Clinical trial NCT03228914
Conditions: Endoscopic Sinus Surgery Nasal Polyps
Sponsor: The University of Texas Health Science Center, Houston
Start date: 2018-06-14; Completion date: 2018-08-29
Enrollment: 20 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to compare the effects of Oxymetazoline and Epinephrine (which are 2 different nasal decongestants both of which are routinely used before sinus surgery) on blood loss and the surgeon's view of the surgical field during sinus surgery.

Detailed description:

Arms: arm 1: Pledgets will be soaked in 0.05% oxymetazoline solution Two pledgets with the associated medication will be placed into the nasal cavity; one along the floor of the nose and another directed towards the middle meatus. arm 2: Pledgets will be soaked in 1:1000 epinephrine solution Two pledgets with the associated medication will be placed into the nasal cavity; one along the floor of the nose and another directed towards the middle meatus.
Interventions: intervention 1: Oxymetazoline intervention 2: Epinephrine
Intervention descriptions: intervention 1: Pledgets will be soaked in 0.05% oxymetazoline solution Two pledgets with the associated medication will be placed into the nasal cavity; one along the floor of the nose and another directed towards the middle meatus. intervention 2: Pledgets will be soaked in 1:1000 epinephrine solution Two pledgets with the associated medication will be placed into the nasal cavity; one along the floor of the nose and another directed towards the middle meatus.

Protocol documents:
Prot_SAP_000.pdf: 
UT Houston Protocol Template 
Adapted from NIH protocol template and ICH Guidelines 
IRB NUMBEPRag: eHS1Co-fM7S-17-0415 
IRB APPROVAL DATE: 08/02/2017 
 
 
 
 
 
 
 
 
 
 
 
Comparing blood loss and visualization after the preoperative use of topical 0.05% 
Oxymetazoline versus 1:1000 epinephrine prior to endoscopic sinus surgery 
 
NCT03228914 
 
Version Date: 08/02/2017 
 
 


UT Houston Protocol Template 
Adapted from NIH protocol template and ICH Guidelines 
IRB NUMBEPRag: eHS2Co-fM7S-17-0415 
IRB APPROVAL DATE: 08/02/2017 
 
Protocol Title: 
Comparing blood loss and visualization after the preoperative use of topical 
0.05% Oxymetazoline versus 1:1000 epinephrine prior to endoscopic sinus 
surgery. 
Principal Investigator: 
William Yao, MD 
 
Co-Investigators: 
Martin Citardi, MD 
Amber Luong, MD, PhD 
Brett Jensen, MD 
 
Study Coordinator: 
N/A 
 
Population: 
Patients undergoing endoscopic sinus surgery (ESS) for CRS with or 
without nasal polyposis 
 
Number of Sites: 
Single site 
 
Study Duration: 
Study will continue until 50 patients are enrolled, likely 6 months to 1 
year 
Subject Duration: 
Study intervention will only be at the time of surgery. Normal surgery 
post-operative visits will occur with no additional study obligations 
 
 
General Information 
The study will be a single center prospective randomized double blinded study to compare 
blood loss and visualization of the surgical field following the preoperative use of pledgets 
soaked in 0.05% Oxymetazoline solution or 1:1000 concentrated Epinephrine. 
 
Background Information 
The development of functional endoscopic sinus surgery (FESS) in the early 1970s revolutionized the 
treatment of sinus disease by allowing for magnified direct visualization of complex sinus anatomy. FESS 
has now become by far the preferred surgical treatment modality of Otolaryngologist for the treatment 
of chronic sinus disease.8 The goals of FESS are to improve aeration and drainage of the paranasal 
sinuses by the meticulous removal of diseased air cells thereby reducing the frequency of infections.7,8 
Due to the significant vascularity of the area bleeding presents one of the primary challenges in 
endoscopic sinus surgery as even slight hemorrhage can cause a dramatic reduction in visibility of the 
surgical field which can lead to prolonged operative time and increased risk of complications.2,3,5 
 
The use of several topical vasoconstrictors prior to endoscopic sinus surgery including cocaine, 
norepinephrine, epinephrine, phenylephrine and oxymetazoline have been described in the literature.3,5 
Historically topical cocaine was used very commonly but has fallen out of favor given the addictive 
potential and associated side effects of tachycardia, hypertension and enhancement of the excitatory 
effects of epinephrine.3,5,6 The use of phenylephrine, a selective alpha agonist, has also been largely 
abandoned due to its unacceptable side effect profile including hypertensive crisis, cardiopulmonary 
compromise, pulmonary edema, and death. 3,5 


UT Houston Protocol Template 
Adapted from NIH protocol template and ICH Guidelines 
IRB NUMBEPRag: eHS3Co-fM7S-17-0415 
IRB APPROVAL DATE: 08/02/2017 
 
Due to its favorable safety profile the use of Oxymetazoline has become increasingly popular.4,5,6 
However, some authors believe the vasoconstrictive properties of oxymetazoline are inferior which 
could potentially lead to increased intraoperative hemorrhage. Desires for improved control of 
intraoperative hemorrhage and visualization has led to increased interest in the use of concentrated 
epinephrine prior to FESS. 4,5,9,14 
 
Concentrated epinephrine has been demonstrated to be safe when applied topically.5,9 There have been 
reported adverse events and even deaths related to the mistaken submucosal injection of concentrated 
epinephrine.5,9,13,14   This risk can be successfully mitigated with careful preparation as well as dying of 
the more concentrated epinephrine solution with either surgical marking pens or fluorescein strips 
(FULGLO; Akorn Pharmaceuticals, Lake Forest, IL) to differentiate them from local anesthetic intended 
for injection.5,14 When used as intended epinephrine has been demonstrated to have an excellent safety 
profile.3,5,14 To date there have been no studies directly comparing the effects of oxymetazoline and 
epinephrine for preoperative vasoconstriction prior to FESS.3,11 
 
 
 
Objectives 
Aim 1: Compare the Surgical field during functional endoscopic sinus surgery after the use of 
0.05% Oxymetazoline or 1:1000 concentrated Epinephrine for decongestion 
Hypothesis: There will be improved visualization in the concentrated epinephrine arm. 
 
Aim 2: Compare the blood loss functional endoscopic sinus surgery after the preoperative use 
of 0.05% Oxymetazoline or Epinephrine 
Hypothesis: There will be less bleeding in the epinephrine arm 
 
Aim 3: Compare the surgical time to complete one sinus side during functional endoscopic sinus 
surgery after the preoperative use of 0.05% Oxymetazoline or Epinephrine 
Hypothesis: There will be no difference in surgical time 
 
 
Study Design 
The study will be a single center prospective randomized double blinded pilot study to compare 
blood loss and visualization of the surgical field following the preoperative use of pledgets 
soaked in Oxymetazoline or Epinephrine. 
 
The inclusion criteria will be patients undergoing bilateral endoscopic sinus surgery (ESS) in 
which the same sinuses and procedures on both sides are the same for CRS with or without 
nasal polyposis. Exclusion criteria will be pregnancy, known coagulopathy, an international 
normalized ratio greater than 1.3, a partial thromboplastin time greater than 50 seconds, use of 
non-steroidal anti-inflammatory drugs in the last 10 days (2 or more doses), use of any 
antiplatelet agents (eg, warfarin, clopidogrel, berlinta) poorly controlled hypertension with a 


UT Houston Protocol Template 
Adapted from NIH protocol template and ICH Guidelines 
IRB NUMBEPRag: eHS4Co-fM7S-17-0415 
IRB APPROVAL DATE: 08/02/2017 
 
preoperative systolic blood pressure of 160mm Hg or greater or a diastolic blood pressure of 
90mm Hg or greater, or having any adverse reaction to topical epinephrine or oxymetazoline. 
 
The study will be a paired design study with one nasal cavity receiving epinephrine and the 
other receiving oxymetazoline . The 1:1000 epinephrine and oxymetazoline solutions both 
comes in a 30cc vial and each pledget will be wrung out in a similar fashion to keep volume 
administered similar. The side each drug will be placed on will be randomized using a block 
randomization scheme on the day of surgery with a block size of four. Two pledgets with the 
associated medication will be placed into the nasal cavity; one along the floor of the nose and 
another directed towards the middle meatus. 
 
As a part of routine preoperative workup all patients receive preoperative computed 
tomography scans of the paranasal sinuses with a navigation protocol. These scans will be 
assessed using the Lund-Mackay staging system, a standardized radiological grading system 
used to evaluate CT scans of chronic rhinosinusitis patients. The sinonasal mucosa will also be 
scored by the surgeon on the day of surgery using a mucosal grading system we have used 
previously which was modified from a mucosal grading system originally used for grading 
patients with allergic fungal rhinosinusitis.2 
 
The patients will be recruited from the practices of 3 fellowship trained rhinologists within our 
institution. 
 
All data will be deidentified and assigned a random number. Data will be stored on a password 
protected file on a password protected computer. 
Our primary endpoint will be to compare surgical field visualization after the use of epinephrine 
or Oxymetazoline using the Boezaart grading scale, an inexpensive standardized rating scale 
used to analyze surgical field visualization during sinus surgery. The operative field will be rated 
at the conclusion of the procedure by the surgeon. A representative 1 minute video will also be 
selected for each side. These videos will be blindly reviewed and rated by all 3 surgeons using 
the Boezaart scale. 
Our secondary endpoint will be to compare the amount of blood loss use after the use of 
epinephrine or Oxymetazoline. This will be done by subtracting the amount of irrigation used 
from the volume collected in the suction canisters to estimate blood loss. The Neptune 2 Waste 
Management System (NWMS, Stryker, Kalamazoo, Michigan), a closed suction system that 
digitally measures the amount of fluid suctioned will be used for more accurate measuring of 
fluid suctioned. 
 
Both Oxymetazoline and Epinephrine soaked pledgets are routinely used preoperatively before 
sinus surgery both within our institution and nationally. The choice of which is based on 
surgeon preference. Both have well established safety profiles. (Higgins, Korkmaz, Orlandi) 


UT Houston Protocol Template 
Adapted from NIH protocol template and ICH Guidelines 
IRB NUMBEPRag: eHS5Co-fM7S-17-0415 
IRB APPROVAL DATE: 08/02/2017 
 
 
Study Population 
The inclusion criteria will be patients undergoing endoscopic sinus surgery (ESS) for CRS with or 
without nasal polyposis. Exclusion criteria will be pregnancy, known coagulopathy, an 
international normalized ratio greater than 1.3, a partial thromboplastin time greater than 50 
seconds, use of non-steroidal anti-inflammatory drugs in the last 10 days (2 or more doses), 
poorly controlled hypertension with a preoperative systolic blood pressure of 160mm Hg or 
greater or a diastolic blood pressure of 90mm Hg or greater, or having any adverse reaction to 
topical epinephrine or oxymetazoline. 
 
The patients will be recruited from the practices of 3 fellowship trained rhinologists within our 
institution. 
 
Study Procedures 
 
As a part of routine preoperative workup all patients receive preoperative computed tomography scans 
of the paranasal sinuses with a navigation protocol. These scans will be assessed using the Lund-Mackay 
staging system, a standardized radiological grading system used to evaluate CT scans of chronic 
rhinosinusitis patients. The sinonasal mucosa will also be scored by the surgeon on the day of surgery 
using a mucosal grading system. 
 
All patients will undergo general anesthesia using a standardized anesthesia protocol using Propofol and 
inhalational anesthetics. Total intravenous anesthesia will not be used. Preoperative Decadron will not 
be used in patients enrolled in the study. 
 
The patients will have pledgets soaked in epinephrine 1:1,000 in one nasal cavity and pledgets soaked in 
oxymetazoline 0.05% to the contralateral side for topical vasoconstriction and decongestion. Both 
1:1000 epinephrine and oxymetazoline solutions comes in a 30cc vial and each pledget will be 
wrung out in a similar fashion to keep volume administered similar. The solutions will be prepared 
prior to the procedure so that the surgeon will be blinded to which topical vasoconstrictor is used on 
each side. All topical solutions will be dyed with fluorescein strips (FULGLO; Akorn Pharmaceuticals, Lake 
Forest, IL) to differentiate them from local anesthetic intended for injection. Laterality of the study 
medication will be randomized through block randomization with a block size of four. 
 
Following topical vasocontriction, pledgets will be removed and all patients will receive injections of 1% 
lidocaine with epinephrine 1:100,000 into the middle turbinate and sphenopalatine area as is routinely 
performed prior to sinus surgery. Complete functional endoscopic sinus surgery will then be 
performed as indicated using typical sinus surgery instruments. Intraoperative imaging will be 
recorded and deidentified for later review by blinded reviewers. 
The operative field will be rated at the conclusion of the procedure by the surgeon. A 
representative 1 minute video from each side will later be blindly reviewed and rated by all 3 
surgeons using the Boezaart scale. 
 
There will be no additional visits or time commitments for the patients outside of routine post- 
operative follow up. 


UT Houston Protocol Template 
Adapted from NIH protocol template and ICH Guidelines 
IRB NUMBEPRag: eHS6Co-fM7S-17-0415 
IRB APPROVAL DATE: 08/02/2017 
 
Data and Safety Monitoring 
All data will be deidentified and assigned a random number. Moreover, the deidentified data 
will be stored on a password protected file on a password protected computer. 
No adverse events are anticipated. The study should provide no additional risk to the patient. 
 
Any potential adverse events or unanticipated problems will be monitored by the research 
team and reported as discovered. The research team has a pre-scheduled monthly meetings 
where this study will be discussed. 
 
Statistics 
Statistical significance will be defined as less than 0.05. For quantitative data a 2-tailed paired t- 
test will be used.  Categorical data will be compared using the McNemar’s test. For non 
normally distributed data a Wilcoxon rank-sum test will be used. All patients who are 
administered both randomized preoperative topical vasoconstrictors will be included in the 
study. 
 
The blood loss of 355 ± 393mL seen in sevoflurane group from a previous study we performed 
in which we used oxymetazoline was used to calculate sample size.2 With a proposed difference 
of 150ml of blood loss with a targeted power of 0.8 and a targeted Type 1 error rate of 5% a 
sample size of 50 was calculated we will plan to enroll 50 patients. 
 
 
Ethics 
No other IRB approval will be sought. 
 
Informed consent will be obtained by one of the study investigators at the patient’s 
preoperative visit in clinic or in the preoperative waiting area. 
 
All data will be deindentified and assigned a random number. Data will be stored on a password 
protected file on a password protected computer. 
 
Data handling and record keeping 
All data will be deindentified and assigned a random number. Data will be stored on a password 
protected file on a password protected computer in the principal investigators office. All videos 
obtained will be de-identified and kept at the principal investigator’s password protected 
computer in a locked office. 
 
 
Quality control and assurance 
Quality of video data and photographs will be assessed intraoperatively. A Storz representative 
will be available to aid with video equipment if technical difficulties were to occur. 


UT Houston Protocol Template 
Adapted from NIH protocol template and ICH Guidelines 
IRB NUMBEPRag: eHS7Co-fM7S-17-0415 
IRB APPROVAL DATE: 08/02/2017 
 
There are no plans to have third party monitoring. 
 
Publication Plan 
We plan to submit the paper for publication to a high-quality ENT or Rhinology journal. Results 
will be available to the patients if requested. 
 
 
References 
 
1. Anderhuber, W., C. Walch, E. Nemeth, H. J. Semmelrock, A. Berghold, G. Ranftl, and H. Stammberger. 
“Plasma Adrenaline Concentrations during Functional Endoscopic Sinus Surgery.” The Laryngoscope 109, 
no. 2 Pt 1 (February 1999): 204–7. 
2. Gomez-Rivera, Fernando, Davide Cattano, Uma Ramaswamy, Chirag B. Patel, Alfonso Altamirano, Li- 
Xing Man, Amber Luong, Zhongxue Chen, Martin J. Citardi, and Samer Fakhri. “Pilot Study Comparing 
Total Intravenous Anesthesia to Inhalational Anesthesia in Endoscopic Sinus Surgery: Novel Approach of 
Blood Flow Quantification.” The Annals of Otology, Rhinology, and Laryngology 121, no. 11 (November 
2012): 725–32. 
3. Higgins, Thomas S., Peter H. Hwang, Todd T. Kingdom, Richard R. Orlandi, Heinz Stammberger, and 
Joseph K. Han. “Systematic Review of Topical Vasoconstrictors in Endoscopic Sinus Surgery.” The 
Laryngoscope 121, no. 2 (February 2011): 422–32. doi:10.1002/lary.21286. 
4. Khosla, Akhil J., Francisco G. Pernas, and Patricia A. Maeso. “Meta-Analysis and Literature Review of 
Techniques to Achieve Hemostasis in Endoscopic Sinus Surgery.” International Forum of Allergy & 
Rhinology 3, no. 6 (June 2013): 482–87. doi:10.1002/alr.21126. 
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Concentrated Topical Epinephrine Use in Endoscopic Endonasal Surgery.” International Forum of Allergy 
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Otolaryngologic Clinics of North America 39, no. 3 (June 2006): 463–473, viii. 
doi:10.1016/j.otc.2006.01.006. 
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Is Safe in Endoscopic Sinus Surgery.” American Journal of Rhinology & Allergy 24, no. 2 (April 2010): 
140–42. doi:10.2500/ajra.2010.24.3454. 
10. Riegle, E. V., J. B. Gunter, R. P. Lusk, H. R. Muntz, and K. L. Weiss. “Comparison of Vasoconstrictors for 
Functional Endoscopic Sinus Surgery in Children.” The Laryngoscope 102, no. 7 (July 1992): 820–23. 
doi:10.1288/00005537-199207000-00012. 
11. Rodriguez Valiente, A., A. Roldan Fidalgo, and D. Laguna Ortega. “Bleeding Control in Endoscopic Sinus 
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Epinephrine in Otolaryngology.” The Laryngoscope 118, no. 11 (November 2008): 1928–30. 
doi:10.1097/MLG.0b013e318180ec8d. 


UT Houston Protocol Template 
Adapted from NIH protocol template and ICH Guidelines 
IRB NUMBEPRag: eHS8Co-fM7S-17-0415 
IRB APPROVAL DATE: 08/02/2017 
 
14. Yao, William C., Rachel M. Regone, and Masayoshi Takashima. “Staining Intraoperative Topical 
Solutions with Fluorescein: Enhancing the Safety of Sinus Surgery.” International Forum of Allergy & 
Rhinology 5, no. 9 (September 2015): 870–74. doi:10.1002/alr.21531.