Clinical trial NCT05867342
Conditions: Intraoperative Bleeding
Sponsor: Stanford University
Start date: 2017-05-12; Completion date: 2018-08-22
Enrollment: 40 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
In endoscopic sinus surgery a clear surgical field of view is a very important aspect for good surgical outcome. This study is to evaluate the preoperative preparation to acquire best surgical field of view by comparing between the use of topical adrenaline and the use of combination of topical adrenaline with infiltration of 1% lidocaine with adrenaline in patients scheduled for endoscopic sinus surgery for rhinosinusitis.

Detailed description:

Arms: arm 1: Participants receive topical 1:1000 epinephrine plus saline in one nostril, and topical 1:1000 epinephrine plus infiltration of 1% lidocaine with 1:100,000 epinephrine in the other nostril, during endoscopic visualization while undergoing Endoscopic sinus surgery (ESS).
Interventions: intervention 1: Epinephrin intervention 2: 1% lidocaine with epinephrin 1:100,000 intervention 3: Saline
Intervention descriptions: intervention 1: Topical application of 2 pieces of Epinephrin (1:1,000)-soaked cottonoid in nasal cavity intervention 2: 4 ml intranasal infiltration of 1% lidocaine with epinephrine (1:100,000) at 2 sites (2 ml infiltration at each site) intervention 3: 4 ml intranasal infiltration of saline at 2 sites (2 ml infiltration at each site)

Protocol documents:
Prot_000.pdf: 
 
Effects of Adrenaline Infiltration on Surgical Field of View in 
Endoscopic Sinus Surgery 
NCT05867342 
March 27, 2018 
1. 
PURPOSE OF THE STUDY 
a. 
Brief Summary 
Minimizing bleeding during endoscopic sinus surgery is important for optimal patient 
outcome. Since there is a great variation in the structure of the sinuses among the 
population, without a clear surgical field, there may be inadvertent injury to the 
surrounding structures or an incomplete opening of sinuses. We hope to learn the best 
method for controlling bleeding i the field of view to help optimize the surgical outcome. 
b. 
Objectives 
We hope to learn the preparation for the best field of view with minimal bleeding that 
may interfere with the visualization for endoscopic sinus surgery. Studies in the past 
commonly looked at the estimated blood loss which may not reflect the actual surgical 
field. We would like to assess the actual surgical field to help determine the best possible 
technique to optimize endoscopic sinus surgery. 
c. 
Rationale for Research in Humans 
Human subjects must be used because the purpose of the study is to study the method 
which provides the best field of view for endoscopic sinus surgery in human. 
2. 
STUDY PROCEDURES 
a. 
Procedures 
We will first perform chart review to screen for patients who were scheduled for 
endoscopic sinus surgery for rhinosinusitis that meet both our inclusion and exclusion 
criteria. We will check the date of the patient’s next visit to meet them and explain the 
study protocol and ask for their consent. If they consent to the study, on the day which 
they have the surgery we will follow the protocol, giving topical adrenaline on both side 
and infiltrating lateral nasal wall with the medication according to the study (patient will 
receive 1% xylocaine with adrenaline (1:100,000) on one side and saline on the 
contralateral side, they will be randomized to which side receive which solution for 
infiltration). The Estimated blood loss on each side and the duration of the surgery on 
each side will also be recorded. The Video of the surgery will be evaluated by 2 different 
otolaryngologists to give grading score for surgical field of view using Wormald Surgical 


Field Grading Scale. Patients will have regular post operative follow up as for endoscopic 
sinus surgery. At the patient's first follow up at 1 week after the surgery, the patient will 
be asked to fill out a questionnaire about the postoperative bloody discharge they 
experienced. 
b. 
Procedure Risks 
Any medications may lead to inadvertent effects, however the use of infiltration of 
xylocaine with adrenaline is widely accepted and has originally been used in preparation 
for endoscopic sinus surgery and also for variety of surgical procedures both under 
general and local anesthetic. With correct route and dosage given, infiltration performed 
by specialist under a well-controlled circumstance as under general anesthesia where 
patient's vital signs are closely monitored we believe that it is safe to perform the 
procedure. Topical adrenaline has recently gained popularity among a number of 
surgeons world wide in the use for endoscopic sinus surgery and has known to be safe 
and potent with great result in bleeding control. 
c. 
Use of Deception in the Study 
Deception will not be used to enroll the patient. We will not perform the procedure 
without the patient’s consent. 
d. 
Use of Audio and Video Recordings 
Video recording will be performed in the study (our department usually has all the 
surgeries recorded as a routine procedure). This will be reviewed by 2 otolaryngologists 
at Stanford's university (attendings or rhinology fellows). The otolaryngologist reviewing 
and grading the video will be blinded to which side of the sinus surgery was  performed 
under only topical adrenaline or with the  combination of both topical and infiltration of 
adrenaline. The  video given will be labeled  by the number and not by name of the 
patient and the video will be  secure with  passcode lock external hard disk. 
e. 
Alternative Procedures or Courses of Treatment 
Many different methods and many different agents have been used to help reduce 
bleeding in endoscopic sinus surgery. Currently, adrenaline has become the consensus as 
the best agent used for this purpose; however, there is no one consensus method of 
delivery, each center practices according to their experience for the best of the patients. 
At our center, half of the team use only topical adrenaline before the surgery and the 
other half combine infiltration of xylocaine with adrenaline with topical adrenaline. 
Therefore, the alternative at our center depends on the surgeon’s experience between 
topical adrenaline only and topical adrenaline combine with infiltration. In this study the 
participant instead of one or the other will get a combination of pure topical on one side 
and combine topical with infiltration on the other side of the nasal cavity. Using both 
topical and infiltration of adrenaline may result in less bleeding and better field of view, 
however infiltration of adrenaline may have potential side effect e.g. cardiovascular and 
central nervous system side effects. However, xylocaine with adrenaline is a widely used 
anesthesia and administering at appropriate dosage and route under an extremely well 
controlled environment as being under general anesthesia in the operating room where all 
patient's vital signs are monitored shouldn't be risky. Now that topical adrenaline is more 


widely used than before we want to examine the benefit of additional infiltration of 
adrenaline to the surgical field of view to determine the best optimal practice for 
endoscopic sinus surgery. 
f. 
Will it be possible to continue the more (most) appropriate therapy for the 
participant(s) after the conclusion of the study? 
After the study, the participants will be able to use any therapy that is appropriate for 
them. 
g. 
Study Endpoint(s) 
The study will end after the required number of participant has been enrolled. Since both 
method is the standard we currently perform at the department we do not expect any 
harmful results to the participants. 
3. 
BACKGROUND  
a. 
Past Experimental and/or Clinical Findings 
In the past there have been studies which tried to address the best methods to help 
optimize the surgical field. However, none has actually compared the injection of 
adrenaline to the control using a proper endoscopic grading score (which is a more 
accurate way of assessing visual field in comparison to using the estimated blood loss). 
Since estimated blood loss may give just a crude estimate of the surgical field, we suspect 
that it may be the reason why the previous studies couldn't demonstrate the significant of 
infiltration of adrenaline to the surgical field of view in endoscopic sinus surgery. 
b. 
Findings from Past Animal Experiments 
Animal studies were not identified in our literature review. 
4. 
RADIOISOTOPES OR RADIATION MACHINES 
N/A 
5. 
DEVICES USED IN THE STUDY 
N/A 
6. 
DRUGS, BIOLOGICS, REAGENTS, OR CHEMICALS USED IN THE STUDY 
a. 
Investigational Drugs, Biologics, Reagents, or Chemicals 
N/A 
b. 
Commercial Drugs, Biologics, Reagents, or Chemicals 
Commercial Product 1 
Name: 
1%Xylocaine with adrenaline 
Dosage: 
1% 
Administration Route 
Intranasal infiltration 
New and different use? (Y/N) 
No 


7. 
DISINFECTION PROCEDURES FOR MEDICAL EQUIPMENT USED ON BOTH HUMANS AND 
ANIMALS 
N/A 
8. 
PARTICIPANT POPULATION 
a. 
Planned Enrollment 
(i) 40 participants to be enrolled at Stanford 
(ii) total of 40 participants overall (the study will only be performed at Stanford) 
(iii) the participants will be the patients from the rhinology clinics who have sinusitis that 
have failed medical treatment and were scheduled for endoscopic sinus surgery 
b. 
Age, Gender, and Ethnic Background 
Age range 18-75 years old 
Both males and females 
All ethnic backgrounds 
c. 
Vulnerable Populations 
Potentially vulnerable subjects (including children, pregnant women, economically and 
educationally disadvantaged, decisionally impaired, homeless people, employees and 
students) will not be enrolled in the study. 
d. 
Rationale for Exclusion of Certain Populations 
Women and minorities are included, however children are not included since endoscopic 
sinus surgery is not widely perform in children. 
e. 
Stanford Populations 
The study will not involve participants who are laboratory personnel, employees and 
students. 
f. 
Healthy Volunteers 
We do not take healthy volunteers for the study since they would have no indications for 
the surgery. 
g. 
Recruitment Details 
We will identify the participants for recruitment by chart review prior to their 
preoperative visit. No flyers or other advertisement will be used in the study. 
h. 
Eligibility Criteria 
i. 
Inclusion Criteria 
1. Patients between the age of 18-75 years old who were diagnosed with recurrent 
acute or chronic rhinosinusitis that are recalcitrant to medical treatment and were 
scheduled for endoscopic sinus surgery 


ii. 
Exclusion Criteria 
1. Patients who have asymmetrical disease on the two sides (Lund Mackay score 
difference of 2 or more) 
2. Patients who have endoscopic sinus surgery for treatment of tumor or disease other 
than sinusitis 
3. Patients with nasal polyps 
4. Patients with underlying uncontrolled hypertension 
5. Patients with bleeding disorder or are unable to discontinue antiplatelet or 
anticoagulant before the surgery 
6. Patients who are allergic to adrenaline or to xylocaine 
7. Patients who are not consent to the procedure 
i. 
Screening Procedures 
Screening will be done by chart review. Personal health information, e.g., patient’s 
history, symptoms, prior treatment, endoscopic and computer tomography of paranasal 
sinus findings may be reviewed to see if the patient may fit the inclusion criteria. If the 
patient meets the criteria then on the patient's preoperative visit we will explain the study 
and discuss enrollment. No additional laboratory test apart from their routine preoperative 
test will be required. 
j. 
Participation in Multiple Protocols 
Participants will not be enrolled in more than one study. The consent form will include 
the question to whether they are enrolled in other studies or not and the protocol director 
taking the consent will ask the question before explaining the research protocol. 
k. 
Payments to Participants 
There is no payment for enrolling in the study. 
l. 
Costs to Participants 
There will be no charge to the participant. 
m. 
Planned Duration of the Study 
The probable duration of the entire study is 10 months. The estimated total time per 
participant is approximately 2 weeks, starting on the day for screening and asking for 
consent from the participant which will usually be on the preoperative visit which is 
usually about a week before the surgery. Conducting the actual study will happen during 
the time the participant is in the operating room, then at the first postoperative visit which 
usually take place 1 week after the surgery, a short questionnaire will be given for the 
participant to fill out. 
9. 
RISKS 
a. 
Potential Risks 
i. 
Investigational devices 


The study doesn't involve an investigational device. 
ii. 
Investigational drugs 
The study doesn't involve an investigational drug. 
iii. 
Commercially available drugs, biologics, reagents or chemicals 
Irritation to infiltration site, persistent paresthesia, central nervous system excitatory or 
depressant effect which may cause headache, nausea, ringing in the ear, confusion, 
cardiovascular effect such as bradycardia, hypotension and cardiovascular collapse or 
tachycardia, palpitations and hypertension, hypersensitivity reaction.  
 
Correct route and dosage of the medication is important to avoid the adverse effects, the 
medication will be infiltrated by specialist the study. 
iv. 
Procedures 
The procedure is intranasal infiltration of 1% xylocaine with adrenaline which is a 
routine procedure in endoscopic sinus surgery. 
v. 
Radioisotopes/radiation-producing machines 
There will be no use of radioisotopes/radiation-producing machine for the study. 
vi. 
Physical well-being 
We do not anticipate that participants in this study will be placed at risk in terms of 
physical well-being. 
vii. 
Psychological well-being 
We do not anticipate that participants in this study will be placed at risk in terms of 
psychological well-being. 
viii. 
Economic well-being 
We do not anticipate that participants in this study will be placed at risk in terms of 
economic well-being. 
ix. 
Social well-being 
We do not anticipate that participants in this study will be placed at risk in social well-
being. 
x. 
Overall evaluation of risk 
Low risk 
b. 
International Research Risk Procedures 
N/A 
c. 
Procedures to Minimize Risk 


Overall potential risk to the patient should be very low. The patient will get the 
infiltration right before the surgery after general anesthesia where the vital signs will be 
closely monitored in the intra operative setting by anesthesiologist. Also any intranasal 
bleeding from the surgery is easily controlled in the operating room under endoscopic 
view with medications and equipment set up ready for the surgery. 
d. 
Study Conclusion 
The participants will only be given one dose of the infiltration throughout the study. If 
any adverse effects were to happen, the participant will be terminated from the study and 
will be closely taken care of. As the infiltration will take place in the operating room after 
the patient is under general anesthesia, where the patient will be fully monitored, any 
adverse effects would be easily detected at a very early stage and best appropriate 
treatment will be given. 
e. 
Data Safety Monitoring Plan 
i. 
Data and/or events subject to review 
Monitoring will include bleeding intraoperatively and postoperatively, the visual 
field grading scale score, patient's vital sign intraoperatively, the overall blood loss 
on each side, the operative time on each side. 
ii. 
Person(s) responsible for Data and Safety Monitoring 
The protocol director, co-protocol director and academic sponsor will be responsible 
for data and safety monitoring of the study. 
iii. 
Frequency of DSMB meetings 
The protocol director will meet with the other researchers conducting the study on a 
weekly basis (every Monday evening) to review the protocol. 
iv. 
Specific triggers or stopping rules 
Any major complications secondary to the study will terminate the study. However, 
this is very unlikely since intranasal infiltration of xylocaine with adrenaline is a 
routine procedure perform for endoscopic sinus surgery and infiltration at correct 
dosage and by specialist under well controlled environment shouldn't result in any 
major complications. 
v. 
DSMB Reporting 
The IRB will be informed if any abnormal outcomes were to occur. 
vi. 
Will the Protocol Director be the only monitoring entity? (Y/N) 
Yes 
vii. 
Will a board, committee, or safety monitor be responsible for study monitoring? 
(Y/N) 
No 


f. 
Risks to Special Populations 
N/A 
10. 
BENEFITS 
The study will help determine the best surgical field for endoscopic sinus surgery which will lead 
to optimal sinus surgery with the best result for the patient in the future. 
11. 
PRIVACY AND CONFIDENTIALITY 
All participant information and specimens are handled in compliance with the Health Insurance 
Portability and Accountability Act (HIPAA) and privacy policies of Stanford University, Stanford 
Health Care, and Stanford Children’s Health. 

SAP_001.pdf: 
 
Effects of Adrenaline Infiltration on Surgical Field of View in 
Endoscopic Sinus Surgery 
NCT05867342 
February 1, 2020 
1. 
STATISTICAL METHODS 
A prestudy power analysis was completed with Monte Carlo simulations to estimate the 
necessary sample size. A sample size of 38 patients in total would give the power of 82% with 
type l error of 0.05 to detect the difference in Wormald scale between the 2 groups. Patient-level 
demographics and baseline clinical factors were summarized with mean (standard deviation) for 
continuous variables and with n (%) for categorical variables. The comparisons of clinical 
variables (all continuous) between both sides of the nose were performed using paired t test. To 
estimate the effect of 1% lidocaine with 1:100,000 epinephrine, we constructed a mixed effect 
models with random slope by accounting for within-subject correlation. All the models were 
adjusted for age, gender, preoperative Lund-Mackay score, preoperative Lund-Kennedy score, 
and medication use. Surgery time was found to be right-skewed; therefore, it was log-transformed 
in the model, and the regression coefficient was exponentiated to represent the percentage 
difference. We performed reliability testing for the Wormald scale graded by 2 graders, by 
calculating the intraclass correlation coefficient (ICC) as well as its 95% confidence interval (CI).