Conditions: Epistaxis
Keywords: tranexamic acid epistaxis emergency medicine intranasal TXA
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 35
Healthy volunteers: no

Brief summary:
It is estimated that epistaxis results in 4.5 million emergency department visits per year throughout the United States. Due to the adverse effects of standard treatment options for epistaxis, tranexamic acid (TXA) may be considered an attractive option. In previous studies, when used with nasal packing, TXA showed faster time to control of bleeding. The goal of this study is to determine the efficacy and safety of topical intranasal TXA applied via atomizer for patients with epistaxis who present to the emergency department.

Detailed description:
This is a prospective, randomized, single-center, double-blinded, placebo controlled study comparing efficacy and safety of topical intranasal tranexamic acid for epistaxis. The primary outcome was time to control of bleeding and secondary outcomes were length of stay in the emergency department, re-bleeding within the first 24 hours, and re-bleeding at one week. Safety outcomes were the incidence of thromboembolic events and other drug-related adverse events.

Patients aged 18 years of age or older and diagnosed with anterior epistaxis were included. Patients were excluded if they were unable to consent, do not have a valid telephone number, pregnant women, prisoners, cognitively impaired individuals, diagnosis of posterior epistaxis, major trauma, bleeding disorder (such as thrombocytopenia or hemophilia), hemodynamically unstable, or had a known hypersensitivity to study medication.

Patients were randomly assigned to tranexamic acid treatment group or placebo group. After consenting, patients received TXA (100 mg/1mL) or 0.9% sodium chloride (1 mL) in to the affected nostril(s) via intranasal atomization device. If bleeding did not cease, two repeat doses were allowed and after twenty minutes of continued bleeding the study physician could treat with any additional treatment options. Patients were contacted via telephone within one week to inquire about incidences of re-bleeding or any complications.

Arms:
arm 1: TXA (100 mg/1mL) sprayed in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s). arm 2: 0.9% Sodium Chloride (1mL) in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).

Interventions: intervention 1: Tranexamic Acid intervention 2: 0.9% Sodium Chloride
Intervention descriptions: intervention 1: TXA (100 mg/1mL) in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s). intervention 2: 0.9% Sodium Chloride (1mL) in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).

Protocol document:
Prot_ICF_000.pdf: 
PROTOCOL TITLE: Topical Intranasal Tranexamic acid for Epistaxis in the 
Emergency Department 
 
Page 1 of 13 
 
Revised February 6, 2017 
1) Protocol Title 
Topical Intranasal Tranexamic Acid for Epistaxis in the Emergency 
Department 
02/06/2017 
2) Author of Protocol 
     UC Davis Researcher: 
         Aimee Moulin, MD  
Brian Dang, PharmD  
         Brittany Traylor, PharmD 
Christopher Adams, PharmD  
         Verena Schandera, MD  
         Howard McKinney Jr, PharmD 
         James Catlin, PharmD 
 
3) IRB Review History 
This protocol has not been submitted for review by an external IRB.  
4) Objectives 
Determine the efficacy and safety of topical intranasal tranexamic acid for 
patients with epistaxis that present to the emergency department.  
The primary outcome of the study will be the time to control of bleeding 
after the administration of tranexamic acid.  The secondary outcomes will be 
the length of stay in the emergency department, re-bleeding within first 24 
hours and one week.  Safety endpoints will include the incidence of 
thromboembolic events within one week and the incidence of any other 
drug-related adverse event. 
The hypothesis is that topical administration of tranexamic acid  will have 
comparable if not better time to control of bleeding, length of stay in the 
emergency department, re-bleeding at 24 hours and one week as well as 
minimal adverse effects compared to placebo.  
5) Background 
 
Epistaxis is defined as a nasal bleed of any cause, and is a commonly occurring 
condition that is usually self-limiting and rarely requires medical attention.  Nares 
are highly vascularized mucosa with intricate folds and irregularities in the interior 
surface, and blood vessels closest to the surface of the mucosa are most prone to 
breakage and rupture. 1-2  The majority of epistaxis occurs anteriorly near the 
Kiesselbach’s plexus; however, posterior epistaxis, which occurs at a lower 
incidence, usually occurs around the sphenopalatine artery and may result in airway 
compromise and aspiration of blood. 1-3  The causes of epistaxis are often due to 
mucosa dryness/irritation, nose picking, or facial traumas.  Additionally, there are 


PROTOCOL TITLE: Topical Intranasal Tranexamic acid for Epistaxis in the 
Emergency Department 
 
Page 2 of 13 
 
Revised February 6, 2017 
disease states that place patients at a higher risk of epistaxis such as blood dyscrasia 
(i.e. platelet disorders), hemophilia, neoplasms or other disease states that require 
anticoagulants (i.e. warfarin, heparin, etc.).1-2  It is estimated that epistaxis results in 
4,500,000 emergency department visits per year throughout the United States.3  
 
The standard of care and initial treatment of epistaxis is to applying direct pressure 
to the front of the nose.  For patients that require additional medical intervention, 
the currently recommended treatment options include chemical or electrical cautery, 
nasal packing, hemostatic foams and gels, and topical vasoconstrictive agents.4-6  
Silver nitrate sticks applied to the location of the bleed is the usual method for 
chemical cauterization; however, the complications from this procedure are 
rhinorrhea, crusting, ulceration and possibly even perforation of the septum.  Nasal 
packing with gauze or nasal tampons can also be performed to mitigate the 
bleeding, although this procedure may have complications such as the development 
of bacterial infections since the nasal packing becomes a viable living environment 
for bacteria.  Additionally, extraction of the packing may result in the removal of 
the formed clot and could cause resumption of epistaxis.  A more effective way to 
prevent re-bleeding is the use of hemostatic agents such as Surgicel®, Gelfoam®, 
and Avitene® which promote thrombogenesis and can be left in the nares.  
Additional treatment options are topical vasoconstrictive agents, such as 
oxymetazoline, which stimulates alpha adrenergic receptors in the nares resulting in 
vasoconstriction of the arteries and reduction of bleeding.  Topical vasoconstrictors 
are usually not effective alone and are often used in combination with other 
modalities.  Over use of vasoconstrictive agents may also result in worsening of 
epistaxis.  Due to the pitfalls of these treatment options, tranexamic acid may be 
considered an attractive option.  
 
Tranexamic acid (TXA) has been used in a variety of different hemorrhagic disease 
states. TXA is FDA approved for treatment of menorrhagia and tooth extraction for 
hemophilia patients7; however, there are many off-label uses of this drug especially 
for surgical and trauma patients.  TXA is a synthetic amino acid that reversibly 
blocks the lysine binding site on plasminogen.7 When this happens plasminogen is 
still converted to plasmin but has no proteolytic activity; therefore, TXA allows for 
the stabilization of a clot and prevents clot degradation. TXA is available as a 100 
mg/mL intravenous solution as well as a 650 mg oral tablet.  The half-life of TXA 
is between 2 to 11 hours and is excreted in the urine primarily as unchanged drug.7-8  
TXA is a well-tolerated drug with minimal adverse effects. Thromboembolic events 
are reported rarely;  <1% occurrence for all formulations.7-8  Other reported adverse 
effects include diarrhea, vomiting, and visual disturbances.7-8  
 
TXA has been used in previous studies and case reports of epistaxis. White et. al. 
used oral TXA for the treatment of epistaxis.9   Patients received TXA 1,000 mg by 
mouth three times a day for 10 days.  The result of the trial showed that oral TXA 
reduced the amount of mild re-bleeds.  Adverse events from oral TXA were 
minimal, but it was noted that one person developed superficial thrombophlebitis of 


PROTOCOL TITLE: Topical Intranasal Tranexamic acid for Epistaxis in the 
Emergency Department 
 
Page 3 of 13 
 
Revised February 6, 2017 
both legs following discharge from the hospital. Another study by Tibbelin et. al. 
used TXA gel (1,500 mg/15 mL) applied to the nasal cavity once for ongoing 
nosebleeds.10   The study found no difference in resolution of bleeding within 30 
minutes or re-bleeding at 3 and 8 days; however, the TXA group had patients with 
more moderate and severe bleeds than the placebo group (P<0.01).  There were no 
adverse events observed in their study.  A more recent study by Zahed et. al. used a 
cotton pledget soaked in 500 mg/5 mL of TXA and then anteriorly packed into the 
nares.11   The results of the study showed that more patients had resolution of 
bleeding within ten minutes, more patients were discharged from the hospital at two 
hours, and there were fewer incidents of re-bleeding at 24 hours and at one week. 
No drug-related adverse events occurred during the study.  From this data, we can 
extrapolate that the use of TXA seems to be beneficial for epistaxis with minimal 
risk of adverse events for patients.  
 
In this study, TXA will be applied topically into the affected nares of patients with 
epistaxis.  The advantage of topical TXA compared to nasal packing is that it is a 
quick, simple procedure that can be performed by a physician.  Additionally, 
minimal manipulation of the nostrils is required and the risk of removing or 
disrupting the forming clot is also minimal.  The goal of this study is to determine 
the efficacy and safety of topical TXA for patients with epistaxis that present to the 
emergency department. 
 
6) Inclusion and Exclusion Criteria 
Data will be prospectively collected from patients aged 18 years of age or 
older that are seen in the emergency department and diagnosed with anterior 
epistaxis.  Patients that will be excluded are those unable to consent, do not 
have a valid telephone number, pregnant women, prisoners, cognitively 
impaired individuals, diagnosis of posterior epistaxis, major trauma, 
bleeding disorder such as thrombocytopenia or hemophilia, 
hemodynamically unstable, and a known hypersensitivity to study 
medication.  
Patients will be screened for inclusion and exclusion criteria once patients 
have been assigned a room/location in the emergency department.  
Screening of patients will be done by the Emergency Medicine Research 
Associate Program (EMRAP), medical staff, and study investigators.  The 
study investigators will perform informed consent of potential subjects and 
enrollment in the study.  
7) Number of Subjects 
a) Study- Wide: 
Not applicable, as this is a single-center study.  
b) Local: 


PROTOCOL TITLE: Topical Intranasal Tranexamic acid for Epistaxis in the 
Emergency Department 
 
Page 4 of 13 
 
Revised February 6, 2017 
All patients that have signed the consent form will be enrolled in the trial. 
We estimate that we will enroll a total of 70 patients in a 1:1 ratio in the 
study group to placebo group.  Assuming time to control of bleed for the 
TXA group to be 10 minutes (SD ± 5 minutes) and the placebo group to 
be 15 minutes, the study will need to enroll 16 patients in each arm to 
obtain 80% power with an alpha of 0.05.   
 
8) Recruitment Methods 
a) Study-Wide: 
Not applicable, as this is a single-center study  
b) Local: 
Patients that present to the emergency department during the enrollment 
time (Jan 2016 – January 2020) will be asked if they would like to be 
included in the study.  If so the patient will be requested to fill out an 
informed consent form (HRP-502) and HIPAA Authorization Research 
form (see attachment).  
c) HIPAA: 
In order to identify prospective subjects for the study, the screeners and 
investigators will only need to know the primary diagnosis of epistaxis, 
age, and health conditions.  No other health information will be accessed 
without consent.  It would be impractical to get HIPAA Authorization 
prior to looking at diagnosis due to the high volume of patients that 
present at the emergency department.  
All personal health information (PHI) will be de-identified and stored in 
an encrypted file to which only the primary investigator and primary study 
personnel have access.  PHI, electronic, and hard copies will be deleted 
upon completion of the study.  PHI will not be reused or disclosed to any 
other person or entity.  
PHI to be accessed will include name, medical record number, age, 
medication administration record (MAR), laboratory data, patient 
flowsheets, patient history/demographics, medications profile and progress 
notes found within the electronic medical record (EMR).   Name and 
medical record will not be attached to the other described data to minimize 
risk of loss of confidentiality.   
9) Compensation to the Subjects 
 
If a subject is injured as a result of being in this study, the University of California 
will provide necessary medical treatment.  Depending on the circumstances, the 
costs of the treatment may be covered by the University or the study sponsor or may 
be billed to the patient’s insurance company just like other medical costs.  The 


PROTOCOL TITLE: Topical Intranasal Tranexamic acid for Epistaxis in the 
Emergency Department 
 
Page 5 of 13 
 
Revised February 6, 2017 
University and the study sponsor do not normally provide any other form of 
compensation for injury. 
 
10) Study Timelines 
 
Date 
Activity 
December 2015  
UCDMC IRB approval 
February 2016 – January 2020 
Recruitment, data collection 
February 2016 – January 2020 
Data analysis 
November 2016 – January 2017 
First interim analysis 
TBD (at completion of study) 
Study presentation and manuscript preparation 
 
11) Study Endpoints 
 
Primary efficacy endpoint:  
• Time from administration of intervention until control of bleeding  
Secondary efficacy endpoints: 
• Length of stay in the emergency department 
• Re-bleeding within the first 24 hours 
• Re-bleeding within one week  
Safety endpoints 
• Incidence of thromboembolic events  
• Incidence of other drug-related adverse events  
12) Procedures Involved 
Prospective, randomized, single-center, double-blinded, placebo controlled 
study comparing efficacy and safety of topical intranasal tranexamic acid. 
Screening of subjects will be done by EMRAP, medical staff, and study 
investigators.  Once a diagnosis of epistaxis is identified, the research 
personnel will screen for inclusion and exclusion criteria.  If inclusion 
criteria are met, the study investigators will request consent from the patient 
for participation in the study.  
Upon completion of consent, investigator will collect the following baseline 
characteristics: Age, sex, past medical conditions, home medications, 
laboratory values (complete blood count, coagulation values), and pertinent 
home medications.  
Following collection of baseline characteristics, computerized 
randomization will assign patients to either receive topical intranasal TXA 
or placebo. The Investigational Drug Services (IDS) will set up block 
randomization using randomizer.org. IDS will not be involved in 
administration of TXA or placebo to the patient. Both groups will have 


PROTOCOL TITLE: Topical Intranasal Tranexamic acid for Epistaxis in the 
Emergency Department 
 
Page 6 of 13 
 
Revised February 6, 2017 
medical personnel apply direct pressure to both nares prior to starting the 
study and during the treatment period using standard of care procedures 
and/or equipment, with or without an ice pack.  For patients within the two 
study groups, study protocol will then be initiated for whichever study arm 
the patient is randomized to. In case of emergency, the subject’s data will be 
unblinded. 
IDS will be in charge of storage, dispensing, labeling, and distribution of all 
study medications.  IDS standards will be in place to ensure the integrity of 
the study.  
For patients randomized to the TXA treatment arm, medication will be 
prepared as follows: TXA 1-2 mL will be drawn up into intranasal mucosal 
atomization device.   
For patients randomized to the TXA treatment arm, medication will be 
administered as follows: Physician will administer 1 mL (100 mg) to each 
affected nostril(s) via the atomization device.  Additional doses may be 
repeated up to two times to each affected nostril (TXA 100 mg/1 mL) at 
providers’ discretion.  
For patients randomized to the placebo treatment arm, medication will be 
prepared as follows: Normal Saline 1-2 mL will be drawn up into intranasal 
mucosal atomization device.  
For patients randomized to the placebo treatment arm, medications will be 
administered as follows: Physician will administer 1 mL to each affected 
nostril via the atomization device.  Additional doses may be repeated up to 
two times to each affected nostril(s) (Normal Saline 1 mL) at providers’ 
discretion.  
Following 30 minutes following administration of the medications, the 
provider will be allowed to provide additional medical intervention as they 
feel is necessary.  
Patients will be monitored during this time for tolerability and safety.  
Data collected will include: time of administration of drug or 
intervention(s), time to control of bleeding, length of stay in the emergency 
department, additional interventions required, and any incidence of adverse 
events.  Data will be collected on a data collection form (see attached), 
which will then be transcribed into an electronic data form.  
Prior to patient discharge, a valid telephone number will be obtained and 
patients will be informed that they will be contacted via telephone within 
one week to inquire about incidences of re-bleeding or any complications.  
13) Data and/or Specimen Management and Confidentiality 
 
All procedures regarding data management and confidentiality will apply locally at 
UCDMC.  All data for this study will be retrieved and reviewed from electronic 


PROTOCOL TITLE: Topical Intranasal Tranexamic acid for Epistaxis in the 
Emergency Department 
 
Page 7 of 13 
 
Revised February 6, 2017 
medical records and documented on data collection forms.  Patient sensitive 
information will be coded with a unique, anonymous identification number and kept 
on an encrypted UCDMC computer or on the encrypted Research Electronic Data 
Capture (REDCap server) with passwords only accessible by the research personnel 
directly associated with this study.  The code sheet will be kept secure and separate 
from the dataset.  Information will be stored on the UCDMC password-protected 
servers within password-protected electronic folders.  This information will be 
accessible to study personnel only.  Any patient-sensitive information on hard 
copies will be locked and stored in a work area accessible only to authorized study 
personnel.  
 
Upon completion of the full-scale research study, all identifiers in hard copy format 
will be disposed of in the patient confidentiality bins and later shredded.  Electronic 
data will be permanently deleted from any UCDMC computers and the REDCap 
server. 
 
14) Data and/or Specimen Banking 
No biological specimens will be banked for later use.  All data information 
will be banked for a future study. All patient identifiers will be stripped 
from the data collected and only anonymous identifiers will be kept.  Data 
will be stored on an encrypted UCDMC computer Data will be kept until the 
completion of a larger study.  Data will not be released to any other entity 
outside of UCDMC.  
 
15) Provisions to Monitor the Data to Ensure the Safety of Subjects 
The study investigators will review data at 15%, 25%, 50%, and 75% of 
enrollment period to ensure patient safety.  Upon findings of increased 
potential for patient harm or adverse events, the study investigators will 
report findings to IRB immediately.  The study investigators will review 
documentation of adverse events noted during the treatment timeframe as 
well as during one week follow-up phone calls.  If over 50% of the patient 
population requires emergent medical attention that is directly related to 
study medication, the study will be suspended until analysis of adverse 
event is complete.  
16) Withdrawal of Subjects 
Subjects have the right to withdraw from the study at any time. Subjects 
may withdraw from the study by informing the investigator and/or the 
treating physician.  
Subjects may be withdrawn from the research without their consent if there 
are any major deviations from study protocol that jeopardizes the integrity 
of the study. This may include but is not limited to: incorrect dose of study 


PROTOCOL TITLE: Topical Intranasal Tranexamic acid for Epistaxis in the 
Emergency Department 
 
Page 8 of 13 
 
Revised February 6, 2017 
medication, incorrect administration of study medication, incomplete 
documentation, and inability to contact patient during follow-up.  
 
17) Risks to Subjects 
Reasonably foreseeable risks associated with intranasal administration are 
nasal irritation and allergic dermatitis.  Due to the small volume and amount 
of intranasal TXA that will be used, we do not anticipate any side effects of 
parenteral TXA to be associated with intranasal TXA.  
Foreseeable economic risk may be due to re-admission to the emergency 
department or hospital due to re-bleeding.  
For both arms of the study, if epistaxis continues even after administration 
of TXA or placebo the risk are blood volume loss which may cause anemia, 
longer length of stay in the ED, requirement for additional interventions, and 
patient discomfort.  
No foreseeable psychological or social risk.  
 
18) Potential Benefits to Subjects 
Direct potential benefits to the patients may be faster control of bleeding, 
decreasing need for invasive procedure, decrease risk of re-bleed, faster time 
to discharge, and fewer adverse effects.  
 
19) Vulnerable Populations 
This study will not include vulnerable populations. 
 
20) Multi-Site Research 
This study will only be a single-center study.  


PROTOCOL TITLE: Topical Intranasal Tranexamic acid for Epistaxis in the 
Emergency Department 
 
Page 9 of 13 
 
Revised February 6, 2017 
21) Community-Based Participatory Research 
 
The community has not and will not be involved in the development of this research 
design. 
 
22) Sharing of Results with Subjects 
 
Research results will not be provided to the subjects involved. 
 
23) Setting 
 
Research will be conducted inside the emergency department at the University of 
California, Davis Medical Center (UCDMC) located at 2315 Stockton Blvd, 
Sacramento, CA 95817.  Investigators will identify patients and recruit potential 
patients inside the emergency department.  All medication preparation, medication 
administration, and procedures will be performed by the IDS or within the 
emergency department.  
 
No community advisory board will be involved with this study.  
 
24) Resources Available 
 
Aimee Moulin, M.D. is currently an attending physician in the Emergency 
Department as well as the Assistant Emergency Medicine Residency Program 
Director, Coordinator of Intern Rotations, and Assistant Professor at for the UC 
Davis School of Medicine.  Dr. Moulin received her Doctorate of Medicine at the 
University of Southern California and completed her emergency medicine residency 
at USC + LA County Medical Center.  Dr. Moulin has had several years of clinical 
experience in the UC Davis Emergency Department providing clinical care as well 
as research support identifying, and participating in clinical research.  In addition, 
Dr. Moulin has had experience in quality improvement both as the Quality 
Improvement Director for the ED at Sutter Sacramento and through quality 
improvement projects involving faculty from the Department of Psychiatry and the 
Psychiatric Evaluation Service at UCDMC.  Dr. Moulin also serves as a 
board/committee member for many different professional organizations including 
the California American College of Emergency Physicians, Western Journal of 
Emergency Medicine, Emergency Care Psychiatric Committee for the Sierra 
Sacramento Valley Medical Society, and the California Office of Statewide Health 
Planning and Development.  Additionally, Dr. Moulin has had multiple articles 
published in journals including: Western Journal of Emergency Medicine, 
American Journal of Emergency Medicine, and the Journal of Emergency 
Medicine. 
 


PROTOCOL TITLE: Topical Intranasal Tranexamic acid for Epistaxis in the 
Emergency Department 
 
Page 10 of 13 
 
Revised February 6, 2017 
Brittany Traylor, Pharm.D., BCPS is the director for the PGY2 Emergency 
Medicine Pharmacy Residency at UCDMC.  Dr. Traylor joined the UCDMC team 
in 2012 following her PGY2 training at The University of Arizona Medical Center 
in Tucson, Arizona in emergency medicine.  Dr. Traylor is currently responsible for 
the oversight of planning, implementing and management of clinical pharmacy 
practice in the emergency department, assuring efficient and effective clinical 
services among ED pharmacists, residents, and students.  In addition to her 
responsibilities in the ED at UCDMC, she has since obtained faculty positions at 
UC San Francisco School of Pharmacy as a Health Sciences Assistant Professor. In 
2013, Dr. Traylor was recognized by her colleagues by being awarded the 
Pharmacy Service Excellence Award. 
 
Christopher B. Adams, Pharm.D. is currently an Emergency Department clinical 
pharmacist at UCDMC.  During his formal pharmacy education he was a co-
investigator evaluating diagnostic criteria in heart failure patients.  His research 
efforts during his residency training culminated in a presentation at the Western 
States Pharmacy Residency Conference, an abstract published in Clinical 
Toxicology (DOI: 10.3109/15563650.2014.940163) and poster presentations at the 
ASHP Midyear Clinical Meeting and Exposition (Dec 2011 and Dec 2014), United 
Healthcare Consortium Conference (Dec 2012), The ACCP Annual Meeting (Oct 
2013) and the America Academy of Clinical Toxicology’s Annual Meeting of the 
North American Congress of Clinical Toxicology (Oct 2014).  Dr. Adams was 
awarded the 2014 ASHP Pharmacy Resident Practice-Based Research Grants for 
his work on “Survey of Emergency Medicine Pharmacy Education Opportunities 
for Students and Residents” (doi: 10.1310/hpj5008-690) and was a co-authored on 
an editorial entitled “Student Commentary: Purpose and Impact of Introductory 
Pharmacy Practice Experiences,” which was accepted for publication in 
Pharmacotherapy in 2011. 
 
Verena Schandera, M.D. is currently a Post-Graduate Year Two Emergency 
Medicine Resident at UCDMC.  Dr. Schandera completed her Bachelors of Science 
in Human Biology and also completed her Doctorate of Medicine at the University 
of California San Diego (UCSD).  During medical school, she was involved in 
clinical research with the UCSD Neuroscience Department; which involved 
measuring hippocampal volume in children with cystinosis and evaluating memory 
function. Dr. Schandera presented her findings from this study at the UCDS 
Summer Research Conference.  While at UCDMC, Dr. Schandera has been 
involved in quality improvement projects in the Emergency Department looking at 
safe patient sign outs.   
 
Howard McKinney Jr, Pharm.D. is currently a clinical pharmacists in the 
emergency department at UCDMC. Dr. McKinney completed his Bachelor of Arts 
with a major in biology and minor in Spanish literature at the University of 
California San Diego and completed his Doctorate of Pharmacy at the University of 
California San Francisco. Dr. McKinney was also one of the founding staff 


PROTOCOL TITLE: Topical Intranasal Tranexamic acid for Epistaxis in the 
Emergency Department 
 
Page 11 of 13 
 
Revised February 6, 2017 
members of the San Francisco Regional Poison Control Center, a Poison 
Information Specialist, and a member of the Board of Directors for the American 
Board of Applied Toxicology (ABAT). In addition, Dr. McKinney is also a member 
of the American Academy of Clinical Toxicology, International Society of 
Toxicology, and North American Society of Toxicology.  
 
James Catlin Pharm.D. is currently a Post-Graduate Year One Pharmacy resident at 
UCDMC. Dr. Catlin received his Doctorate of Pharmacy at the University of 
Florida. After completion of his PGY-1 year, Dr. Catlin will be the incoming PGY-
2 Emergency Medicine Pharmacy resident 2016-2017. During his PGY-1 year, he 
completed his retrospective study regarding initial dose of diuretics for patients with 
heart failure that present to the emergency department. His results were presented at 
the Western States Conference in San Diego, CA in May 2016.  
 
25) Prior Approvals 
This study has not had prior approvals.  
26) Provisions to Protect the Privacy Interests of Subjects 
All steps will be taken to ensure privacy interest of the patient. Patients will 
be informed of their rights to place limits on whom they interact or whom 
they provide personal information to.  It is within their right to request any 
research personnel to be removed or become involved with their care during 
the treatment period.  
All healthcare professionals and research personnel involved in the patient’s 
care are obligated to answer any questions or concerns the patient may have 
during the treatment period and into the follow-up period.  
Research team will be permitted to access patient information that pertains 
to the care of the patient or relevant to the study’s objectives after the 
consent and HIPAA forms are signed by the patient.  
27) Compensation for Research-Related Injury 
Due to minimal risk of research-related injury, no compensation will be 
provided.  
28) Economic Burden to Subjects 
Subjects are responsible for all medical care outside of study medication 
cost and supply.  
29) Consent Process 
 
The consent process will take place within the emergency department.  
Once prospective subjects are identified and all criteria are met, investigator will 
obtain consent as soon as possible.  Since this study will require access to personal 
health information, subjects are required to sign a HIPAA Authorization for 


PROTOCOL TITLE: Topical Intranasal Tranexamic acid for Epistaxis in the 
Emergency Department 
 
Page 12 of 13 
 
Revised February 6, 2017 
Research form at the time of consent.  For the enrollment of non-English speaking 
subjects, the study will follow HRP-090 SOP – Informed Consent Process for 
Research.   
 
30) Process to Document Consent in Writing 
 
The study will follow the SOP: Written Documentation of Consent.  Consent for 
participation in this study will be documented by the attached HRP-502 form. 
Following agreement of consent, paper document will be filed in patient’s unique 
identifier folder. 
 
31) Drugs or Devices 
 
☒ I confirm that all investigational drugs will be received by the Investigational 
Drug Service (IDS).  The IDS will store, handle, and administer those drugs so 
that they will be used only on subjects and be used only by authorized 
investigators. 
 
☒ I confirm that all investigational devices will be labelled in accordance with 
FDA regulations and stored and dispensed in such a manner that they will be used 
only on subjects and be used only by authorized investigators. 
References 
 
1. Morgan DJ, Kellerman R. Epistaxis: evaluation and treatment. Prim Care. 
2014;41(1):63-73. 
2. Dunn CJ, Goa KL. Tranexamic acid: a review of its use in surgery and other 
indications. Drugs. 1999;57(6):1005-32. 
3. Pallin DJ, Chng YM, Mckay MP, Emond JA, Pelletier AJ, Camargo CA. 
Epidemiology of epistaxis in US emergency departments, 1992 to 2001. Ann 
Emerg Med. 2005;46(1):77-81. 
4. Kucik CJ, Clenney T. Management of epistaxis. Am Fam Physician. 
2005;71(2):305-11. 
5. Villwock JA, Jones K. Recent trends in epistaxis management in the United 
States: 2008-2010. JAMA Otolaryngol Head Neck Surg. 2013;139(12):1279-84. 
6. Singer AJ, Blanda M, Cronin K, et al. Comparison of nasal tampons for the 
treatment of epistaxis in the emergency department: a randomized controlled trial. 
Ann Emerg Med. 2005;45(2):134-9. 
7. Lexicomp Online®, Hudson, Ohio: Lexi-Comp, Inc.; August 28, 2015. 
8. Tranexamic acid [package insert]. Acella Pharmaceutals, LLC. Alpharetta, Ga.  
9. White A, O'reilly BF. Oral tranexamic acid in the management of epistaxis. Clin 
Otolaryngol Allied Sci. 1988;13(1):11-6. 


PROTOCOL TITLE: Topical Intranasal Tranexamic acid for Epistaxis in the 
Emergency Department 
 
Page 13 of 13 
 
Revised February 6, 2017 
10. Tibbelin A, Aust R, Bende M, et al. Effect of local tranexamic acid gel in the 
treatment of epistaxis. ORL J Otorhinolaryngol Relat Spec. 1995;57(4):207-9. 
11. Zahed R, Moharamzadeh P, Alizadeharasi S, Ghasemi A, Saeedi M. A new and 
rapid method for epistaxis treatment using injectable form of tranexamic acid 
topically: a randomized controlled trial. Am J Emerg Med. 2013;31(9):1389-92. 
12. Utkewicz MD, Brunetti L, Awad NI. Epistaxis complicated by rivaroxaban 
managed with topical tranexamic acid: case report and literature review. Am J 
Emerg Med. 2015 
13. Klepfish A, Berrebi A, Schattner A. Intranasal tranexamic acid treatment for 
severe epistaxis in hereditary hemorrhagic telangiectasia. Arch Intern Med 
2001;161:767-767. 
14. Aguilera X, Martínez-zapata MJ, Hinarejos P, et al. Topical and intravenous 
tranexamic acid reduce blood loss compared to routine hemostasis in total knee 
arthroplasty: a multicenter, randomized, controlled trial. Arch Orthop Trauma 
Surg. 2015;135(7):1017-25. 
15. Waldow T, Szlapka M, Haferkorn H, et. al. Prospective clinical trial on dosage 
optimizing of tranexamic acid in non-emergency cardiac surgery procedures. Clin 
Hem Micro 2013;55:457-468.  
16. Wolfe TR, Braude DA. Intranasal Medication Delivery for Children: A Brief 
Review and Update. Pediatrics 2010;126:532-537.  
 
 


Permission to Take Part in a Human Research Study 
Page 1 of 7 
Version 2-6-17 
For IRB Use  
 
 
 
 
 
 
 
Document Revision Date:July 22, 2015 
 
Title of research study: Topical Intranasal Tranexamic Acid for Epistaxis in the 
Emergency Department 
Investigator: Aimee Moulin, MD, Brittany Traylor, PharmD, Christopher Adams, PharmD, 
Verena Schandera, MD, Howard McKinney Jr, PharmD, and James Catlin, PharmD 
Why am I being invited to take part in a research study? 
We invite you to take part in a research study because you have presented to the emergency 
department with a nosebleed.  
What should I know about a research study? 
Experimental Subject's Bill of Rights  
• Someone will explain this research study to you, including: 
o The nature and purpose of the research study. 
o The procedures to be followed. 
o Any drug or device to be used. 
o Any common or important discomforts and risks. 
o Any benefits you might expect. 
o Other procedures, drugs, or devices that might be helpful, and their risks and 
benefits compared to this study.  
o Medical treatment, if any, that is available for complications.  
• Whether or not you take part is up to you. 
• You can choose without force, fraud, deceit, duress, coercion, or undue influence. 
• You can choose not to take part. 
• You can agree to take part now and later change your mind. 
• Whatever you decide it will not be held against you. 
• You can ask all the questions you want before you decide. 
• If you agree to take part, you will be given a signed and dated copy of this document.  
Who can I talk to? 
If you have questions, concerns, or complaints, or think the research has hurt you, you may talk 
to the Principal Investigator or the Research Coordinator at (916-734-6498). In the case of an 
emergency, dial 911 from any phone. 
 
For non-emergency issues you can call the UCDMC Hospital Operator (916-734-2011), tell the 
Operator you are participating in a research study and you wish to talk to Emergency Department 
Clinical Pharmacist or you may call (916) 703-6110. Emergency Department Clinical Pharmacist is 
available from 7 am to 1 am, 7 days a week including holidays. If you are unable to contact a 
pharmacist, you may leave a voicemail and someone will return your call promptly. In the case of an 
emergency, dial 911 from any phone. 
This research has been reviewed and approved by an Institutional Review Board (“IRB”). 
Information to help you understand research is on-line at 


Permission to Take Part in a Human Research Study 
Page 2 of 7 
Version 2-6-17 
For IRB Use  
 
 
 
 
 
 
 
Document Revision Date:July 22, 2015 
 
http://www.research.ucdavis.edu/policiescompliance/irb-admin/.You may talk to a IRB staff 
member at (916) 703-9151, IRBAdmin@ucdmc.ucdavis.edu, or 2921 Stockton Blvd, Suite 
1400, Room 1429, Sacramento, CA 95817 for any of the following: 
• Your questions, concerns, or complaints are not being answered by the research team. 
• You cannot reach the research team. 
• You want to talk to someone besides the research team. 
• You have questions about your rights as a research subject. 
• You want to get information or provide input about this research. 
Why is this research being done? 
We are interested in evaluating the benefits of topical intranasal tranexamic acid for patients 
with epistaxis (nosebleeds). Tranexamic acid is not currently approved by the FDA for the 
treatment of nosebleeds.  
How long will the research last? 
We expect that you will be in this research study for one week following your discharge from 
the emergency department.  
How many people will be studied? 
This study will only be conducted at UCDMC and we expect to enroll about 70 people. 
What are my responsibilities if I take part in this research? 
If you take part in this research, you will be responsible for reporting back to emergency 
department if you have a major nosebleed lasting over 20 minutes after discharge and 
informing the study investigator of any adverse events.  
What happens if I do not want to be in this research? 
You may decide not to take part in the research and it will not be held against you. 
Instead of being in this research study, your choices may include: continue standard treatment 
at the discretion of the caring provider.  
Potential risk of alternatives includes but is not limited to: more invasive procedure, nasal 
discomfort, prolonged bleeding, infection, and longer time to discharge from the emergency 
department.  
Potential benefits of alternatives include but are not limited to: faster resolution of bleed, faster 
time to discharge from the emergency department, and less discomfort.   
What happens if I say yes, but I change my mind later? 
You can leave the research at any time and it will not be held against you. All data that has 
been collected up until the time you decided to withdraw consent will still be used but no 
further data will be collect. 
 


Permission to Take Part in a Human Research Study 
Page 3 of 7 
Version 2-6-17 
For IRB Use  
 
 
 
 
 
 
 
Document Revision Date:July 22, 2015 
 
What happens if I say yes, I want to be in this research? 
• If you agree to be in the study, below is a diagram illustrating the flow and pathways of 
the study.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• If you meet the inclusion criteria and agree to be in the study, the treatment you get will 
be chosen by chance, like flipping a coin. Neither you nor the study doctor will choose 
what treatment you get. You will have an equal chance of being given each treatment. 
• In addition to direct pressure to the nares, you will receive tranexamic acid or placebo, 
which will be administered as a spray into the affected nostril(s). The study drug or 
placebo will be administered by an intranasal atomization device, which will spray a fine 
mist into your nostril(s). The study doctor will have the option of repeating this step twice 
during the first 30 minutes if bleeding is not controlled. The repeat doses will be the 
same as the initial dose.  
Randomization 
Tranexamic Acid 
(TXA) 
Direct pressure + TXA 100mg/1 
mL to affected nostril(s) via 
intranasal atomizer  
Screening and enrollment 
Placebo 
Direct pressure + Normal Saline 
1 mL to affected nostril(s) via 
intranasal atomizer  
Repeat initial dose x 2 
If bleeding not controlled 
Repeat initial dose x 2  
If bleeding not controlled 
Standard of Care 
If bleeding not controlled 
Follow-up 
via telephone 
1 week  
30 mins 


Permission to Take Part in a Human Research Study 
Page 4 of 7 
Version 2-6-17 
For IRB Use  
 
 
 
 
 
 
 
Document Revision Date:July 22, 2015 
 
• If you are still bleeding after 30 minutes from the start of treatment, the study doctor 
may decide to perform other treatment options to stop the bleeding. Some standard 
treatment options are chemical or electrical cautery, nasal packing, hemostatic foams or 
gels, and/or topical vasoconstrictive agents.  
You will be contacted within a week from your initial visit via telephone for follow-up. 
The investigator will ask you questions regarding re-bleeding occurrences and if you 
have experienced any side effects.  
• We estimate that the length of the treatment period will be around 30 minutes; however, 
your duration of stay in the emergency department may vary depending if you require 
additional treatment or have other medical needs. 
• The doctor may order blood draws prior to the start of the study and may order 
additional blood draws at his/her discretion. The usual blood volume for a blood draw is 
approximately 6 mL.  
• During the study you may interact with many healthcare providers in the emergency 
department such as but not limited to doctors, nurses, and pharmacists.  
• The study will only be conducted at UCDMC during your stay in the emergency 
department.  
• In case of an emergency, your study doctor can find out which treatment you were 
given.  
 
Is there any way being in this study could be bad for me? 
Tranexamic acid is a medication that is generally very well tolerated and many patients do not 
have any side effect to the drugs at all. Some rare side effects that have been reported are: 
nausea, vomiting, and diarrhea. Side effects that happen even at a lower frequency are: blood 
clots, visual changes, and seizures. If the bleeding continues even after administration of TXA 
the risk are blood volume loss which may cause anemia, longer length of stay in the ED, 
requirement for additional interventions, and patient discomfort. 
There is a potential risk to privacy; however, the research team takes your privacy very 
seriously and will keep confidentiality as a top priority. The data collected will be de-identified 
and password-protected.  
Your economic risks for participating in this study is that you may have to come back to the 
emergency department or seek medical attention if you have a re-bleed that last over 20 
minutes after discharge.   
In addition to these risks, this research may hurt you in ways that are unknown. These may be 
a minor inconvenience or may be so severe as to cause death. 
Risk of Ranodmization – This study involves two different treatments. Some people in the 
study will get a placebo instead of TXA. There is a risk that the treatment you receive may be 
inferior or may cause more side effects than the other treatment.  


Permission to Take Part in a Human Research Study 
Page 5 of 7 
Version 2-6-17 
For IRB Use  
 
 
 
 
 
 
 
Document Revision Date:July 22, 2015 
 
Will being in this study help me in any way? 
We cannot promise any benefits to you or others from your taking part in this research. 
However, possible benefits include faster resolution of nose bleed, faster time to discharge 
from emergency department, and decreasing your chances of having a re-bleed.  
What happens to the information collected for the research? 
Efforts will be made to limit use or disclosure of your personal information, including research 
study and medical records, to people who have a need to review this information. We cannot 
promise complete confidentiality. Organizations that may inspect and copy your information 
include the IRB and other University of California representatives responsible for the 
management or oversight of this study.  
During your participation in this research, data will be collected about you. The de-identified 
data and any specimens, such as blood or tissue, are taken from you for this study; they will 
become the property of the University of California. The specimens may be used in this 
research, may be used in other research, and may be shared with other organizations. The 
specimens could lead to discoveries or inventions that may be of value to the University of 
California or to other organizations. Under state law you do not have any right to money or 
other compensation stemming from products that may be developed from the specimens. 
 
The sponsor, monitors, auditors, the IRB, the Food and Drug Administration will be granted 
direct access to your research records to conduct and oversee the study. We may publish the 
results of this research. However, we will keep your name and other identifying information 
confidential. 
If we access protected health information (e.g., your medical record), you will be asked to sign 
a separate form to give your permission. Your medical records may become part of the 
research record.  If that happens, your research records may be looked at by the sponsor of 
this study and government agencies or other groups associated with the study.  They may not 
copy or take your personal health information from your medical records unless permitted or 
required by law. 
Federal law provides additional protections of your medical records and related health 
information. These are described in the UC Davis Health System Notice of Privacy Practices 
(http://www.ucdmc.ucdavis.edu/compliance/pdf/notice.pdf) and in an attached document. 
Can I be removed from the research without my OK? 
The person in charge of the research study or the sponsor can remove you from the research 
study without your approval. Possible reasons for removal include incorrect dose of study 
medication, incorrect administration of study medication, incomplete documentation, and 
inability to contact patient during follow-up.  
We will tell you about any new information that may affect your health, welfare, or choice to 
stay in the research. 


Permission to Take Part in a Human Research Study 
Page 6 of 7 
Version 2-6-17 
For IRB Use  
 
 
 
 
 
 
 
Document Revision Date:July 22, 2015 
 
What else do I need to know? 
The cost of tranexamic acid will be covered by the study but you or your health plan will be 
billed for the costs of routine medical care you received during the study. These cost may 
include operating room fees, other pharmacy charges, treatments, hospitalizations, scans, etc.  
You will be expected to pay for the usual deductibles and co-payments, and for any routine 
care that is not covered. Only the costs of research or experimental procedures will be paid by 
the study. You will be charged for standard medical care including but not limited to: diagnostic 
labs, procedures, and medical supplies.  You will not be charged for study medication and the 
medical supplies used to administer these medications.  
For more information about possible costs, please contact the research team. The research 
team can follow UC Davis Uninsured Non-Emergency Estimate Policy (Policy ID 1883) to work 
with their department and Decision Support Services to get you a cost estimate. 
It is important that you promptly tell the person in charge of the research if you believe that you 
have been injured because of taking part in this study. If you are injured as a result of being in 
this study, the University of California will provide necessary medical treatment. Depending on 
the circumstances, the costs of the treatment may be covered by University or the study 
sponsor or may be billed to your insurance company just like other medical costs. The 
University and the study sponsor do not normally provide any other form of compensation for 
injury.  For more information about compensation, you may call the IRB Administration at (916) 
703-9151 or email at IRBAdmin@ucdmc.ucdavis.edu. 
You will not be compensated for taking part in this study. 
  


Permission to Take Part in a Human Research Study 
Page 7 of 7 
Version 2-6-17 
For IRB Use  
 
 
 
 
 
 
 
Document Revision Date:July 22, 2015 
 
Signature Block for Capable Adult 
Your signature documents your permission to take part in this research. 
 
 
 
Signature of subject 
 
Date 
 
 
Printed name of subject 
 
 
 
Signature of person obtaining consent 
 
Date 
 
 
 
Printed name of person obtaining consent 
 
 
[Add the following block if a witness will observe the consent process. E.g., short form of consent documentation or illiterate subjects.] 
My signature below documents that the information in the consent document and any other written information 
was accurately explained to, and apparently understood by, the subject, and that consent was freely given by the 
subject. 
 
 
 
Signature of witness to consent process 
 
Date 
 
 
Printed name of person witnessing consent process 
 

SAP_001.pdf: 
 
 Statistical Analysis Plan (SAP) 
Atomized Intranasal Tranexamic Acid for Epistaxis in the Emergency Department: 
A Pilot Study (EpisTXA Trial) 
 
 
 
 
Principal investigator 
Aimee Moulin, MD 
Professor of Emergency Medicine 
University of California Davis School of Medicine 
Sacramento, CA 
 
Author 
Brian Dang, PharmD 
University of California Davis Medical Center 
Sacramento, CA 
 
Clinical Trials.gov identifier 
NCT02930941 
 
Version 
1.3 
Date: 
02/06/2017 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
SIGNATURE PAGE 
 
 
Principal Investigator:                    ________________________________ 
                                                             Aimee Moulin, MD 
 
 
Author:                                              ________________________________ 
                                                             Brian Dang, PharmD 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
Contents 
Introduction .................................................................................................................................................. 4 
Study Design ................................................................................................................................................. 4 
Sample size calculation ................................................................................................................................. 6 
Aims and objectives ...................................................................................................................................... 6 
Outcomes ...................................................................................................................................................... 6 
Primary outcome: ..................................................................................................................................... 6 
Secondary outcomes:................................................................................................................................ 6 
Safety outcomes ....................................................................................................................................... 6 
Population and subgroup to be analyzed ..................................................................................................... 6 
Populations: .............................................................................................................................................. 6 
Subgroups: ................................................................................................................................................ 7 
Analyses ........................................................................................................................................................ 7 
Primary outcome ...................................................................................................................................... 7 
Secondary outcome .................................................................................................................................. 7 
Missing data .................................................................................................................................................. 7 
References .................................................................................................................................................... 7 
 
 
 
 
 
 
 
 


 
 
Introduction 
 
The aim of this study is to test the efficacy and safety of nasal atomization of tranexamic acid 
(TXA) for epistaxis at a single centered academic tertiary hospital. This is a randomized 
controlled trial with a primary outcome of time to control of bleeding and secondary outcome of 
length of stay in the ED, rebleeding within 24 hours & one week, and adverse events.  
 
This statistical analysis plan (SAP) will give a more detailed description of the outcomes and 
analysis performed.  
 
Study Design 
This study is a prospective, double-blinded, placebo-controlled pilot study conducted at an 
academic tertiary care medical center with 24-hour emergency medical services. The study will 
be performed at the University of California Davis Medical Center (UCDMC) between February 
18, 2016 and December 31, 2019. The Emergency Department at UCDMC has approximately 
80,000 annual ED visits and is located in Sacramento, California. 
 
Inclusion criteria will be patients greater than or equal to 18 years of age and diagnosed with 
anterior epistaxis.  Patients will be excluded if they were unable to consent, pregnant, prisoners, 
cognitively impaired, diagnosed with posterior epistaxis, major trauma, hemodynamic 
instability, bleeding disorders, and hypersensitivity to the study drug. Patients will be screened 
for inclusion and exclusion criteria once they had been assigned a room/location. The 
Emergency Medicine Research Associate Program (EMRAP), medical staff, and study 
investigators conducted screening for eligible patients.  
 
Randomization will be conducted by the Investigational Drug Services (IDS) using a web-based 
computerized randomization program (randomizer.org1). Randomization will be performed in 
blocks of four. IDS will perform sterile compounding for all study medications. TXA or normal 
saline 6 mL will be placed into a clear 10 mL vial with white labels containing only study 
information. Vials will be placed into a locked refrigerator within the emergency department. 
After obtaining consent, the study kit, which includes a nasal atomizer, syringe, and vials, is 
removed from the fridge in sequential order and delivered to the treating provider. 
 
Following the enrollment of patients, both groups will receive direct pressure to the nares 
applied by a medical professional.  In addition to direct pressure, patients will receive either 
tranexamic acid 100 mg/1 mL or placebo (normal saline 1 mL) to each affected nostril(s) via a 
nasal atomization device.  Additional doses may be repeated up to two times to each affected 
nostril at the discretion of the treating providers. Following 20 minutes from the administration 
of the medications, the provider will be allowed to provide any standard of care medical 


intervention. Prior to discharge, patients will be informed that they would be contacted at 24 
hours and one week to inquire about incidences of rebleeding and any complications. 
 
 
Screening 
 
 
 
 
 
Enrollment 
 
 
  
 
Treatment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Follow-up 
 
 
 
 
 
 
 
 
 
 
 
Presenting to ED with complaint of 
epistaxis 
Direct pressure applied 
Normal Saline 0.9% 1 mL 
per affected nostril (may 
repeat x 2) 
TXA 1 mL per affected 
nostril (may repeat x 2) 
Follow-up 1 week 
Provide overview of trial, process, risk, 
benefits, and consent form 
Exclusion: 
• Unable to consent pregnant 
• Prisoners  
• Cognitively impaired 
• Posterior epistaxis 
• Major trauma 
• Hemodynamic instability 
• Bleeding disorders 
• Hypersensitivity to the study 
Follow-up 24 hours 
Additional treatment if 
necessary 
Additional treatment if 
necessary 
Not interested 


 
Sample size calculation 
Data from a previous trial using topical TXA for epistaxis were used to calculate sample size. 
Zahed and colleagues conducted a prospective randomized control trial using a cotton pledget 
soaked with TXA 500 mg/5 mL and inserted into the bleeding nostril (Am J Emerg Med. 
2013;31(9):1389-92.). This was compared to anterior nasal packing group who were treated 
with a cotton pledget soaked with lidocaine-epinephrine 2% and 1:100,000. Nasal packing was 
removed after three days. The primary end point of the study was bleeding control within 10 
minutes. Bleeding was controlled within 10 mins for 71% (76 of 107) in the TXA group compared 
to 31.2% (34 of 109) in the nasal packing group (OR 2.27; 95% CI 1.68-3.06; P<0.001).  
Based off this study, we assumed that the mean or median time to control of bleeding would be 
10 minutes and assumed that 68% of patients will fall within 5 minutes of that control of 
bleeding time. Previous studies have not reported time to resolution of bleeding. Based on the 
effectiveness of TXA in the Zahed study, we expected to see a 50% difference in time to 
resolution of bleeding between the two groups. In order to detect at 50% (5 minutes) difference 
between groups with a standard deviation of 5 minutes, we will need 16 patients in each group 
to achieve 80% power with a 2-sided α set to 0.05. A total number of 32 patients would be need 
to meet power.  
Aims and objectives 
The study is testing to see if atomized tranexamic acid is effective and safe for the treatment of 
anterior epistaxis.  
Outcomes 
Primary outcome: Time to resolution of bleeding (minutes). Time of resolution of bleeding 
was started after the application of the study drugs.  
Secondary outcomes: 
i. Length of stay in the ED (minutes) 
ii. Rebleeding at 24 hours. Study investigators conducted a phone call follow-up 24 
hours after study enrollment. Patients reported any rebleeding episodes since 
treatment with study drug.  
iii. Rebleeding at 1 week. Study investigators conducted a phone call follow-up 1 
week after study enrollment. Patients reported any rebleeding episodes since 
treatment with study drug. 
Safety outcomes 
iv. Any reported events during ED visit, 24-hour phone call follow-up, and 1 week 
phone call follow-up.  
Population and subgroup to be analyzed 
Populations:  


Intention-to-treat (ITT) for all randomized study subjects.   
Per Protocol (PP) will be used for patients that are missing primary outcomes. 
Subgroups: Due to small sample size, no subgroup analysis will be performed.  
Analyses 
Data that is normally distributed will be reported by mean and standard deviation; whereas, skewed 
data will be reported as median and interquartile range. Descriptive statistics will be used for secondary 
outcomes. SAS® software version 9.4 for Windows®3 will be used for all statistical analysis 
Primary outcome 
The primary outcome will compare time to resolution of bleeding in minutes between the 
treatment and control group.  
Secondary outcome 
Length of stay in the ED in minutes will be compared between treatment and control group. 
Rebleeding within 24 hours and one week will be reported as percentage of patients reported 
bleeding during those time periods in each group. Adverse effects during the treatment period 
and at follow-up will also be reported as percentage reporting a specific adverse event.  
Missing data 
 
No imputations will be made for missing data.  
References 
1. "Research Randomizer." Research Randomizer. N.p., n.d. Web. 1 Feb. 2016. 
2. Zahed R, Moharamzadeh P, Alizadeharasi S, Ghasemi A, Saeedi M. A new and rapid method for 
epistaxis treatment using injectable form of tranexamic acid topically: a randomized controlled 
trial. Am J Emerg Med. 2013;31(9):1389-92. 
3. SAS Institute Inc 2013. SAS/ACCESS® 9.4 Interface to ADABAS: Reference. Cary, NC: SAS Institute 
Inc.