Clinical trial NCT04230681
Conditions: Obstructive Sleep Apnea Tonsillitis
Sponsor: Washington University School of Medicine
Start date: 2020-02-26; Completion date: 2022-04-01
Enrollment: 189 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
A RCT to compare hydromorphone versus fentanyl for pain control following tonsillectomy or adenotonsillectomy surgery.

Detailed description:
This is a randomized clinical trial with masked assessment, comparing recovery indices for patients receiving intermediate acting versus short acting opioid analgesia using hydromorphone or fentanyl as intraoperative analgesics. An otherwise standardized anesthetic and analgesic regimen will be utilized, consistent with routine care at SLCH. Patients will be randomized 1:1 in block sizes of 5 per group. Patients will be randomized to receive either hydromorphone or fentanyl throughout the perioperative period by opening a sealed protocol envelope.

Arms: arm 1: None arm 2: None
Interventions: intervention 1: Hydromorphone intervention 2: Fentanyl
Intervention descriptions: intervention 1: Patients will be randomized to one of two opioids for the treatment of post-operative pain. intervention 2: Fentanyl

Protocol documents:
Prot_SAP_001.pdf: 
CONFIDENTIAL: This document is the intellectual property of Greg Miller, MD and Michael Montana, MD, PhD. Acceptance 
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3/26/2020 
 
Page 1 of 15 
RESEARCH PROTOCOL 
 
A RANDOMIZED CONTROLLED TRIAL TO COMPARE HYDROMORPHONE VS 
FENTANYL IN CHILDREN UNDERGOING TONSILLECTOMY SURGERY 
 
 
 
 
Alan Hifko, MD 
Clinical Research Coordinator, Anesthesiology 
ahifko@wustl.edu 
 
Judith Lieu, MD 
Professor, Otolaryngology 
lieujudithe@wustl.edu 
 
Greg Miller, MD 
CA3 Resident, Anesthesiology 
g.c.miller@wustl.edu 
 
Michael C. Montana, MD, PhD 
Assistant Professor, Pediatric Anesthesiology 
montana@wustl.edu 
 
 
 
Original Version: January 22, 2020 
 
Revision: February 12, 2020 
 
Revision: March 26, 2020 
 
 
 
 
 
 
 


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Page 2 of 15 
SYNOPSIS 
 
Objective - To compare hydromorphone versus fentanyl for pain control following 
tonsillectomy or adenotonsillectomy surgery. 
 
Study Period - 2 years 
 
Number of Patients - 300 pediatric patients presenting for tonsillectomy or 
adenotonsillectomy at St. Louis Children’s Hospital (SLCH) 
 
Study Treatment - Hydromorphone vs fentanyl dosed per study design  
 
Study Design - This is a randomized clinical trial with masked assessment, comparing 
recovery indices for patients receiving intermediate acting versus short acting opioid 
analgesia using hydromorphone or fentanyl as intraoperative analgesics. An otherwise 
standardized anesthetic and analgesic regimen will be utilized, consistent with routine 
care at SLCH. Patients will be randomized 1:1 in blocks of 4 within strata. Patients will be 
randomized to receive either hydromorphone or fentanyl throughout the perioperative 
period by opening a sealed protocol envelope.  
 
Inclusion Criteria 
1. Children ages 2 to 15 years old  
2. Presenting for tonsillectomy or adenotonsillectomy surgery 
3. American Society of Anesthesiologists Physical Status (ASAPS) Classification 1, 
2 or 3 
4. Provide Informed Consent / Assent (as appropriate) 
 
Exclusion Criteria 
1. Additional Concurrent surgeries, exclusive of myringotomy tubes, minor oral/nasal 
procedures (e.g. frenulectomy), and endoscopic procedures 
2. Revision tonsillectomy or revision adenotonsillectomy surgery 
3. Known pregnancy 
4. Any condition which would make the participant, in the opinion of the investigator 
or the attending anesthesiologist caring for the patient, unsuitable for the study.  
 
Measurements - We will compare the incidence of administration of analgesic rescue 
medication in the post-operative recovery area. We will also compare post-operative pain 
scores and the amount of opioid pain medications administered to patients 
postoperatively 
expressed 
in 
morphine 
equivalents. 
Optional 
opioid 
plasma 
concentrations will be measured at three time points using mass spectroscopy. 
Additionally, we will compare the rates of post-operative respiratory complications, PONV, 
and length of PACU stay between patients administered fentanyl vs. hydromorphone. 
Finally, we will assess patient and family satisfaction with treatment through a survey sent 
on POD 3 as well as validated NIH PROMIS questionnaires. 
 


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Page 3 of 15 
Outcomes - Perioperative analgesic efficacy and side effect comparisons between 
hydromorphone and fentanyl in children undergoing tonsillectomy surgery. 
 


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3/26/2020 
 
Page 4 of 15 
1. Introduction 
1.1. Study Abstract: Every year hundreds of children undergo tonsillectomy surgery at St. 
Louis Children’s Hospital (SLCH) and many of these children experience significant 
postoperative pain. Severe postoperative pain can delay recovery and hospital discharge 
if it impedes eating and drinking. This pain can also lead to significant patient and parental 
anxiety, and may worsen patient anxiety for future health care related experiences. 
Opioids are commonly used to treat severe pain; however, opioids also have attendant 
side effects such as sedation, postoperative respiratory depression (e.g. apnea), and 
nausea and vomiting. Fentanyl and hydromorphone are the primary opioids used at SLCH 
in the operating theater and the immediate postoperative period. Fentanyl has a shorter 
duration of action than hydromorphone and is often chosen in the belief that using the 
shortest-acting opioid will reduce the risks of sedation and apnea. However, there is 
limited evidence to suggest that this is the case. Interestingly nurses in the SLCH Post 
Anesthesia Care Unit have noted a subjective difference in pain levels in patients 
receiving hydromorphone versus fentanyl with the perception that patients administered 
hydromorphone, on average, require fewer doses of rescue opioid analgesics. In addition, 
a recently completed prospective study of fentanyl vs. hydromorphone for pain control in 
patients undergoing eye muscle surgery suggests that hydromorphone provides both 
lower pain ratings and faster PACU recovery. Our goal is to determine whether there is a 
difference in post-operative outcomes between patients receiving fentanyl or 
hydromorphone post tonsillectomy.  
1.2. Research Questions 
1.2.1. Is there a difference in the rate of administration for rescue opioid analgesic 
medications in children undergoing tonsillectomy who are administered hydromorphone 
as compared to fentanyl perioperatively? 
1.2.2 Is there a difference in the postoperative pain score in children undergoing 
tonsillectomy who are administered hydromorphone as compared to fentanyl 
perioperatively? 
1.2.3. Is there a difference in the cumulative morphine equivalents administered 
postoperatively 
in 
children 
undergoing 
tonsillectomy 
who 
are 
administered 
hydromorphone as compared to fentanyl perioperatively? 
1.2.4. Is there a difference in post anesthesia care unit length of stay in children 
undergoing tonsillectomy who are administered hydromorphone as compared to fentanyl 
perioperatively? 
1.2.5. Is there a difference in nausea or the number of vomiting episodes postoperatively 
and 72 hours after discharge in children undergoing tonsillectomy who are administered 
hydromorphone as compared to fentanyl perioperatively? 


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Page 5 of 15 
1.2.6. Is there a difference in pain scores reported by the parent 72 hours after discharge 
in children undergoing tonsillectomy who are administered hydromorphone as compared 
to fentanyl perioperatively? 
1.2.7. Is there a difference in the number of desaturation events, defined as SPO2 < 90% 
for 2 minutes or less than 85% for 1 minute, postoperatively in children undergoing 
tonsillectomy who are administered hydromorphone as compared to fentanyl 
perioperatively? 
1.2.8. Is there a difference in the number of witnessed apneic events postoperatively or 
at 72 hours after discharge in children undergoing tonsillectomy who are administered 
hydromorphone as compared to fentanyl perioperatively? 
1.2.9. Is there are difference in patient and family satisfaction with care between children 
undergoing tonsillectomy who are administered hydromorphone as compared to fentanyl 
perioperatively? 
1.3. Purpose of the Study Protocol. The proposed project will test whether there is a 
difference in multiple metrics of pain between patients who receive hydromorphone or 
those who receive fentanyl during tonsillectomy. The results of this study should inform 
the way anesthesiologists approach the treatment of pain following the most common 
pediatric surgical procedure at SLCH, and in the United States. If a difference is found, 
appropriate dissemination of findings could influence the universal approach taken for 
pain control in the most common pediatric surgery. 
2. Background 
2.1. Prior Literature and Studies. Tonsillectomy is the most common pediatric operation 
performed in the United States, with more than 500,000 tonsillectomies performed 
annually1. The primary indication for tonsillectomy is childhood obstructive sleep apnea 
(OSA), defined by periodic, partial or complete obstruction of the upper airway during 
sleep. OSA is a common disorder in pediatric patients, with a prevalence of 1-3%2. It is 
as common as childhood asthma and children with OSA often require tonsillectomy 
surgery to correct their OSA2. As mentioned, the treatment of OSA is the primary 
indication for more than 75% of children undergoing tonsillectomy with or without 
adenoidectomy3. Unfortunately, children at high risk for OSA are three times more likely 
to have post-tonsillectomy respiratory complications and apneic adverse events than 
children at low risk for OSA4,5 and the rate of complications in patients with OSA post-
tonsillectomy (16 –27%) is substantially increased compared to that of the general 
pediatric post-operative population (0 –1.3%) 6-10. These complications include oxygen 
desaturation, hypercapnia, obstructive apneas requiring CPAP or airway instrumentation, 
unexpected ICU admission, and in rare cases, death. Concerns for a heightened risk of 
opioid induced respiratory depression make the peri-operative use of opioids in children 
with OSA particularly challenging and controversial.  


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Page 6 of 15 
There is currently not a standard of practice for pain management for tonsillectomy 
surgery at SLCH. Published guidelines recommend decreasing opioid doses in all 
patients with sleep apnea, for fear of respiratory depression, however they do not give 
recommendations regarding the use of short vs. intermediate acting opioids11. The nurses 
in the SLCH PACU have subjectively noted a decreased need for opioid rescue analgesia 
when hydromorphone is administered intraoperatively as compared to fentanyl. 
Additionally, a recently completed prospective study of fentanyl versus hydromorphone 
for pain control in patients undergoing eye muscle surgery at SLCH suggests that 
hydromorphone results in lower pain scores and faster PACU recovery12. There are 
limited data comparing different opioids in pediatric tonsillectomy surgery published in the 
literature. As far as we are aware, this will be the first randomized controlled trial 
comparing the intermediate acting opioid hydromorphone to the shorter acting opioid 
fentanyl for this patient population. 
2.2. Rationale for the Study. Providing safe and effective pain control is important for 
these patients. Subjective observations indicate that hydromorphone may provide 
superior pain control as compared to fentanyl. This hypothesis has not been rigorously 
tested. We aim to ameliorate this deficit.  
3. Study Objectives 
3.1. Primary Aim. The primary aim of our study is to compare the need for rescue opioid 
analgesic medication between patients receiving fentanyl and hydromorphone following 
adenotonsillectomy surgery. We will also compare post-operative pain scores between 
the two groups, and the amount of opioid pain medications administered to patients 
postoperatively expressed in morphine equivalents. Patients will be randomized 1:1 in the 
operating room to receive either fentanyl or hydromorphone during the perioperative 
period. We hypothesize that compared to fentanyl, the use of hydromorphone will result 
in lower need for rescue opioid analgesic in post-surgical recovery.  
3.2. Secondary Aims. The secondary aims of our study are to compare pain scores, the 
rates of post-operative respiratory complications, PONV, and length of PACU stay 
between patients administered fentanyl vs. hydromorphone. We hypothesize that there 
will be no differences between patients who receive fentanyl and those who receive 
hydromorphone. 
 
3.3. Rationale for Selection of Outcome Measures. These are the primary concerns for 
care of patients following tonsillectomy surgery. Nearly all patients will have postoperative 
pain, and many will experience some degree of postoperative nausea and vomiting. 
Respiratory complications are possible after emergence from a general anesthetic, 
especially after the use of opioids in the perioperative setting, and especially after 
tonsillectomy surgery.  
 
 
 


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Page 7 of 15 
4. Study Design 
4.1. Overview. This is a randomized clinical trial with masked assessment, comparing 
recovery indices for patients receiving longer acting versus shorter acting opioid 
analgesia using hydromorphone or fentanyl as intraoperative analgesics. An otherwise 
standardized anesthetic and analgesic regimen will be utilized, as consistent with routine 
care at SLCH. 
 
4.2. Inclusion Criteria  
4.2.1. Children ages 2 to 15 years old  
4.2.2. Presenting for tonsillectomy surgery or adenotonsillectomy surgery 
4.2.3. American Society of Anesthesiologists Physical Status (ASAPS) 
Classification 1, 2 or 3 
4.2.3. The caregiver of the child must be able to provide informed consent and the 
child must be able to provide assent (as appropriate) 
 
4.3. Exclusion Criteria 
4.31. Additional Concurrent surgeries, exclusive of myringotomy tubes, minor 
oral/nasal procedures (e.g. frenulectomy), and endoscopic procedures 
4.3.2. Revision tonsillectomy or revision adenotonsillectomy surgery 
4.3.3. Known pregnancy 
4.3.4. Any condition which would make the participant, in the opinion of the 
investigator, unsuitable for the study 
 
4.4. Ethical Considerations. All patients will receive pain medication as well as medication 
to control for postoperative nausea and vomiting as per routine care at SLCH. The 
attending anesthesiologist will accompany the child to the PACU, and rescue drugs will 
be available if additional pain medication is needed or if there is concern for respiratory 
distress. Both medications (hydromorphone and fentanyl) to be compared are standard 
of care analgesics at SLCH and on formulary.  
 
4.5. Risks and Benefits. We do not know if patients will benefit from the intervention. For 
future patients, it is anticipated that investigators may be able to determine whether one 
of the pain medications has a better potential to reduce the need for rescue analgesia 
without a concomitant increase in side effect following tonsillectomy surgery. There is a 
possibility that parents may feel uncomfortable answering some items on the 
questionnaires. 
 
4.6.  Early Withdrawal of Subjects. Patients may be withdrawn from the study if during 
surgery an additional procedure is required or if the lead study physician (MCM) 
determines it is not in the best interest of the patient to continue in the study. Caregivers 
may decide to withdraw their child from the study at any time without penalty. Withdrawn 
children will be replaced with a new subject to maintain a consistent number of enrolled 
patients in each group.  
 
4.7. Study Medications, Administration, and Blood Plasma Concentration Measurements 


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4.7.1. Hydromorphone. Hydromorphone hydrochloride (4,5α-epoxy-3-hydroxy-17-
methylmorphinan-6-one hydrochloride) is a hydrogenated ketone of morphine. 
Hydromorphone hydrochloride is a pure opioid agonist with the principal therapeutic 
activity of analgesia. A significant feature of the analgesia is that it can occur without loss 
of consciousness. Opioid analgesics also suppress the cough reflex and may cause 
respiratory depression, mood changes, mental clouding, euphoria, dysphoria, nausea, 
vomiting and electroencephalographic changes. Many of the effects described above are 
common to the class of mu-opioid analgesics, which includes morphine, oxycodone, 
hydrocodone, codeine, and fentanyl. Hydromorphone has been most extensively studied 
in adults, however it is commonly used in pediatrics both in the perioperative and inpatient 
settings. At therapeutic plasma levels in adults, hydromorphone is approximately 8-19% 
bound to plasma proteins. Hydromorphone is extensively metabolized via glucuronidation 
in the liver, with greater than 95% of the dose metabolized to hydromorphone-3-
glucuronide along with minor amounts of 6-hydroxy reduction metabolites. Only a small 
amount of the hydromorphone dose is excreted unchanged in the urine. Most of the dose 
is excreted as hydromorphone-3-glucuronide along with minor amounts of 6- hydroxy 
reduction metabolites. The terminal elimination half-life of hydromorphone after an 
intravenous dose is about 2.3 hours in adult FDA studies13. 
 
4.7.2. Fentanyl. Fentanyl citrate (N-1-phenethyl-4-piperidyl propionanilide citrate) is a 
potent opioid agonist with principal therapeutic activities of analgesia and sedation. As 
with other potent opioid agonists, the most common serious adverse reactions reported 
to occur with fentanyl are respiratory depression, apnea, rigidity, and bradycardia; if these 
remain untreated, respiratory arrest, circulatory depression, or cardiac arrest could occur. 
Other adverse reactions that have been reported are hypertension, hypotension, 
dizziness, blurred vision, nausea, emesis, diaphoresis, pruritus, urticaria, laryngospasm 
and anaphylaxis. Like hydromorphone, fentanyl has been most extensively studied in 
adults but is commonly used in the pediatric patient population, especially in the 
perioperative period. In adults, the pharmacokinetics of fentanyl can be described as a 
three-compartment model, with a distribution time of 1.7 minutes, redistribution of 13 
minutes and a terminal elimination half-life of 219 minutes. Fentanyl plasma protein 
binding capacity decreases with increasing ionization of the drug. It accumulates in 
skeletal muscle and fat, and is released slowly into the blood. Fentanyl, which is primarily 
metabolized by the liver, demonstrates a high first pass clearance and releases 
approximately 75% of an intravenous dose in urine, mostly as metabolites with less than 
10% representing the unchanged drug. Approximately 9% of the dose is recovered in the 
feces, primarily as metabolites. The onset of action of fentanyl is almost immediate when 
the drug is given intravenously; however, the maximal analgesic and respiratory 
depressant effect may not be noted for several minutes14. 
 
4.7.3. Administration. The study will be conducted in the operating room and in the PACU. 
In the operating room, patients will receive a general anesthetic with an endotracheal tube 
directed by the attending anesthesiologist as per routine care at SLCH. Standard ASA 
monitors, which include pulse oximetry, non-invasive blood pressure monitoring, 
telemetry, heart rate monitoring, and end tidal CO2 and oxygen monitoring will be 


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3/26/2020 
 
Page 9 of 15 
connected to the patient as per standard of care. Patients will be randomized to receive 
either hydromorphone or fentanyl in the operating room determined by opening a sealed 
protocol envelope. Administration and dosing of the randomized opioid to each case will 
be under the direction of the primary anesthesia team under the direction of the pediatric 
anesthesiologist caring for the child. In addition to the randomized opioid, patients will 
receive non-opioid analgesics and PONV prophylaxis as per routine care at SLCH. 
Blinding will be achieved using syringes prepared by SLCH investigational pharmacy. 
 
4.7.4 Optional opioid Plasma Concentration Assessments. Approximately 3 mls of whole 
blood will be collected from patients at three time points: 1) within 10 minutes of 
administration of study drug, 2) within 10 minutes of PACU arrival, and 3) within 10 
minutes of PACU discharge. Blood samples will be collected through an additional IV line 
placed in the surgical suite after anesthesia is given. Opioid (hydromorphone or fentanyl) 
blood levels will be measured using mass spectrometry. This type of analysis does not 
require apriori knowledge of the medication administered and will maintain the masking 
protocol. A Population Pharmacokinetic Analysis will be performed. The patient may 
decline to participate in the blood draw component of the study and remain in the study 
for data collection relating to the primary endpoint. Additionally, failed or missed blood 
draws in individual patients will not adversely affect the population analysis.  
 
4.8. Treatment Regimen. Patients will receive a general anesthetic as per the standard 
of care at SLCH. Analgesia will include opioids and non-opioid adjuvants for pain in 
addition to anti-emetics per routine care at SLCH. Airway maintenance will be via an 
endotracheal tube supervised by the anesthesiologist responsible for the care of the 
patient in the operating room. 
 
4.9. Method for Assigning Subjects to Treatment Groups. Patients will be randomized to 
either hydromorphone or fentanyl in the preoperative area prior to presenting to the 
operating room by investigational pharmacy staff. Randomization will be 1:1 in blocks of 
4 within strata. Stratification will be done by age group (2-7, 8-12, and 13-15), and OSA 
diagnosed using sleep polysomnography within the last year. 
.  
 
4.10. Preparation of the Study Drugs. Equi-analgesic dose tables poorly accommodate 
differences in rapid redistribution between drugs. Establishing a definitive therapeutic 
equivalence between hydromorphone and fentanyl for the patient population, type of 
stimulus, and duration of procedure is challenging a priori. Previous data gather at SLCH 
and clinical expertise guide our dosing choices. Hydromorphone, when utilized as the 
sole opiate intraoperatively is dosed with median 10 ± 4 mcg/kg with16 mcg/kg as the 
80th percentile, and fentanyl is dosed with median 0.9±0.5 mcg/kg, with 1.5 mcg/kg at the 
80th percentile. We will use these current medians to guide our dosing. We will initiate 
medication dosing of patients with hydromorphone 10 mcg/kg, and fentanyl 1 mcg/kg. 
Conveniently, formulary preparation of hydromorphone is at 500 mcg / ml and fentanyl at 
50 mcg/ml. Thus, blinding should be achievable as the same volume of medication (ml/kg) 
can be safely administered for each drug.  


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Page 10 of 15 
Regarding feasibility, we conducted an informal survey of attending 
anesthesiologists at SLCH. We had an approximately 50% response rate and all were 
willing to give these two drugs at the proposed doses in a blinded fashion.  
 
 
 
5. Study Procedures 
5.1. Screening for Eligibility. The patient’s medical record will be screened for: age of 
child, type of surgical procedure planned, history of previous surgery, classification score 
for anesthesia, whether child is in custody of a legal caregiver, and ability to 
consent/assent to the study. 
 
5.2. Enrollment. The surgery schedule at SLCH is posted in advance therefore it is 
straightforward to determine daily if there are eligible subjects to approach for inclusion. 
The patient’s medical history is available to screen for eligibility criteria prior to asking if 
they would be interested in participating. The day prior to the surgery, a nurse may contact 
the family to deliver preoperative instructions. At this time, the family may be told a study 
is being conducted and given details on possible participation. Additionally, the research 
team will identify potential patients on the day of surgery that may qualify for the study. A 
member of the research team will then approach the family in the private room in the 
surgical preoperative area to discuss the study and review the consent form. The study 
group will consist of 300 patients who are presenting for tonsillectomy surgery or 
tonsillectomy and adenoidectomy surgery. Enrollment completion will be achieved once 
consent for up to 360 patients is obtained, assuming a 20% drop-out rate from the study, 
with an end goal of 300 patients.  
 
5.3. Schedule of Measurements. Consenting families will be evaluated with the YPAS-m 
scale prior to surgery. At the time consent is obtained, parents will also be asked to 
complete a brief demographic data form. Any preoperative sleep studies (also known as 
polysomnograms) that subjects had previously received will be reviewed. After surgery, 
the post-operative recovery nurse will evaluate the patient’s pain using rFLACC scale on 
arrival to the Post Anesthesia Care Unit (PACU), and then every five minutes during the 
patient’s stay. This is standard of care.  
After transferring from Phase I recovery, a member of the research team will 
continue to evaluate patient’s pain using the same scale on arrival and before discharge. 
The patient’s level of pain (rFLACC) and need for any additional analgesic medications 
will also be evaluated. rFLACC is standard of care at SLCH and all personnel are well 
versed in its application. After discharge, the patient will receive a telephone call or text 
at 24 hours after surgery to evaluate post-operative nausea and vomiting and the level of 
pain at home. The need for additional pain medication will also be assessed. This is 
standard of care at SLCH and performed for all patients who are discharged the day of 
surgery, regardless of type of surgery. Respiratory events will be assessed initially using 
SpO2 monitoring immediately after arrival to the PACU, followed by clinical assessment 
after PACU discharge. Postoperative nausea and vomiting is assessed using observation 
and patient verbalization. 


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Page 11 of 15 
Patient and family satisfaction with care will be assessed using a survey on 
postoperative day 3, as well as the validated NIH PROMIS questionnaires for Pediatric 
Self-Report (ages 8-17) and Parent Proxy Report (ages 5-17). We will use the following 
NIH PROMIS questionnaires: Pain Behavior, Pain Interference, and Pain Quality.  
PROMIS questionnaires will be sent to patients via e-mail through the REDCap server 
on postoperative day 7 (+ 1 day).  
 
5.4. Safety and Compliance Monitoring. All patients will be monitored by an 
anesthesiologist for the first 5 minutes in the PACU and then every 5 minutes by a 
registered nurse until discharged from the PACU to the Same Day Surgery unit. 
Monitoring is continuous until the patient recovers from anesthesia and then every 5 
minutes x3, then every 15 minutes until PACU discharge. The same tool, the rFLACC, is 
used throughout the hospitalization to assess pain. Postoperative nausea and vomiting 
is assessed using observation and patient verbalization. 
 
5.5. Medical Monitoring. The PI will be monitoring all unblinded data as it is collected 
throughout the study and share the information with the anesthesiologists and the 
surgeons. In general, the Department of Anesthesiology has developed a specific set of 
Standard Operating Procedures (SOPs) for clinical research. All individuals working on 
study are required to read and be familiar with and compliant with the SOPs. The SOPs 
are in part developed from and are compliant with the Institutional Guidelines, including 
those for a) Interactions with the Washington University Human Subjects Review 
Committee, b) Informed Consent Development and Implementation, c) Subject 
Recruitment and Screening, d) Subject Management While on Study, e) Adverse Event 
Reporting. The potential risks of this study are attributable to the use of opioids in the 
perioperative period.  
As already per routine care at SLCH, there will always be a non-study team 
attending anesthesiologist available both in the operating room and in the PACU to care 
for the patient in the event of any potential adverse event. This includes the availability of 
any resuscitation medications and/or equipment including but not limited to naloxone and 
emergent airway equipment. 
 
5.6. Data Collection Procedures for Adverse Events. An adverse event would be evident 
as the study data on pain control, respiratory events, and PONV are collected as per 
routine standard of care. 
 
5.7. Reporting of Adverse Events. Any adverse event will be reported to the IRB within 7 
days as required. Any occurrences of serious adverse events or death will be reported 
within 24 hours. 
 
6. Statistical Plan 
6.1. Sample Size Determination and Sample Size Estimation. Sample size estimations 
were performed to determine the number of patients required to see a 50% reduction in 
the patients requiring rescue analgesia between the group receiving fentanyl and the 


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3/26/2020 
 
Page 12 of 15 
group receiving hydromorphone. Each estimation assumed achieving 80% Power, Alpha 
of 5%, 2 study groups at 1:1 ratio, and 20% attrition (equivalent by study group).  
Multiple power curves were calculated. As examples, assuming the proportion 
using rescue analgesics among patients in the fentanyl study group was 36% compared 
to a 50% reduction down to 18% for the hydromorphone group, a power analysis 
comparing independent proportions would require a total sample size of 228 participants. 
If 50% of the Fentanyl study group utilized rescue analgesics, detecting a 50% reduction 
down to 25% for the Hydromorphone group, a power analysis comparing independent 
proportions would require a total sample size of 139 participants (Fig. 1). We selected 
300 patients based on an assumed proportion of 0.35 in the fentanyl group requiring 
rescue opioid analgesia and a goal of 50% reduction in patients requiring analgesia.  
 


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Figure 1: Sample size estimation curves. P2 = Fentanyl. 
 
 
 
6.2. Analysis Plan. De-identified data will be entered into an excel spreadsheet and then 
SPSS will be used for data analysis. Demographic data will be summarized using 
descriptive statistics and the two groups will be examined for baseline differences. 
Descriptive statistics will include proportions, means, and standard deviation to determine 
statistically significant differences (p<0.05). If the differences at baseline are significant, 
confounders will be addressed using multivariate adjustment techniques. Alpha level 0.05 
will be used. 
 
7. Data Handling and Record Keeping 
7.1. Confidentiality and Security. The consent forms and all questionnaires will be 
collected and stored in a locked file drawer in a locked office. Responses to 
questionnaires will be entered into a password protected computer. All study data will be 
entered into a database on a password protected computer. Only study team members 
will have access to the data. All reporting of data will be in the aggregate. 
 
8. Risks, Study Monitoring and Administration 
8.1. Monitoring. Studies conducted in the Department of Anesthesiology follow the 
Washington University Institutional Review Board Policies and Procedures (last revision 
January 21, 2019). All individuals working on the study are required to read and be familiar 
with and compliant with the IRB Policies and Procedures. The specific monitoring plan for 
this investigation is commensurate with the risks and the size and complexity of the 
investigations planned. The potential risks are attributable to the use of opioids in the 
perioperative period. Both drugs of interest are standard of care medications and on 
formulary at SLCH. Thus, the risk of study participation is nearly identical to that incurred 
with having a tonsillectomy at SLCH, regardless of study participation. Based on the small 
size and relatively low risk nature of the protocol, the investigating physicians are involved 
in the monitoring plan. Additionally, a board-certified anesthesiologist practicing in 
pediatric anesthesia at SCLH who is not a member of the research team will be included 
in the monitoring of all adverse events. These individuals will review the annual summary 
60
80
100
120
140
160
180
200
220
240
260
280
300
320
340
360
0
0.2
0.4
0.6
0.8
1
Power (1-β err prob)
 = 0.2
 = 0.25
 = 0.3
 = 0.35
 = 0.4
Proportion p2
z tests - Proportions: Difference between two independent proportions
Tail(s) = Two. Proportion p1 = 0.2. α err prob = 0.05. Allocation ratio N2/N1 = 1
Total sample size


CONFIDENTIAL: This document is the intellectual property of Greg Miller, MD and Michael Montana, MD, PhD. Acceptance 
of this document constitutes the agreement by the recipient that no unpublished information contained herein will be 
published or disclosed without prior written approval.  
 
3/26/2020 
 
Page 14 of 15 
of adverse events. All reports of a Serious Adverse Event, or an Unexpected Adverse 
Event will be reviewed and reported to the IRB. The investigators will follow the 
requirements for principle investigator reporting requirements as outlined in Section X of 
the IRB Policies and Procedures.   
 
8.2. Funding and Conflicts of Interest. Departmental funding; an intramural ICTS grant is 
pending. No conflicts of interest for any of the study team members. 
 
8.3. Study Timetable. The study is expected to start immediately after receiving IRB 
approval. Data collection will take 24-36 months; analysis another 3-6 months. 
 
9. Publication Plan 
Publication in a peer-reviewed medical journal is expected following completion of the 
data collection and analysis of the results. Presentation at regional and/or national 
meetings is also anticipated. Establishing best practices for the use of opioids in children 
is a high priority in pediatric anesthesia, and we anticipate national interest in this 
research. 
 
10. Management of Intercurrent Events 
10.1. Adverse Experiences: The investigator will closely monitor subjects for evidence of 
adverse events. All adverse events will be reported and followed until satisfactory 
resolution. The description of the adverse experience will include the time of onset, 
duration, intensity, etiology, relationship to the study drug (none, unlikely, possible, 
probable, highly probable), and any treatment required. 
 
10.2. Premature Discontinuation: If a subject withdraws from the study, the subject will be 
replaced to provide the required number of subjects. Subjects will be withdrawn without 
penalty if the investigator decides that discontinuation is in the best interest of the subject, 
or the subject requests withdrawal from the study.  
 


CONFIDENTIAL: This document is the intellectual property of Greg Miller, MD and Michael Montana, MD, PhD. Acceptance 
of this document constitutes the agreement by the recipient that no unpublished information contained herein will be 
published or disclosed without prior written approval.  
 
3/26/2020 
 
Page 15 of 15 
10. References  
 
1. 
Friedman NR, Perkins JN, McNair B, Mitchell RB: Current practice patterns for 
sleep-disordered breathing in children. Laryngoscope 2013; 123: 1055-8 
2. 
Brown KA: Outcome, risk, and error and the child with obstructive sleep apnea. 
Paediatr Anaesth 2011; 21: 771-80 
3. 
Bhattacharyya N, Lin HW: Changes and consistencies in the epidemiology of 
pediatric adenotonsillar surgery, 1996-2006. Otolaryngol Head Neck Surg 2010; 143: 
680-4 
4. 
De Luca Canto G, Pacheco-Pereira C, Aydinoz S, Bhattacharjee R, Tan HL, 
Kheirandish-Gozal L, Flores-Mir C, Gozal D: Adenotonsillectomy Complications: A Meta-
analysis. Pediatrics 2015; 136: 702-18 
5. 
Cote CJ, Posner KL, Domino KB: Death or neurologic injury after tonsillectomy in 
children with a focus on obstructive sleep apnea: houston, we have a problem! Anesth 
Analg 2014; 118: 1276-83 
6. 
Leong AC, Davis JP: Morbidity after adenotonsillectomy for paediatric obstructive 
sleep apnoea syndrome: waking up to a pragmatic approach. J Laryngol Otol 2007; 121: 
809-17 
7. 
McColley SA, April MM, Carroll JL, Naclerio RM, Loughlin GM: Respiratory 
compromise after adenotonsillectomy in children with obstructive sleep apnea. Arch 
Otolaryngol Head Neck Surg 1992; 118: 940-3 
8. 
Brown KA, Laferriere A, Lakheeram I, Moss IR: Recurrent hypoxemia in children 
is associated with increased analgesic sensitivity to opiates. Anesthesiology 2006; 105: 
665-9 
9. 
Wilson K, Lakheeram I, Morielli A, Brouillette R, Brown K: Can assessment for 
obstructive sleep apnea help predict postadenotonsillectomy respiratory complications? 
Anesthesiology 2002; 96: 313-22 
10. 
Patino M, Sadhasivam S, Mahmoud M: Obstructive sleep apnoea in children: 
perioperative considerations. Br J Anaesth 2013; 111 Suppl 1: i83-95 
11. 
American Society of Anesthesiologists Task Force on Perioperative Management 
of patients with obstructive sleep a: Practice guidelines for the perioperative management 
of patients with obstructive sleep apnea: an updated report by the American Society of 
Anesthesiologists Task Force on Perioperative Management of patients with obstructive 
sleep apnea. Anesthesiology 2014; 120: 268-86 
12. 
Hajdini H, Steurer LM, Balakas K, Ercole PM: A Randomized Controlled Trial to 
Compare Pain Medications in Children Undergoing Strabismus Surgery. J Perianesth 
Nurs 2019 
13. 
Dilaudid and Dilaudid HP injection: Hydromorphone hydrochloride. FDA Drug 
Access Data and Labels. ,  
14. 
Fentanyl Citrate Injection, USP. FDA Drug Access Data and Labels.,  
 
 

ICF_002.pdf: 
 
FOR IRB USE ONLY 
IRB ID #: 201912042 
APPROVAL DATE: 12/22/20 
RELEASED DATE: 12/22/20 
EXPIRATION DATE: 12/21/21 
 
 
9/8/2020 
 
Page 1 of 12 
 
 
INFORMED CONSENT DOCUMENT 
 
Project Title: 
A randomized controlled trial to compare hydromorphone vs fentanyl 
in children undergoing tonsillectomy surgery 
 
Principal Investigator: 
Michael Montana, MD PhD 
 
Research Team Contact: Alan Hifko, MD, 314-273-0783 
 
 
 If you are the parent/guardian of a child under the age of 18 who is being invited to participate in this 
study, the word “you” in this document refers to your child.  As the parent/guardian, you will be 
asked to read and sign this document to give permission for your child to participate.   
 If you are under the age of 18 and reading this document, the word “you” in this document refers to 
you.  You will be asked to read and sign this document to indicate your willingness to participate. 
 
This consent form describes the research study and helps you decide if you want to participate.  It 
provides important information about what you will be asked to do during the study, about the risks and 
benefits of the study, and about your rights and responsibilities as a research participant. By signing this 
form you are agreeing to participate in this study. 
 You should read and understand the information in this document including the procedures, 
risks and potential benefits.  
 If you have questions about anything in this form, you should ask the research team for more 
information before you agree to participate.   
 You may also wish to talk to your family or friends about your participation in this study. 
 Do not agree to participate in this study unless the research team has answered your 
questions and you decide that you want to be part of this study.  
 
You are invited to take part in a randomized controlled trial to compare hydromorphone vs fentanyl in 
children undergoing tonsillectomy surgery because you are scheduled for tonsillectomy surgery.  This is 
a research study conducted by Dr. Michael Montana having to do with the management of pain after a 
tonsillectomy surgery.   The purpose of this research study is to compare two pain medications that are 
regularly given following a tonsillectomy surgery.  Those pain medications are called hydromorphone 
and fentanyl.   Both of these drugs are routinely prescribed for pain control during and after a 
tonsillectomy.  We will compare the use and effect of the medication prescribed to you on your pain, 
specifically, how often and how much of the medication is given to you, measurements of your pain, if 
the medication affects how you breathe, if you develop an upset stomach, and length of time you spend 
in the post-surgical recovery room.   
 
You should carefully consider the information in this consent document and discuss it with the research 
team. You should understand why you might want to participate, or why you might not want to 
participate. The study is sponsored by the National Institutes of Health. You may choose to participate 
or not. 


 
FOR IRB USE ONLY 
IRB ID #: 201912042 
APPROVAL DATE: 12/22/20 
RELEASED DATE: 12/22/20 
EXPIRATION DATE: 12/21/21 
 
9/8/2020 
 
Page 2 of 12 
 
If you agree to participate in this study, you will be asked to provide informed consent, and then we will 
begin to collect personal, medical and health information from your medical record. If you meet all the 
requirements to participate, you will be randomly assigned to receive one of the two study drugs; either 
the hydromorphone or fentanyl.  This means that the study treatment you receive will be determined 
purely by chance, like flipping a coin.   
 
Following consent, but before your surgery, we will ask you questions regarding your feelings about 
your tonsillectomy.  You are free to skip any questions that you prefer not to answer. 
 
You will be in the study for approximately 8 days. You will be asked to come to St. Louis Children’s 
Hospital for the procedures in the study. These will include an optional set of 3 blood draws to see how 
the pain medication, either hydromorphone or fentanyl, is processed through your body over time.  
These samples would be taken through an additional IV line placed in the surgical suite after anesthesia 
is given.  If you agree, blood samples will be taken at the following time points:  1) within 10 minutes of 
receiving hydromorphone or fentanyl, 2) within 10 minutes of your arrival in the surgical recovery area, 
called the PACU, 3) within 10 minutes of your discharge from the PACU.   
  
You may choose to stop participating and withdraw from the study at any time. If you withdraw from 
the study, the research team may continue to use the information already collected about you.   
 
There are some risks to you if you agree to volunteer for this study. The most serious/most common 
risks are breach of confidentiality. The risks to you are described in more detail later in this consent 
document. There is no direct benefit to you but you may help someone else in the future.  
 
All of the above information will be further explained and is listed in more detail in the consent 
document below.  
 
If you decide to take part in this study, you will be asked to sign at the end of this document, after you 
have had a chance to review all of the information. Do not sign unless you understand the purpose of the 
study, what you will be asked to do, and the risks that may be involved. The research team must give 
you a copy of this signed consent document. 
 
 
WHAT IS THE PURPOSE OF THIS STUDY? 
 
This is a research study.  We invite you to participate in this research study because you are scheduled 
for a tonsillectomy surgery.  
 
The purpose of this research study is to compare two pain medications that are regularly given following 
a tonsillectomy surgery.  Those pain medications are called hydromorphone and fentanyl.   Both of these 
drugs are routinely prescribed for pain control during and after a tonsillectomy.  We will compare the 
use and effect of the medication prescribed to you on your pain, specifically, how often and how much 
of the medication is given to you, measurements of your pain, if the medication affects how you breathe, 
if you develop an upset stomach, and length of time you spend in the post-surgical recovery room.   
 


 
FOR IRB USE ONLY 
IRB ID #: 201912042 
APPROVAL DATE: 12/22/20 
RELEASED DATE: 12/22/20 
EXPIRATION DATE: 12/21/21 
 
9/8/2020 
 
Page 3 of 12 
Hydromorphone is approved by the U.S. Food and Drug Administration to treat pain.  However, the use 
of hydromorphone has not been approved for use in children and is considered investigational in this 
study.    
 
Fentanyl is approved by the U.S. Food and Drug Administration to treat pain. 
 
WHAT WILL HAPPEN DURING THIS STUDY? 
 
The consent process is the first part of being in this study. If you provide informed consent and are 
eligible to continue in the study, we will begin to collect personal, medical and health information from 
your medical record. If you meet all the requirements to participate, you will be randomly assigned to 
receive one of the two study drugs; either the hydromorphone or fentanyl.  This means that the study 
treatment you receive will be determined purely by chance, like flipping a coin.   
 
Following consent, but before your surgery, we will ask you questions regarding your feelings about 
your tonsillectomy.  Your parent will also be asked to answer questions about their experiences and 
feelings about your tonsillectomy. You are free to skip any questions that you prefer not to answer.  
 
During the operation and in the post-operative care unit we will record the analgesic medications you 
receive, as well as safety mentoring information such as heart rate, blood pressure, and SPO2.  
 
Post-operative pain scores will be measured upon arrival, every 5 minutes for the first 15 minutes, 
followed by every 15 minutes for the first hour, hourly while in the PACU, as well as at the time of 
discharge and prior to administration of rescue medication, if rescue medication is needed. 
Follow up surveys to assess pain, adverse events, and overall satisfaction will be sent to you by email on 
post-operative day 3 (± 1 day), and 7 (± 1 day).  
 
We will also offer an optional set of 3 blood draws to see how the pain medication, either 
hydromorphone or fentanyl, is processed through your body over time.  These samples would be taken 
through an additional IV line placed in the surgical suite after anesthesia is given.  If you agree, blood 
samples will be taken at the following time points:  1) within 10 minutes of you receiving 
hydromorphone or fentanyl, 2) within 10 minutes of your arrival in the surgical recovery area, called the 
PACU, 3) within 10 minutes of your discharge from the PACU.   
 
Please place your initials in the blank next to Yes or No for the question below: 
 
You may place an additional IV line during surgery for the purposes of collecting 3 blood samples 
from me:  
 
 
_____ Yes 
_____ No 
Initials 
Initials 
 
 
 
 


 
FOR IRB USE ONLY 
IRB ID #: 201912042 
APPROVAL DATE: 12/22/20 
RELEASED DATE: 12/22/20 
EXPIRATION DATE: 12/21/21 
 
9/8/2020 
 
Page 4 of 12 
Will you save my research information and/or biospecimens to use in future research studies? 
  
We would like to use the blood and data we are obtaining in this study for studies going on right now as 
well as studies that are conducted in the future.  These studies may provide additional information that 
will be helpful in understanding pain management, or other diseases or conditions, including research to 
develop investigational tests, treatments, drugs or devices that are not yet approved by the U.S. Food and 
Drug Administration.  It is unlikely that what we learn from these studies will have a direct benefit to 
you.  There are no plans to provide financial compensation to you should this occur.  By allowing us to 
use your blood and data you give up any property rights you may have in the blood and data. 
 
We will share your blood and data with other researchers. They may be doing research in areas similar 
to this research or in other unrelated areas.  These researchers may be at Washington University, at other 
research centers and institutions, or industry sponsors of research.  We may also share your research data 
with large data repositories (a repository is a database of information) for broad sharing with the 
research community.  If your individual research data is placed in one of these repositories only 
qualified researchers, who have received prior approval from individuals that monitor the use of the 
data, will be able to look at your information.   
 
If you change your mind and do not want us to store and use your blood and data for future research you 
should contact the research team member identified at the top of this document.  The blood and data will 
no longer be used for research purposes. However, if some research with your blood and data has 
already been completed, the information from that research may still be used. Also, if the blood and data 
has been shared with other researchers it might not be possible to withdraw the blood and data to the 
extent it has been shared. 
 
Please place your initials in the blank next to Yes or No for each of the questions below: 
 
My blood and data may be stored and used for future research as described above. 
 
_____ Yes 
_____ No 
Initials  
Initials 
 
My blood and data may be shared with other researchers and used by these researchers for the 
future research as described above. 
 
_____ Yes  
_____ No 
Initials  
Initials 
 
Identifiers may be removed from your private information including blood and data and used for future 
research or shared with others. If this occurs, we will not ask you for additional consent.  
 
HOW MANY PEOPLE WILL PARTICIPATE? 
 
Approximately 300 people will take part in this study conducted by investigators at Washington 
University.   
 


 
FOR IRB USE ONLY 
IRB ID #: 201912042 
APPROVAL DATE: 12/22/20 
RELEASED DATE: 12/22/20 
EXPIRATION DATE: 12/21/21 
 
9/8/2020 
 
Page 5 of 12 
HOW LONG WILL I BE IN THIS STUDY? 
 
If you agree to take part in this study, your involvement will last for approximately 8 days for your 
surgery, recovery time, and follow up surveys. This time commitment may vary from participant to 
participant. 
 
WHAT ARE THE RISKS OF THIS STUDY? 
 
You may experience one or more of the risks indicated below from being in this study. In addition to 
these, there may be other unknown risks, or risks that we did not anticipate, associated with being in this 
study.  
 
Some risks described in this consent document, if severe, may cause death.  
 
Risk of IV Placement 
There is a chance that you will have some bruising or bleeding at the IV insertion site. 
 
Hydromorphone 
Likely / Common  
Nausea 
Vomiting 
Sleepiness 
 
Less Likely / Less Common 
Low blood pressure, low heart rate 
Low breathing rate 
 
Rare   
Very low breathing rate; cessation of breathing.  
 
Fentanyl 
Likely / Common  
Nausea 
Vomiting 
Sleepiness 
 
Less Likely / Less Common 
Low blood pressure, low heart rate 
Low breathing rate 
 
Rare   
Very low breathing rate; cessation of breathing.  
 
Women Capable of Becoming Pregnant 
If you are a woman capable of becoming pregnant, we will ask you to have a pregnancy test before 
beginning this study.  You must use effective birth control methods and try not to become pregnant 


 
FOR IRB USE ONLY 
IRB ID #: 201912042 
APPROVAL DATE: 12/22/20 
RELEASED DATE: 12/22/20 
EXPIRATION DATE: 12/21/21 
 
9/8/2020 
 
Page 6 of 12 
while participating in this study.  If you become pregnant, there may be unknown risks to your unborn 
child, or risks to your unborn child that we did not anticipate.  There may be long-term effects of the 
treatment being studied that could increase the risk of harm to an unborn child.  You must tell the doctor 
if your birth control method fails while you are on the study. If you believe or know you have become 
pregnant while participating in this research study, please contact the research team member identified at 
the top of this document as soon as possible.  Please discuss with the research team how long you need 
to wait before becoming pregnant after completing the treatment or procedures on this study. 
 
Breach of Confidentiality 
One risk of participating in this study is that confidential information about you may be accidentally 
disclosed.  We will use our best efforts to keep the information about you secure.  Please see the section 
in this consent form titled “How will you keep my information confidential?” for more information. 
 
WHAT ARE THE BENEFITS OF THIS STUDY? 
 
You may or may not benefit from being in this study.   
 
However, we hope that, in the future, other people might benefit from this study because knowing the 
differences in drugs used for pain management could improve the way we manage pain for 
tonsillectomy patients.    
 
WHAT OTHER TREATMENT OPTIONS ARE THERE? 
 
Before you decide whether or not to be in this study, your doctor will discuss the other options that are 
available to you.  Instead of being in this study, you could simply not participate and continue with the 
care prescribed by your medical team.    
 
WILL IT COST ME ANYTHING TO BE IN THIS STUDY? 
 
As part of this study you will receive tests and procedures that are similar to what you would receive 
during routine clinical care of your condition.  Your health plan/insurance company will be billed for 
some or all of these costs, and you will be responsible for any co-pays and deductibles that are normally 
required by your health plan/insurance.  Not all insurance plans cover the costs associated with being in 
a study. Even if they do, you may be responsible for more out-of-pocket expenses, such as co-pays and 
deductibles, when there are more tests and procedures or more expensive tests and procedures involved 
in the study than if you were to receive routine clinical care outside the study.   
 
If you wish to know whether there are more tests and procedures or more expensive tests and procedures 
in the study, you should ask your study doctor.   
 
If you wish to know whether your insurance will pay, you should contact them directly, or speak with 
the study team about obtaining a financial pre-certification prior to enrolling in the study. 
 
WILL I BE PAID FOR PARTICIPATING? 
 
You will be paid for being in this research study. You will need to provide your social security number 


 
FOR IRB USE ONLY 
IRB ID #: 201912042 
APPROVAL DATE: 12/22/20 
RELEASED DATE: 12/22/20 
EXPIRATION DATE: 12/21/21 
 
9/8/2020 
 
Page 7 of 12 
(SSN) in order for us to pay you. You may choose to participate without being paid if you do not wish to 
provide your social security number (SSN) for this purpose.  You may also need to provide your address 
if a check will be mailed to you. If your social security number is obtained for payment purposes only, it 
will not be retained for research purposes.    
 
You will receive a $25 Amazon Gift card at the end of your study participation. 
 
WHO IS FUNDING THIS STUDY? 
 
The National Institutes of Health (NIH) is funding this research study.  This means that Washington 
University is receiving payments from the NIH to support the activities that are required to conduct the 
study.  No one on the research team will receive a direct payment or increase in salary from the NIH for 
conducting this study. 
 
WHAT IF I AM INJURED AS A RESULT OF THIS STUDY? 
 
Washington University investigators and staff will try to reduce, control, and treat any complications 
from this research. If you feel you are injured because of the study, please contact the investigator at 
314-565-8119 and/or the Human Research Protection Office at 1-(800)-438-0445.  
 
Decisions about whether payment for medical treatment for injuries relating to your participation in 
research will be made by Washington University If you need to seek medical care for a research-related 
injury, please notify the investigator as soon as possible.  
 
HOW WILL YOU KEEP MY INFORMATION CONFIDENTIAL? 
 
Other people such as those indicated below may become aware of your participation in this study and 
may inspect and copy records pertaining to this research.  Some of these records could contain 
information that personally identifies you. We will keep your participation in this research study 
confidential to the extent permitted by law.   
 Government representatives (including the Office for Human Research Protections) to complete 
federal or state responsibilities 
 The U.S. Food and Drug Administration 
 The National Institutes of Health (NIH) 
 The sponsor (NIH) may also inspect any part of your medical record for the purposes of auditing 
the conduct of the study. 
 Hospital or University representatives to complete Hospital or University responsibilities 
 Information about your participation in this study may be documented in your health care records 
and will be available to anyone with access to your health care record, including your health 
insurance company.  This information may also be released as part of a release of information 
request. 
 The last four digits of your social security number may be used in hospital or University systems 
to track billing information for research procedures. 
 Washington University’s Institutional Review Board (a committee that oversees the conduct of 
research involving human participants) and the Human Research Protection Office. The 


 
FOR IRB USE ONLY 
IRB ID #: 201912042 
APPROVAL DATE: 12/22/20 
RELEASED DATE: 12/22/20 
EXPIRATION DATE: 12/21/21 
 
9/8/2020 
 
Page 8 of 12 
Institutional Review Board has reviewed and approved this study.  
 Any report or article that we write will not include information that can directly identify you.  
The journals that publish these reports or articles require that we share your information that was 
collected for this study with others to make sure the results of this study are correct and help 
develop new ideas for research. Your information will be shared in a way that cannot directly 
identify you. 
 
To help protect your confidentiality, you will be assigned a study ID number and we will use that ID to 
manage all your study related information and blood samples.  This includes paper documents, 
electronic documents and blood specimens that we collect from you during your participation.  
Additionally, the key to the ID code linking code numbers to names will be kept at a separate location, 
under lock and key, and only the research team will have access to it.  We will destroy the link between 
your ID and your identifiers at the end of the study.    
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law. This Web site will not include information that can identify you. At most, the Web site will 
include a summary of the results. You can search this Web site at any time.  
 
 To further protect your privacy, this research is covered by a Certificate of Confidentiality from the 
federal government. This means that the researchers can refuse to disclose information that may identify 
you in any legal or court proceeding or to anyone who is not connected with the research except if:  
 there is a law that requires disclosure, such as to report child abuse and neglect, or harm to self or 
others;  
 
you give permission to disclose your information, including as described in this consent form; or 
 it is used for other scientific research allowed by federal law. 
You have the right to share your information or involvement in this study with anyone at any time. You 
may also give the research team permission to disclose your information to a third party or any other 
person not connected with the research.  
 
Are there additional protections for my health information? 
Protected Health Information (PHI) is health information that identifies you. PHI is protected by federal 
law under HIPAA (the Health Insurance Portability and Accountability Act). To take part in this 
research, you must give the research team permission to use and disclose (share) your PHI for the study 
as explained in this consent form.  The research team will follow state and federal laws and may share 
your health information with the agencies and people listed under the previous section titled, “How will 
you keep my information confidential?” 
 
Once your health information is shared with someone outside of the research team, it may no longer be 
protected by HIPAA.   
 
The research team will only use and share your information as talked about in this form or as permitted 
or required by law.  When possible, the research team will make sure information cannot be linked to 
you (de-identified).  Once information is de-identified, it may be used and shared for other purposes not 
discussed in this consent form. If you have questions or concerns about your privacy and the use of your 
PHI, please contact the University’s Privacy Officer at 866-747-4975.  
 


 
FOR IRB USE ONLY 
IRB ID #: 201912042 
APPROVAL DATE: 12/22/20 
RELEASED DATE: 12/22/20 
EXPIRATION DATE: 12/21/21 
 
9/8/2020 
 
Page 9 of 12 
Although you will not be allowed to see the study information, you may be given access to your health 
care records by contacting your health care provider.  
 
If you decide not to sign this form, it will not affect 
 your treatment or the care given by your health provider. 
 your insurance payment or enrollment in any health plans.   
 any benefits to which you are entitled. 
However, it will not be possible for you to take part in the study. 
 
If you sign this form: 
 You authorize the use of your PHI for this research 
 This authorization does not expire. 
 You may later change your mind and not let the research team use or share your information 
(you may revoke your authorization).  
 To revoke your authorization, complete the withdrawal letter, found in the Participant section 
of the Human Research Protection Office website at 
https://hrpo.wustl.edu/participants/withdrawing-from-a-study/ or you may request that the 
investigator send you a copy of the letter.    
 
 
 
o If you revoke your authorization: 
 The research team may only use and share information already collected for 
the study. 
 Your information may still be used and shared as necessary to maintain the 
integrity of the research, for example, to account for a participant’s 
withdrawal from the research study or for safety reasons. 
 You will not be allowed to continue to participate in the study. 
 
 
Can we contact you by email? 
 
We would like to contact you by email for the purposes listed below.  Some of these emails may contain 
health information that identifies you. 
 Follow up surveys which will include questions about pain, adverse reactions, and overall 
satisfaction. Follow up surveys will be sent on post-operative day 3 (± 1 day) and day 7 (± 1 
day). 
 
Only the research team will have access to your email communications.  We will only communicate by 
email to send you the information listed above.  If you have any questions or need to contact us for an 
urgent or emergent situation, please contact the research team member identified at the top of this 
document. 
 
You should be aware that there are risks associated with sending your health information via email.   
 There is always a risk that the message could be intercepted or sent to the wrong email 
address.  To avoid sending messages to the wrong email address, the first email we send you 
will be a test message to ensure we have the correct email address. 


 
FOR IRB USE ONLY 
IRB ID #: 201912042 
APPROVAL DATE: 12/22/20 
RELEASED DATE: 12/22/20 
EXPIRATION DATE: 12/21/21 
 
9/8/2020 
 
Page 10 of 12 
 When using any computer you should be careful to protect your username and password.  
Make sure you log-out before getting up from the computer.   
 If you share a home computer with other family members, and do not want them to know you 
are participating in this study make sure you provide an email address that only you can 
access.  
 Your employer will have access to any email communications sent or received on any 
electronic devices used for work or through a work server. 
  
Do you agree to allow us to send your health information via email?   
 
_____ Yes  
_____ No 
Initials  
Initials 
 
 
IS BEING IN THIS STUDY VOLUNTARY? 
 
Taking part in this research study is completely voluntary.  You may choose not to take part at all.  If 
you decide to be in this study, you may stop participating at any time. Any data that was collected as 
part of your participation in the study will remain as part of the study records and cannot be removed.   
 
If you decide not to be in this study, or if you stop participating at any time, you won’t be penalized or 
lose any benefits for which you otherwise qualify.   
 
What if I decide to withdraw from the study? 
 
You may withdraw by telling the study team you are no longer interested in participating in the study or 
you may send in a withdrawal letter. A sample withdrawal letter can be found at 
https://hrpo.wustl.edu/participants/withdrawing-from-a-study/ under Withdrawing from a Research 
Study. 
 
Will I receive new information about the study while participating? 
 
If we obtain any new information during this study that might affect your willingness to continue 
participating in the study, we’ll promptly provide you with that information. 
 
Can someone else end my participation in this study? 
 
Under certain circumstances, the investigator might decide to end your participation in this research 
study earlier than planned.  This might happen for no reason or because in our judgment it would not be 
safe for you to continue.  
 
WHAT IF I HAVE QUESTIONS? 
 
We encourage you to ask questions.  If you have any questions about the research study itself, please 
contact: Dr. Montana at 314-565-8119. If you experience a research-related injury, please contact: Dr. 
Montana at 314-565-8119. 


 
FOR IRB USE ONLY 
IRB ID #: 201912042 
APPROVAL DATE: 12/22/20 
RELEASED DATE: 12/22/20 
EXPIRATION DATE: 12/21/21 
 
9/8/2020 
 
Page 11 of 12 
 
If you have questions, concerns, or complaints about your rights as a research participant, please contact 
the Human Research Protection Office 1-(800)-438-0445, or email hrpo@wustl.edu.   General 
information about being a research participant can be found on the Human Research Protection Office 
web site, http://hrpo.wustl.edu.  To offer input about your experiences as a research participant or to 
speak to someone other than the research staff, call the Human Research Protection Office at the number 
above. 
 
 
This consent form is not a contract. It is a written explanation of what will happen during the study if 
you decide to participate. You are not waiving any legal rights by agreeing to participate in this study. 
As a participant you have rights and responsibilities as described in this document and including: 
 To be given enough time before signing below to weigh the risks and potential benefits and 
decide if you want to participate without any pressure from the research team or others. 
 To understand all of the information included in the document, have your questions answered, 
and receive an explanation of anything you do not understand. 
 To follow the procedures described in this document and the instructions of the research team to 
the best of your ability unless you choose to stop your participation in the research study. 
 To give the research team accurate and complete information. 
 To tell the research team promptly about any problems you have related to your participation, or 
if you are unable to continue and wish to stop participating in the research study. 
Your signature indicates that this research study has been explained to you, that your questions have 
been answered, and that you agree to take part in this study.  You will receive a signed and dated copy 
of this form. 
 
Parent/Guardian Name and Relationship to Participant: 
 
By signing this form you are agreeing to participate in this study and providing permission for your 
child to participate. 
 
Do not sign this form if today’s date is after EXPIRATION DATE: 12/21/21. 
 
 
_______________________________ 
(Child’s name – printed) 
 
 
__________________________________________ 
_______________________________ 
(Signature of Parent/Guardian) 
 
 
 
(Date) 
 
 
__________________________________________ 
_______________________________ 
(Name of Parent/Guardian- printed)  
 
 
(Relationship to participant – printed) 
 


 
FOR IRB USE ONLY 
IRB ID #: 201912042 
APPROVAL DATE: 12/22/20 
RELEASED DATE: 12/22/20 
EXPIRATION DATE: 12/21/21 
 
9/8/2020 
 
Page 12 of 12 
Statement of Person Who Obtained Consent 
 
The information in this document has been discussed with the participant or, where appropriate, with the 
participant’s legally authorized representative.  The participant has indicated that they understand the 
risks, benefits, and procedures involved with participation in this research study. 
 
 
__________________________________________ 
_______________________________ 
(Signature of Person who Obtained Consent) 
 
(Date) 
 
 
___________________________________________ 
(Name of Person who Obtained Consent - printed)