Clinical trial NCT04541147
Conditions: Pain, Postoperative
Sponsor: Duke University
Start date: 2021-04-14; Completion date: 2023-12-26
Enrollment: 24 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine if a post-operative course of oral dexamethasone affects opioid usage in pediatric patients undergoing tonsillectomy.

Patients who are scheduled to undergo tonsillectomy or adenotonsillectomy are randomized to receive either 1) a post-operative steroid course of oral dexamethasone in addition opioids, acetaminophen,NSAIDs or 2) opioids/acetaminophen/NSAIDS alone. All drugs are prescribed per approved FDA labeling. Children between the ages of 4-17 will be considered for enrollment.

Participants (or with the aid of parents/legal guardian for subjects unable to complete on their own) will complete a diary twice a day to record pain medication administration and visual pain scale. Remaining steroid and opioid medication will be measured at the routine post-operative appointment that occurs 4 - 6 weeks following surgery.

Detailed description:

Arms: arm 1: oral dexamethasone of 0.5mg/kg/day (max of 8mg/day), administered on post-operative days 1,3,5,7 in addition to standardized course of analgesics (opioids/acetaminophen/NSAIDs). arm 2: standardized course of analgesics (opioids/acetaminophen/NSAIDs)
Interventions: intervention 1: Dexamethasone intervention 2: Analgesics
Intervention descriptions: intervention 1: dexamethasone solution or tablet (depending on age of patient) at 0.5mg/kg/day max of 8mg/day, administered on post-operative days 1,3,5,7. intervention 2: standardization of post-operative analgesics (narcotics and non-narcotic medication).

* Oxycodone solution or tablet (depending on age of patient) at 0.05-0.1 mg/kg/dose every 6hrs; max 5mg (obese/OSA); prescribe 30 doses
* Acetaminophen 10-15 mg/kg/dose every 6 hours; max 500mg per dose; prescribe 56 doses (over the counter medication)
* Ibuprofen 5-10 mg/kg/dose every 6 hours; max 200 mg/dose; prescribe 56 doses (over the counter medication)

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
 
 
 
 
 
 
 
Randomized control trial of postoperative course of oral dexamethasone and effect on opioid usage in 
pediatric tonsillectomies in a tertiary care center 
 
Document Date: October 5, 2023 
 
NCT04541147 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Purpose of the Study 
 
The purpose of this study is to determine if a post-operative course of oral dexamethasone affects 
opioid usage in pediatric patients undergoing tonsillectomy.  Children and young adults, 4-21 years of 
age undergoing elective tonsillectomy within the Duke Health System without contraindication for 
steroid use will be enrolled. We hypothesize that a post-operative course of steroids will reduce opioid 
use. 
 
Primary Objectives: 
• 
To understand the effect, positive or negative, that post-operative steroids have on post-
operative pain control and analgesic use to optimize post-operative pain regimens 
• 
To assess the feasibility of reducing opioid use in post-operative tonsillectomy in pediatric 
patients 
 
 
Background & Significance 
 
We are in an opioid epidemic. Pain control while minimizing opioid use is a major goal. 
Adenotonsillectomy is one of the most common ENT surgeries, done on both children and adults. In 
2013, a codeine black box warning was passed, changing pain management for adenotonsillectomy in 
children. In February 2019, AAO-HNS included a recommendation for a single intravenous 
dexamethasone dose intraoperative for all pediatric tonsillectomies as a way to reduce post-operative 
nausea and vomiting, pain, and first oral intake. Additionally, it recommended that clinicians encourage 
the use of ibuprofen and acetaminophen to improve post-operative pain control and reduce opioid use. 
Further, oxycodone and morphine are suggested as preferable opioids given their lack of metabolism by 
CYP2D6 and therefore lower likelihood of unintended sedation (Mitchell 2019, Batisaki 2017, Tan 2017). 
There is wide variation in current post-operative narcotic prescribing practices (Horton, 2019). Chua et 
al., 2019 in their large cohort analysis using insurance claims did not show a change in return visits for 
pain associated with opioid prescription fills. 
 
Literature on post-operative steroid courses with pediatric tonsillectomy have mixed results in terms of 
pain scores and post-operative benefits. Redman et al., 2018 in their retrospective chart review (n= 
1200) utilized three post-operative doses of dexamethasone and noted a decreased number of patient 
phone calls and decreased rate of hemorrhage in the steroid group. Park et al., 2015, a randomized 
clinical trial (RCT) (n=198), showed decreased pain, quicker return to normal diet and increased re-
epithelization one week post-operatively in the 7-day post-operative prednisolone steroid group. Palme 
et al.,2000, in their double blind placebo controlled RCT (n=50) also utilized a 7-day post-operative 
course of prednisolone and demonstrated decreased nausea post-operatively and less paracetamol use 
in the 8 days after surgery. This study included children and adults > 5 years old. Maccassey et al., 2012, 
in their double blinded placebo controlled RCT (n=215) a 5 day prednisolone course and did not 
demonstrate a significant difference in post-operative nausea, pain and sleep. Generally short courses of 
post-operative steroids are considered safe and there were no adverse side effects noted in the above 
studies. There is a deficit of literature however on the effects of these short steroid courses on opioid 
use in pediatric tonsillectomies. 


 
Literature on post-operative steroids with adults and children greater than 12 years old undergoing 
tonsillectomy is also mixed. Plante et al., 2012 in a systematic review of RCTs identified 29 RCTs (n=2674 
patients) demonstrated comparable rates of bleeding with systemic steroids during tonsillectomy but 
increased incidence of intervention. This study is reflected in the 2014 SFORL guidelines recommending 
against the concurrent use of steroids and NSAIDS medication post tonsillectomy (Paganelli 2014). 
Batistaki et al.,2017 reviewed 7 RCT pediatric tonsillectomy studies, of which included perioperative 
dexamethasone doses with majority of studies showing reduced opioid use or increased time to first 
opioid dose. However these studies did not evaluate post-operative courses of steroids. Lachance et al., 
2008 preformed a similar design to the present study with the exception of subjects being adults. In this 
multicentric, double blind, placebo controlled, RCT (n=102) patients were randomized to receive a 4 day 
dexamethasone taper versus placebo.There was no statistically significant difference in visual analog 
pain scales scores or hydromorphone consumption between the two groups (Lachance, 2008). Stewart 
et al., 2002 in their double blind RCT (n=200) utilizing 8 day post-operative courses of steroids and/or 
anti-inflammatory v. placebo,  showed lower pain scores in a combination group of dexamethasone and 
piroxicam as well as less analgesic requirement in the 10 days following surgery (Stewart, 2002). 
There is a lack of research however on post-operative courses of steroids and optimal pain regimen for 
pediatric tonsillectomy. Specifically there is a deficit of research on the effect of post-operative steroid 
courses and opioid utilization, which the present study hopes to in part address.  
 
 
Design & Procedures 
 
This is a randomized control trial of pediatric subjects who are scheduled to undergo tonsillectomy or 
adenotonsillectomy. Patients will be randomized to receive a post-operative steroid course of oral 
dexamethasone in addition to opioids/acetaminophen/NSAIDs or opioids/acetaminophen/NSAIDS 
alone. All drugs will be given per approved FDA labeling, Dosing regimen in line with Cramer et al., 
(2020). Randomization will be based on odd or even day of surgery to be determined at time of 
scheduling surgery (at least 24 hours prior to surgery), with odd day receiving steroids. Patients will be 
considered off study after their follow-up appointment approximately 4-6 weeks post operatively. 
Steroid dosage will be weight based dexamethasone solution or tablet (depending on age/preference of 
patient) at 0.5mg/kg/day max of 8mg/day, administered on post-operative days 1,3,5,7. This is based on 
current practices of surgeons at Duke and in line with post-operative steroid courses utilized in the 
literature (Park 2015, Maccassey 2012, Redman 2018, Lachance 2008, Palme 2000). 
 
There will be standardization of post-operative analgesics (narcotics and non-narcotic medication).  
• 
Oxycodone solution or tablet (depending on age of patient) at 0.05-0.1 mg/kg/dose every 6hrs; 
max 5mg (obese/OSA); prescribe 30 doses 
• 
Acetaminophen 10-15 mg/kg/dose every 6 hours; max 500mg per dose; prescribe 56 doses 
(over the counter medication) 
• 
Ibuprofen 5-10 mg/kg/dose every 6 hours; max 200 mg/dose; prescribe 56 doses (over the 
counter medication) 
 


Patients (or with the aid of parents/legal guardian for subjects unable to complete on their own) will 
complete a pain diary electronically twice a day (AM and PM) for 14 days post operatively. Variables 
elicited will include: Pain score (Visual analog scale and Oucher as utilized in Park et al 2015, last 
analgesic administration (time before survey), missed steroid doses (if applicable), tolerance of 
soft/regular diet, and analgesic consumption (e.g. ibuprofen, acetaminophen, oxycodone) over the 
preceding 12 hours, as well as nausea/emesis fever, bleeding, and insomnia. 
 
Post-operative complications including emergency department (ED) presentation, readmission or re-
operation within 30 days of surgery will be recorded as well as if admitted post operatively: post-
operative length of stay, medication administration and oral intake during hospitalization. 
Subjects/parents/legal guardians will be called within two weeks (plus or minus 5 business days) 
postoperatively to check in on compliance and any complications. 
 
Remaining steroid and opioid medication will be measured either in person at the post-op visit or via 
video conference within 4-6 weeks postoperatively for research purposes only. Zoom or Webex will be 
used in this case. If performed via video and the patient was prescribed tablets, they will count the pills 
in front of the PI or study team. If performed via video and the patient is using solution, the patient will 
be asked to use syringe/dropper to suck up the medicine until it is gone. They will hold the 
syringe/dropper close to the camera so the PI or study team can see how many mLs are left. 
If for some reason the subject needs additional steroids postoperatively, this will be noted and they will 
be removed from the study regardless of which arm they are in. Chart review data and collected 
responses will be included in analysis. Total follow up period of 2-6 weeks. 
 
Other variables to be collected on enrolled subjects will include demographics including MRN of the 
subject, name of subject and parent/guardian, phone number of parent/guardian, email address of the 
parent/guardian, age, gender, race/ethnicity, weight, BMI, tonsil size, surgical details including surgeon, 
operative technique and date, indication for surgery, American Society of Anesthesiologists (ASA) 
category, length of hospital stay, comorbidities and pain medication refills. Data will be collected and 
stored within an encrypted Redcap database. 
 
 
Selection of Subjects 
  
Inclusion Criteria 
• 
Age 4-21 years at time of surgery 
• 
Scheduled for tonsillectomy or adenotonsillectomy surgery 
 
Exclusion Criteria 
• 
Prior history of intracapsular tonsillectomy 
• 
Previous diagnoses of Down Syndrome or developmental delay 
• 
Presence of gastrostomy (g) tube 
• 
A contraindication to steroids or steroid usage within 30 days prior to surgery including 
diabetes, allergy to steroid, already on chronic steroid, immune deficiency 
• 
Active infection at the time of surgery 


• 
Concurrent invasive operative procedures at the time of surgery (Excluding: Exam under 
Anesthesia; Auditory Brainstem Response, Imaging studies, Pressure Equalization tubes, Direct 
Laryngoscopy +/- Bronchoscopy without intervention). 
• 
Unable to read or speak English 
• 
Pregnant or breastfeeding females 
 
 
Subject Recruitment and Compensation 
 
We anticipate enrolling a total of 60 subjects at Duke University Medical Center (DUMC) including the 
Children’s Health Center, South Durham clinics and Duke Raleigh. 
  
Patients will be identified from pediatric Head and Neck clinics at Duke and Duke Raleigh. Patients who 
meet the inclusion and exclusion criteria listed above will be approached for possible study participation 
after a member of the clinical care team asks the patient’s/parent or guardian’s permission to be 
contacted by the study team. The study coordinator (or member of the research team) will then review 
the records, and upon determination that the patient is deemed eligible for this protocol, the clinical 
research coordinator (CRC) will contact the patient. This may occur in clinic or via phone using an IRB 
approved phone script. If the patient/parent or guardian indicates interest in study participation, the 
study coordinator will thoroughly explain the required elements of informed consent and all aspects of 
the study to the subject including inclusion/exclusion criteria, risks, benefits, and alternative to study 
participation. 
  
Compensation of $50 will be given to subjects at the end of their study participation. 
 
 
Risk/Benefit Assessment 
 
The risk of being part of this research study is that the decision on post-operative course of treatment is 
randomized – the clinical care team will not make that decision. However, both dexamethasone and 
oxycodone are routinely prescribed for pain management. Common side effects of dexamethasone are 
nausea, vomiting, stomach upset, swelling, headache, dizziness, mood changes, such as depression, 
mood swings, or personality changes, trouble falling asleep, anxiety, low potassium levels (causing 
symptoms such as tiredness), high blood glucose, high blood pressure.  
 
Dexamethasone and oxycodone are known to increase the risk of birth defects and miscarriage in 
humans when taken during pregnancy and may have risks for breastfed infants.  Therefore, females who 
are pregnant, planning a pregnancy, or breastfeeding are not allowed to participate in studies using 
dexamethasone or oxycodone. 
 
If the participant could possibly become pregnant and has a partner who is able to father children, a 
blood pregnancy test will be performed, and it must be negative to continue in the study.    
 


The participant may benefit from this study if they are randomized to use of dexamethasone as we 
believe this will reduce the use of oxycodone. Participants randomized to oxycodone alone will not have 
any benefit beyond standard of care. There may be benefit to society as a whole as we hope this 
research will potentially reduce opioid use post-operatively and help us to understand the effect that 
post-operative steroids have on pain control and analgesic use to optimize post-operative pain 
regimens. 
 
 
Data Analysis & Statistical Considerations 
 
Statistical Analyses: The primary efficacy endpoint is dose of opioids used post-surgery in the two 
treatment arms. Secondary endpoints are pain scores, rate of change of pain scores and rate of 
complications post-surgery. The continuous outcomes will be analyzed using either a two-sample t-test 
or non-parametric Wilcoxon test, depending on whether the time is normal or non-normal. Associations 
between treatment arms and categorical variables will be examined using Chi-squared tests. Analysis 
will be conducted under Intent-To-Treat (ITT), and any missing will be imputed under missing at random 
(MAR). Statistical significance will be fixed at a two-tailed 0.05 alpha level. The analysis of secondary and 
exploratory efficacy endpoints and other additional analysis will be described further in the Statistical 
Analysis Plan (SAP). Secondary endpoints will be examined with and without adjusting for multiple 
comparisons, using Bonferroni correction. Safety endpoints and other assessments such as readmission/ 
and presentation to emergency for dehydration, pain or post-operative bleeds, and need for operative 
intervention as under data & safety monitoring below, will be evaluated descriptively and will include all 
subjects randomized to the study. In addition, complete case analyses will also be conducted. Analysis 
will be conducted using SAS 9.4 (SAS Institute, Inc., Cary, NC). The lead statistician for the study is Dr. 
Kuchibhatla who is responsible for study design, monitoring of the study, and statistical analysis plan 
(SAP) and the analyses will be conducted by a previously identified BERD statistician. 
 
Power and Sample Size Calculations: No studies exist for this sample where the primary outcome is 
opioid use post-surgery. Hence, based on the study, Park et al., we use change in pain score in the 
treatment groups similar to this study as the primary outcome for sample size calculations; the mean 
change/SD in the non-steroidal and steroidal treatment arms are 2.64(2.6) and 1.4(1.5), respectively. For 
70% power to reject the null hypothesis of equal means with the means/standard deviations listed 
above, and for a significance level (alpha) of 0.15 using a two-sided two-sample unequal-variance t-test, 
the study requires a sample size of 24 in each treatment, for a total of 48 (PASS-2016, 2018). Accounting 
for about 20% drop out, we plan to recruit about 29 per arm for a total of 58. 
 
PASS 16 Power Analysis and Sample Size Software (2018). NCSS, LLC. Kaysville, Utah, USA, 
ncss.com/software/pass. 
 
 
Data & Safety Monitoring 
 
The PI will ensure proper data and safety monitoring. Any serious adverse events such as will be 
reported by the PI to the IRB within 5 business days. Events that are considered both serious and 


unanticipated will be reported to the IRB within 24 hours of the PI’s knowledge of the event. The PI will 
reconsider study design and procedures in discussion with the IRB should adjustments be warranted. 
Adverse events will be monitored from the time of surgery until 14 days post-operatively. 
  
A serious adverse event would be considered bleeding requiring operation and readmission for 
dehydration. 
  
Adverse Events would include IV fluids given in the ED, bleeding that is not treated operatively, 
insomnia, nausea, fever and constipation from opioids.