Conditions: Chronic Pain
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 83
Healthy volunteers: no

Brief summary:
This is a randomized, prospective, double-blind , placebo-controlled trial examining the effects of intraoperative dexmedetomidine infusion on pain in patients undergoing lumbar spinal fusion surgery. One hundred ten subjects (55 in each arm) will be enrolled. Subjects, over the age of 18, undergoing lumbar spinal fusion will be considered eligible for enrollment. Subjects will receive either intraoperative dexmedetomidine or placebo of normal saline infusion. They will be followed for approximately six weeks postoperatively.

Detailed description:

Arms:
arm 1: Dexmedetomidine is an alpha-2-adrenergic agonist. It is commonly used for sedation and as an adjunct to general anesthetics. arm 2: saline placebo

Interventions: intervention 1: Dexmedetomidine intervention 2: Placebo Saline
Intervention descriptions: intervention 1: The drug will be administered with a loading dose of 0.5 mcg/kg given over 20 min followed by an infusion at 0.6 mcg/kg/hr. The infusion will be stopped during closure of the fascia. intervention 2: Placebo will be administered with a loading dose of 0.5 mcg/kg given over 20 min followed by an infusion at 0.6 mcg/kg/hr. The infusion will be stopped during closure of the fascia.

Protocol document:
Prot_SAP_000.pdf: 
 
 
Official Title: 
Randomized, Double-blind, Placebo-controlled Study on the Effects of 
Intravenous Dexmedetomidine on Pain in Patients Undergoing Elective 
Spinal Surgery   
NCT Number: 
NCT03325972 
Study Number: 
14-00915 
Document Type:  
Study Protocol and Statistical Analysis Plan 
Date of the 
Document: 
• 
July 27, 2021 
 
 


Randomized, placebo-controlled study on the effects of intravenous dexmedetomidine on 
pain in patients undergoing elective spinal surgery  
New York University Langone Medical Center, Department of Anesthesiology, 
Perioperative Care and Pain Medicine 
 
 
 
Study Drug: 
Dexmedetomidine 
 
Principal Investigator:  
Lisa Doan, MD 
 
 
 
 
 
 
 
 
 
 
Initial version: February 4, 2016 
Amended: 
January 4, 2017 
Amended: 
May 20, 2021 


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Study Number: S14-00915 
Introduction 
This document is a protocol for a human research study. This study is to be conducted in 
accordance with US government research regulations, applicable international standards of good 
clinical practice, and institutional research policies and procedures. 
Study Rationale 
It has been observed in a meta-analysis that intravenous dexmedetomidine, an alpha-two-agonist, 
decreases postoperative cumulative opioid consumption and/or pain intensity (1). Furthermore, 
this meta-analysis demonstrated that the perioperative use of intravenous dexmedetomidine 
decreased the risk of postoperative nausea and did not lengthen recovery times (1). An article by 
Bekker et al. also demonstrated improvement in quality of recovery after major spinal surgery 
with the use of intraoperative dexmedetomidine infusion (2). Conversely, a study on 
intraoperative dexmedetomidine infusion in patients undergoing multilevel spine surgery found 
dexmedetomidine use did not reduce opioid consumption or pain scores (3). However, in this 
study both treatment and placebo groups received a dose of methadone preoperatively, 
potentially affecting the outcomes.  
The use of opioids with nonopioid analgesics (acetaminophen, nonsteroidal anti-inflammatory 
drugs, ketamine and alpha-two agonists) has increased in popularity with aims to decrease 
postoperative opioid requirements and subsequently opioid induced adverse effects. Thus the 
effects of dexmedetomidine on perioperative pain control are important to study. Outcomes 
beyond the immediate perioperative period are important to study as well. It is hypothesized that 
intraoperative dexmedetomidine infusion will have a positive effect on pain control in patients 
undergoing lumbar spinal fusion.  
Study Objective 
The aim of the proposed study is to examine the effect of intravenous dexmedetomidine on 
patients undergoing lumbar spinal fusion.  
The primary outcome is opioid consumption during the first 48 hours after surgery. We 
hypothesize that intraoperative dexmedetomidine will decrease opioid use by 30%.  
The secondary outcomes include numeric rating scale scores during the first 48 hours after the 
procedure and at approximately 6 weeks, morphine equivalents during the first 48 hours and at 
approximately 6 weeks, hemodynamic changes from baseline in the intraoperative and 48 hour 
postoperative period, pressor use in the intraoperative and 48 hour postoperative period, duration 
of PACU and hospital stay, and scores on the QoR-15 and Short Form McGill Pain 
Questionnaire. 
Overall Study Design and Plan 
This is a randomized, assessor-blinded, placebo-controlled study. Anesthesiologists will be 
aware of patients’ group assignments, but patients and assessors will not be. 


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One hundred ten subjects (55 in each arm) will be enrolled. Subjects, over the age of 18, 
undergoing lumbar spinal fusion (allowing for surgeries extending into thoracic and sacral 
segments) under general anesthesia will be screened for eligibility to participate in the study. 
Subjects will be screened, recruited, and randomized during the preadmission visit or the day of 
surgery. Those patients whose recruitment is completed on the day of surgery will have been 
given details of the study during the preadmission visit. Eligible subjects will be randomized to 
one of the two treatment groups in a 1:1 ratio to receive either IV dexmedetomidine or matching 
placebo. Both men and women will be recruited, and there is no limitation as to racial and ethnic 
origin. 
Patients will be randomized using a block randomization scheme generated via the website 
randomization.com (http://www.randomization.com). The anesthesiologist will be informed of 
the randomization. 
Participation in the study will not alter the patient’s anesthetic management. Routine anesthesia 
monitors used during general anesthesia will be used. Arterial and/or central lines will be placed 
at the discretion of the anesthesiologist. After pre-oxygenation, general anesthesia will be 
induced with lidocaine (1 mg/kg), propofol (1-2 mg/kg), and fentanyl (up to 5 mcg/kg). Tracheal 
intubation will be facilitated with rocuronium (0.6 mg/kg). Anesthesia will be maintained with 
air/oxygen (60%/40%), propofol infusion, fentanyl infusion, and muscle relaxant if indicated. 
The anesthesiologist will be allowed to administer additional doses of propofol and fentanyl at 
his/her discretion. The bispectral index will be targeted from 40 to 60. Patients will receive either 
intravenous dexmedetomidine infusion (0.5 mcg/kg loading dose over 20 min followed by an 
infusion at 0.6 mcg/kg/hr) or placebo starting prior to surgical incision. The dexmedetomidine 
infusion will be stopped during closure of the fascia. Mean arterial pressures less than 65 will be 
treated with vasoactive agents, chosen at the discretion of the anesthesiologist. All patients will 
receive ondansetron 4 mg prior to the end of operation. Patients will be awakened and extubated 
in the OR and will be transferred to the PACU after following simple commands. All patients 
will also be able to receive rescue doses of opioids as indicated by a Numeric Pain Rating Scale 
score >2 or upon request. There is no restriction on the use of analgesics throughout the hospital 
stay. Patients are followed until postoperative day 2 and followed up by telephone call 
approximately 6 weeks postoperatively. 
Study site: Tisch Hospital  
 
Outcome measures 
The primary endpoint will be morphine equivalents used during the first 48 hours after surgery. 
We hypothesize patients who receive dexmedetomidine will require 30% less opioids than those 
who do not receive dexmedetomidine. 
Secondary endpoints include:  
1) Numeric Pain Rating Scale (NRS)scores during the first 48 hours after the procedure and at 
approximately 6 weeks;  


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2) morphine equivalents during the first 48 hours and at approximately 6 weeks,  
3) hemodynamic changes from baseline in the intraoperative and 48 hour postoperative period; 
4) pressor use in the intraoperative and 48 hour postoperative period;  
5) duration of PACU stay;  
6) duration of hospital stay;  
7) scores on the QoR-15;  
8) scores on Short Form McGill Pain Questionnaire.  
The QoR-15 measures patients’ overall satisfaction with postoperative recovery. The QoR-15 
will be administered preoperatively to establish baseline scores and repeated on postoperative 
days 1 and 2 and at approximately 6 weeks. The Short Form McGill Pain Questionnaire 
measures the subjective experience of pain and will be administered preoperatively and on 
postoperative days 1 and 2 and at approximately 6 weeks. 
Safety endpoints include:  
1) hemodynamic changes requiring pressor use in the intraoperative and 48 hour postoperative 
period and  
2) hemodynamic changes requiring termination of drug infusion. 
Study Population 
Inclusion criteria 
1. Adults, 18 and over, who will undergo lumbar spinal fusion, including surgeries 
extending into thoracic and sacral segments,  
2. Subject is non-lactating and is either: 
a. Not of childbearing potential 
b. Of childbearing potential but is not pregnant at time of surgery as determined by 
pre-surgical pregnancy testing 
3. Subject is ASA physical status 1, 2, or 3 
Exclusion criteria 
1. <18 years of age 
2. Subject is pregnant or breastfeeding 
3. Any subject whom the investigators deem unable to complete any/all research related 
tasks 
4. Subjects who are cognitively impaired (by history) 
5. Subject requires antipsychotic medications 
6. Subject has received treatment with alpha-2 agonists or antagonists within 2 weeks 
prior to surgery 
7. Subject has known allergy to dexmedetomidine 


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8. Subjects with impaired renal or hepatic function 
9. Subjects with advanced heart block 
10. Subjects with severe ventricular dysfunction 
Subject Identification, Recruitment, and Consent 
IRB approved study flyers will be distributed to the surgeons’ offices and the pre-admissions 
testing clinic (PAT) at the Ambulatory Care Center (ACC). Patients will be approached at PAT 
or after contacting the researchers through flyers. We will be approaching all subjects (male and 
female) who are undergoing lumbar spinal surgery (including those undergoing surgery 
extending to the thoracic or sacral segments) and who are 18 years or older. 
Because of Covid, patients are not going into PAT and having virtual visits, surgeons have said 
we can contact their patients by phone and/or email. Subjects will be identified by surgical 
coordinators – the list they send includes whether or not the patients have opted-in for contact, 
and we would only reach out to those who have opted in. 
Additionally, for surgeons agreeable to the study, we can search their surgery schedules on 
EPIC. We will send them a list of potential participants to get their approval to contact them. No 
PHI will be used to search through EPIC, rather the surgery schedules for the month ahead will 
be reviewed. From that we can see minimum inclusion/exclusion criteria (age/type of surgery), 
and we can pre-screen people who may qualify and ask surgeons for permission to contact them. 
We will forward surgeons the phone script and email template for approval, as well as the flyer, 
which was reviewed by them when study was initiated. 
The upcoming surgical schedules will be reviewed by the PI and research coordinators only.  
Any recruitment information sent by email will utilize Send Safe email. 
1) Recruitment over the phone  
a. The telephone script will be used to communicate the reason they are being 
contacted and subjects will be asked if they are interested in participating in this 
specific study. Research team members will call prospective subjects or arrange a 
video conference session (WebEx only). The following methods will be 
implemented to obtain informed consent.  
i. The prospective subject will be emailed a copy of the informed consent via 
SendSafe to review. If prospective subject is interested in participating, a 
phone call or webex can take place, and consent can be obtained in person 
on the day or surgery. 
ii. The prospective subject will be emailed a copy of the informed consent 
form via SendSafe after on-site discussion taking place between study 
personnel and prospective subject or an initial telephone call or video 
conference takes place between study personnel and the remote prospective 
subject and the research team member will obtain prospective subject 
signature in-person on the day of surgery. The prospective subject can print 
and sign a physical copy and return later in person. 
 


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A general discussion regarding the study will be done in a private area. The subject will have the 
opportunity to ask questions during the PAT visit or telephone call until the day of surgery, and 
all questions will be answered. Consents will be done at the PAT visit or on the day of surgery. 
A copy of the signed consent will be placed in the medical record as well as given to the patient. 
The original consent will be collected as a source document and securely stored. 
Early Withdrawal of Subjects 
Subjects may be withdrawn from the study prior to completion due to safety issues, consent 
withdrawal, or failure to adhere to protocol requirements. Adverse effects of dexmedetomidine 
include bradycardia and hypotension. The anesthesiologist is not blinded as to study drug. If 
adverse effects such as bradycardia and hypotension are considered excessive and due to 
dexmedetomidine based on the anesthesiologist’s clinical judgment, the study drug can be 
stopped at any time.  
Data Collection and Follow-up for Withdrawn Subjects 
Data on morbidity related to hemodynamic changes will be collected on subjects withdrawn 
from the study. Survival data will also be collected on subjects withdrawn from the study up to 
the end of the approximately 6 week follow-up period. For patients who have withdrawn 
consent, attempts will be made to obtain permission to record survival data. Three phone calls 
will be made prior to considering a patient lost to follow-up. 
Study Drug 
Description 
Dexmedetomidine is an alpha-2-adrenergic agonist. It is commonly used for sedation and as an 
adjunct to general anesthetics. Side effects include hypotension, bradycardia, atrial fibrillation, 
and nausea. 
The use of dexmedetomidine, in this case, is exempt from an IND. 
Treatment Regimen 
Intravenous dexmedetomidine or saline placebo will be given prior to surgical incision. The drug 
will be administered with a loading dose of 0.5 mcg/kg given over 20 min followed by an 
infusion at 0.6 mcg/kg/hr. The infusion will be stopped during closure of the fascia.  
Method for Assigning Subjects to Treatment Groups 
Patients will be randomized using a block randomization scheme generated via the website 
randomization.com (http://www.randomization.com). The anesthesiologist will be informed of 
the randomization. 
Preparation and Administration of Study Drug  
Study drugs will be prepared and administered as indicated above by the anesthesiologist.  
Subject Compliance Monitoring  


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Subjects will be asked to track opioid and adjunctive analgesic use at approximately 6 weeks 
postoperatively.  
Prior and Concomitant therapy 
Subjects’ preoperative medications will be recorded. Intraoperatively subjects may receive 
fentanyl at the discretion of the anesthesiologist. Postoperatively there are no restrictions on the 
use of opioids and adjunctive analgesics. 
Study Drug Storage 
Study medications will be kept in the Omnicell machine in the operating room suite. 
Dispensing of Study Drug – covered in a preceding paragraph, treatment regimen. 
Study Procedures 
The following procedures will be done at each visit. 
Visit 1: Consenting, NRS, QoR-15 and McGill Short Form 
(Day of surgery): Randomization and administration of dexmedetomidine or placebo 
Visit 2/POD1: NRS, QoR-15 and McGill Short Form 
Visit 3/POD2: NRS, QoR-15 and McGill Short Form 
Visit 4/~6 weeks post-op: NRS, QoR-15 and McGill Short Form and list of medications taken 
Statistical Analysis 
Sample Size Justification 
Previous studies of the analgesic effects of dexmedetomidine in patients without chronic opioid 
consumption have yielded a mean difference in postoperative opioid consumption of 30-50%. 
Hypothesizing a 30% reduction in analgesic use, power analysis yields n=55 patients in each arm 
with a 5% type I error rate and 80% power. An interim analysis will be done after 55 total 
patients have been recruited such that if statistically significant differences are found further 
patient recruitment will be halted to avoid unnecessary risk.  
Interim Data analysis 
Although this is a low risk study, an interim analysis will be done after 55 total patients have 
been recruited such that if statistically significant differences are found in primary endpoints 
further patient recruitment will be halted to avoid unnecessary risk. The interim data analysis 
will be of primary and secondary endpoints. 
Data Analysis 
Differences between groups will be analyzed with an unpaired student’s t- test. For non-normally 
distributed data, the Kruskall-Wallis test will be used for global significance, and the Mann-


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Whitney U test will be used for subsequent pairwise comparisons. Univariate analysis of 
postoperative opioid consumption as a function of preoperative opioid use, sex, and 
comorbidities will be done. A multivariate regression analysis will be done to assess potentially 
confounding variables. 
Subject Population(s) for Analysis 
All-treated subjects (randomized into the study and received dexmedetomidine or placebo) will 
be included in the analysis of both primary and secondary endpoints. 
Safety and Adverse Events 
Definitions 
Unanticipated Problems Involving Risk to Subjects or Others: Any incident, experience, or 
outcome that meets all of the following criteria: 
• Unexpected in nature, severity, or frequency (i.e. not described in study-related documents 
such as the IRB-approved protocol or consent form, etc.) 
• Related or possibly related to participation in the research (i.e. possibly related means 
there is a reasonable possibility that the incident experience, or outcome may have been 
caused by the procedures involved in the research) 
• Suggests that the research places subjects or others at greater risk of harm (including 
physical, psychological, economic, or social harm). 
Adverse Event – An adverse event (AE) is any symptom, sign, illness or experience that 
develops or worsens in severity during the course of the study. Intercurrent illnesses or injuries 
should be regarded as adverse events. Abnormal results of diagnostic procedures are considered 
to be adverse events if the abnormality: 
• results in study withdrawal 
• is associated with a serious adverse event 
• is associated with clinical signs or symptoms 
• leads to additional treatment or to further diagnostic tests 
• is considered by the investigator to be of clinical significance 
Serious Adverse Event – Adverse events are classified as serious or non-serious. A serious 
adverse event is any AE that is: 
• fatal 
• life-threatening 
• requires or prolongs hospital stay 
• results in persistent or significant disability or incapacity 
• a congenital anomaly or birth defect 
• an important medical event 
Important medical events are those that may not be immediately life threatening, but are clearly 
of major clinical significance. They may jeopardize the subject, and may require intervention to 


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prevent one of the other serious outcomes noted above. For example, drug overdose or abuse, a 
seizure that did not result in in-patient hospitalization or intensive treatment of bronchospasm in 
an emergency department would typically be considered serious. 
All adverse events that do not meet any of the criteria for serious should be regarded as non-
serious adverse events.  
Adverse Event Reporting Period – The study period during which adverse events must be 
reported is normally defined as the period from the initiation of any study procedures to the end 
of the study treatment follow-up. For this study, the study treatment follow-up is defined as ~6 
weeks following the last administration of study treatment. 
Preexisting Condition – A preexisting condition is one that is present at the start of the study. A 
preexisting condition should be recorded as an adverse event if the frequency, intensity, or the 
character of the condition worsens during the study period. 
General Physical Examination Findings – At screening, any clinically significant abnormality 
should be recorded as a preexisting condition. At the end of the study, any new clinically 
significant findings/abnormalities that meet the definition of an adverse event must also be 
recorded and documented as an adverse event. 
Post-study Adverse Event – All unresolved adverse events should be followed by the investigator 
until the events are resolved, the subject is lost to follow-up, or the adverse event is otherwise 
explained. At the last scheduled visit, the investigator should instruct each subject to report any 
subsequent event(s) that the subject, or the subject’s personal physician, believes might 
reasonably be related to participation in this study. 
Abnormal Laboratory Values – A clinical laboratory abnormality should be documented as an 
adverse event if any one of the following conditions is met:  
• The laboratory abnormality is not otherwise refuted by a repeat test to confirm the 
abnormality 
• The abnormality suggests a disease and/or organ toxicity 
The abnormality is of a degree that requires active management; e.g. change of dose, 
discontinuation of the drug, more frequent follow-up assessments, further diagnostic 
investigation, etc. 
Hospitalization, Prolonged Hospitalization or Surgery – Any adverse event that results in 
hospitalization or prolonged hospitalization should be documented and reported as a serious 
adverse event unless specifically instructed otherwise in this protocol. Any condition responsible 
for surgery should be documented as an adverse event if the condition meets the criteria for an 
adverse event.  
Neither the condition, hospitalization, prolonged hospitalization, nor surgery are reported as an 
adverse event in the following circumstances: 
• Hospitalization or prolonged hospitalization for diagnostic or elective surgical procedures 
for a preexisting condition. Surgery should not be reported as an outcome of an adverse 


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event if the purpose of the surgery was elective or diagnostic and the outcome was 
uneventful. 
• Hospitalization or prolonged hospitalization required to allow efficacy measurement for 
the study. 
• Hospitalization or prolonged hospitalization for therapy of the target disease of the study, 
unless it is a worsening or increase in frequency of hospital admissions as judged by the 
clinical investigator. 
Recording of Adverse Events – At each contact with the subject, the investigator must seek 
information on adverse events by specific questioning and, as appropriate, by examination. 
Information on all adverse events should be recorded immediately in the source document, and 
also in the appropriate adverse event module of the case report form (CRF). All clearly related 
signs, symptoms, and abnormal diagnostic procedures results should recorded in the source 
document, though should be grouped under one diagnosis. 
All adverse events occurring during the study period must be recorded. The clinical course of 
each event should be followed until resolution, stabilization, or until it has been determined that 
the study treatment or participation is not the cause. Serious adverse events that are still ongoing 
at the end of the study period must be followed up to determine the final outcome. Any serious 
adverse event that occurs after the study period and is considered to be possibly related to the 
study treatment or study participation should be recorded and reported immediately. 
Reporting of Serious Adverse Events and Unanticipated Problems 
This section describes the requirements for reporting specific types of unanticipated problems 
including adverse events. 
Investigators must conform to the adverse event reporting timelines, formats and requirements of 
the various entities to which they are responsible, but at a minimum those events that must be 
reported are those that are: 
• related to study participation, 
• unexpected, and  
• serious or involve risks to subjects or others  
(see definitions). 
For Narrative Reports of Safety Events – If the report is supplied as a narrative, the minimum 
necessary information to be provided at the time of the initial report includes: 
• Study identifier 
• Study Center 
• Subject number 
• A description of the event 
• Date of onset 
• Current status 
• Whether study treatment was discontinued 
• The reason why the event is classified as 
serious 
• Investigator assessment of the association 
between the event and study treatment 
Investigator reporting: notifying the IRB – Federal regulations require timely reporting by 
investigators to their local IRB of unanticipated problems posing risks to subjects or others. The 


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following describes the NYULMC IRB reporting requirements, though Investigators at 
participating sites are responsible for meeting the specific requirements of their IRB of record. 
Investigator Reporting: Notifying the IRB 
Federal regulations require timely reporting by investigators to their local IRB of unanticipated 
problems posing risks to subjects or others. The following describes the NYULMC IRB 
reporting requirements. 
Report promptly, but no later than 5 working days: 
Researchers are required to submit reports of the following problems promptly but no later than 
5 working days from the time the investigator becomes aware of the event: 
• Unanticipated problems including adverse events that are unexpected and related 
– Unexpected: An event is “unexpected” when its specificity and severity are not 
accurately reflected in the protocol-related documents, such as the IRB-approved 
research protocol, any applicable investigator brochure, and the current IRB-
approved informed consent document and other relevant sources of information, such 
as product labeling and package inserts.  
– Related to the research procedures: An event is related to the research procedures if 
in the opinion of the principal investigator or sponsor, the event was more likely than 
not to be caused by the research procedures.  
– Harmful: either caused harm to subjects or others, or placed them at increased risk 
Other Reportable events: 
The following events also require prompt reporting to the IRB, though no later than 5 working 
days: 
• Complaint of a research subject when the complaint indicates unexpected risks or the 
complaint cannot be resolved by the research team. 
• Protocol deviations or violations (includes intentional and accidental/unintentional 
deviations from the IRB approved protocol) for any of the following situations: 
– one or more participants were placed at increased risk of harm  
– the event has the potential to occur again 
– the deviation was necessary to protect a subject from immediate harm 
• Breach of confidentiality 
• Incarceration of a participant when the research was not previously approved under 
Subpart C and the investigator believes it is in the best interest of the subject to remain on 
the study. 
• New Information indicating a change to the risks or potential benefits of the research, in 
terms of severity or frequency. (e.g. analysis indicates lower-than-expected response rate 
or a more severe or frequent side effect; Other research finds arm of study has no 
therapeutic value; FDA labeling change or withdrawal from market) 


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Reporting Process 
The reportable events noted above will be reported to the IRB using the form: “Reportable Event 
Form” or as a written report of the event (including a description of the event with information 
regarding its fulfillment of the above criteria, follow-up/resolution and need for revision to 
consent form and/or other study documentation). 
Copies of each report and documentation of IRB notification and receipt will be kept in the 
Clinical Investigator’s study file. 
Data Acquisition and Storage 
Data Safety and Monitoring Plan 
The principal investigator, Dr. Lisa Doan, will be primarily responsible for monitoring the study. 
All adverse events will be collected and evaluated every 6 months. The study principal 
investigator will evaluate the data to determine whether to continue the study or to change the 
protocol to decrease risk. 
Adverse events will include events reported by the subject and thought to be associated with the 
research. Unanticipated problems and adverse events will be gathered by study investigators. 
Adverse events will be evaluated throughout the hospital stay and during telephone call follow-
up. Any serious adverse effects will be reported to the IRB according to regulatory requirements. 
Because patients are having major surgery, we will only be reporting those serious adverse 
events that are directly related to the study drug, and will report them to the IRB within 24 hours 
of discovery. All patients having a serious adverse event will be followed until it is resolved. 
Reports summarizing the data safety monitoring reviews will otherwise be submitted to the IRB 
annually. 
Data Handling and Record Keeping 
Confidentiality and HIPAA 
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA). 
Those regulations require a signed subject authorization informing the subject of the following: 
• What protected health information (PHI) will be collected from subjects in this study 
• Who will have access to that information and why 
• Who will use or disclose that information 
• The rights of a research subject to revoke their authorization for use of their PHI. 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of subject 
authorization. For subjects that have revoked authorization to collect or use PHI, attempts should 
be made to obtain permission to collect at least vital status (i.e. that the subject is alive) at the 
end of their scheduled study period. 


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All of the patient data used in this study will be kept confidential and will be used for 
professional purposes only. All research data will be collected in Case Report Forms (CRFs). 
Clinical safety data, screening information, informed consent, and progress notes will be 
collected in Source Documents. Patient records will be accessible only to study personnel in 
locked drawers or in password protected computers in locked rooms of the Department of 
Anesthesiology, Perioperative Care and Pain Medicine suite. Only those investigators directly 
involved in the protocol will have access to these records. Patient records will be coded for 
analysis and publication. After completion of the study data will be kept for five years before 
secure disposal. 
Source Documents 
Source data is all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial. Source 
data are contained in source documents. Examples of these original documents, and data records 
include: hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ 
diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated 
instruments, copies or transcriptions certified after verification as being accurate and complete, 
microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and 
records kept at the pharmacy, at the laboratories, and at medico-technical departments involved 
in the clinical trial. 
Case Report Forms 
The study case report form (CRF) is the primary data collection instrument for the study. All 
data requested on the CRF must be recorded. All missing data must be explained. If a space on 
the CRF is left blank because the procedure was not done or the question was not asked, write 
“N/D”. If the item is not applicable to the individual case, write “N/A”. All entries should be 
printed legibly in black ink. If any entry error has been made, to correct such an error, draw a 
single straight line through the incorrect entry and enter the correct data above it. All such 
changes must be initialed and dated. DO NOT ERASE OR WHITE OUT ERRORS. For 
clarification of illegible or uncertain entries, print the clarification above the item, then initial and 
date it. 
Study Monitoring, Auditing and Inspecting 
Study Monitoring Plan 
As noted above, reportable events will be monitored on an ongoing basis. The study will be 
monitored every 6 months for adverse events. The principal investigator will evaluate the data to 
determine whether to continue the study or to change the protocol to decrease risk. An interim 
analysis will be done after 65 total patients have been recruited such that if statistically 
significant differences are found further patient recruitment will be halted to avoid unnecessary 
risk. 
Auditing and Inspecting 


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The investigator will permit study related monitoring, audits, and inspections by the IRB/EC, 
government regulatory bodies, and University Compliance and quality assurance groups of all 
study related documents (e.g. source documents, regulatory documents, data collection 
instruments, study data, etc.). The investigator will ensure the capability for inspections of 
applicable study-related facilities (e.g. pharmacy, diagnostic laboratory, etc.). 
Participation as an investigator in this study implies acceptance of potential inspection by 
government regulatory authorities and applicable University compliance and quality assurance 
offices. 
Ethical Considerations 
This study is to be conducted accordance with applicable US government regulations and 
international standards of Good Clinical Practice, and applicable institutional research policies 
and procedures. 
This protocol and any amendments will be submitted to a properly constituted Institutional 
Review Board (IRB) in agreement with local legal prescriptions, for formal approval of the study 
conduct. The decision of the IRB concerning the conduct of the study will be made in writing to 
the investigator and a copy of this decision will be provided to the sponsor before 
commencement of this study. 
All subjects for this study will be provided a consent form describing this study and providing 
sufficient information for subjects to make an informed decision about their participation in this 
study. See Attachment for a copy. This consent form will be submitted with the protocol for 
review and approval by the IRB for the study. The formal consent of a subject, using the IRB 
approved consent form, must be obtained before that subject undergoes any study procedure. The 
consent form must be signed by the subject or legally acceptable surrogate, and the investigator-
designated research professional obtaining the consent. 
As stated previously, research subjects will be approached at PAT or after contacting the 
researchers through flyers. We will be approaching all subjects (male and female) on chronic 
opioid therapy who are undergoing lumbar spinal surgery (including those undergoing surgery 
extending to the thoracic or sacral segments) and who are 18 years or older. A general discussion 
regarding the study will be done in a private area either at pre-admission testing (PAT) or in the 
pre-operative area on the 4th floor. Subjects approached in PAT will also have the time to 
consider and decide and sign the consent in pre-op. The subject will have the opportunity to ask 
questions during the PAT visit until the day of surgery, and all questions will be answered. A 
copy of the signed consent will be placed in the medical record as well as given to the patient. 
The original consent will be collected as a source document and securely stored. 
Risk/Benefit Assessment 
Risks 
Other than general risk associated with anesthesia and surgery, there are few risks associated 
with the study drug which is in routine use in the surgical setting. 


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authorized in writing by the study sponsor 
The use of dexmedetomidine is a standard of care in the perioperative period. Risks most 
commonly associated with dexmedetomidine administration include bradycardia and 
hypotension. Anesthesia providers routinely handle such eventualities in all surgeries. If 
necessary, vasoactive agents may be administered. There is no additional risk of study drug use 
compared to routine anesthetic use. 
The following risks are outlined in the informed consent document: 
Cardiovascular: Hypotension (24-56%) and hypertension (28%) may occur. Bradycardia (5-
42%) or other change in heart beat may occur. 
Central nervous system: Agitation or anxiety may occur (5-14%). 
Respiratory: Respiratory depression (2-10%), pleural effusion (2%), or wheezing (<1%) may 
occur. 
Endocrine and metabolic: Hypokalemia (9%), hyperglycemia (7%), hypoglycemia (5%), 
hypocalcemia (1%), or hypomagnesemia (1%) may occur. 
Renal: Acute renal failure (2-3%) or decreased urine output (1%) may occur. 
Additionally, there is the possible risk of loss of confidentiality associated with participating in a 
research study. All information pertaining to this study will be kept in a locked file cabinet in a 
locked office area. The risk of loss of confidentiality is considered to be minimal. However, the 
researchers involved in this study will take every precaution necessary to ensure that privacy is 
protected. 
Potential Benefits 
There are conflicting studies on whether perioperative dexmedetomidine administration 
decreases opioid consumption following surgery. This study will elucidate whether 
dexmedetomidine will have a beneficial effect on perioperative pain control which may benefit 
subjects who receive the drug as well as others in the future. 
Study Finances 
Funding Source 
The study will be supported by departmental funds.  
Conflict of Interest 
No one involved with the study has any conflicts. 
Subject Stipends or Payments: There is no cost to the study subject and the subject will not be 
compensated for participating in the study. 
Publication Plan 


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Abstracts and peer-reviewed publications will be prepared when appropriate. 
 


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authorized in writing by the study sponsor 
References 
 
1. Blaudszun G, Lysakowski C, Elia N, Tramer M. Effect of perioperative systemic alpha 2 
agonists on postoperative morphine consumption and pain intensity. Anesthesiology 2012; 6: 
1312-1322. 
2. Bekker A, Haile M, Kline R, Didehvar S, Babu R, Martiniuk F, Urban M. The effect of 
intraoperative infusion of dexmedetomidine on the quality of recovery after major spinal surgery. 
Journal of Neurosurgical Anesthesiology 2013 Jan; 25(1):16-24. 
3. Naik B, Nemergut E, Kazemi A, Fernandez L, Cederholm S, McMurry T, Durieux M. The 
effect of dexmedetomidie on postoperative opioid consumption and pain after major spine 
surgery. Anesth Analg 2016; 122(5): 1646-53.