Clinical trial NCT03457116
Conditions: Rhinoplasty Non-steroidal Ant Inflammatory Drugs Opioid Use
Sponsor: NYU Langone Health
Start date: 2018-01-30; Completion date: 2020-11-02
Enrollment: 70 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to compare the efficacy and safety of oral opiate pain medication vs non-steroidal ant inflammatory drugs (NSAIDs) in the treatment of postoperative rhinoplasty pain. This study will also evaluate potential contributing factors affecting the efficacy of these pain control methods. Patients will be randomized to receive either NSAIDs in the form of 400mg of Ibuprofen or Norco (hydrocodone 5mg- acetaminophen 325mg) to be used for post-operative pain. The study will then compare which is more effective in controlling post operative pain.

Detailed description:

Arms: arm 1: 400mg of Ibuprofen arm 2: Norco (hydrocodone 5mg- acetaminophen 325mg)
Interventions: intervention 1: Norco intervention 2: NSAID
Intervention descriptions: intervention 1: 20 tablets of Hydrocodone 5mg-Acetaminophen 325mg (Norco) intervention 2: Ibuprofen 400mg for post-operative pain

Protocol documents:
Prot_SAP_000.pdf: 
Page 1 of 7 
PI: Judy Lee 
Study Number: 17-01389 
ClinicalTrials.gov Identifier: NCT03457116 
Version Date: January 17, 2018 
 
Prospective Randomized Trial comparing Narcotics vs NSAIDs for post-operative analgesia in 
outpatient Rhinoplasty  
Purpose of the Study and Background 
Hypothesis 
That narcotic pain medication is not required to treat post-operative pain in outpatient rhinoplasty.  
Purpose of the Study 
The purpose of this study is to compare the efficacy and safety of oral opiate pain medication vs non-
steroidal anti-inflammatory drugs (NSAIDs) in the treatment of postoperative rhinoplasty pain. This study 
will also evaluate potential contributing factors affecting the efficacy of these pain control methods.   
Background   
With the rise of opioid addiction within the United States and its adverse consequences, limiting or 
eliminating narcotic prescriptions after outpatient surgery should be a priority for all surgeons. In 2012, 
4.2 billion prescriptions were written in the United States, 289 million (6.8%) for opioids1, and of which 
hydrocodone was the number one most prescribed medication 2. It is believed there are 3.8 million 
misusers of pain relievers3, resulting in a prescription opioid abuse problem costing an estimated 55.7 
billion dollars4.  All physicians, including otolaryngologists, must find effective ways to combat this 
epidemic, while still providing appropriate postoperative care. As ambulatory procedures make up the 
majority of otolaryngologic surgeries performed in the United States, limiting or eliminating narcotic 
prescriptions for these cases should be a primary goal amongst otolaryngologists.  
Rhinoplasty and septorhinoplasty are common procedures performed by Otolaryngologist and facial 
plastic surgeons with generally low complication rates. There is little data describing a patient’s post-
operative pain course. The majority of these procedures are performed at outpatient surgical centers or in 
an ambulatory hospital setting with immediate discharge home after recovery. Otolaryngologists routinely 
prescribe opioids for these procedures without an understanding of their patients’ requirements for pain 
medications.  This leads to overprescribing and eventual left-over narcotics.  A recent study found 67% of 
patients had surplus narcotics from the initial prescription and 91% of those patients kept that medication 
at home following urological surgery5. Additionally, another study found that patients after upper 
extremity surgical procedures relating to soft tissue only required a mean 5.1 opioid pills after surgery and 
in general patients were being prescribed 3 times greater the amount of opioid medications than needed 4. 
Currently at New York University Langone Hospital, it is standard practice to prescribe >12 narcotic pills 
to patients undergoing most procedures; however, there are no guidelines or criteria to assist in managing 
our patients’ post-operative pain medications.  
 
Study Design  
The study is a prospective, randomized, clinical trial enrolling patients undergoing rhinoplasty or 
septorhinoplasty with Dr. Judy Lee, Dr. Jeffrey Markey or Dr. Matthew White in the Department of 


Page 2 of 7 
PI: Judy Lee 
Study Number: 17-01389 
ClinicalTrials.gov Identifier: NCT03457116 
Version Date: January 17, 2018 
 
Otolaryngology-Head and Neck Surgery at New York University. The length of the study participation 
will be approximately 1 week for each patient.   
The randomization process will involve using Microsoft Excel rand() function, which generates and 
evenly distributed random decimal x between 0 and 1.  If 0 < x < 0.5, the patient will be randomized to 
the NSAID group.  If 0.5 <= x < 1, the patient will be randomized to the Norco group.  This will be 
performed after a patient agrees and consents to participation in this study. 
Patients will qualify for surgery if they require a septorhinoplasty for nasal airway obstruction or choose 
to undergo a rhinoplasty for cosmetic purposes. All patients who are recommended a rhinoplasty will be 
offered participation in this randomized clinical trial. After their surgery, all patients will be discharged 
home. Patients will be randomized into the opioid or NSAID arm of the trial. The control arm will be 
prescribed 20 tablets of Hydrocodone 5mg-Acetaminophen 325mg (Norco) and the test arm prescribed 
Ibuprofen 400mg for post-operative pain. Patients will be contacted via telephone on post-operative day 0 
and post-operative day 1 and then seen in the office on post-operative day 7 to evaluate the patients. Each 
patient will be asked regarding their level of comfort or discomfort, and how effective they feel their pain 
regiment is. Outcome measure will be both objective and subjective. A pain scale from 0-10 will be 
utilized to assess a patient’s pain objectively. Additionally, each patient will be asked if they felt their 
pain was subjectively controlled (yes/no).  In each arm, a survey will be used to assess the frequency of 
usage, the dose, timing and amount of the specific analgesic consumed. Patients within the NSAID arm of 
the trial will have the ability to speak with their surgeon to escalate their level of analgesia if their pain is 
unable to be controlled on any post-operative day. This will be recorded in the results. Additional 
outcome measures will be recorded such as open vs closed rhinoplasty, use of osteotomies, concurrent 
septoplasty or turbinate reduction. Adverse effects, complications and demographics will also be 
examined.  
 
Characteristics of the Research Population 
Number of subjects ( 
We used similar previous studies to predict baseline pain scores as well as expected improvements after 
surgery6,7. With 30 subjects for each group, we can detect the difference between the intervention group 
with mean 1.6 and the control group with mean 2.6 (SD=1.3) by assuming a 80% power and 5% type-I 
error under a two-sided Two-Sample T-Test 
 
Numeric Results for Two-Sample T-Test 
Null Hypothesis: Mean1=Mean2. Alternative Hypothesis: Mean1<>Mean2 
The standard deviations were assumed to be unknown and equal. 
  
                                        Allocation 
Power           N1        N2          Ratio         Alpha           Beta        Mean1        Mean2           S1              S2 
0.80000          25        25          1.000      0.05000      0.20000             2.6             1.5             1.3             1.3 
0.80000          30        30          1.000      0.05000      0.20000             2.6             1.5             1.3             1.3 
0.80000          35        35          1.000      0.05000      0.20000             2.6             1.7             1.3             1.3 
 
 


Page 3 of 7 
PI: Judy Lee 
Study Number: 17-01389 
ClinicalTrials.gov Identifier: NCT03457116 
Version Date: January 17, 2018 
 
 
Gender of subjects 
The gender of subjects should be roughly equal within each treatment arm 
Age of Subjects 
Patients will be between the ages of 18-70. 
Racial and Ethnic Origin 
Patients should be a representative group across all racial and ethnic origins.  There are no exclusion 
criteria based on race or ethnicity. 
Inclusion Criteria 
Patients 18-70 years old undergoing septorhinoplasty or rhinoplasty for either obstructive or aesthetic 
reasons. All approaches to rhinoplasty and surgical techniques utilized will be included.  This will include 
patients that undergo additional procedures during the rhinoplasty including osteotomies, turbinate 
reduction, septoplasty, nasal valve repair and ear cartilage graft. These procedures are commonly 
performed as part of the rhinoplasty.  
Exclusion Criteria 
Patients who undergo a rhinoplasty requiring a rib cartilage graft for the procedure as this is known to 
cause significant pleuritic chest pain. Additionally, patients receiving functional endoscopic sinus surgery 
concurrently with the rhinoplasty will be excluded. Patients with known history of gastrointestinal bleeds, 
peptic ulcer disease or who have other comorbidities that prevent them from taking NSAIDs. Patients 
with a history of radiation, active head and neck malignancy or other pain disorders such as various 
rheumatologic diseases will be excluded to decrease confounding factors in the control of pain. Anyone 
who is allergic to either of the medications.  
Vulnerable Subjects 
There will be no vulnerable subjects enrolled in this study  
Methods and Procedures 
Methods and Procedures  
The rhinoplasties and surgical techniques involved will be performed at the surgeons’ discretion, utilizing 
either an open or closed approach. Incision types, cartilage grafts, techniques and correction methods will 
be determined by the surgeon for each individual patient and no patient will be excluded based on the 
techniques used. Nasal splints may be used in the patient’s nose based on the procedures performed.  All 
patients post operatively will have an aquaplast nasal splint placed over the bridge of their nose in the 
standard fashion.  Patients will then be given and instructed on pain medication use depending on the 
treatment arm in which they were placed. The narcotic group will be given a prescription for twenty 
Norco tablets (5mg hydrocodone- 325mg acetaminophen) and be told to take for pain every 4-6 hours as 
needed. This is consistent with the standard of care within the department and follows the manufacturer 
labeling for pain management The NSAID treatment arm will be instructed to take 400mg Ibuprofen 


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PI: Judy Lee 
Study Number: 17-01389 
ClinicalTrials.gov Identifier: NCT03457116 
Version Date: January 17, 2018 
 
every 4-6 hours for pain as needed consistent with the manufacturer labeling and the American Pain 
society use. All patients will be contacted on POD0 and POD1 to determine what their pain score is on a 
numerical scale and whether or not they believe their pain control has been effective. Patients within the 
NSAID treatment arm, at any point post operatively, will be able to request a prescription for narcotics if 
they feel that their pain is not well controlled. On POD7, the patients will be given a survey to document 
the total number of doses of pain medication taken (1 Norco tab vs 400mg Ibuprofen), number of days 
requiring pain medication, need to call for a prescription and side effects noted. The study for each patient 
will be concluded at that time point.  
Data Analysis and Data Monitoring 
Data analysis will be performed with the help of Binhuan Wang, a biostatician at NYU affiliated with the 
Department of Otolaryngology. He will not have any access to PHI, and will only be given de-identified 
patient data.  The primary outcome to be compared will be the overall pain control based on the pain scale 
using a two-sample proportion test. We will also compare complication rates, necessity of a patient phone 
call, and subjective pain control.  
Data Storage and Confidentiality  
Data storage will be kept in a REDCAP database file.  This ensures patient confidentiality.  Any 
presentations or papers will not include any protected health information (PHI).  Patient information 
entered into the database will include demographic information as well type of surgery performed, any 
complications, and survey results.  Only Dr. Lee, Dr. Garber, Dr. White and Dr. Markey will be granted 
access to entering information into this database file.  These individuals will have access to the linking 
key. 
 
Risk/Benefit Assessment 
Subject Safety 
Patients will be monitored for safety by each specific surgeon performing their case. They will see their 
patients in the postoperative period based on current standard of care, and will address any complications 
that their patients may have. Complications will be treated with the current standard of care.  
Any patient within the treatment arm requiring higher levels of pain control will be allowed to have a 
prescription called by their primary surgeon, as needed. These patients’ data will be included and used as 
a secondary outcome measure to compare.  
Risks 
NSAIDs are known to cause an increased risk of gastrointestinal adverse events including bleeding, 
ulceration and perforation of the stomach or intestines. Additionally, other adverse reactions include 
heartburn, nausea, dyspepsia, vomiting.  
Norco, as with all opioid medications have a risk associated with addiction, abuse and misuse. 
Additionally, they can cause respiratory depression. The acetaminophen within Norco has been associated 
with liver failure.   


Page 5 of 7 
PI: Judy Lee 
Study Number: 17-01389 
ClinicalTrials.gov Identifier: NCT03457116 
Version Date: January 17, 2018 
 
The risk of randomization exists in any randomized study.  It is possible that one treatment is superior, or 
that one treatment poses additional risk compared to the other.  These outcomes will be monitored at 
regular intervals throughout the study, as described in the data safety monitoring plan. 
Protection against risks 
Patients that enroll in this study are not subject to any additional risks than they would encounter if they 
underwent rhinoplasty without involvement in the study. For patients in the treatment group, they will 
have the option to increase their pain medication regiment, as needed. The primary surgeon will 
electronically prescribe pain medication for the patient if they feel at any point during their study that 
their pain is not managed appropriately. This will be explained to the patients prior to enrolling within the 
study. Additionally, all patients will be informed of the side effects and risk factors associated with 
narcotic and NSAID use prior to the surgery. Patients will be monitored on POD0, POD1 and POD7, and 
will have the ability to contact their physicians if they notice any side effects or problems related to the 
pain medications that are listed above.  
Potential Benefits to the subjects 
The patients benefit by potentially not requiring the use of narcotics and the known side effects related to 
narcotics. Decreasing narcotic use can lead to less addiction and abuse within society.  
Data Safety monitoring plan 
Data and adverse events will be monitored by the principal investigator, who has performed hundreds of 
rhinoplasty procedures. Adverse events will include post-operative bleeding, infection, significant 
gastrointestinal illness related to NSAIDs such as bleeding, ulceration or perforation or events of 
respiratory depression or liver failure related to Norco use. Any adverse events will be recorded in the 
patient’s chart and within the REDCAP database. Safety information will be collected at the postoperative 
clinic visits (POD0, POD1, and POD7). Reportable Adverse events will be reported within 48 hours of 
their occurrence. 
Interim analysis of the data will be conducted every 2 months to assess safety and/or identify whether a 
treatment arm demonstrates superiority in efficacy. The treatment outcomes, as well as complications, 
will be routinely analyzed at these intervals. If, after a minimum of 15 subjects in each arm, one treatment 
arm is statistically significant in pain control on the objective pain scale of 1-10 (based on a t-test 
comparing two means), the study will be closed early. Additionally, if it is determined that the risk of a 
major complication is significantly higher in one arm compared to the other (based on a Fisher’s exact 
test), the study will be closed early. . A major complication would be respiratory depression requiring 
hospitalization, significant bleeding event, or a reaction related to the pain medications requiring 
hospitalization. The reason for the minimum number of subjects as stated above is to avoid statistical 
error due to sample size.  
These interim analyses of data safety monitoring will be communicated to the IRB via email.  


Page 6 of 7 
PI: Judy Lee 
Study Number: 17-01389 
ClinicalTrials.gov Identifier: NCT03457116 
Version Date: January 17, 2018 
 
Subject Identification, Recruitment and 
Consent/Assent 
 
Method of Subject Identification and Recruitment 
Patients presenting to the offices of Dr. Judy Lee, Dr. Jeffrey Markey or Dr. Matthew White requiring a 
septorhinoplasty or rhinoplasty for nasal obstruction or cosmetic deformity, with or without septal 
deviation. Each clinician will be part of the recruitment process and will be the ones to explain the study 
to each patient.  
Process of Consent 
Each clinician will explain the study and both parts of the trial to each patient. The clinicians will explain 
the consent form to each patient. This will be done privately during their office visit. The patients will be 
scheduled for surgery after this office visit. If the patient is agreeable to the study, they will sign the 
consent form for the trial and surgery  at a pre-operative visit  
Subject Capacity 
This study involves only patients who are capable of making their own medical decisions and are able to 
sign their own consent forms. 
Subject/Representative Comprehension 
Patients will only be eligible for study participation if they are able to demonstrate comprehension of the 
risks, benefits, and alternatives of surgery, as well as the risks, benefits, and alternatives of being involved 
in this study. 
Debriefing Procedures 
After the completion of the study, patients will be informed of the outcomes from the trial.  
Consent Forms 
Each patient will be required to understand and sign a consent form for enrollment in this study.  In 
addition, they will sign another consent form for surgery. 
Documentation of Consent 
All study consent forms will be kept on file in Dr. Judy Lee’s office 
Costs to the Subject 
There are no additional costs to the subject.  The subject and/or their health insurance may be billed for 
the costs of medical care during this study if these expenses would have happened even if they were not 
in the study, or if their insurance agrees in advance to pay.  These costs will be billed to their insurance 
company.  If the subject’s insurance does not cover these costs or they do not have insurance, these costs 
will be the subject’s responsibility. 
Payment for Participation 
Patients will not be paid or incentivized for participation in this study.  
References 
1.  
Levy B, Paulozzi L, Mack KA, Jones CM. Trends in Opioid Analgesic-Prescribing Rates by 


Page 7 of 7 
PI: Judy Lee 
Study Number: 17-01389 
ClinicalTrials.gov Identifier: NCT03457116 
Version Date: January 17, 2018 
 
Specialty, U.S., 2007-2012. Am J Prev Med. 2015;49(3):409-413. 
doi:10.1016/j.amepre.2015.02.020. 
2.  
Manchikanti L, Helm S, Fellows B, et al. Opioid epidemic in the United States. Pain Physician. 
2012;15(3 Suppl):ES9-38. doi:10.1016/j.emc.2015.11.002. 
3.  
2. Substance Abuse and Mental Health Services Administration. Results from the 2015 National 
Survey on Drug Use and Health: Summary of National Findings. Vol H-41.; 2015. 
https://www.samhsa.gov/data/sites/default/files/NSDUH-FFR1-2015/NSDUH-FFR1-
2015/NSDUH-FFR1-2015.pdf. 
4.  
Birnbaum HG, White AG, Schiller M, Waldman T, Cleveland JM, Roland CL. Societal Costs of 
Prescription Opioid Abuse, Dependence, and Misuse in the United States. Pain Med. 
2011;12(4):657-667. doi:10.1111/j.1526-4637.2011.01075.x. 
5.  
Bates C, Laciak R, Southwick A, Bishoff J. Overprescription of postoperative narcotics: A look at 
postoperative pain medication delivery, consumption and disposal in urological practice. J Urol. 
2011;185(2):551-555. doi:10.1016/j.juro.2010.09.088. 
6.  
Church CA, Stewart IV C, O-Lee TJ, Wallace D. Rofecoxib versus hydrocodone/acetaminophen 
for postoperative analgesia in functional endoscopic sinus surgery. Laryngoscope. 
2006;116(4):602-606. doi:10.1097/01.MLG.0000208341.30628.16. 
7.  
Fathi M, Zare MA, Bahmani HR, Zehtabchi S. Comparison of oral oxycodone and naproxen in 
soft tissue injury pain control: a double-blind randomized clinical trial. Am J Emerg Med. 
2015;33(9):1205-1208. doi:10.1016/j.ajem.2015.05.021.