Clinical trial NCT04149964
Conditions: Post-operative Pain Sinus Surgery
Keywords: Post-operative pain Sinus pain Sinus surgery Septum Pain deviated septum
Sponsor: William Beaumont Hospitals
Start date: 2019-11-27; Completion date: 2022-09-21
Enrollment: 65 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will evaluate if the use of acetaminophen round the clock (scheduled doses) will lead to less opiate use in the first week post-operative (after surgery) in sinus/septum surgery patients. Participants will be randomized like a flip of a coin to either the standard of care pain treatment of acetaminophen 325 mg as needed for pain plus opiates (acetaminophen/hydrocodone) as needed for breakthrough pain; OR to the study arm of acetaminophen 650 mg every 6 hours plus opiates (Oxycodone)as needed for breakthrough pain.

Detailed description:
Pain control in the postoperative period following septum and/or sinus surgery is controversial, as there is no consensus statement regarding current guidelines to direct clinical practice. Recent legislation limits opioid prescription length to 5 days only, which brings into question whether legislation will affect prescribing practices of physicians and whether or not giving patients an alternative to opiates will be a more efficacious route.

Current prescribing practices for septum and sinus surgery of the Otolaryngology private practice group includes as-needed acetaminophen 325 mg and as-needed acetaminophen/hydrocodone 7.5 mg/325 mg. If it can be demonstrated that use of 650 mg acetaminophen in scheduled doses of every 6 hours can decrease postoperative opiate use in the first week without significantly increase in patient pain, this may be deployed as an effective strategy of pain control as the use of opiates has come under scrutiny and attempts are being made to decrease or limit the use of these medications in the medical setting.

This study would look to demonstrate that scheduled doses of acetaminophen as opposed to reactionary as-needed acetaminophen can control post-operative pain to the point where narcotics would not be necessary.

Arms: arm 1: Standard of Care Post-operative pain medication, Acetaminophen 325 mg every 6 hours as needed for pain plus acetaminophen/hydrocodone 7.5 mg/325 mg 1 tab every 4 hours as needed for pain. arm 2: Acetaminophen 650 mg 1 tab every 6 hours round the clock plus Oxycodone 5 mg 1 tab every 6 hours as needed for breakthrough pain,.
Interventions: intervention 1: Acetaminophen 325 mg Oral Tablet intervention 2: Acetaminophen 650 mg Oral Tablet intervention 3: OxyCODONE 5 mg Oral Tablet intervention 4: Acetaminophen/Hydrocodone 325 mg/7.5 mg oral tablet
Intervention descriptions: intervention 1: Standard of Care Acetaminophen 325 mg every 6 hours as needed for pain intervention 2: Acetaminophen 650 mg scheduled every 6 hours round the clock for pain intervention 3: Oxycodone 5 mg every 4 hours as needed for breakthrough pain intervention 4: Acetaminophen 325 mg/ Hydrocodone 7.5 mg oral tablet every 4 hours as needed for breakthrough pain

Protocol documents:
Prot_SAP_000.pdf: 
TITLE:   
Postoperative Pain Control in Septum and Sinus Surgery 
NCT 04149964 
Approval date: 10/31/2019  
Protocol and Statistical Analysis Plan 


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Investigator-Initiated Protocol – Eric Cox, DO and David Seel, DO
TITLE
Postoperative pain control in septum and sinus surgery: A novel approach
STUDY OVERVIEW
Rationale/Background:
The purpose of this study is to investigate if a new protocol of post-operative pain management 
in sinus/septum surgery patients will lead to less opiate use in the first week. Current 
prescribing practices for septum and sinus surgery of the ENT private practice group that is 
included in this study includes as needed 325 mg acetaminophen and as needed 
acetaminophen/hydrocodone, usually 7.5 mg/325 mg. If it can be demonstrated that use of 
scheduled 650 mg acetaminophen drastically decreases postoperative opiate use in the first 
week, thought could given to reducing the number of opiates prescribed, or even eliminating 
opiate use all together.
Pain control in the postoperative period following septum and/or sinus surgery is controversial, 
as there is no consensus statement regarding current guidelines to direct clinical practice. 
Our study would look to demonstrate that scheduled doses of acetaminophen as opposed to 
reactionary as needed acetaminophen would control post-operative pain to the point where 
narcotics would not be necessary. 
Objectives/Endpoints:
Primary objective: to investigate if postoperative pain control with scheduled acetaminophen 
alone versus as needed acetaminophen will lead to decrease use of opiates in the first week of 
the postoperative period
Secondary objective: To investigate if postoperative subjective pain scores are different 
between the control arm of acetaminophen as needed with as 
needed hydrocodone/acetaminophen versus scheduled acetaminophen with oxycodone as 
needed
Methodology:
The study methodology will be conducted as follows. Patients will be identified for the study 
who present day of for previously scheduled sinus/septum surgery. After consent is obtained by 
information sheet, patients will be randomized into one of two different study arms. The 
randomization will occur using a patient randomization sheet provided by the Beaumont 
Biostatistician Office.
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One arm of the study will be given instructions to take acetaminophen 325 mg every 6 hours as 
needed to control postoperative pain and will be given a prescription for no more than 3 days 
of 7.5 mg/325 mg acetaminophen/hydrocodone with instructions to take this medication as 
needed every 4 hours for breakthrough pain. This is the current prescribing practices of the 
otolaryngologists included in the study. The study arm of the study, which is also a prescribing 
practice being used at Beaumont Farmington Hills, will be given instructions to take 650 mg 
acetaminophen only on a scheduled basis of every 6 hours and will be given no more than 3 
days of 5 mg oxycodone with instructions take this medication for breakthrough pain only every 
4 hours. The patients will be given these specific opiate strengths as they are equal morphine 
equivalents. All patients will have clear instructions on how to use the medication with 
instructions clearly imprinted on the medication bottles.
Scripts will be written by the consent provider prior to discharge from the hospital, per 
randomization.
The two arms of the study will then be given a survey at the first postoperative visit, 
approximately 1 week plus or minus 3 days, with questions regarding total amount of opiates 
taken as well as postoperative subjective pain scores. If patients are unable to follow up in the 
aforementioned time frame, a phone survey will be conducted by the principle investigator. 
Risks and Benefits:
There are no risks to the patients undergoing this study, as both protocols used are accepted 
means of controlling postoperative pain, and both groups are given similar medications, albeit 
with different instructions. Additionally, there are no benefits to those enrolled, both financial 
and clinically.
Eligibility Criteria:
1) Undergoing primary sinus surgery, primary septum surgery, or primary sinus/septum 
surgery
2) 18 years of age or older
3) Male or female
4) No known allergies to or contraindications to the use of acetaminophen, hydrocodone, 
or oxycodone
5) Patients discharged to home after surgery
Data Analysis:
The data collected will be analyzed in order to determine the total amount of opioids used 
between the two groups. Analysis will also look into any characteristic differences between the 
two groups and whether post-operative pain scores differed subjectively. The results will be 
used to, hopefully, show that opioids in the post-operative period following sinus/septum 
surgery are not needed, and that pain control can be accomplished using scheduled Tylenol. 
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The hope of this study is to produce a journal-worthy article that would be accepted for 
publishing, in terms of data dissemination. 
Sample Size:
Tentatively, 200. 
Data Safety Monitoring Plan:
Study does not involve greater than minimal risk.
Summarize Existing Study Data:
A study published by Gray et al in 2018 found that most all otolaryngologists prescribe opiates 
in the postoperative period and that there was no significant difference in prescribing practices 
between geographic regions or practice setting. They did, however, find that there was a 
significant difference in adjuvant pain management strategy between academic centers and 
private practice physicians.
 
A study published in 2019 by Harvard University found that almost 95% of patients undergoing 
sinus surgery were prescribed an opiate postoperatively. Of those patients, 91.4% got the 
prescription filled, and 73.1% reported taking no opiates at their first follow up appointment. 
Given these findings, one has to wonder if opiates should even be prescribed in the 
postoperative period and wonder where those unused opiates went. Another study published 
in 2018 by Wayne State University found that the mean opioid prescription length in a cohort of 
570 surgeons was 5.4 days, which brought into question whether recent legislation limiting 
opioid prescription length to 5 days would have an impact, if at all, on prescription length. This 
again brings into question whether legislature will truly affect prescribing practices of 
otolaryngologists and whether or not giving patients an alternative to opiates would be a more 
efficacious route. Another study published in 2013 by University Hospital Jena looked at pain 
control for postoperative day one in patients undergoing primary endoscopic sinus surgery and 
found that patients reporting significant pain were typically younger and that their pain 
management was insufficient with a routine of acetaminophen and piritramide.
References:
Gray, ML, Fan, CJ, Kappauf, C, et al. Postoperative pain management after sinus surgery: a 
survey of the American Rhinologic Society. Int Forum Allergy Rhinol. 2018; 8: 1199– 1203.
Sethi, R. K., Miller, A. L., Bartholomew, R. A., Lehmann, A. E., Bergmark, R. W., Sedaghat, A. R. 
and Gray, S. T. (2019), Opioid prescription patterns and use among patients undergoing 
endoscopic sinus surgery. The Laryngoscope, 129: 1046-1052. doi:10.1002/lary.27672
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Arianpour, K., Nguyen, B., Yuhan, B., Svider, P. F., Eloy, J. A., & Folbe, A. J. (2018). Opioid 
Prescription Among Sinus Surgeons. American Journal of Rhinology & Allergy, 32(4), 323–
329. https://doi.org/10.1177/1945892418773578
Patient Questionnaire
Patient code : ____________________
Date : __________________________
Demographics
Gender:
Male
Female
Rather not specify
Age: ____________
The following questions are about pain related to your surgery that you experienced during the first 7 days 
after your operation. Please fill out this survey to the best of your ability.
Q1. On this scale, please indicate the least pain you had in the first 7 days:
0
1
2
3
4
5
6
7
8
9
10
no pain
worst pain 
possible
Q2. On this scale, please indicate the worst pain you had in the first 7 days:
0
1
2
3
4
5
6
7
8
9
10
no pain
worst pain 
possible
Q3. How often were you in severe (e.g. requiring break-through pain medication) pain in the first 7 
days? 
Please circle your best estimate of the percentage of time you experienced severe pain: 
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
never in 
severe pain
always in 
severe pain
Q4. How often did you take acetaminophen (Tylenol)? 
As needed
Every 6 hours
Q5. How many opiate narcotics did you take in total? 
   
________________________
Did not fill prescription
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Q6. Did you use any other forms of pain medication, over the counter or prescribed? 
Yes
No
Q7. If you answered “yes” to Q6, which medication(s)?
Q8. Do you take pain medication, including narcotics, for any other medical conditions?
Yes
No
Thank you for your time and feedback 
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Statistical Analysis Plan  
 
Demographic and outcome data will be stratified by study arm and summarized using mean (SD) or 
median (IQR) for continuous data and compared using a t-test or Mann-Whitney U test.  Categorical 
data will be  summarized using frequency (percent) and compared using Fisher's exact test