Clinical trial NCT02162433
Conditions: Adenotonsillar Hypertrophy Obstructive Sleep Apnea Tonsillitis Adenoiditis
Sponsor: Massachusetts Eye and Ear Infirmary
Start date: 2015-03-01; Completion date: 2018-04-23
Enrollment: 92 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The investigators aim to investigate the effect of dexmedetomidine on the perioperative respiratory complications in this patient population undergoing both awake and deep tracheal extubation.

Detailed description:
We propose a prospective double-blinded randomized controlled trial. 336 pediatric patients presenting to Massachusetts Eye and Ear Infirmary (MEEI) for adenotonsillectomy who are eligible for the study based on inclusion and exclusion criteria will be recruited. A Clinical Pharmacy specialist, will be in charge of preparing the dexmedetomidine and placebo doses and will randomize the patients to four equally numbered groups. The anesthesiologist will receive the assignment for the extubation method in a sealed envelope from the Clinical Pharmacy specialist. Multiple parameters will be recorded in perioperative period to quantify perioperative adverse respiratory events.

Arms: arm 1: Awake extubation receiving dexmedetomidine. arm 2: Awake extubation receiving placebo (normal saline). arm 3: Deep extubation receiving dexmedetomidine. arm 4: Deep extubation receiving placebo (normal saline).
Interventions: intervention 1: Normal Saline intervention 2: Dexmedetomidine
Intervention descriptions: intervention 1: to arms 2,4. Serves as the placebo. intervention 2: to arms 1,3

Protocol documents:
ICF_000.pdf: 
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Does dexmedetomidine decrease the incidence of untoward airway events after 
deep or awake extubation in patients undergoing adenotonsillectomy with or 
without myringotomy and tube placement? 
 
 
 
NCT #: NCT02162433 
 
 
 
1/29/2018 
 
 


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MASSACHUSETTS EYE AND EAR 
243 Charles Street 
Boston, Massachusetts 02114 
 
PROTOCOL  TITLE:  Does dexmedetomidine decrease the incidence of untoward 
airway events after deep or awake extubation in patients undergoing 
adenotonsillectomy with or without  myringotomy and tube placement? 
 
HSC PROTOCOL #:  14-019H 
 
PRINCIPAL INVESTIGATOR:   Makara Cayer, M.D. 
 
 
Why is this research study being conducted? 
 
You are being asked about your child taking part in a study to 1) compare two standards of care 
treatments at Mass Eye and Ear and, 2) determine whether an anesthesia medication that is often 
used in medical practice is indeed effective in lowering the risk of certain breathing complications.  
 
You are being asked about your child taking part in this research study because your child is 
scheduled to have his or her adenoids and/or tonsils removed (have an Adenotonsillectomy). 
 
This study is designed to answer two questions: 
1) Which method, deep or awake, is best in lowering the risk of breathing problems during 
breathing tube extubation?  Deep extubation is when the breathing tube is taken out while a 
person is still deeply under anesthesia.  Awake extubation means the breathing tube is taken 
out while the patient is starting to come out of anesthesia but is not fully awake.  We do not 
know which method works better.  Both of these methods are commonly used in medical 
practice at Mass Eye and Ear.   
 
2) Testing Dexmedetomidine to determine if it is effective in reducing breathing problems when 
the breathing tube is removed after Adenotonsillectomy. This medication is commonly used by 
anesthesiologists with children, but we do not know if it really helps. In this study, we have 
permission from the FDA to research this medication in our study.  
 
“Extubation” is the medical term used for removing a breathing tube after surgery.  
 
 
 
 
 
SUBJECT ID: 
ORDER OF ENROLLMENT: 


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Who is doing this research study and where will the study take place? 
 
This study is sponsored by the Department of Anesthesia at Mass. Eye and Ear and has obtained 
permission from your surgeon to conduct this study. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law. This website will not include information that can identify your child. At most, the website will 
include a summary of the results. You can search this website at any time. 
 
How long will this study take and what will happen in this study? 
 
About 336 children will take part in this research study at MEE. 
 
This study does not involve any extra study visits. We are simply asking your permission to conduct it 
and to call you 24 hours after discharge to ask about your child’s pain level.  We are also asking your 
permission to access your child’s surgery records for this research study.  
 
If you allow your child to participate in this study, your child will be randomly assigned to 1 of 4 
groups: 
(1) Dexmedetomidine with awake extubation; 
(2) Dexmedetomidine with deep extubation; 
(3) Placebo (normal saline, which has no medicinal effect) with awake extubation; 
(4) Placebo (normal saline, which has no medicinal effect) with deep extubation.  
 
The assignment is random, like the flip of a coin and is done by the Pharmacist. Neither you nor the 
anesthesiologist will know which study medication (Dexmedetomidine or placebo) will be given at 
time of surgery or which method is used to remove the airway tube. The study medication will be 
given through a catheter that is normally inserted in your child’s arm as part of your child’s clinical 
care.  
 
At the time of your child’s discharge, we will give you a sheet to record any breathing issues. We will 
ask you to record the amount of pain medication you give your child. We will contact you by phone or 
email 24 hours following your child’s surgery to ask about the pain level, pain medication used, and 
whether your child has any nausea, vomiting, or respiratory complications.  
 
What are the risks and possible discomforts from being in this research study? 
Dexmedetomidine may cause bradycardia (slow heart rate) and hypotension (low blood pressure), 
which are easily treatable. These complications normally occur in 10-20% of pediatric cases.  
The awake method of airway removal may cause some bleeding and coughing. The deep method, 
may cause laryngospasm (temporary cramp in the larynx). Both anesthesiologists and nurses in 
charge of your child will be closely monitoring as part of standard of care and know how to handle 
these routine complications 


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What are the possible benefits from being in this research study? 
 
Your child may or may not receive any direct benefit from taking part in this study.  However future 
children may benefit from determining which method and anesthesia work best.  
 
What are the alternatives to taking part in this study? 
 
Your child will undergo deep or awake extubation, whether or not you agree to take part in this 
research study.  Your child may or may not receive Dexmedetomidine per discretion of the 
anesthesiologist in charge.  Your alternative is to not participate. 
 
Can I decide to stop taking part in this study? 
Your child’s participation in this research study is entirely voluntary, and you may withdraw your 
permission even after signing this consent. The quality of care your child will receive at the 
Massachusetts Eye and Ear, the payment for your child’s health care, and your child’s health care 
benefits will not be affected if you decide not to participate or if you withdraw your child from the 
study.  
 
To withdraw from the study, you can inform a member of the research team at any time and tell them 
that you no longer want your child to take part.  
 
Your child doctors may also choose to withdraw your child from the research: 
 
 If the anesthesiologist determines that the research assigned extubation method should not be 
used clinically; 
 
 If the surgeon or anesthesiologist determines that it is clinically in the best interest for your 
child not to have the study medications at time of surgery; 
 
 If there are complications such as low heart rate and lowe blood pressure.  
 
 
Will I receive payment for taking part in this study? 
 
You will not receive a payment for allowing your child to participate in this study. 
 
What will I have to pay for if I take part in this research study? 
 
There are no additional costs for participation. You will still be responsible for any co-pays required by 
your child’s insurance company for standard treatment. 
 
What happens if I am injured as result of taking part in this research study? 


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We will offer you the care needed to treat any injury that directly results from taking part in this 
research study.  We reserve the right to bill your insurance company or other third parties, if   
appropriate, for the care you get for the injury.  We will try to have these costs paid for, but you may 
be responsible for some of them.  For example, if the care is billed to your insurer, you will be 
responsible for payment of any deductibles and co-payments required by your insurer. 
 
Injuries sometimes happen in research even when no one is at fault.  There are no plans to pay you 
or give you other compensation for the injury aside from what was described above.  However, you 
are not giving up any of your legal rights by signing this form. 
If you think you have been injured or have experienced a medical problem as a result of taking part in 
this research study, tell the researcher in charge of the study as soon as possible.  The researcher's 
name and phone number are listed on this consent form. 
Contact information if you have questions or concerns about this study 
 
You are free to ask any questions you may have regarding the study or about your child’s rights and 
treatment as a research subject. Further information about any aspect of this study is available now 
or at any time during the course of the study from the study coordinator, Alex Ciaramella at 617-573-
4016 or the principal investigator, Dr. Makara Cayer at 617-573-3380. 
 
Additionally, you may contact the Office of Research and Academic Affairs, at (617) 573-3446 if you 
have any questions or concerns about your child’s rights and treatment as a research subject. 
 
 
If I take part in this research study, how will you protect my confidentiality? 
 
We cannot guarantee total confidentiality.  However, we will code your data so that we will not directly 
link information that identifies to your data.  We will use a study code and keep the link between your 
identifiers and the code in a separate, password-protected file.  We will keep all data in a locked area 
and allow access only to study staff.  
 
We may publish the results of this research study in a medical book or journal or use the results to 
teach others.  However, we will not use your name and other identifying information for these 
purposes without your specific authorization.  
 
If I take part in this research study, how will you protect my privacy? 
 
During this research, we will collect identifiable information about your health.  In the rest of this 
section, we refer to this information simply as “health information.”  In general, under federal law, 
health information is private.  All health care providers subject to the Health Insurance Portability and 
Accountability Act (HIPAA) are required to protect the privacy of your information.  The research staff 


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at the MEE is required to comply with HIPAA and to ensure the privacy of your information.  However, 
there are exceptions to this rule, and you should know who may be able to see, use, and share your 
health information for research and why they may need to do so.  
 
In this study, we may collect health information about you from: 
 
Past, present, and future medical records 
Research procedures, research office visits, tests, interviews and questionnaires  
 
What is the purpose of collecting, using, and sharing of your protected health information? 
 
We are asking you to take part in the research study described in this research consent form.  In 
order for you to participate, we need to be able to collect, use and share your protected health 
information. 
 
If you decide to be in this study, the researcher will get information that identifies you and your 
personal health information.  This may include information that might directly identify you, such as 
your name, date of birth, phone number, and medical record number.    
 
Who may see, use, and share your identifiable health information and why they may need to do so 
 
 MEE research staff involved in this study 
 The sponsor(s) of study drug/device, and the people or groups it hires to help perform this 
research 
 Other researchers, health care providers and medical centers that are part of this study and 
their ethics boards 
 A group that oversees the data (study information) and safety of this research 
 Non-research staff within MEE who need this information to do their jobs (such as for 
treatment, payment (billing), or health care operations) 
 The MEE ethics board that oversees the research and the MEE research quality improvement 
programs 
 People from organizations that provide independent accreditation and oversight of hospitals 
and research 
 People or groups that we hire to do work for us, such as data storage companies, insurers and 
lawyers 
 Federal and state agencies (such as the Food and Drug Administration, the Department of 
Health and Human Services, the National Institutes of Health, and other U.S. or foreign 
government bodies that oversee or review research) 
 Public health and safety authorities (For example, if we learn information that could mean harm 
to you or others, we may need to report this, as required by law) 
 


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We share your health information only when we must, and we ask anyone who receives it from us to 
protect your privacy.  However, once we share your information outside of MEE, we cannot promise 
that it will remain private.  Some of the individuals or agencies listed above may not have to follow the 
same privacy and security rules that we follow and therefore may not be required to provide the same 
type of confidentiality protection. 
 
Because research is an ongoing process, we cannot give you an exact date when we will destroy or 
stop using or sharing your health information.  We will collect, use, and share your health information 
until the end of this research study, which may be after your direct participation in the research project 
ends.  
 
Your privacy rights: 
 
You have the right not to sign the form that allows us to use and share your health information for 
research; however, if you do not sign it, you cannot take part in this research study.  You have the 
right to take away your permission for us to use and share your health information for this research 
study at any time.  If you want to withdraw your permission, you must notify the person in charge of 
this research study in writing.  Once you withdraw your permission, you cannot continue to take part 
in this study.  
 
When you withdraw your permission, we will not gather new health information that identifies you 
after that date.  If you withdraw your permission, we will not be able to take back information that has 
already been used or shared with others.   
 
You have the right to see and get a copy of your health information that we used or shared for 
treatment or for payment.  To ask for this information, please contact the person in charge of this 
research study.  For some studies, you may only get such information after the research is finished.  
Statement of the Person Giving Informed Consent and Authorization 
 I have read this consent form 
 This research study has been explained to me, including the risk and possible benefits 
(if any), other possible treatments or procedures, and other important parts of the study. 
 I have had the opportunity to ask questions. 
 I understand the information given to me. 
 I will be given a signed copy of this form to keep. 
 
 


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Signature of Parent(s)/Guardian for Child 
 
I give my permission for my child to take part in this research study and agree to allow his/her health 
information to be used and shared as described above.  
 
_______________________________________ 
 
________________ ________________ 
Parent(s)/Guardian for Child  
 
 
 
Date 
 
 
Time 
 
 
___________________________________   
Print Name  
 
Child Assent (children 14 to 16) 
Statement of Child Giving Assent 
 
 This research study has been explained to me, including risks and possible benefits (if any), other 
possible treatments or procedures, and other important parts of this study. 
 I have had the opportunity to ask questions, and my questions have been answered. 
 
 
I agree to take part in this research study and agree to allow my health information to be used as shared as 
described above. 
 
 
___________________________________________ 
 
________________ 
________________ 
Child, Ages 14-16 
 
 
 
 
 
Date 
 
 
Time 
 
Signature of Study Doctor or Person Obtaining Consent 
 
 I have explained the research to the study subject. 
 I have answered all questions about this research study to the best of my ability. 
 
 
____________________________________________  
________________ 
________________ 
Study Doctor or Person Obtaining Consent 
 
 
Date 
 
 
Time 

SAP_002.pdf: 
Protocol Title: Does dexmedetomidine decrease the incidence of untoward airway events after 
deep or awake extubation in patients undergoing adenotonsillectomy with or without 
myringotomy and tube placement? 
NCT: NCT02162433 
Document Date: 2/7/2020 
 
Statistical Plan 
The primary endpoint was the occurrence of one or more postoperative respiratory 
complications, including desaturation to less than 95% for more than 10 seconds, breath holding, 
complete or partial laryngospasm, bronchospasm, croup, persistent cough, negative pressure 
pulmonary edema, and stridor. Secondary outcomes included incidence of emergence agitation, 
incidence of postoperative nausea and vomiting, length of time from the end of surgery to 
leaving the operating room, length of stay from admission to PACU to discharge home, 24-hour 
postoperative pain control, and any unplanned hospital admission due to perioperative 
respiratory adverse events.  
The primary outcome was analyzed by counting the number of patients who experienced any of 
the listed postoperative respiratory complications. The patients were separated into four groups: 
awake extubation/dexmedetomidine, awake extubation/placebo, deep 
extubation/dexmedetomidine, and deep extubation/placebo. The number of patients who 
experienced any complications was divided by the total number of patients randomized per 
group. This resulted in the percentage of patients who experienced any postoperative 
complications.  
The secondary outcomes were assessed as following: the number of patients exhibited incidences 
of agitation, nausea and vomiting were counted; the length of time from end of surgery to 
leaving the operating room was averaged, the mean and standard deviation per randomization 
group was reported; the 24-hour postoperative pain control requirement was assessed by 
counting how many patients needed pain medication post-op for up to 24 hours; and the number 
of patients who had any unplanned hospital admission due to perioperative respiratory adverse 
events was counted per randomization group and reported.  

Prot_001.pdf: 
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Page 1 of 42 
Does dexmedetomidine decrease the incidence of untoward airway 
events after deep or awake extubation in patients undergoing 
adenotonsillectomy with or without myringotomy and tube placement? 
 
 
 
NCT #: NCT02162433 
 
 
 
1/29/2018 
 
 


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COVER PAGE  
Clinical Protocol Title: Does dexmedetomidine decrease the incidence of 
untoward airway events after deep or awake extubation in patients undergoing 
adenotonsillectomy with or without myringotomy and tube placement? 
HSC #: 14-019H 
 
IRBNet ID: 551737 
Version number and date: 
11, 10/26/2016 
Phase of clinical investigation: N/A 
Name of all sites (if applicable): N/A 
IND/IDE number: 122254                                                                        
Investigational drug(s) or device(s): 
Dexmedetomidine hydrochloride (Precedex) 


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Regulatory Sponsor:     
Department of Anesthesia 
Mass. Eye and Ear, 243 Charles St., Boston, MA 02114 
 
Funding Sponsor:  
Curing Kids Fund 
 
Study Monitor 
Medical Director:  
Sunil Eappen, M.D. 
Department of Anesthesia 
Mass. Eye and Ear, 243 Charles St., Boston, MA 02114 
617-523-7900  
 
Investigator(s): 
Makara Cayer, M.D. 
Department of Anesthesia 
Mass. Eye and Ear, 243 Charles St., Boston, MA 02114 
617-523-7900 
 
Study Coordinator(s): 
Alex Ciaramella  
Department of Anesthesia 
Mass. Eye and Ear, 243 Charles St., Boston, MA 02114 
617-523-4016 
 
 
 


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Statistician: 
Rong Guo 
Mass. Eye and Ear, 325 Cambridge St., Boston, MA 02114 
617-523-5583 
 
Clinical Laboratory(ies), Technical Department(s), and Institution(s) 
Providing Clinical Study Services: 
Department of Anesthesia, Pharmacy, and PACU nursing at Massachusetts Eye 
and Ear Infirmary. 


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STUDY DESIGN SCHEMATIC 
 
 
 


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1. CLINICAL PROTOCOL 
 
1.1 Background 
Adenotonsillectomy (T&A) is the most frequently performed surgical procedure 
in the pediatric population. T&A is associated with a high incidence of 
perioperative respiratory adverse events (11.2%)1 including coughing, breath-
holding, desaturation, partial or complete laryngospasm, bronchospasm, and 
negative pressure pulmonary edema. These respiratory complications in the 
postoperative period frequently lead to prolonged post-anesthesia care unit 
(PACU) and hospital stays in this patient population. Therefore, the 
postoperative period can be highly stressful for both children and their 
parents.2 
 
The incidence of these respiratory adverse events is highest following tracheal 
extubation and in the recovery period.3 Consequently, during emergence from 
anesthesia, tracheal extubation constitutes the most perilous event that may 
determine the incidence of adverse respiratory complications in the 
postoperative period. There remains a controversy as to whether tracheal 
extubation should be performed in a deeply anesthetized patient or in an 
awake patient.3 Given the serious nature of the respiratory complications 
following T&A, the identification of an adjuvant drug therapy that could 
decrease these untoward events would be highly desirable. 
 
Dexmedetomidine hydrochloride is a highly selective α2-adrenoceptor agonist. 
Its properties include sedation, anxiolysis, analgesia with little respiratory 
depression.2,4 In addition, dexmedetomidine has minimal effect on coagulation 
parameters.5 The potential risks of the use of dexmedetomidine, bradycardia 
and hypotension, are very rare.2 
 


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The use of this agent has been increasing in the pediatric population 
undergoing different surgical procedures.6,7,8,9 The drug’s opioid-sparing 
property in patients undergoing T&A is of particular interest. Pain-control in 
patients undergoing T&A can be extremely challenging, as many of these 
children may have an altered central opioid function that could enhance their 
responsiveness to opioid drugs.2,10,11 This 
hypersensitivity to opioids, potentially leading to severe respiratory 
complications, increases the risk of perioperative adverse airway events, thus 
limiting the application of such drugs in this population. 
 
Dexmedetomidine is an attractive drug for managing pediatric patients 
undergoing T&A: it combines mild analgesic effects, opioid-sparing properties, 
and minimal respiratory depression.2,4 Dexmedetomidine also appears to be a 
safe and effective agent in reducing the incidence of early emergence agitation 
in children after tonsillectomy.12 
 
However, the effects of dexmedetomidine on postoperative adverse airway 
events have not been fully studied, and the literature is limited to two studies. 
In one study investigating emergence agitation in sixty children undergoing 
T&A, Guler et al also studied untoward airway events in these patients.6 In this 
investigation, one group received dexmedetomidine 0.5 μg/kg over 5 minutes, 
while the control group received a placebo five minutes before the end of 
surgery. The number of severe coughs per patient in the dexmedetomidine 
group was significantly reduced compared to the control group (p < 0.05). 
Another study by Akin et al compared the effects of dexmedetomidine to 
midazolam administered as premedication on ninety patients undergoing T&A. 
The midazolam group resulted in five cases of laryngospasm, compared to the 
dexmedetomidine group, which exhibited none.13 
 
 


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Given the serious nature of untoward respiratory events in the perioperative 
period associated with T&A, coupled with the paucity of literature on the 
effects of dexmedetomidine on these events, we aim to investigate the effect of 
dexmedetomidine on the perioperative respiratory complications in this patient 
population undergoing both awake and deep tracheal extubation.             
 
References:  
 
1. Ye J, Liu H, Zhang G, et al. Postoperative respiratory complications of 
adenotonsillectomy for obstructive sleep apnea syndrome in older 
children: prevalence, risk factors, and impact on clinical outcome. J 
Otolaryngol Head Neck Surg. 2009; 38(1):49-58. 
 
2. He XY, Cao JP, Shi XY, et al. Dexmedetomidine versus morphine or 
fentanyl in the management of children after tonsillectomy and 
adenoidectomy: A meta-analysis of randomized controlled 
trials. Ann Otol Rhinol Laryngol 2013; 122(2):114-120. 
 
3. Ungern-Sternberg BS, Davies K, Hegarty M, et al. The effect of deep vs. 
awake extubation on respiratory complications in high-risk children 
undergoing adenotonsillectomy: A randomized controlled trial. Eur J 
Anaesthesiol 2013; 30:529–536. 
 
4. Venn RM, Hell J, Grounds RM. Respiratory effects of dexmedetomidine 
in the surgical patient requiring intensive care. Crit Care 2000; 4:302-308. 
 
5. Mizrak A, Karatas E, Saruhan R, Kara F, Oner U, Saricicek V, Baysal E. 
Does dexmedetomidine affect intraoperative blood loss and clotting tests 
in pediatric adenotonsillectomy patients? J Surg Res 2013; 179(1):94-98. 
 
6. Chrysostomou C, Schulman SR, Herrera Castellanos M, et al. A phase 
2/3, Multicenter, Safety, Efficacy, and pharmacokinetic study of 
dexmedetomidine in preterm and term neonates. J Pediatr 2014; 164(2): 
276-282. 
 
7. Guler G, Akin A, Tosun Z, et al. Single-dose dexmedetomidine reduces 
agitation and provides smooth extubation after pediatric 
adenotonsillectomy. Pediatr Anesth 2005; 15:762–766. 
 
8. Su F, Nicolson SC, Zuppa AF. A dose-response study of 
dexmedetomidine administered as the primary sedative in infants 
following open heart surgery. Pediatr Crit Care Med 2013; 14(5): 499-507. 


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9. Cai Y. et al. Efficacy and safety of spontaneous ventilation technique 
using dexmedetomidine for rigid bronchoscopic airway foreign body 
removal in children. Pediatr Anaesth 2013; 23: 1048-1053. 
 
10. Brown KA, Laferrière A, Moss IR. Recurrent hypoxemia in young 
children with obstructive sleep apnea is associated with reduced opioid 
requirement for analgesia. Anesthesiology 2004; 100:806-810.  
 
 
11. Brown KA, Laferrière A, Lakheeram I, et al. Recurrent hypoxemia in 
children is associated with increased analgesic sensitivity to opiates. 
Anesthesiology 2006; 105:665-669.  
 
12. Meng QT, Xia ZY, Luo T, et al. Dexmedetomidine reduces emergence 
agitation after tonsillectomy in children by sevoflurane anesthesia: A 
case-control study. Int J Pediatr Otorhinolaryngol 2012; 76:1036–1041.  
 
13. Akin A, Bayram A, Esmaoglu A, et al. Dexmedetomidine vs midazolam 
for premedication of pediatric patients undergoing anesthesia. Pediatr 
Anaesth 2012; 22:871-876. 
 
Provide a brief description of, and justification for, the proposed route of 
administration, dosage, dosage regimen, and duration of dosing of the 
investigational drug(s) or the investigational device(s) 
0.5 µg/kg of dexmedetomidine diluted in NaCl 0.9% with a maximum 
concentration of 4 µg/ml will be administered through the infusion pump 
over 5 minutes.  
 
Summarize the nature of the individuals (e.g., age range, sex, disease state or 
underlying condition) who will be included in the proposed clinical 
evaluation 
Children 3-16 years of age undergoing adenotonsillectomy.  


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Specify whether or not (i.e., to your knowledge) the investigational drug(s) or 
device(s) has been marketed in any other country. Specify if the 
investigational drug(s) or device(s) has been withdrawn from research or 
market in any country for any reason related to its safety or effectiveness. If 
the drug or device has been the subject of controlled clinical trials, detailed 
information of such trials that is relevant to an assessment of the drug’s or 
device’s effectiveness for the proposed investigational use should also be 
provided. 
N/A 
 
 
 
 


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2. STUDY OBJECTIVES 
 
2.1 Primary Objective 
We aim to investigate the effect of dexmedetomidine on the perioperative 
respiratory complications in this patient population undergoing both 
awake and deep tracheal extubation.             
(Note: For Phase 1 clinical research studies, the primary objective should be 
an evaluation of the safety of the investigational drug or device) 
2.2 Secondary Objective(s) 
We also aim to investigate the effect of dexmedetomidine on the 
incidence of nausea and vomiting as well as emergence agitation. In 
addition, we will evaluate the effect of dexmedetomidine on the 
requirement of postoperative pain control medication.   


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3. STUDY DESIGN 
3.1 Study Design Description 
We propose a prospective double-blinded randomized controlled trial. 
336 pediatric patients presenting to Massachusetts Eye and Ear Infirmary 
(MEEI) for adenotonsillectomy with or without myringotomy and tube 
placement who are eligible for the study based on inclusion and 
exclusion criteria will be recruited. A Clinical Pharmacy specialist, will in 
charge of preparing the dexmedetomidine and placebo doses and will 
randomize the patients to four equally numbered groups. The 
anesthesiologist will receive the assignment for the extubation method in 
a sealed envelope from the Clinical Pharmacy specialist. Multiple 
parameters will be recorded in perioperative period to quantify 
perioperative adverse respiratory events. 1- Oxygen saturation will be 
measured at the following intervals: 5 minutes prior to extubation; 
immediately before extubation; every minute for the first 10 minutes 
following extubation; and subsequently, every 5 minutes for the ensuing 
20 minutes. The following parameters will be noted:  
1- desaturation to less than 95% for more than 10 seconds;  
2- breath holding;  
3- complete or partial laryngospasm;  
4- bronchospasm;  
5- croup;  
6- number of episodes of persistent cough (three or more consecutive 
coughs);  
7- negative pressure pulmonary edema; 
8- stridor. 
 


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Add sub studies (if applicable): 
 
We will also investigate the following parameters: 
1) Incidence of emergence agitation;  
2) Incidence of postoperative nausea and vomiting (PONV); 
3) Length of time from end of surgery to leaving the operating 
room;  
4) The length of stay from admission to the PACU to discharge 
home;  
5) 24-hour postoperative pain control requirements assessed by the 
questionnaire given to parents at the time of discharge; 
6) Any unplanned hospital admission due to perioperative 
respiratory adverse events. 
 
3.2 Allocation to Treatment (Incorporate only if the proposed clinical study 
involves multiple treatment arms) 
1. Awake extubation receiving dexmedetomidine;  
2. Awake extubation receiving placebo; 
3. Deep extubation receiving dexmedetomidine; 
4. Deep extubation receiving placebo. 
 
3.2.1 Randomization Procedures:  
The Clinical Pharmacy specialist preparing dexmedetomidine and placebo 
for study will apply randomization and the anesthesiologist will receive 
the assignment for extubation method in a sealed envelope. 
 
 


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3.2.2 Masking Procedures:  
The patient, anesthesiologist and data analyst will be blinded as to which 
group receives which medication. All members of the perioperative care 
will remain blinded to the study drug arm. 
 
3.2.3 Breaking the Mask (only if proposed study is masked) 
The mask will be broken in case of severe bradycardia or hypotension, 
and the patient will be withdrawn from the study. 
Severe bradycardia is define as follows: 
 Children 3-5 years of age: heart rate < 60 beats per minute; 
 Children 6-16 years of age: heart rate <50 beats per minute; 
Severe hypotension is defined as a drop in systolic blood pressure of 
more than 40% drop compared to the baseline systolic blood pressure. 
The treatment of bradycardia in children involves the administration of 
atropine or epinephrine, and in case of isolated hypotension, depending 
on the severity, fluid, phenylephrine or epinephrine will be administered.  


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4. SUBJECT SELECTION 
 
4.1 Subject Inclusion Criteria 
 Patients between 3 to 16 years of age undergoing adenotonsillectomy 
with or without myringotomy and tube placement; 
 ASA class 1 or 2. 
4.2 Subject Exclusion Criteria 
 Known allergy or hypersensitivity reaction to dexmedetomidine; 
 Organ dysfunction (renal/hepatic failure or leukemia); 
 Cardiac disease (congenital or acquired); 
 Airway or thoracic malformation;  
 Cerebral palsy;  
 Hypotonia;  
 Need for premedication with midazolam, ketamine, or dexmedetomidine; 
 Current/recent upper respiratory infection (within four weeks prior to 
the surgery); 
 Asthma; 
 Allergy or intolerance to clonidine; 
 
Non-English speaking parents/patients 


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5. STUDY DRUG(S)/DEVICE(S)  
 
5.1 Study Drug/Device Information 
Dexmedetomidine is an FDA approved drug for use in adults.  
Dexmedetomidine is not an FDA approved drug for use in children. 
0.5 µg/kg of dexmedetomidine diluted into 4 µg/ml concentration and 
drawn up to the appropriate volume with NaCl 0.9% will be administered 
through the infusion pump over a 5-minute period. 
Overweight and obese patients will receive a dose of dexmedetomidine 
based on their estimated lean body mass. 
The volume of normal saline administered to control patients will mimic 
the volume of dexmedetomidine in the treatment group and will be 
administered through an infusion pump over a 5-minute period. The 
volume of NaCl 0.9% for the placebo works out to be 0.125 ml/kg. 
 
5.2 Study Drug/Device Compliance/Adherence  
N/A 
 
5.3 Study Drug Supplies 
Formulation and Packaging 
Precedex (dexmedetomidine hydrochloride) injection is a sterile, non-
pyrogenic solution suitable for intravenous infusion following dilution. 
Dexmedetomidine hydrochloride is the S-enantiomer of medetomidine 
and is chemically described as (+)-4-(S)-[1-(2,3-dimethylphenyl)ethyl]-1H-
imidazole monohydrochloride. Precedex has a molecular weight of 236.7 
with the empirical formula of C13H16N2 • HCl.  


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The structural formula is: 
 
 
 
 
 
 
Dexmedetomidine hydrochloride is a white or almost white powder that 
is freely soluble in water and has a pKa of 7.1. Its partition coefficient in-
octanol: water at pH 7.4 is 2.89. Precedex is supplied as a clear, colorless, 
isotonic solution with a pH of 4.5 to 7.0. Each mL of Precedex Injection, 
Concentrate contains 118 mcg of dexmedetomidine hydrochloride 
equivalent to 100 mcg of dexmedetomidine and 9 mg of sodium chloride 
in water. Each mL of Precedex Injection contains 4.72 mcg of 
dexmedetomidine hydrochloride equivalent to 4 mcg dexmedetomidine 
and 9 mg of sodium chloride in water. The solution is preservative-free 
and contains no additives or chemical stabilizers. Dexmedetomidine is 
not FDA approved for use children undergoing adenotonsillectomy. 
 
Preparing and Dispensing 
The dexmedetomidine and placebo syringes will be prepared by an 
independent investigator (Clinical Pharmacy specialist) not involved in 
the perioperative care of the study patients.  
 
 
 


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Administration 
Dexmedetomidine will be diluted in NaCl 0.9% to a concentration of 4 
µg/ml. 0.5 µg/kg dexmedetomidine will be administered to the patients 
through an infusion pump over 5 minutes.  
Normal Saline (Placebo) 0.125 ml/kg will be administered to the patients 
through an infusion pump over 5 minutes. 
The procedure will be investigator-directed for the study drugs. We will 
inform the research subjects before the surgery that they will receive 
either dexmedetomidine or a placebo during the anesthesia process. 
 
5.4 Study Drug/Device Storage and Accountability 
Precedex Injection, Concentrate 
Precedex (dexmedetomidine hydrochloride) injection, Concentrate 200 
mcg/2 mL (100 mcg/mL) is available in 2 mL clear glass vial. Vials are 
intended for single use only. 
 
NDC No. Container Size 
0409-1638-02 Vial 2 mL 
 
Precedex Injection 
Precedex (dexmedetomidine hydrochloride) injection is available as 
200 mcg/50 mL (4 mcg/mL) and 400 mcg/100 mL (4 mcg/mL) in 50 mL 
and 
100 mL clear glass bottles, respectively.  
 
NDC No. Container Size 
0409-1660-50 Bottle 50 mL 
0409-1660-10 Bottle 100 mL 
 


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Dexmedetomidine vials and placebo (sodium chloride 0.9%) vials will be 
stored in the Pharmacy at controlled room temperature (15-25 degrees 
Celsius). The Pharmacist will maintain drug accountability records for 
both dexmedetomidine and sodium chloride. All activities related to drug 
receipt, drug dispensation to subjects, and drug waste will be 
documented on the drug accountability log for each 
medication. Additionally, a perpetual inventory is maintained for each 
medication. 
 
5.5 Other Medications 
The following drugs are part of the anesthesia process and will be 
administered to all patients undergoing surgery regardless of the  
proposed research study protocol:  
 Administration 
- 
Acetaminophen 15 mg/kg orally to the maximum of 650 mg at 
least 30 minutes prior to surgery; 
- 
Patients 10 years or older will receive LMX-4 cream (Lidocaine 4%; 
Ferndale Pharmaceuticals; Deed; UK) on the dorsum of both hands 
30 minutes prior to surgery, unless contraindicated; 
- 
Propofol 1-3mg/kg IV in patients undergoing IV induction and 1-
2mg/kg IV in patients undergoing inhalational induction; 
- 
Remifentanil 1-2 μg/kg IV; 
- 
Dexamethasone (0.5 mg/kg to a maximum of 10 mg) IV; 
- 
Ondansetron (0.1 mg/kg to a maximum of 4 mg) IV; 
- 
Morphine 0.05- 0.1 mg/kg IV. 


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 Rescue Medication or Therapy 
- 
Atropine 0.02 mg/kg for bradycardia; 
- 
Phenylephrine 1 mcg/kg for hypotension; 
- 
Epinephrine 1 mcg/kg in case of severe bradycardia or 
hypotension. 


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6. BIOSPECIMEN COLLECTION (IF APPLICABLE) 
 
 
6.1 Specimen preparation, handling, and shipping 
 
N/A 
6.2 Instruction for specimen preparation, handling and storage 
 
N/A 
6.3 Specimen shipment 
 
N/A 
6.4 Future use of stored specimens 
 
N/A 


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7. STUDY PROCEDURES 
 
7.1 Recruitment Procedures 
A letter with detailed summary of the study will be sent to referring 
physicians to provide the letter to study eligible patients and their family 
members at the time of pre-operation. The referring physician will also 
explain to them that the study coordinator will be approaching them on 
the day of the surgery to discuss. 
7.2 Screening Procedures 
Pregnancy test for children of more than 12 years of age will be 
performed. Patients will also be screened for any conditions that increase 
the risk of complications, allergies or intolerance, current medications, 
and ASA classification. 
 
7.3 Enrollment/Baseline Procedures 
All patients meeting inclusion criteria and not excluded by exclusion 
criteria. 
 
7.4 Study Drug or Device Procedures 
Dexmedetomidine and normal saline will be infused through an infusion 
pump. 
 
7.5 Standard of Care Procedures 
Deep or awake extubation of patients. 
 


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7.6 Follow-up Procedures (Incorporate only if follow-up procedures will be 
performed) 
We will contact all study subjects by phone 24 hours after discharge in 
order to assess their pain level and pain control requirement. This follow-
up will be performed only in study participants. 
 
7.7 Unscheduled Visits 
N/A 
7.8 Early Termination 
In case of severe bradycardia or hypotension requiring CPR following 
dexmedetomidine administration, the patient’s participation in the study 
will be terminated. The data from patients withdrawn from the study will 
not be used. 
 
7.9 Schedule of Activities (Study Table) 
Provide a table that summarizes the clinical protocol procedures; to 
include the procedures that will be performed at screening, during the 
study drug administration, and at follow-up (if applicable) to the study 
drug or device administration. Please contact HSC@meei.harvard.edu if 
you would like to see an example. 
 


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Preoperative 
Evaluation 
 
 
 
 
 
 
 
 
 
 
 
 
 Children ≥ 12 years old will be screened by pregnancy 
testing. 
 Research only: We will discuss the research study with 
the patient and family in the pre-operative area; the risks 
and benefits will be explained to the patient and family 
by the anesthesiologist two hours before the surgery. 
 Research only: Patients’ parents will be asked to sign a 
consent form, and the patient, if eligible, will sign a child 
assent.  
 Patient demographics and characteristics, including ASA 
classification and comorbid conditions, will be recorded.  
 Patients will receive acetaminophen 15 mg/kg to the 
maximum of 650 mg orally at least 30 minutes prior to 
surgery in the preoperative holding area on the pediatric 
floor.  
 Research only: Patients will be assigned to four groups 
according to the pharmacy randomization: 1-awake 
extubation receiving dexmedetomidine; 2-awake 
extubation receiving placebo; 3-deep extubation 
receiving dexmedetomidine; 4-deep extubation receiving 
placebo.   
 An IV catheter will be placed in all children 10 years or 
older in the preoperative holding area on the surgical 
floor. 
 Standard ASA monitors, including pulse-oximetry, ECG, 
non-invasive blood pressure, and capnography, will be 
used in all patients. 


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 Research only: The anesthesiologist will be informed as 
to whether the patient belongs to the deep or awake 
extubation group in a sealed envelope. 
 Research only: All members of the perioperative team 
will be blinded to the drug arm of the study. 
 Patients will be transferred to the operation room.  
Intraoperative 
Phase 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Induction: The anesthesia process will start with 
intravenous (IV) induction with propofol (1-3mg/kg) (for 
children ≥ 10 years old) or inhalation induction with 70% 
nitrous oxide and 8% sevoflurane (for children <10 years 
old). After inhalational induction, an IV will be placed in 
children < 10 years old, and propofol 1-2mg/kg. Next, all 
children will be administered remifentanil 1-2 µg/kg and 
then intubated with a cuffed endotracheal tube. 
 Research only: Study intervention: Following tracheal 
intubation, patients will receive either dexmedetomidine 
(dexmedetomidine 0.5 µg/kg diluted in NaCl 0.9% to 
achieve concentration of 4µg/ml) or a placebo (same 
volume of NaCl 0.9%), both over a 5-minute time period. 
 Maintenance: The maintenance of anesthesia will be 
achieved with sevoflurane. All children will receive 
dexamethasone (0.5 mg/kg to a maximum of 10 mg), 
ondansetron (0.1 mg/kg to a maximum of 4 mg) for 
antiemetic prophylaxis, and morphine 0.05-0.1 mg/kg 
for pain control. The dose of morphine will be adjusted 
for patients with OSA to receive 0.05 mg/kg. 


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  Extubation: At the end of the procedure, all patients will 
be placed on 100% oxygen: at this point, they will 
undergo either deep or awake tracheal extubation based 
on the prior randomization. However, the 
anesthesiologist will be able to overrule this decision 
based on his/her clinical judgment should the alternate 
method of extubation be indicated at the end of the case. 
Awake extubation will be performed when the patient 
demonstrates stable vital signs and adequate tidal 
volume, combined with one or more of the following 
responses: following commands, eye opening, 
purposeful movement, or coughing. Deep extubation will 
be performed when the patient’s end-tidal sevoflurane 
level is greater than one minimum alveolar concentration 
(MAC), and he/she is in the surgical plane of anesthesia. 
Postoperative 
Phase 
 
 
 
 
 
 
 
 
 
 
 
 
 All patients will be transported to PACU in lateral 
decubitus position on a facemask receiving oxygen or 
blow by oxygen ( 6L/min). Oxygen will be administered 
for 30 minutes continuously once in the PACU.   
 The anesthesiologist will remain with the patient until 
he/she is stable enough to be handed off to the PACU 
nurse.  
 After 30 minutes, supplemental oxygen can be 
discontinued if patient is able to maintain an oxygen 
saturation of greater than 95% on room air. 
 Research only: Oxygen saturation will be measured at the 
following intervals: 5 minutes prior to extubation; 
immediately prior to extubation; every minute for the 


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Postoperative 
Phase 
Continued 
first 10 minutes following extubation; and subsequently, 
every 5 minutes for the ensuing 20 minutes. 
 Research only: Heart rate and blood pressure will be 
measured at the following intervals: upon arrival at the 
PACU; every subsequent 5 minutes for the first 30 
minutes. 
 Research only: Multiple parameters will be recorded in 
perioperative period to quantify perioperative adverse 
respiratory events: 1- desaturation to less than 95% for 
more than 10 seconds will be noted; 2- breath holding; 3- 
complete or partial laryngospasm; 4- bronchospasm; 5- 
croup; 6- number of episodes of persistent cough (more 
than three consecutive coughs); 7- negative pressure 
pulmonary edema; and 8-stridor. 
 Research only: In addition to the above measures, the 
patient’s pain level in the PACU will be assessed using 
the FLACC Scale or Wong Baker faces charts, depending 
on the age of the patient.  
 Research only: Finally, the following parameters will also 
be recorded by the Study coordinator or 
anesthesiologist: 1- occurrence of emergence agitation 
using the PAED Scale; 2- episodes of vomiting; 3- length 
of time from the end of surgery to leaving the operating 
room; 4- length of stay in minutes from admission to the 
PACU to discharge home; 5- any unplanned hospital 
admission due to perioperative respiratory adverse 
events. 
 


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Discharge 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Patients meeting the discharge criteria will be discharged 
home. 
 Patients with planned or unplanned hospital overnight 
admission will be discharged to the pediatric floor or 
PICU depending on the patient’s disposition. 
 Research only: During discharge home, the patient’s 
parents will be given a sheet to record breathing issues, 
including hoarseness, snoring (longer than 10 seconds), 
breath holding, and severe coughing. Parents will also be 
asked to record the amount of pain medication 
administered postoperatively to their children during the 
first 24 hours. They will also be asked to record any 
incidence of nausea and vomiting. Patients will be 
followed up to ascertain how they fared postoperatively. 
All data from the parents’ sheet will be recorded. 
 In patients admitted overnight, breathing issues, 
including hoarseness, snoring (longer than 10 seconds), 
breath holding, and severe coughing will be recorded. 
The amount of pain medication administered during the 
first 24-hours postoperatively will be noted, as will be 
any incidence of nausea and vomiting.  
Data Analysis 
 Research only: Data will be analyzed using chi-square or 
Fisher’s exact test for all four groups and pairwise 


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comparison between any 2 groups.  
 


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8. SAFETY AND EFFECTIVENESS ASSESSMENTS 
 
8.1 Safety Assessments 
The vital signs of the patient will be continuously monitored during the 
procedure. Heart rate and blood pressure will be monitored during the 
entire surgery for bradycardia and hypotension. Vital signs will be 
monitored in the PACU in order to detect any respiratory complications 
or adverse effects due to medications.  
 
8.2 Effectiveness Assessments 
Oxygen saturation will be monitored continuously intraoperatively, as 
well as postoperatively in the recovery room. For the purpose of this 
study, oxygen saturation will be recorded at the following intervals: 5 
minutes prior to extubation; immediately before extubation; every minute 
for the first 10 minutes following extubation; and subsequently, every 5 
minutes for the ensuing 20 minutes. Blood pressure and heart rate will be 
monitored intraoperatively every 5 minutes, on arrival in the PACU, then 
every 5 minutes in the recovery room for the first 30 minutes.  
 
The following parameters will also be monitored and recorded in the 
perioperative period to quantify adverse respiratory events:  
1- desaturation to less than 95% for more than 10 seconds;  
2- breath holding;  
3- complete or partial laryngospasm;  
4- bronchospasm;  
5- number of episodes of persistent cough (three or more 


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consecutive coughs);  
6- croup;  
7- negative pressure pulmonary edema; 
8- stridor. 
The occurrence of one or more of these postoperative respiratory complications 
constitutes the primary outcome measure for analysis in this study. 


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9. ADVERSE EVENT RECORDING AND REPORTING 
 
9.1 Recording Requirements 
Research subjects will be monitored for adverse events during and after 
the procedure. All observed adverse events regardless of study group or 
suspected causal relationship to the study drug will be recorded in the 
subjects’ case histories (source data) and electronic anesthesia records. 
For all adverse events, any pertinent information will be collected to 
permit: 1- adequate determination of the outcome of the event (whether 
the event should be classified as a serious adverse event); and, 2- 
assessment of the casual relationship between the adverse event and the 
study drug.  
Adverse events associated with the study drug will be followed until the 
event resolves and the patient stabilizes to a level acceptable to the 
Sponsor-Investigator. 
 
 
9.2 REPORTING PROCEDURES 
 REPORTING OF ADVERSE EVENTS TO FDA 
Adverse events will be reported to the FDA. 
  Reporting Adverse Events to Other External Entities 
Adverse events will be reported to the manufacturer of Precedex.  
 
 Reporting Adverse Events to the Human Studies Committee  
Any adverse effects including hypotension and bradycardia will be 
reported.  


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9.3 Withdrawal of Subjects due to Adverse Events? 
In case of severe hypotension and bradycardia, we will withdraw the 
subjects from the study. In case of severe hypertension, the subjects will 
also be withdrawn from the study  
 


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10. STATISTICAL METHODS/DATA ANALYSIS 
 
10.1 Primary endpoint(s) or outcome measure(s) 
The occurrence of one or more of these postoperative respiratory 
complications constitute the primary outcome measure for analysis in 
this study:  
1- Desaturation to less than 95% for more than 10 seconds; 
2- Breath holding; 
3- Complete or partial laryngospasm; 
4- Bronchospasm; 
5- Croup; 
6- Number of episodes of persistent cough (three or more 
consecutive coughs); 
7- Negative pressure pulmonary edema; 
8- Stridor. 
 
10.2 Secondary endpoints or outcome measure(s) 
We will also investigate the following parameters: 
1. Incidence of emergence agitation;  
2. Incidence of postoperative nausea and vomiting (PONV); 
3. Length of time from the end of surgery to leaving the operating 
room;  
4. The length of stay from admission to the PACU to discharge home;  
5. 24-hour postoperative pain control requirements; 
6. Any unplanned hospital admission due to perioperative respiratory 
adverse events. 


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10.3 Sample Size Determination 
Based on the study by Patel et al comparing the untoward outcomes in 
children undergoing awake versus deep extubation after 
adenotonsillectomy, a difference in complication rate has been shown 
between the two groups, with 11% (2 out of 18) versus 30% (6 out of 20), 
respectively, exhibiting airway complications during extubation.1 Based 
on these results, a two-group χ 2 test with a 0.05 two-sided significance 
level would have an 80% power to detect the difference between the 
‘awake’ group and ‘deep’ group given a sample size of 71 in each group. 
Guler et al compared untoward events after awake extubation in patients 
undergoing tonsillectomy who received dexmedetomidine 0.5 mcg/kg 
during the procedure to a placebo group who did not: they observed that 
the rate incidence of severe cough was significantly lower in the 
dexmedetomidine group (0%) compared to the placebo group (30%).2 
Based on these results, a two-group χ 2 test with a 0.05 two-sided 
significance level would have an 80% power to detect the difference 
between the ‘dexmedetomidine’ group  and ‘placebo’ group given a 
sample size of 22 in each group. 
Since we will be comparing the results of the ‘deep’ versus ‘awake’ as well 
as those of the ‘dexmedetomidine’ versus ‘placebo’ outcomes, each group 
will require a sample size of 71. 
We anticipate that, at most, 15% of randomized patients will not provide 
complete data on their assigned drug/extubation combination 
randomized arm because the anesthesiologist overrules the assigned 
extubation method due to the clinical needs of the patient during the 
case. Therefore, in order to assure that there will be at least 71 subjects 
on each study arm with complete data, we will enroll and randomize a 


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total of 336 patients with equal probability to the four arms (84 patients 
in each group) using a block randomization scheme. 
References: 
1. 1- Patel RI, Hannallah RS, Norden J, et al. Emergence airway 
complications in children: a comparison of tracheal extubation in 
awake and deeply anesthetized patients. Anesth Analg 1991; 73:266–
270. 
 
2. Guler G, Akin A, Tosun Z et al. Single-dose dexmedetomidine reduces 
agitation and provides smooth extubation after pediatric 
adenotonsillectomy. Pediatr Anaesth 2005; 15:762–766. 
 
10.4 Analysis Population (if applicable) 
Children between 3 months and 16 years old undergoing 
adenotonsillectomy constitute the population of analysis. 
10.5 Effectiveness Analysis (if applicable) 
N/A 
 
10.6 Safety Analysis 
A Data Safety Monitoring Board will conduct a safety analysis after the 
following numbers for patient recruitment in each arm have been 
reached:  
 40 total patients recruited with approximately 10 patients in each 
group 
 84 total patients recruited with approximately 21 patients in each 
group 
 168 total patients recruited with approximately 42 patients in each 
group 
 252 total patients recruited with approximately 63 patients in each 
group  


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This data reflects approximately 12%, 25%, 50%, and 75% of the total 
estimated subject recruitment population, respectively. The Data Safety 
Monitoring Board will specifically monitor for any adverse events in each 
group. In case of serious concerns regarding adverse events in either 
group, the study will be terminated. 
 
10.7 Interim Analysis  
A statistician will perform an interim analysis when half of the sample 
size for each group has been recruited 


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11. DATA AND SAFETY MONITORING  
 
11.1 Data and Safety Monitoring Plan  
The research coordinator will be responsible for data gathering. The 
study coordinator will be responsible for filling out the data collection 
sheet in the OR with input from the anesthesiologist assigned to the 
patient. The research coordinator or principal investigator will record the 
data collection sheet in the PACU. The anesthesiologist assigned to the 
patient will monitor for any adverse events. In case of severe bradycardia 
or hypotension following dexmedetomidine administration, the mask will 
be broken and the patient will be withdrawn from the study. All 
anesthesiologists involved in the study have access to the protocol and 
their feedback and concerns have been already added to the protocol. 
Progress notes of the study will be sent to the IRB annually. A statistician 
will perform an interim analysis when half of the sample size for each 
group has been recruited. A Data Safety Monitoring Board will be 
responsible for safety monitoring. 
 


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12. DATA HANDLING, RECORD-KEEPING AND MONITORING 
 
12.1 Data Recording, Record-Keeping and Monitoring  
The Source Data are the clinical findings and observations, laboratory 
and test data, and other information contained in the Source Documents 
and electronic anesthesia records. The Source Documents are the original 
records (and certified copies of original records) including, but not 
limited to, hospital medical records, physician or office charts, physician 
or nursing notes, subject diaries or evaluation checklists, pharmacy 
dispensing records, and recorded data from automated instruments, x-
rays, etc. All Source data and documents will be stored in patients’ paper 
and LMR charts. The electronic anesthesia records will be searched for 
any deviation from the study protocol, including drug administrations 
and vital signs. 
 
All research data collected, including monitoring data, will be recorded as 
research records on an MEEI password protected computer. The signed 
parental consent forms and child assents will be locked in the drawers 
located in anesthesia office on the 7th floor of MEEI main building. Only 
the study coordinator and the principal investigator have access to these 
drawers. 
 
 


Massachusetts Eye and Ear Infirmary 
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VERSION11.0: 10/26/2016 
Page 40 of 42 
 
13. STUDY DISCONTINUATION CRITERIA 
 
13.1 Discontinuation of Individual Research Subjects 
In case of any major drug side effects (bradycardia and hypotension) or 
at the patient or parents’ request, patient participation will be 
terminated. 
 
13.2 Sponsor-Investigator Discontinuation of the Clinical Research Study 
In case of significant advantages or disadvantages, the principal 
investigator or sponsor will discontinue the clinical research study.  


Massachusetts Eye and Ear Infirmary 
SUPP M - Clinical Trial Template 
 
 
VERSION11.0: 10/26/2016 
Page 41 of 42 
 
14. APPENDICES 
 
14.1 Schedule of Events  
1. Parents will be informed about the research at the time of the surgery 
scheduling and will receive the consent form from the surgeon’s office; 
2. Patients will present to MEEI two hours prior to surgery on the day of the 
surgery and will be assessed by the anesthesiologist; 
3. Parents of patients who meet the inclusion and exclusion criteria will be 
informed about the study; 
4. Written consent will be obtained from the parents and eligible children 
will be asked to sign an assent form;  
5. Patients will be randomized to one of the four study groups by the 
pharmacy 
6. All patients will receive oral acetaminophen in the preoperative area; 
7. An IV will be placed preoperatively on the surgical floor in all patients ≥ 
10 years; 
8. Prior to induction, the anesthesiologist will be informed about which 
method of extubation the patient will undergo; 
9. All patients will undergo parent-present induction; 
10. Patients will receive all the intraoperative induction medication 
according to the study protocol; 
11. Patients < 10 years will undergo inhalational induction; 
12. Patients ≥ 10 years will undergo IV induction; 
13. Patients will receive dexmedetomidine or placebo infusion after 
induction; 
14. At the end of the procedure, the patients will undergo either deep or 
awake extubation according to the prior randomization; 


Massachusetts Eye and Ear Infirmary 
SUPP M - Clinical Trial Template 
 
 
VERSION11.0: 10/26/2016 
Page 42 of 42 
15. The anesthesiologist will record all the study data in the OR until the 
patient has been handed off to the PACU nurse; 
16. After extubation, the patient will be transferred to the PACU and handed 
off to the PACU nurse; 
17. A data recorder will record all the study data during patient’s PACU stay; 
18. During discharge, parents will be asked to fill out a data sheet during the 
first 24-hours after discharge; 
19. A follow-up phone call will be made 24 hours after discharge to obtain 
parent-documented data. 
 
14.2 Case Report Form(s) 
14.3 DSMB Charter