Clinical trial NCT03605914
Conditions: Pain Control After Functional Endoscopic Sinus Surgery and Septoplasty
Sponsor: The University of Texas Health Science Center, Houston
Start date: 2018-08-01; Completion date: 2020-07-05
Enrollment: 100 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to compare the level of pain control in patients receiving non-steroidal anti-inflammatory drugs (NSAIDs) to those receiving opioids in the postoperative period after endoscopic sinus surgery (ESS) and/or septoplasty.

Detailed description:

Arms: arm 1: The non-steroidal anti-inflammatory drug (NSAID) used in this study is diclofenac. arm 2: The Opioid used in this study is Norco. Norco is a combination medication that contains both an opioid pain reliever (hydrocodone) and a non-opioid pain reliever (acetaminophen).
Interventions: intervention 1: diclofenac intervention 2: Norco
Intervention descriptions: intervention 1: The non-steroidal anti-inflammatory drug (NSAID) used in this study is diclofenac. intervention 2: The opioid used in this study is Norco. Norco is a combination medication that contains both an opioid pain reliever (hydrocodone) and a non-opioid pain reliever (acetaminophen).

Protocol documents:
Prot_SAP_000.pdf: 
UT Houston Protocol Template 
Adapted from NIH protocol template and ICH Guidelines 
IRB NUMBEPRag: eHS1Co-fM6S-18-0242 
IRB APPROVAL DATE: 06/26/2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Are NSAIDs effective enough for postoperative pain control after functional 
endoscopic sinus surgery and septoplasty? 
 
NCT03605914 
 
Version Date: 6/26/2018 
 
 


UT Houston Protocol Template 
Adapted from NIH protocol template and ICH Guidelines 
IRB NUMBEPRag: eHS2Co-fM6S-18-0242 
IRB APPROVAL DATE: 06/26/2018 
 
Protocol Title: 
Are NSAIDs effective enough for postoperative pain control after functional 
endoscopic sinus surgery and septoplasty? 
Principal Investigator: 
Martin Citardi MD 
 
Co-Investigators: 
Alok Saini MD, William Yao MD, Amber Luong MD PhD, Zi Yang Jiang, MD 
 
Study Coordinator: 
None 
 
Population: 
100 adult patients undergoing functional endoscopic sinus surgery and/or 
septoplasty with Drs. Citardi, Luong, or Yao at Memorial Hermann-Texas 
Medical Center and the Plaza Ambulatory Surgery Center will be included 
Number of Sites: 
Single site / UTHEALTH 
 
Study Duration: 
We anticipate recruitment will take 9 months. 
 
Subject Duration: 
Each subject will be followed for 5 days after surgery. 
 
 
 
General Information 
 
Endoscopic sinus surgery (ESS) is a common procedure performed in the US with roughly 500,000 
cases occurring annually. Many surgeons prescribe opioid pain medications for pain control in the 
postoperative period. Given the current opioid epidemic, studies ought to determine the true 
necessity of their use to prevent unnecessary narcotic usage. 
 
Background Information 
 
Endoscopic sinus surgery is an extraordinarily common procedure performed in the US. Currently, 
there is no standardized postoperative pain regimen. Generally, most surgeons prescribe opioids for 
postoperative pain control in patients undergoing functional endoscopic sinus surgery. Traditionally, 
rhinologists have avoided the use of non-steroidal anti-inflammatory drugs (NSAIDs) due to fear of 
increased bleeding risks in the postoperative period. However, opioids have their own side effects, 
including respiratory depression, constipation, addiction, and nausea/vomiting. Recently, our group 
has found the use of NSAIDs to be safe and effective in the postoperative period. There is now 
equipoise regarding the medication of choice for pain control after FESS. No definitive study has 
compared the level of pain control in patients receiving NSAIDs to those receiving opioids in the 
postoperative period after ESS. In fact, there is a significant paucity of data regarding postoperative 
pain scores in patients undergoing ESS. 
 
Our hypothesis is that NSAIDs, specifically diclofenac, are safe and effective in the postoperative 
period after ESS. We believe that NSAIDs will provide pain relief that is non-inferior to opioids in the 
days following ESS. To our knowledge, no studies have compared the use of NSAIDs to opioids in the 
postoperative period following ESS. If our hypothesis is true, this study will provide the basis for a 
significant shift in prescribing patterns following ESS and obviate the need of opioid usage in the 
roughly 500,000 patients undergoing ESS annually. 
 
Objectives 


UT Houston Protocol Template 
Adapted from NIH protocol template and ICH Guidelines 
IRB NUMBEPRag: eHS3Co-fM6S-18-0242 
IRB APPROVAL DATE: 06/26/2018 
 
 
Our primary objective is to compare overall pain score (10 cm visual analog scale) at 24 hours post- 
surgery between patients receiving diclofenac sodium to those receiving acetaminophen- 
hydrocodone following ESS and/or septoplasty. 
 
Secondary objectives will be to compare average, most severe, and least severe 24 hour pain score 
at 48 hours, 72 hours, and 120 hours post-surgery between patients receiving diclofenac sodium to 
those receiving acetaminophen-hydrocodone following ESS. Additional secondary objectives will be 
to determine the rate of bleeding complications in patients receiving diclofenac sodium to those 
receiving acetaminophen-hydrocodone following ESS as well as noting the rates of constipation and 
nausea/vomiting in each group. 
 
Study Design 
 
We propose to perform a randomized, controlled study to compare the safety and efficacy of 
diclofenac sodium when compared to the acetaminophen-hydrocodone following ESS. Patients will 
be randomized by computer-generated sequencing in conjunction with a standard envelope system. 
 
Our primary outcome will be the overall pain score on a 100 mm visual analog scale at 24 hours 
following ESS. 
 
Secondary outcome measures will be the overall pain scores, most severe pain score experienced in 
the 100 mm VAS, and least severe pain score experienced at 48 hours, 72 hours, and 120 hours 
following ESS. An additional secondary outcome will be the number of bleeding complications as 
defined as those requiring a trip to the emergency room or requiring intervention or epistaxis as 
well as rates of constipation and nausea/vomiting among participants in each group. 
 
Study Population 
 
Inclusion criteria will be English speaking adults (age >18) who are candidates for endoscopic sinus 
surgery as determined by medical necessity by the treating rhinologist. 
 
Exclusion criteria will be allergy to either NSAIDs or opioids, contraindication to NSAIDs (ex. gastritis, 
chronic kidney disease), surgical plan exceeding basic endoscopic sinus surgery, use of anti- 
coagulation, the presence of any pain disorder, the current usage of any analgesic medication, 
history of opioid addiction, pregnancy, history of chronic pain or fibromyalgia, current daily use of 
NSAIDs, acetaminophen, opioids or other analgesics (pregabalin, tramadol, etc). 
 
All patients scheduled for surgery will be offered inclusion in the study. 
 
Study Procedures 
 
This study will require no additional study visits beyond the routine clinical postoperative visits. 
 
An electronic REDCap database will be created and postoperative pain surveys will be emailed to 
each patient at 24 hours, 48 hours, 72 hours, and 120 hours post-ESS. 
 
Background information including age, sex, history of migraines, temporomandibular joint disorder, 
fibromyalgia, pain disorders and the current use of pain medication or NSAIDs will be input into the 
REDCap database prior to surgery. 
 
Data and Safety Monitoring 
 
No adverse events are expected. Epistaxis after ESS is not uncommon and patients receive 
instructions regarding postoperative epistaxis as standard procedure. 
 
Any unexpected events (including adverse events, protocol deviations, other problems) will be 
reported directly to the principal investigator at the time of the incident. 


UT Houston Protocol Template 
Adapted from NIH protocol template and ICH Guidelines 
IRB NUMBEPRag: eHS4Co-fM6S-18-0242 
IRB APPROVAL DATE: 06/26/2018 
 
 
On the first day of every month after study initiation, information regarding bleeding events 
experienced postoperatively will be reviewed. In the event of a >5% increase in bleeding rate in the 
group receiving diclofenac, the study will be halted. 
 
Statistics 
 
Based off of a small pilot series of 9 patients, the means score 24 hours after FESS was 30 with a 
range of 10-75 and standard deviation of 22.8. 
 
Sample calculations were performed for a non-inferiority limit of 15mm on the 100mm VAS score, 
90% power, alpha of 0.025, with an estimated standard deviation of 22.8. 
 
41 patients are calculated to be required in each group for a total patient count of 82 
 
Due to roughly an anticipated 10% dropout (failure to complete survey at 24 hours), we plan to 
recruite 100 patients 
 
Interim analysis for safety purposes will only be performed via the proportionality test for epistaxis 
requiring unplanned visits to the emergency room or physician’s office. The anticipated baseline 
rate for this complication is 1% each month of the trial. The trial will be terminated if a significant 
number of epistaxis beyond the baseline is found in the NSAID group. 
 
Analysis for primary and secondary outcomes will be performed via a t-test for two independent 
means for pain scores at 24, 48, 72, and 120 hours after FESS 
 
Analysis of other secondary outcomes of patients’ experiences with epistaxis, constipation, and 
nausea/vomiting is to be done via the proportionality test 
 
All randomized subjects with returned questionnaires will be included in the statistical analysis. 
 
Analysis is performed with STATA 14 (College Station, TX) 
 
Ethics 
 
IRB approval will be sought from CPHS. 
 
Patients will be offered inclusion in the clinic and will be consented at that time if they elect to 
participate. 
 
Data handling and record keeping 
 
All data will be maintained in the UTHEALTH REDCap database. Data will only be accessible by the 
principal investigator and co-investigator Saini. 
 
The only identifying information that will be stored in the REDCap database will be the patient’s 
Allscripts MRN and email address. Once all information is collected, medical record numbers and 
email addresses will be removed from the dataset so that the information is no longer identifiable. 
 
Quality control and assurance 
 
Co-investigator Saini will aggregate data directly from Allscripts for input into the REDCap database. 
This will ensure that data is accurate, consistent, complete and reliable. 
 
There are no plans to have ongoing third party monitoring. 
 
Publication Plan 
 
The study results will be submitted to the American Rhinologic Society for oral presentation for the 
Spring 2019 meeting. 
 
The results will not be directly returned to the study participants. 
 
ATTACHMENTS 


UT Houston Protocol Template 
Adapted from NIH protocol template and ICH Guidelines 
IRB NUMBEPRag: eHS5Co-fM6S-18-0242 
IRB APPROVAL DATE: 06/26/2018 
 
 
1. Schematic of Study Design 
2. Study Schedule 
3. Consent Document 
4. Case Report Form 


UT Houston Protocol Template 
Adapted from NIH protocol template and ICH Guidelines 
IRB NUMBEPRag: eHS6Co-fM6S-18-0242 
IRB APPROVAL DATE: 06/26/2018 
 
Sinus Surgery 
Postop Day 1 
Pain Survey 1 
Postop Day 2 
Pain Survey 2 
Postop Day 3 
Pain Survey 3 
Postop Day 5 
Pain Survey 4 
Schematic Design of Study 
 
 
 
 
 
 
 
 
 
 
 


UT Houston Protocol Template 
Adapted from NIH protocol template and ICH Guidelines 
IRB NUMBEPRag: eHS7Co-fM6S-18-0242 
IRB APPROVAL DATE: 06/26/2018 
 
Study Schedule 
1. Study Initiates: 
April 1, 2018 
2. Data Collection Concludes 
January 1, 2018 
3. Data Analysis Complete 
February 1, 2018 
4. Submission for Publication 
March 1, 2018