Clinical trial NCT03661346
Conditions: Chronic Sinusitis
Sponsor: The University of Texas Medical Branch, Galveston
Start date: 2017-03-01; Completion date: 2018-03-30
Enrollment: 28 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to compare esmolol and labetalol bleeding and intra-operative visibility scores in functional endoscopic sinus surgery.

Detailed description:
BACKGROUND: Improved intraoperative visibility during functional endoscopic sinus surgery (FESS) decreases the risk of serious orbital or skull base injuries. Beta blockers are among several methods used to reduce mean arterial pressure (MAP), heart rate (HR) and mucosal bleeding. Labetalol (mixed alpha-1-beta blocker) reduces HR and MAP; however, its alpha-1 blockade may mitigate topical epinephrine decongestant effects. Esmolol (selective beta-1 blocker) does not have direct antagonistic effects on topical epinephrine. This study compares the hemodynamic parameters (rate of blood loss, MAP control, HR) and intraoperative visibility during FESS between esmolol and labetalol.

Arms: arm 1: Patients receiving esmolol when intra-operative MAP \> 80 mmHg. arm 2: Patients receiving labetalol when intra-operative MAP \> 80 mmHg
Interventions: intervention 1: Labetalol intervention 2: Esmolol
Intervention descriptions: intervention 1: Aliquots of 20mg of Labetol

• Maximum Dose - 300mg total for case intervention 2: Infusion - 0.1mg/kg/min

• Maximum Dose - after 30 minutes, 0.3mg/kg/min

Protocol documents:
Prot_003.pdf: 
 
 
    The University of Texas Medical Branch   
 
 
 
 
 
 
 
Title: Comparison of blood loss and intraoperative visibility between Labetalol and 
Esmolol: A randomized controlled trial 
 
 
Principal Investigator:  Mohamad R. Chaaban, MD, MSCR, MBA 
 
Funding Sponsor: Departmental  
 
IND number: N/A 
 
Version number and date: 1.0_01/23/2016   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
1. Introduction and Purpose 
 
Bleeding during endoscopic sinus surgery (ESS) affects the ability of the surgeon to 
identify key structures such as the skull base, orbit, nerves and major vessels. 
Rhinologists have examined multiple ways to decrease intraoperative bleeding as 
well as improve endoscopic visibility.  
 
This study hypothesizes that intraoperative blood pressure control with esmolol 
decreases blood loss and improves operative visibility during ESS as compared to 
labetalol. The effect will be objectively studied by comparing estimated blood loss 
and intraoperative visibility utilizing validated intraoperative bleeding/ visibility scores. 
In addition, patients will be stratified in accordance to their severity of their disease 
according to their Lund Mackay scores based on their CT scan findings that are 
routinely obtained prior to surgery. 
 
The short half-life and the ability of continuous infusion of esmolol provides a tighter 
control of intraoperative blood pressure. Additionally, its selective beta blockade 
avoids antagonizing the effect of the topical epinephrine vasoconstrictor that is used 
intraoperatively during ESS.   
 
If the study demonstrated a significant difference between the groups, it would 
potentially affect our selection of beta blockers during ESS. The potential benefits 
include providing safe, complete surgery and potentially decreasing cost. The 
complications that could potentially arise from poor intraoperative visibility include 
CSF leak and orbital injuries that could lead to lead to blindness. 
 
2. Background  
 
During ESS, bleeding from the mucosal surfaces often interferes with visualization of 
the anatomy and increases the small risks of serious complications such as injuring 
the skull base leading to a cerebrospinal fluid leak or an injury to the eye. 
Additionally, the bleeding interferes with visualization during the procedure and a 
reduction of the bleeding would result in greater ease and thoroughness of the sinus 
surgery.  
 
Historically, several ways have been used to decrease intraoperative bleeding. 
Controlled hypotension (keeping the mean arterial pressure between 50 and 60) has 
been used using either the anesthetic agents alone or using either sodium 
nitroprusside or esmolol drips [1-3].The use of these medications increases the risk 
of serious side effects such as cyanide toxicity and myocardial depression. Recent 
studies have shown that controlled hypotension is associated with increased 
morbidity and mortality. The latter was found to be in the range of 20 to 60 deaths in 
100,000 patients mainly as a consequence of ischemic organ failure [4]. There is also 
good evidence that decreasing the MAP below 70 can even increase intraoperative 
bleeding due to local arteriolar vasodilatation which results from decreased blood 
flow to the tissues, increased local carbon dioxide concentration and decreased pH. 


[3,5].Another mechanism that can explain this is an increase in cardiac output during 
controlled hypotension resulting from reflex tachycardia specially with the use of a 
pure vasodilator like sodium nitroprusside [6]. 
 
There are multiple factors which contribute to blood loss during surgery, including, 
but not limited to surgical and anesthetic technique. At the University of Texas 
Medical Branch, the endoscopic surgical technique is fairly uniform and comparable 
to practices throughout the world. Most of the endoscopic sinus surgery is performed 
under general anesthesia. There is a suggestion among ENT physicians and 
anesthesiologist that different blood pressure medications affect intraoperative 
visibility and possibly lead to less intraoperative blood loss. It is also thought that 
intraoperative topical decongestants (specifically epinephrine) work by binding to 
alpha receptors. Labetalol, which is an alpha and beta blocker, may interfere with the 
effect of this topical decongestant. [7-9] The goal of this investigation is to formally 
evaluate this notion utilizing two very commonly used blood pressure medications: 
Labetalol and esmolol. This study does not use any medications that are not routinely 
used during endoscopic sinus surgery at the University of Texas Medical Branch. 
 
3. Concise Summary of Project:  
 
Subjects who are scheduled for routine endoscopic sinus surgery will be recruited 
(n=40). The subjects in this prospective study will be randomized to either receive 
labetalol or esmolol.  Current standard of care in preventing hypertension during 
sinus surgery due to stimulation and injection and application of sympathetic agents 
includes, narcotic administration, increasing volatile agent (Sevoflurane), esmolol, 
labetalol and other agents (hydralazine, nicardipine and nitroprusside). It is not 
known the impact these anti-hypertensive agents have on blood loss or blood in 
surgical field. 
Intraoperatively, topical epinephrine pledgets will be used for decongestion similar to 
what is done routinely in endoscopic sinus surgery. 
Intraoperative visibility will be scored utilizing two validated endoscopic visbility 
scores. In addition, at the end of surgery the estimated blood loss will be calculated 
by subtracting the amount of irritagation used during surgery from the amount of 
blood in the suction canisters. 
In addition, the surgical video will be recorded and the intraoperative visibility will also 
be recorded by an independent observer. 
In addition to the demographics and our primary outcome, secondary outcomes will 
be collected including duration of anesthesia, duration of surgery, final CO2, 
postoperative bleeding, visit to the ED following discharge, need for medical attention 
following discharge, surgeon satisfaction on a likert scale (1-10), need for surgical re-
intervention, and pain score after surgery, as well as time spent in recovery, use of 
anti-emetics postop, and nurses notes on as regards to pain and recovery. 
 
Subjects may be excluded from the study if the anesthesiologist deemed it necessary 
that the protocol drug can not be used on the patient for any reason. Otherwise, it is 
expected that the surgeries will be routinely performed and the study outcome 


variables do not interfere with the routine.  
 
 4. Study Procedures: 
 
This will be a prospective randomized study comprising subjects (n=40) over 18 
years of age scheduled for ESS. The inclusion criteria will be male or female patients 
with ASA physical status 1 (normal otherwise healthy patient) or 2 (patient with mild 
systemic disease) and patients who have chronic sinusitis with or without nasal 
polyps.  Exclusion criteria include: pregnancy, asthma, obstructive pulmonary 
diseases, sinus bradycardia and severe bradycardia, sick sinus syndrome, heart 
failure, end-stage renal disease, stroke, diabetes mellitus, preoperative use of 
nonsteroidal anti-inflammatory medications (NSAIDS) or aspirin (ASA) within the last 
week, and a body mass index (BMI) greater than 40. Additionally, any patient that the 
anesthesiologist deems unfit for randomization will also be excluded.  
 
We will randomize the patients in blocks of 4 to determine the impact of a specific 
study drug (either esmolol (n=20) or labetalol (n=20) along with sevoflurane to control 
blood pressure on bleeding. The patients will be classified according to their Lund 
Mackay scores, which will be obtained from their routine CT scan performed prior to 
their surgery. 
 
Written informed consent will be obtained. On arrival to the operating room, all the 
patients will be monitored as per usual anesthesia routine. Patients in both groups 
will be induced using 1-2 mg midazolam PRN anxiety, 1-3 mcg/kg fentanyl, 20-40 mg 
lidocaine, 1-2 mg/kg propofol, and 0.05-0.1 mg/kg vecuronium. Thereafter, 
maintenance with general anesthesia will receive 1-2% of sevoflurane (end expired). 
Both groups may receive fentanyl throughout the case at the discretion of the 
anesthesiologist. The dose of fentanyl is not to exceed 5 mcg/kg. The patient's mean 
arterial blood pressure (MAP) will be maintained at 70-80 mm Hg (80 for 
hypertensive patients) by first adjusting the sevoflurane concentration within their 
range (between 1-2 percent for the sevoflurane. If sevoflurane is maximized (Fe sevo 
>2%) and the target MAP is not achieved, then the patients will receive either 
esmolol or labetalol (study drug will be blinded for surgeon). 
  
The surgical procedure will not be altered. All patients will be placed supine with 6 
degrees head up the entire procedure. Local vasoconstriction will be performed first 
with bilateral endonasal application of oxymetazoline soaked pledgets for 2 minutes.   
This is followed by placing topical epinephrine pledgets (1:1000) throughout the 
duration of the case. Our primary Outcome measures will include 1) intraoperative 
visibility utilizing two validated bleeding scores (Wormald and Boezart score) 
intraoperative visibility (1 minute, and every 20 minutes thereafter)  2) estimated 
blood loss at the of end of surgery which will be calculated by subtracting the amount 
of irrigation used from the total blood in the suction canisters. 
Blood loss will be evaluated by the blinded rhinologist (MRC) and an independent 
observer who will review the un-identified endoscopic surgical videos.   
 


In addition to the demographics and our primary outcome, secondary outcomes will 
be collected including duration of anesthesia, duration of surgery, final CO2, 
postoperative bleeding, visit to the ED following discharge, need for medical attention 
following discharge, need for surgical re-intervention, Bispectral index (BIS) 
monitoring intraoperatively (taped on patient forehead), surgeon satisfaction score on 
likert scale (1-10), and pain score after surgery, as well as time spent in recovery, 
use of anti-emetics postop, and nurses notes on as regards to pain and recovery. All 
the medications used in this study are used as part of the standard of care when 
patients develop high intraoperative blood pressure as a result of the usuage of the 
topical decongestants. 
 
Blood pressure control medications: 
Labetalol is a mixed adrenergic receptor antagonist (beta 1> alpha 1 blocker). If 
randomized, the anesthesiology investigator will obtain 3 bottles of labetalol (100 mg 
in 10 mL). Per protocol, aliquots of 10-30 mg of labetalol will be administered SIVP if 
MAP > 80 and sevoflurane [2%]. Initial dose will be 20 mg (within 2 min), followed by 
infusion of 0.25-0.5 µg/min. Maximum dose =  300 mg for case duration. If maximum 
dose is acheived, other agents per discretion of the anesthesiologist will be 
administered.  
 
Esmolol is a specific beta adrenergic antagonist (beta 1>> beta 2). If randomized, the 
anesthesiology investigator will obtain a 2500 mg in 20 mL vial. Esmolol will be 
diluted in 250 mL 0.9% NaCl to achieve a concentration of 10 mg/mL. Per protocol, 
an infusion of esmolol at a rate of 0.1 mg/kg/min if MAP > 80 and sevoflurane [2%]. 
The dose can be titrated up to 0.3 mg/kg/min. If after 30 min, the esmolol dose is 
>0.3 mg/kg/min other agents per discretion of the anesthesiologist will be 
administered.  
 
 
5. Sub-Study Procedures: 
N/A 
 
6. Criteria for Inclusion of Subjects 
 
The inclusion criteria will be male or female patients with ASA physical status 1 
(normal otherwise healthy patient) or 2 (patient with mild systemic disease) and 
patients who have chronic sinusitis with or without nasal polyps and who are 
scheduled for a routine ESS. 
 
7. Criteria for Exclusion of Subjects  
 
Exclusion criteria include: pregnancy, asthma, obstructive pulmonary diseases, sinus 
bradycardia and severe bradycardia, sick sinus syndrome, heart failure, end-stage 
renal disease, stroke, diabetes mellitus, preoperative use of nonsteroidal anti-
inflammatory medications (NSAIDS) or aspirin (ASA) within the last week, and a body 
mass index (BMI) greater than 40.  Subjects may be excluded from the study if the 


anesthesiologist deemed it necessary that the protocol drug cannot be used on the 
patient for any reason. Otherwise, it is expected that the surgeries will be routinely 
performed and the study outcome variables do not interfere with the routine. 
 
8. Sources of Research Material 
 
Intraoperatively, a bleeding score will be used (validated questionnaire) based on the 
visibility. In addition, at the end of the surgery, the estimated blood loss will be 
calculated. All other secondary outcomes will be collected following the completion of 
surgery. These will be obtained from the medical record (duration of anesthesia, 
duration of surgery, final CO2, Bispectral index (BIS) monitoring, postoperative 
bleeding, visit to the ED following discharge, need for medical attention following 
discharge, need for surgical re-intervention, and pain score after surgery, as well as 
time spent in recovery, use of anti-emetics postop, and nurses notes on as regards to 
pain and recovery). 
 
9. Recruitment Method and Consenting Process: 
 
The informed consent for the study will be obtained either in the preoperative clinic 
visit or on the day of the surgery in the pre-operative holding area. Informed consent 
for the study will be separate from the surgical consent. The name of the attending 
surgeon will be written on the study consent together with the name of the attending 
anesthesiologist. The informed consent will then be included in the patients' charts. 
 
10. Potential Risks: 
 
The risks and benefits of the study will be discussed with the patient on obtaining 
written informed consent. Consent for surgery and anesthesia will be done as usual. 
The study adds no risks above those associated with risks of surgery and risk of 
anesthesia. Neither anesthetic technique used here breaches the standard of care 
nor is the surgical technique not altered. There is no clear evidence of any difference 
in between the two groups in the literature in regards to their effect on recovery time 
or their gastrointestinal side effects (nausea and vomiting). 
 
11. Subject Safety and Data Monitoring 
 
Monitoring of the patients will abide by the standards set forth by the American 
Society of Anesthesiology.  Additionally, the standard surgical procedures will be 
applied in this study.   
 
Any adverse event will be reported immediately to the IRB and FDA if it was drug 
related.  Given that the medications used in this study are used routinely by 
anesthesiologists, the reported adverse event will unlikely be related to the study 
itself.  
 
12. Procedures to Maintain Confidentiality 


 
As a patient enters the study, the investigator will assign that patient to the next 
sequential study code number available. All data and subject information will be 
stored in the investigator’s laboratory in locked file cabinets or on a secure computer. 
Access to the data will be restricted to the investigators, nurses, and technicians 
involved in this project.  
13. Potential Benefits 
 
The main benefit is that if there is a difference between the groups then they will have 
less blood loss. The choice of medication for blood pressure control intraoperatively 
will likely be implemented should the results demonstrate any difference between the 
groups. In the event that there was no difference between the groups, then the 
medications can continue to be used without the concern of impaired visibility to the 
endoscopic surgeon. 
 The study adds no risks above those associated with risks of surgery and risk of 
anesthesia. Neither anesthetic technique used here breaches a standard of care nor 
is the surgical technique altered. There is no clear evidence of any difference in 
between the two groups in the literature in regards to their effect on recovery time or 
their gastrointestinal side effects (nausea and vomiting).  
 
14. Biostatistics 
 
Accurate power analysis cannot be done since there is a lot of controversy in the 
older studies. For this reason, our number of patients (N=40) to be included in the 
study was inferred based on the estimated difference in the mean of blood loss 
between the groups as being 110 ml and an estimated standard deviation of the 
mean between the two groups to be 150 and 200 respectively. 
 
If the results of the two groups stratified didn't show a normal distribution, then they 
will be compared using the Wilcoxon rank sum test with P value significant ≤0.05. If 
the results were normally distributed, then a student t -test will be used with P value 
significant ≤ 0.05. 
 
15. Bibliography: 
 
1. Degoute CS, Dubreuil C, Ray MJ, et al. Effects of posture, hypotension and locally 
applied vasoconstriction on the middle ear microcirculation in anaesthetized humans. 
Eur J Appl Physiol Occup Physiol. 1994; 69(5):414-20. 
2. Degoute CS, Ray MJ, Manchon M, Dubreuil C, Banssillon V et al.  Remifentanil and 
controlled hypotension; comparison with nitroprusside or esmolol during 
tympanoplasty.. Can J Anaesth. 2001 Jan; 48(1):20-7 
3. Boezaart AP, van der Merwe J, Coetzee A. Comparison of sodium nitroprusside- and 
esmolol-induced controlled hypotension for functional endoscopic sinus surgery. Can J 
Anaesth.1995 May; 42(5 Pt 1):373-6.  


4. Leigh JM. The history of controlled hypotension. Br. J. Anaesth. 1975 Jul; 47(7):745-9 
5. Lassen NA, Christensen MS et al.  Physiology of cerebral blood flow. Br. J Anaesth. 
1976 Aug; 48(8):719-34.  
6. Jacobi KE, Böhm BE, Rickauer AJ et al. Moderate controlled hypotension with 
sodium nitroprusside does not improve surgical conditions or decrease blood loss in 
endoscopic sinus surgery. J Clin Anesth. 2001 Jun;13(4):319-20.  
7. Puthenveettil N, Rajan S, Kumar L, Nair SG. A comparison of effects of oral 
premedication with clonidine and metoprolol on intraoperative hemodynamics and 
surgical conditions during functional endoscopic sinus surgery. Anesth Essays Res. 
2013 Sep-Dec;7(3):371-58 
8. Panda N, Verma RK, Panda NK. Efficacy and safety of high-concentration adrenaline 
wicks during functional endoscopic sinus surgery. J Otolaryngol Head Neck Surg. 2012 
Apr;41(2):131-7. 
9. Rahimzadeh P, Faiz SH, Alebouyeh MR. Effects of premedication with metoprolol on 
bleeding and induced hypotension in nasal surgery. Anesth Pain Med. 2012 
Winter;1(3):157-61. 

ICF_004.pdf: 
RESEARCH CONSENT FORM
You are being asked to participate as a subject in the research project entitled, Comparison of blood loss and 
intraoperative visibility between Labetalol and Esmolol: A randomized controlled trial, under the direction of 
Dr. Mohamad Chaaban, Assistant Professor, Department of Otolaryngology-Head and Neck Surgery.
PURPOSE OF THE STUDY
The purpose of this study is to compare the differences in visibility and blood loss between two different 
blood pressure medications that are routinely given during endoscopic sinus surgery. You are being asked 
to participate because you are scheduled to undergo a routine endoscopic sinus surgery for your chronic 
sinusitis.
PROCEDURES RELATED ONLY TO THE RESEARCH
You will undergo routine endoscopic sinus surgery. This research study will not alter your 
routine sinus surgery.
If you agree to participate, we will collect data that will be needed for the study including a 
survey that will be performed by the physician. Your age, and gender will also be collected, visit 
to the ED following discharge, need for medical attention following discharge, need for surgical 
re-intervention, and pain score after surgery, as well as time spent in recovery, use of anti-
emetics postop, and nurses notes on as regards to pain and recovery. If you wish to withdraw 
consent for use of this data, you will need to contact Dr. Chaaban and inform him of your 
decision. Any unused data will be destroyed following your withdrawal.
PROCEDURES NOT RELATED TO THIS RESEARCH (i.e., standard of care)
Your endoscopic sinus surgery will not be altered in any way in this procedure. At the time of surgery, the 
diseased sinuses will be opened in a routine fashion as described in your surgical consent.
RISKS OF PARTICIPATION
The potential risks from participation in the study are possible risk from loss of confidentiality that may 
arise from participation in the project.
NUMBER OF SUBJECTS PARTICIPATING AND THE DURATION OF YOUR PARTICIPATION
The anticipated number of subjects involved in the study will be 40 with all subjects being 
selected from University of Texas Medical Branch. The length of time for your participation is 
only during your preoperative visit and during surgery and immediate postop when data will be 
recorded.
BENEFITS TO THE SUBJECT
You will not benefit from your participation in the research project.
OTHER CHOICES (ALTERNATIVE TREATMENT)
Participation in this study is voluntary. The alternative is not to participate in this study and this will not
16-Feb-2017 -
21-Dec-2017


affect the routine care that you will receive.
SAFE WITHDRAWAL FROM THE STUDY
You may withdraw at any time during the study.
REIMBURSEMENT FOR EXPENSES
There will be no reimbursement for participation in this study
COMPENSATION FOR RESEARCH RELATED INJURY
If you are physically injured because of any substance given to you or procedure properly performed on 
you under the plan for this study, your injury will be treated.
Compensation for an injury resulting from your participation in this research is not available from the 
University of Texas Medical Branch at Galveston. You, or your insurance company or health care plan, 
will be billed and you will be responsible for any charges.
You will be responsible for paying any costs related to illnesses and medical events not associated 
with being in this study. There are no plans to provide other forms of compensation. However, you 
are not waiving any of your legal rights by participating in this study. Questions about 
compensation may be directed to the study doctor.
COSTS OF PARTICIPATION
All study-related costs associated with your participation will be paid by the UTMB Otolaryngology 
department. You and/or your insurance company will be charged or held responsible for the costs of your 
routine care.
REASONS FOR THE STUDY INVESTIGATOR TO STOP YOUR PARTICIPATION
If applicable, you should list reasons that the subject’s participation may be stopped without their 
consent. These include cancellation of your surgery for any reason.
USE AND DISCLOSURE OF YOUR HEALTH INFORMATION
Study records that identify you will be kept confidential as required by law. Federal privacy regulations 
provided under the Health Insurance Portability and Accountability Act (HIPAA) provides safeguards for 
privacy, security, and authorized access of your records. These regulations require UTMB to obtain an 
authorization from you for the use and disclosure of your health information. By signing this consent form, 
you are authorizing the use and disclosure of your health information for the purpose of completing the 
research study. Except when required by law, you will not be identified by name, social security number, 
address, telephone number, or any other direct personal identifier in study records disclosed outside of the 
University of Texas Medical Branch (UTMB). For records disclosed outside of UTMB, you will be assigned a 
unique code number. The key to the code will be kept in a locked file in Dr. Chaaban’s office.
If you sign this form, you are giving us permission to collect, use and share your health information. You 
do not need to sign this form. If you decide not to sign this form, you cannot be in the research study. We 
cannot do the research if we cannot collect, use and share your health information. Whether or not you


agree to the research project or give us permission to collect, use or share your health information will not 
affect the care you will be given at UTMB.
Dr. Chaaban will use and disclose your study related test results both to treat you and to complete the 
research study. These would include your demographic information, intraoperative still images of the 
surgery and your hemodynamic profile including blood loss following surgery. With the exception of the 
images, these are routinely obtained and included in your chart. You may see or receive a copy of any 
research information that will be included in your medical record. For all other health information we 
collect on you that will not be included in your medical record, you may not be allowed to access or 
receive a copy of the information until the conclusion of the study.
Your records may be reviewed in order to meet federal or state regulations. Reviewers may include, for 
example, the Food and Drug Administration, UTMB, UTMB IRB. This authorization for the use and 
disclosure of your health information as described above expires upon the conclusion of the research study.
If you change your mind later and do not want us to collect or share your health information, you need to 
contact the researcher listed on this consent form by telephone. You need to say that you have changed 
your mind and do not want the researcher to collect and share your health information. You may also 
need to leave the research study if we cannot collect any more health information. We may still use the 
information we have already collected. We need to know what happens to everyone who starts a research 
study, not just those people who stay in it. The results of this study may be published in scientific journals 
without identifying you by name.
ADDITIONAL INFORMATION
1.
If you have any questions, concerns or complaints before, during or after the research 
study, or if you need to report a research related injury or adverse reaction (bad side 
effect), you should immediately contact Dr. Chaaban at 409-772-2701 or, if after normal 
office hours, pager 409-643-0519.
2.
Your participation in this study is completely voluntary and you have been told that you may refuse to 
participate or stop your participation in this project at any time without penalty or loss of benefits and 
without jeopardizing your medical care at UTMB. If you decide to stop your participation in this 
project and revoke your authorization for the use and disclosure of your health information, UTMB 
may continue to use and disclose your health information in some instances. This would include any 
health information that was used or disclosed prior to your decision to stop participation and needed in 
order to maintain the integrity of the research study. If there are significant new findings or we get any 
information that might change your mind about participating, we will give you the information and 
allow you to reconsider whether or not to continue.
3.
If you have any complaints, concerns, input or questions regarding your rights as a subject 
participating in this research study or you would like more information, you may contact the 
Institutional Review Board Office, at (409) 266-9400. 


The purpose of this research study, procedures to be followed, risks and benefits have been explained to 
you. You have been allowed to ask questions and your questions have been answered to your satisfaction. 
You have been told who to contact if you have additional questions. You have read this consent form and 
voluntarily agree to participate as a subject in this study. You are free to withdraw your consent, including 
your authorization for the use and disclosure of your health information, at any time. You may withdraw 
your consent by notifying Dr. Chaaban at 409-772-2701. You will be given a copy of the consent form 
you have signed.
Informed consent is required of all persons in this project. Whether or not you provide a signed informed 
consent for this research study will have no effect on your current or future relationship with UTMB.
Signature of Subject
Date
Using language that is understandable and appropriate, I have discussed this project and the items listed 
above with the subject
Date
Signature of Person Obtaining Consent

SAP_001.pdf: 
Statistical Analysis Plan: Title Page 
 
 
Blood Loss and Visibility with Esmolol vs. Labetalol in Endoscopic Sinus Surgery: A 
Randomized Trial 
Date: 09/04/2018 
 
 
 


Study Summary and Aims 
 
The purpose of this study is to compare esmolol and labetalol bleeding and visibility outcomes in 
FESS surgery. It is a double-blinded two-armed trial with no placebo control, conducted at a 
tertiary center. Participants include adults with history of CRS with or without nasal polyps, 
undergoing FESS for CRS. 38 patients were enrolled, with 32 receiving study drug (17 esmolol, 
15 labetalol). Total study duration, including recruitment and analysis, was 1 year with no 
follow-up. Treatments involve giving intraoperative 20mg of Labetol (max dose = 300 mg for 
total operation) or infusing 0.1mg/kg/min esmolol (max dose after 30 minutes = 0.3mg/kg/min) 
when MAP rises above 80 mmHg. The primary aim is to evaluate the relative efficacy of these 
drugs in FESS surgery, specifically controlling bleeding and improving visibility.  
 
Study Endpoints 
 
March 2017 – March 2018 enrollment, drug administration only during surgery.  
 
Sample Size Considerations 
 
Futility analysis based on estimated blood loss data to see how many patients would be required 
to show significant differences in blood loss, and therefore mucosal visibility, between drug 
groups. Given the small differences in blood loss per minute during surgery between treatment 
groups (0.63 compared to 0.67), and given the relatively large standard deviations obtained (0.33 
and 0.37), 1,245 patients would be required in each drug group (total N = 2,490), using a non-
paired (two-sided) t-test for the comparison, to show a statistically significant difference between 
the 2 treatments with a power of 0.8 and type I error of 0.05.  
 
These sample size calculations are based on the primary aims of determining a significant 
difference in FESS visibility between the two drugs.  
 
The null hypothesis is that there will be no statistical difference between esmolol and labetalol in 
FESS visibility and bleeding parameters. The alternative hypothesis is that there will be a 
significant difference, in either drug, for improved FESS visibility and bleeding parameters.  
 
The minimum difference that we judge to be statistically significant is a 1-point change on the 
visibility scores (Boezaart 5-point, Wormald 10-point).  
 
Analysis Sets 
 
N/A 
 
Statistical Analysis and Description of Main Tables 
 
All data for the study outcomes was analyzed with the Wilcoxon rank sum test, used to compare 
the confidence interval location shift differences between groups. P-value was based on 
asymptotic Wilcoxon two-sample test with continuity correction of 0.5. The 95% confidence 
interval for the location shift was based on Hodges-Lehmann estimation. Categorical data 


(gender) analyzed with chi-square test. Results were analyzed using the statistical program IBM© 
SPSS© Statistics (Version 24). P-value < 0.05 was considered significant.  
 
Table 1. Demographic Information and Baseline Characteristics of Study Patients 
Characteristics 
Group A (n=13) 
Group B (n=15) 
P-value 
Age, years 
 
 
 
  Mean (SD) 
 
 
 
  Median (Q1, Q3) 
 
 
 
Male, No. (%) 
 
 
 
BMI, kg/m2 
 
 
 
  Mean (SD) 
 
 
 
  Median (Q1, Q3) 
 
 
 
Lund-Mackay score† 
 
 
 
  Mean (SD) 
 
 
 
  Median (Q1, Q3) 
 
 
 
Septoplasty, No. (%) 
 
 
 
 
 
Figure 1. Trial profile 
 


Table 2. Comparing Anesthesia and Surgical Parameters 
Characteristics 
Group A 
Group B 
P-value 
 
(n=13) 
(n=15) 
Location shift† (95%CI) 
Duration, min 
 
 
 
  Surgery 
 
 
 
    Mean (SD) 
 
 
 
    Median (Q1, Q3) 
 
 
 
  Anesthesia 
 
 
 
    Mean (SD) 
 
 
 
    Median (Q1, Q3) 
 
 
 
  PACU 
 
 
 
    Mean (SD) 
 
 
 
    Median (Q1, Q3) 
 
 
 
EBL, mL 
 
 
 
  Mean (SD) 
 
 
 
  Median (Q1, Q3) 
 
 
 
Rate of blood loss, mL/min 
 
 
 
  Mean (SD) 
 
 
 
  Median (Q1, Q3) 
 
 
 
Heart rate (bpm) 
 
 
 
  Mean (SD) 
 
 
 
  Median (Q1, Q3) 
 
 
 
Mean MAP 
 
 
 
  Mean (SD) 
 
 
 
  Median (Q1, Q3) 
 
 
 
Mean Boezaart score 
 
 
 
  Mean (SD) 
 
 
 
  Median (Q1, Q3) 
 
 
 
Mean Wormald score 
 
 
 
  Mean (SD) 
 
 
 
  Median (Q1, Q3) 
 
 
 
† Location shift = Group B – Group A