess incision and drainage in the Emergency Department (ED).

Detailed description:

Arms: arm 1: 2 mcg/kg INF, administered via intranasal route by atomizer syringe arm 2: 0.04ml/kg of sterile water, administered via intranasal route by atomizer syringe
Interventions: intervention 1: Intranasal fentanyl intervention 2: Placebo
Intervention descriptions: intervention 1: Fentanyl Citrate intervention 2: Sterile Water Up to 5Cc

Protocol documents:
ICF_001.pdf: 
1
KEY INFORMATION FOR: Intranasal Fentanyl vs Placebo as adjuncts to local analgesia for pain
control in patients undergoing Emergency Department abscess incision and drainage
We are asking you to choose whether or not to volunteer for a research study about fentanyl versus placebo
(sterile water) in addition to local pain medication injection for emergency department incision and 
drainage of an abscess. This page is designed to give you key information to help you decide whether to 
participate. We have included detailed information after this page. Ask the research team questions. If you 
have questions later, the contact information for the research investigator in charge of the study is below.
WHAT IS THE STUDY ABOUT AND HOW LONG WILL IT LAST?
During the study, you will be given fentanyl OR sterile water through your nose before injection of 
lidocaine (a pain medication) in the area of the abscess. This may reduce the pain you experience during 
injection of lidocaine, as well as, during the drainage of the abscess. We will monitor your vital signs 
during the study. By doing this study, we hope to learn if fentanyl given through the nose is helpful in 
reducing pain during abscess drainage. Your participation in this research will last about 2 hours.
The purpose of this research is to gather information on the safety and effectiveness of fentanyl. This
medication is FDA approved for pain control in adult cancer patients and is likely as safe in non-cancer 
adults treated for pain.
WHAT ARE KEY REASONS YOU MIGHT CHOOSE TO VOLUNTEER FOR THIS STUDY?
You may or may not receive personal, direct benefit from taking part in this study. However, the 
medication may decrease in the amount of pain you are feeling. This research may benefit people who are
experiencing pain during drainage of an infection in the emergency room.
WHAT ARE KEY REASONS YOU MIGHT CHOOSE NOT TO VOLUNTEER FOR THIS 
STUDY?
In this randomized clinical trial you have a 50/50 chance of receiving fentanyl or sterile water. It is possible 
that either of these medications will not reduce the pain you experience during the procedure.
Both medications are commonly used and have a low chance of causing significant side effects although if 
this happens it may be harmful. For a complete description of risks of please refer to the detailed consent
document below.
DO YOU HAVE TO TAKE PART IN THE STUDY?
If you decide to take part in the study, it should be because you really want to volunteer. You will not lose 
any services, benefits or rights or access to care you would normally have if you choose not to volunteer.
WHAT IF YOU HAVE QUESTIONS, SUGGESTIONS OR CONCERNS?
The person in charge of the study is Benjamin Friedman, MD. If you have questions, suggestions, or 
concerns regarding this study or you want to withdraw from the study his contact information is: 718-920-
6626. If you have any questions, suggestions or concerns about your rights as a volunteer in this research, 
contact staff in the Einstein Institutional Review Board (IRB) between the business hours of 9am and 5pm 
EST, Monday-Friday at 718-430-2253 or irb@einstein.yu.edu
IRB NUMBER: 2019-9925
IRB APPROVAL DATE: 02/24/2021
IRB EXPIRATION DATE: 02/23/2022


2
ALBERT EINSTEIN COLLEGE OF MEDICINE 
MONTEFIORE MEDICAL CENTER
DOCUMENTATION OF INFORMED CONSENT AND HIPAA AUTHORIZATION
Introduction
You are being asked to participate in a research study called “Intranasal Fentanyl vs Placebo 
as adjuncts to local analgesia for pain control in patients undergoing Emergency 
Department abscess incision and drainage” Your participation is voluntary -- it is up to you 
whether you would like to participate. It is fine to say “no” now or at any time after you have 
started the study. If you say “no,” your decision will not affect any of your rights or benefits or 
your access to care.
The researcher in charge of this project is called 
the “Principal Investigator.” His name is Benjamin 
Friedman, MD. You can reach Dr. Friedman at: 
Office Address: 111 East 210th Street
Bronx, NY 10467
Telephone #: 718-920-6626
For questions about the research study, or if you 
believe you have an injury, contact the Principal 
Investigator or the IRB.
Support for this research study is provided by 
Montefiore’s Department of Emergency 
Medicine
The Institutional Review Board (IRB) of 
the Albert Einstein College of Medicine 
and Montefiore Medical Center has 
approved this research study. The IRB # 
is in the stamp in the upper right hand 
corner. If you have questions regarding 
your rights as a research subject you may 
contact the IRB office at 718-430-2253 or 
by mail:
Einstein IRB 
Albert Einstein College of Medicine
1300 Morris Park Ave., Belfer Bldg #1002
Bronx, New York 10461
Why is this study being done? 
Abscess incision and drainage is a common and painful procedure performed in the emergency 
department. Injection of local pain medication into the abscess can often itself be painful and 
may not completely prevent pain during the procedure. The goal of this study is to compare 
medications given before the injection or the procedure to further prevent pain.
Fentanyl is a potent opioid medication which has been shown to reduce severe pain. It is used 
with caution because in rare cases it may cause low blood pressure, nausea/vomiting or if used 
often, addiction. 
Alternatively, you may receive sterile water (placebo). This is simply water not containing any 
chemicals or potentially infectious organisms. This study will be done at two Montefiore 
emergency rooms: Jack D. Weiler and Moses. Both fentanyl and sterile water have been 
approved by the US Food and Drug Administration  (FDA) for clinical use.
Why am I being asked to participate? 
IRB NUMBER: 2019-9925
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IRB EXPIRATION DATE: 02/23/2022


3
You have been asked to be a participant in this research study because you will undergo 
abscess incision and drainage in the Emergency Department and you are between 18 and 64 
years old. You will be one of approximately 150 participants in this study.
How long will I take part in this research?
It will take you about two hours today to complete the treatment phase of this research study. 
What will happen if I participate in the study?  
We will spend 10 minutes right now asking you questions about your pain, your medical history, 
your age, and your ethnicity.
We will then determine randomly which medication you will get: either fentanyl OR sterile 
water. There is an equal chance (like flipping a coin) that you will get either one of these 
treatments. Neither you nor your treating provider will know now which medication you received. 
We will look to see which medication you received once we have completed the study one year 
from now. The medication will be given to you in your nose.
Prior to receiving the study medication, a research associate will check your vital signs. The 
research associates will return to check your pain level and your vital signs every 15 minutes for 
the entire two hour study period.
A description of this clinical trial will be available on www.ClinicalTrials.gov, as required by U.S. 
law. This Web site will not include information that can identify you. At most, the Web site will 
include a summary of the results. You can search this Web site at any time.
Are there any risks to me?
A risk of taking part in this study is the possibility of a loss of confidentiality or privacy. Loss of 
privacy means having your personal information shared with someone who is not on the study 
team and was not supposed to see or know about your information. The study team plans to 
protect your privacy – see the Confidentiality section above for details.
Risks of Taking Sterile Water
There is a small chance the medication may go in your lung. This is unlikely to cause any harm 
but may cause some discomfort.
Risks of Taking Fentanyl
Common side effects: flushing, itching, nausea, vomiting, itching, dizziness, feeling light headed, 
drowsiness, constipation
Less common side effects: Low blood pressure, weakness
Uncommon side effects: This medication could make you stop breathing, which can be fatal
IRB NUMBER: 2019-9925
IRB APPROVAL DATE: 02/24/2021
IRB EXPIRATION DATE: 02/23/2022


4
Information Banking (Future Use and Storage)
Information about you will be kept as long as required by regulations and institutional policy, but 
will not be used for future studies.
Will I be paid for being in this research study? 
No. You will not receive any payment or other compensation for taking part in this study. Some 
researchers may develop tests, treatments or products that are worth money. You will not 
receive payment of any kind for your specimens and information or for any tests, treatments, 
products or other things of value that may result from the research.
Will it cost me anything to participate in this study? 
Taking part in this study will not involve added costs to you. All study drugs will be given free of 
charge. You or your insurance company will receive the usual bill for your emergency visit and 
physician services.
What will happen if I am injured because I took part in this study?
If you are injured as a result of this research, only immediate, essential, short-term medical 
treatment as determined by Montefiore, will be available for the injury without charge to you 
personally. 
●
No monetary compensation will be offered. 
●
You are not waiving any of your legal rights by signing this informed consent document. 
●
If additional treatment is required as a result of a physical injury related to the research, 
necessary medical treatment will be provided to you and billed to your insurance 
company or to you as part of your medical expenses. 
Immediately report any discomforts, problems or injuries you experience during the course of 
your participation in the study to Dr. Benjamin Friedman at 718-920-6626.
What else do I have to do?
●
You must tell the research study doctor about any past and present diseases or allergies 
you are aware of and about all medications you are taking.
●
If you do not feel well at any time, tell or call your doctor or the research study doctor 
immediately. 
●
Drugs may cause a reaction that, if not treated promptly, could be life-threatening.  It is 
important that you report all symptoms, reactions and other complaints to your nurse. 
Confidentiality
We will keep your information confidential. Your research records will be kept confidential and 
your name will not be used in any written or verbal reports. Your information will be given a code 
IRB NUMBER: 2019-9925
IRB APPROVAL DATE: 02/24/2021
IRB EXPIRATION DATE: 02/23/2022


5
number and separated from your name or any other information that could identify you. The 
form that links your name to the code number will be kept in a secure manner and only the 
investigator and study staff will have access to the file. All information will be kept in a secure 
manner and computer records will be password protected. Your study information will be kept as 
long as they are useful for this research. Dr. Latev, the principal investigator, will keep your 
study information as long as it is useful for his research on acetaminophen and hydromorphone.
The only people who can see your research records are:
●
the research team and staff who work with them
●
clinicians and staff at Montefiore who review your records for your care
●
groups that review research (the Einstein IRB, and the Office for Human Research 
Protections, and the US Food and Drug Administration)
These people who receive your health information, may not be required by privacy laws to 
protect it and may share your information with others without your permission, if permitted by 
laws governing them.  All of these groups have been asked to keep your information 
confidential.
Allergic Reaction to Study Drug
Any drug can cause an allergic reaction, which could be mild or more serious and can even 
result in death. Common symptoms of an allergic reaction are rash, itching, skin problems, 
swelling of the face and throat, or trouble breathing. If you are having trouble breathing, tell your 
nurse immediately.
THE STUDY MEDICATIONS MAY MAKE YOU VERY DROWSY. YOU SHOULD NOT DRIVE 
YOURSELF HOME AFTER PARTICIPATING IN THIS STUDY.
New Findings
If we learn any significant new findings during the study that might influence your decision to 
participate, we will contact you and explain them.
Are there possible benefits to me? 
You may or may not receive personal, direct benefit from taking part in this study.  The possible 
benefits of taking part in this research study include possible decrease in the amount of pain 
you are feeling. This research may benefit people who are experiencing pain during drainage 
of an infection in the emergency room.
What choices do I have other than participating in this study?
You can refuse to participate in the study. If you decide not to participate, the medical care 
providers at this facility will still give you all of the standard care and treatment that is 
appropriate for you. Your other choices are:
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IRB EXPIRATION DATE: 02/23/2022


6
-
To receive no medication in the nose in addition to local injection of analgesia. You may be 
given additional pain medication by mouth by the treating provider at your request at any 
time during the procedure.
Are there any consequences to me if I decide to stop participating in this study?
No. If you decide to take part, you are free to stop participating at any time without giving a 
reason. This will not affect your care and you will continue to be treated at this facility. However, 
some of the information may have already been entered into the study and that will not be 
removed. 
To revoke (take back) your consent and authorization, you must contact the Principal 
Investigator in writing at the address on page 1 of this form. However, you may first call or speak 
to the Principal Investigator and he will stop collecting new information about you.  If you take 
back your consent and authorization, you will not be allowed to continue to participate in this 
research study. 
Can the study end my participation early?
After you have consented to participate and have been determined to be eligible, you will be 
randomly assigned to receive specific study medications. You will remain in the study for 2 
hours until its completion unless the clinician caring for you believes you are unable to follow the 
protocol or are not fit to participate.
IRB NUMBER: 2019-9925
IRB APPROVAL DATE: 02/24/2021
IRB EXPIRATION DATE: 02/23/2022


7
CONSENT TO PARTICIPATE
I have read the consent form and I understand that it is up to me whether or not I participate. I 
know enough about the purpose, methods, risks and benefits of the research study to decide 
that I want to take part in it. I understand that I am not waiving any of my legal rights by signing 
this informed consent document. I will be given a signed copy of this consent form.
CONSENT TO PARTICIPATE
I have read the consent form and I understand that it is up to me whether or not I participate. I 
know enough about the purpose, methods, risks and benefits of the research study to decide 
that I want to take part in it. I understand that I am not waiving any of my legal rights by signing 
this informed consent document. I will be given a signed copy of this consent form.
Printed name of participant
Signature of participant
Date
Time
Printed name of the research 
associate conducting the 
consent process
Signature
Date
Time
________________________
______________________________________ ______ ____
Printed name of the provider 
conducting the consent 
process 
Signature
Date
T
i
m
e
Time
IRB NUMBER: 2019-9925
IRB APPROVAL DATE: 02/24/2021
IRB EXPIRATION DATE: 02/23/2022

Prot_SAP_002.pdf: 
IRB NUMBER: 2019-9925 
IRB APPROVAL DATE: 05/17/2021 
1 
 
 
CLINICAL STUDY PROTOCOL 
 
Title: A Randomized Trial of Intranasal Fentanyl versus Placebo as an Adjunct to Lidocaine 
Infiltration in Adults undergoing Abscess Incision and Drainage in the Emergency 
Department 
 
Sponsor 
Department of Emergency Medicine/Montefiore Medical Center 
3411 Wayne Ave 
6th Floor, 10467, Bronx, New York, United States 
Protocol Version 
April 20, 2021 


IRB NUMBER: 2019-9925 
IRB APPROVAL DATE: 05/17/2021 
2 
 
 
1 - Introduction 
1.1 Introductory Statement 
Incision and drainage of abscesses is one of the most painful procedures performed in US 
emergency departments. It has historically accounted for 2.5% of all visits and nearly 30% of 
procedures performed in this setting[1, 2]. The incidence of abscesses is increasing at 11% 
annually, more than any other ED diagnosis.[3] Delayed and inadequate treatment of pain for this 
and other procedures is an established and pervasive problem [4-6]. Different ED providers’ 
analgesic practices vary with some using opioids in addition to local infiltration at the roof of the 
abscess or a field block.[7] There is scant literature on proper analgesia during I&D with only small 
trials[8] or textbooks with varying and non-consistent recommendations. [9, 10] 
 
Opioids are effective and safe pharmaceutical agents for analgesia in an emergency setting[11, 12]. 
The reasons for their underutilization are multifactorial. Often providers have a tendency to 
underestimate the patient’s level of pain compared to the patient’s own perception of pain as 
reflected by their self-reported 0-10 Numerical Rating Scale (NRS)[13]. This is further complicated 
by provider discomfort in treating pain with opioids[14]. Additionally, many providers have an 
unfounded bias that opioid use in an emergency setting leads to long-term addiction, especially in 
certain socioeconomic and age groups[5, 15, 16]. It is imperative that the emergency medicine 
community continues to improve analgesic practice by conducting randomized clinical trials 
focused on pain control. 
 
This trial will investigate the efficacy of intranasal fentanyl (INF) as an analgesic adjunct for abscess 
incision and drainage. 
 
2 - Background 
2.1 Background/prevalence of research topic 
 
Bioavailability and Pharmacokinetics 
Fentanyl is a synthetic, short-acting opioid 50-100 times more potent than morphine, with highly 
lipophilic properties suitable for intranasal administration. Low molecular weight, lipophilic drugs 
are highly conducive to rapid-transport via the nasal epithelium.[17] The efficacy may be further 
enhanced due to direct entrance into the CNS via the olfactory mucosa, rather than the blood brain 
barrier. Fentanyl’s intranasal bioavailability varies between 71-89%.[17, 18] INF has an onset of 
action of approximately 7 (4-11 min, median) minutes and no difference in levels of pain compared 
to IV fentanyl up to 120 minutes (duration at least 60-120 minutes). [18, 19] Due to its 
pharmacokinetics and rapid-onset of action, INF will be ideal for abscess incision and drainage, a 
short-duration procedure. 
 
INF in post-operative setting 
 
INF has been studied in the post-operative setting. 
 
In a randomized placebo controlled study by Veldhorst-Janssen 2010, 36 women (mean age 39.2) 
post-op from breast reduction where given a single dose pre-mixed solution of 0.05mg/0.1mL nasal 
spray fentanyl for a total mean dose of 78 mcg during drain removal. INF was more likely to afford 
relief than placebo.[20] 


IRB NUMBER: 2019-9925 
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3 
 
 
Another prospective, double-dummy, double blind RCT (n=48) in orthopedic, thyroid or abdominal 
surgical patients showed similar efficacy of INF compared to IV fentanyl PCA with 21/23 (91%) 
patients in the IN fentanyl group achieving excellent pain relief in 21 min, compared to 24/25 
(96%) patients in the PCA fentanyl group in 22 min.[21] 
 
In a single dose cross-over study of 24 gynecological patients with post-operative pain treated with 
IV vs INF separated by 2 hours, analgesia onset was rapid (5 min) in both groups and no difference 
in outcomes was found. Side-effects were not different with 4 patients in the intranasal group 
experiencing “nasal stinging.”[19] 
 
INF in pediatrics 
 
INF has gained broad acceptance in pediatric emergency medicine. INF is particularly useful in 
pediatric patients who often require short-duration procedural analgesia and are less amenable to 
intravenous catheter placement. 
 
In a randomized study, 47 pediatric patients presenting for long-bone fractures given 1mcg/kg of 
50mcg/mL of INF vs 0.2mg/kg of 10mg/mL of intramuscular morphine (IMM) demonstrated fewer 
side effects with INF than IMM (p<0.001). This study also showed no difference in reduction in pain 
scores and no serious adverse events. One patient in the INF group required rescue analgesia.[22] 
 
When comparing INF (1.4mcg/kg equivalent to 1mcg/kg calculated at 71% bioavailability) to 
intravenous morphine (0.1mg/kg) in 67 children < 18 years of age presenting to the emergency 
department for long bone fractures, VAS pain scores at 30 minutes decreased from 67 to 33 in the 
morphine group and 68 to 37 in the INF group (time=30 min difference 95% CI -4(-16 to 8)). 
Neither group had any cases of respiratory depression, hypotension, or decreased level of 
consciousness. Mean INF dose was 1.7mcg/kg due to additional doses of 15mcg, given as necessary. 
In the INF group 3 patients reported “bad taste” and one had an episode of vomiting 20 minutes 
after intervention. One patient in each group required additional doses of analgesia. [17] 
 
In a study of 189 pediatric patients (3 to 15 years old) presenting for long bone fractures treated 
with 1.5mcg/kg of standard (50mcg/mL) vs high concentration (300mcg/mL) INF, both arms had 
substantial reduction in pain scores. Of these patients, 42(43%) in the standard concentration 
group required rescue medication compared with 25(28%) in the high concentration group.[17] 
 
Fentanyl in the emergency department 
 
The brief duration of action, potency and ease of administration, make fentanyl an optimal choice of 
analgesia in the emergency department. Despite this, fentanyl is used merely 10% as often as 
hydromorphone despite its favorable safety profile. [23] 
 
A study by Imamoglu et al. looking at 115 adult patients receiving INF vs IV fentanyl (n=115) for 
renal colic, showed effective analgesia by both regimen at 15 and 30 min with rescue pain 
medication requirements of 55% in the IN group and 37% in the IV group (n=0.058). Adverse 
events occurred in 22% of patients in the IV group and only 9% in the IN group. None of these were 
serious.[24] 
 
In a retrospective study of 841 patients looking at fentanyl for pre-procedural analgesia: 6 patients 
(0.7%) had mild side effects: nausea (1), vomiting (2), urticaria (1) and pruritis (2). Nine (1.1%) 
had more serious side effects including: respiratory depression (6), hypotension (3), both 


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4 
 
 
hypotension and respiratory depression (1). Four of 6 of the patients who developed respiratory 
depression and 2 of 3 of patients who developed hypotension had alcohol levels > 160mg%. [2] 
Placebo. Administration of sterile water via the intranasal route could conceivably cause analgesia 
through a placebo effect.[25] As an inert sterile fluid it poses no infectious or aspiration risk. 
 
4 - Study Objectives 
4.1 Hypothesis 
2 mcg/kg of INF will provide better pain control than placebo when used as an adjunct to 
conventional local anesthesia to reduce overall pain of the procedure in adult ED patients 
undergoing lidocaine infiltration and subsequent abscess incision and drainage, as measured on a 
0-10 pain scale. 
 
4.2 Primary Objective 
To compare the analgesic efficacy of INF to placebo as analgesic adjunct to conventional local 
anesthesia for the treatment of pain of the overall procedure in adult ED patients undergoing 
lidocaine infiltration and subsequent abscess incision and drainage, as measured on a 0-10 pain 
scale. 
 
 
4.3 Secondary Objectives 
A) To compare pain scores immediately after local analgesic infiltration and after abscess incision, 
instrumentation and packing 
B) To compare patient satisfaction with treatment and provider perception of study medication 
efficacy compared to usual care 
C) To compare side effect profiles and adverse events associated with the administration of INF and 
placebo. 
 
 
5 - Study Design 
5.1 General Design 
 
This will be a randomized, double blind study of 2 mcg/kg INF versus 0.04 mL/kg IN of sterile 
water used adjunctively to local anesthetic in patients 18-64 years of age undergoing abscess I&D in 
two Montefiore EDs. 
 
5.2 Outcome Variables 
5.2.1 Primary Outcome Variables 
The primary outcome is the between group difference in numerical rating scale (NRS) pain scores 
for overall pain of the procedure, defined as anesthetic infiltration plus abscess incision and 
drainage, including breaking up of adhesions, irrigation, and packing as indicated. The time for 
obtaining this primary NRS endpoint will be standardized as the time of completion of application 
of the bandage. The NRS is a reliable and validated measure of pain intensity ranging from 0 – no 
pain, to 10 – worst pain imaginable. 
 
5.2.2 Secondary Outcome Variables 
Secondary efficacy outcomes: difference between groups in NRS pain score immediately after 
infiltration with local anesthetic and difference between groups in NRS scores immediately after the 
completion of incision and drainage procedure, including breaking up adhesions, irrigation, and 
packing as indicated. Additional secondary outcomes include: patient satisfaction with treatment 


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5 
 
 
described by asking “How satisfied are you with the pain medication you received for the 
procedure? (Satisfied, Neutral, Not Satisfied). Provider perception of treatment efficacy compared 
to usual care described categorically as (Better, Same, Worse). The incidence of adverse events and 
side effects in the two groups will be compared as will the frequency of medication use to treat side 
effects/adverse effects in each group. 
 
 
5.3 Eligibility Criteria 
Inclusion criteria 
• 
Age 18 to 64 years of age: This is a study of adult ED patients. 
• 
Presenting to the ED for an abscess requiring incision and drainage 
• 
ED attending physician's judgment that the patient has capacity to provide informed 
consent. 
• 
Patients must be able to understand English or Spanish. 
 
Exclusion criteria 
• 
Use of opioids or tramadol within past 7 days. 
• 
Prior adverse reaction or allergy to opioids. 
• 
Patients who are pregnant 
• 
Patients weight > 100kg 
• 
Chronic pain syndrome: frequently recurrent or daily pain for at least 3 months results in 
modulation of pain perception which is thought to be due to down-regulation of pain 
receptors. Examples of chronic pain syndromes include sickle cell anemia, osteoarthritis, 
fibromyalgia, and peripheral neuropathies. 
• 
Medical condition that might affect metabolism or opioid analgesics such as cirrhosis (Child 
Pugh A or worse) or kidney impairment (CKD 3 or worse) 
• 
Chronic malnutrition, severe hypovolemia (dehydration of blood loss) or hepatic disease 
• 
Alcohol intoxication: history of alcoholism or the presence of alcohol intoxication as judged 
by the treating physician may alter pain perception and has previously increased adverse 
events. 
• 
SBP <100 mmHg: Opioids can produce peripheral vasodilation causing orthostasis. 
• 
HR < 60/min: Opioids can cause bradycardia. 
• 
Oxygen saturation < 95% on room air: For this study, oxygen saturation must be 95% or 
above on room air in order to be enrolled. 
• 
Use of MAO inhibitors in past 30 days: MAO inhibitors have been reported to intensify the 
effects of at least one opioid drug causing anxiety, confusion and significant respiratory 
depression or coma. 
• 
Patients using transdermal pain patches or oral opioid use > 10 days in the prior month: 
frequent opioid use may influence both the amount of pain patients report as well as the 
level of relief they obtain from other treatments. 
• 
Patients with a history of traumatic brain injury, seizures or hallucinations 
• 
Patients with anatomical anomalies or medical conditions precluding intranasal 
administration 


IRB NUMBER: 2019-9925 
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6 
 
 
 
 
6 - Methods 
6.1 Treatment - Drug 
6.1.1 Identity of Investigational Product/New Drug 
Fentanyl and sterile water (placebo) are both FDA approved for clinical use. 
 
6.1.2 Dosage, Admin, Schedule (if applicable) 
 
• 
Arm A: 2 mcg/kg INF, administered via intranasal route by atomizer syringe 
• 
Arm B: 0.04ml/kg of sterile water, administered via intranasal route by atomizer syringe 
o All doses will be calculated rounding patient weight up to the nearest 10kg but not 
exceeding 100kg. Both arms will be given as adjuncts to local anesthetic infiltration 
as standard of care. 
 
6.1.3 Method of Assignment/Randomization 
Randomization will occur in blocks of four based on a random number generator. 
 
6.1.4 Blinding 
Research subjects, clinicians, and research personnel will be blinded. 
 
6.1.5 Packaging/Labelling 
The study packet will contain one item: a package containing either 4mL of fentanyl (50mcg/mL 
concentration = 200 mcg, the maximal dose in this weight-based study of patients <100 kg) or an 
identical appearing package containing 4mL sterile water 
 
6.1.6 Storage Conditions 
Study medications will be stored in the ED PYXIS at each site. 
 
6.1.7 Concomitant therapy 
Patients will receive usual care (typically local infiltration with lidocaine) as determined by the 
treating provider 
 
6.1.8 Restrictions 
Due to intranasal route of administration and dosing, both groups will receive no more than 4mL of 
intranasal solution equivalent to 200mcg of fentanyl or 4mL of sterile water 
 
6.2 Assessments 
6.2.1 Efficacy 
Primary Outcome: 
• 
The primary outcome: overall procedure NRS pain scores in each group 
Secondary Outcomes: 
• 
Baseline NRS pain scores in each group 
• 
NRS pain scores immediately after infiltration with local analgesic 
• 
NRS pain scores after incision, breaking of loculations, irrigation, and packing of abscess as 
indicated 
• 
Difference in proportion of patients satisfied with treatment in each arm 


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7 
 
 
• 
Difference in proportion of providers’ perceived efficacy of study protocol analgesia versus 
standard of care 
• 
Difference in proportion of patients who have one or more side effects in the 60 minutes 
post-procedure 
• 
Incidence of adverse events between groups 
Incidence of nausea, vomiting and pruritis, and adverse events will be measured and recorded at 
120 minutes after the administration of intranasal medication. Pulse oximetry will be continuous 
and vital signs will be recorded every 15 minutes after INF administration until 120 minutes. 
 
6.2.2 Safety 
• 
The Research Associate will remain at the patient's bedside for the first 10 minutes after 
medication administration, during local infiltration and from the time of initial incision until 
dressing application 
• 
At 15 minute intervals after intranasal medication administration of the study medication, 
the RA will measure and record vital signs (including SaO2 by pulse oximeter). 
• 
No further monitoring will be performed after 120 minutes. 
 
6.2.2.1 Adverse Events Definition and Reporting 
Any adverse events will be managed at the discretion of the treating provider. 
All vital signs that fall below the thresholds described above will be reported to the Data Safety 
Monitoring (DSM) individual and included in the annual progress report to the IRB. The DSM 
monitoring will consist of Dr. David Esses, MD, the director of the Moses ED and Dr. Polly Bijur, 
Ph.D, head of the Division of Research of the Department of Emergency Medicine. They will meet 
every month with the PI to 1) monitor adverse events and develop strategies to minimize these; 
and 2) monitor recruitment and enrollment. 
 
6.3 Study Procedures 
• The RAs and attending physicians will identify eligible patients. To participate, patients must have 
capacity to provide informed consent. 
• The healthcare provider and the RA will describe the study to eligible patients and obtain patient 
consent. 
• The RA will weigh patient, obtain a baseline NRS pain score and initial vital sign information. 
• The RA will have the nurse remove the next study packet from the PYXIS, which will be either 4 ml 
vial containing either fentanyl 50mcg/mL or sterile water. The contents will be concealed by the 
research pharmacist. 
• Patients will receive the blinded study medication either 2 mcg/kg of fentanyl or 0.04 mL/kg of 
sterile water (max 4mL) weight based and rounded to the nearest 10kg (excluding patients > 
100kg to prevent excessive opioid dosing) via an atomizer syringe (half of total volume in each 
nostril) 15 minutes prior to local infiltration 
• The RA will prompt the treating provider 15 minutes after local infiltration to ensure prompt 
treatment during an optimal systemic and local analgesic window. If the I&D has not been 
initiated within 30 minutes of INF administration the patient will not be included in the analyses 
due to concern for considerable tapering of INF analgesia (accounted for in sample size 
calculation). 
• At 15 minute intervals following the intranasal medication administration, the RA will obtain vital 
signs (including SaO2 by pulse oximeter), and record incidence of side effects and adverse 
events. 
• The RA will record all medications administered in the ED and the time of their administration 
from the chart and the treating attending physician. 


IRB NUMBER: 2019-9925 
IRB APPROVAL DATE: 05/17/2021 
8 
 
 
 
• 
RAs will record the time of each pertinent procedural step: Initial NRS collection time, 
location of abscess, size of abscess (cm), complexity of procedure (simple: requires minimal 
blunt instrumentation, moderate: requires more than minimal blunt instrumentation, 
complex: requires more than moderate instrumentation), use of packing (yes/no), study 
medication administration time, local infiltration time, incision/instrumentation/packing 
/irrigation time, dressing application time and discharge time. 
 
 
6.4 Statistical Method 
6.4.1 Statistical Design 
The statistical design is parallel group design with patients randomly allocated to the two 
treatments. 
 
 
6.4.2 Sample Size Considerations 
A sample size of 49 patients will support the primary outcome, based on the observed SD of 3.2, if 
the between group difference is no less than 2.8. This  was calculated based on the following 
parameters: alpha = 0.05 and power = 0.8. Although smaller differences may be clinically relevant, a 
between-group difference of 2.8 is generally regarded as a robust difference. 
 
We used nQuery Advisor version 7.0 (Los Angeles, CA) to calculate the sample size. 
 
6.4.3 Planned Analyses 
The planned analyses include: a comparison of the characteristics of the two treatment groups at 
baseline including NRS pain scores at baseline, immediately after infiltration with local anesthetic, 
immediately after abscess incision, overall NRS pain score throughout the procedure assessed at 
the time of dressing application. We will also compare the proportion of patients satisfied with 
treatment, comparison of proportion of providers’ perception of efficacy of treatment compared to 
usual care, adverse events and side effects in the 120 minute period and graphical representation of 
pain over all time points. 
 
 
6.4.3.1 Primary Analyses 
We will calculate the NRS scores between the two treatment arms as overall procedure pain 
collected at the time of dressing application. An independent group t-test will be used to assess 
whether the NRS scores differ between the groups. Descriptive data will be calculated for all 
variables. The characteristics of patients in the two groups will be compared in order to confirm 
adequacy of randomization. If there is unequal distribution of background variables with p values 
of 0.15 or less, we will include them in a multivariable analysis of the outcomes.  
 
6.4.3.2 Secondary Objectives Analyses 
A similar analysis to the primary outcome analysis will be performed for NRS pain immediately 
after local analgesic infiltration, for NRS pain score after abscess incision and (instrumentation 


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9 
 
 
and/or packing if completed) between the two treatment arms. We will calculate the difference in 
the proportion of patients in each group who are satisfied with treatment based upon a categorical 
patient-centered question answered as “Satisfied, Neutral, Not Satisfied.” A chi-square test will be 
used to compare the proportions of patients who are satisfied with treatment. The same analyses 
will be done to determine provider perception of efficacy of analgesia of study medications 
compared to usual care. 
 
6.4.3.3 Safety 
Vital sign data and side-effects, including adverse events, will be obtained and recorded at 15 
minute intervals after medication administration to ensure patient safety. Chi-square tests will be 
used to assess whether the proportion of patients with one or more side effects differs between 
treatment groups. The individual side effects will be described in tables. If there are marked 
differences between the distributions of background characteristics, a multi-variable regression 
will be performed to control for possible confounding. 
 
 
6.4.3.4 Analysis of Subject Characteristics 
• Background characteristics: Age, sex, race/ethnicity, initial pain intensity, nausea and vomiting 
before administration of analgesics. Means and standard deviations, medians and interquartile 
ranges, and proportions will be used to describe the sample as appropriate. 
 
 
7 - Trial Administration 
7.1 Ethical Considerations 
Patients will not receive any compensation for their participation in this study. All data collected 
will be maintained within locked file cabinets or within secure databases (i.e. REDCap). 
 
 
7.2 Subject Confidentiality 
All data collection instruments will be secured within REDCap. The PI and co-investigators will be 
the only ones with access to the full database linking study IDs to patient identifying information. 
 
7.3 Data Collection 
All study data will be entered directly into REDCap by the Research Associates. Signed consent 
forms will be collected and kept under lock and key. 
 
7.4 Data Safety Monitoring Plan 
Data Safety Monitoring: Dr. David Esses, the director of the Moses ED and Dr. Polly Bijur, Ph.D, head 
of the Division of Research of the Department of Emergency Medicine, will meet monthly with the 
PI. This meeting will aim to 1) monitor adverse events and develop strategies to minimize these; 
and 2) monitor recruitment and enrollment. 


IRB NUMBER: 2019-9925 
IRB APPROVAL DATE: 05/17/2021 
10 
 
 
 
 
 
 
 
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