Conditions: Anxiety Burns
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 20
Healthy volunteers: no

Brief summary:
The primary aim of this pilot study is to establish the safety and feasibility of patient-controlled administration with dexmedetomidine for anxiolysis (PCA-DEX) during burn care dressings for patients with burn injury. The secondary aim is to determine the acceptability of PCA-DEX for anxiety symptom management by patients with burn injury and nursing staff caring for these patients. Objectives Primary Aim #1 Safety: To examine the safety of PCA-DEX as determined by the proportion of patients successfully completing the pilot trial without adverse effect which include significant hypotension, bradycardia, or agitation from uncontrolled anxiety. Primary Aim #2 Feasibility: The primary objective of this study is to establish feasibility of subject recruitment and protocol adherence in a pilot study of PCA-DEX in patients with burn injury requiring dressing changes. Feasibility will be defined by the following criteria: a) number and proportion of patients who consent to enrollment, b) proportion of eligible subjects enrolled prior to first dressing change, c) number of days on protocol that patients successfully use the PCS device, d) ability of burn nurses to adjust the pump and adhere to the infusion rates of the PCA-DEX protocol. Secondary Aim #1 Patient Acceptability: A secondary objective of this pilot study is to have patients evaluate PCA-DEX in regards to patients' willingness to use PCA-DEX prior to and during burn dressing changes to self-manage anxiety and their satisfaction ratings with anxiety self-management. Secondary Aim #2 Nurse Acceptability: Another secondary aim of this pilot study is to evaluate the nursing staffs' acceptability of the PCA-DEX protocol for patients' to self-manage anxiety surrounding burn care dressing changes. Hypotheses #1: PCA-DEX protocol will be safe to administer during burn care dressing changes. #2: PCA-DEX will be feasible to implement on the Burn Center at OSUWMC. #3: Patients will favorably appraise PCA-DEX for the self-control of anxiety associated with burn care dressing changes, and be satisfied with PCA-DEX for the management of anxiety. #4: Nursing Staff will favorably appraise PCA-DEX while performing burn care dressing changes.

Detailed description:
Study Procedures Dexmedetomidine PCA Protocol: The PCA-DEX dosing algorithm will consist of a loading dose (0.25 mcg/kg) given intravenously over 10 minutes, administered 10 minutes prior to the start of burn wound care, followed by a continuous basal infusion of 0.4 mcg/kg/hr with 6 allowable patient-controlled self-boluses per hour (0.1 mcg/kg) each with a 10-minute lock-out. Drs. Larry Jones and J. Kevin Bailey or their designate will write the PCA-DEX medication orders. Subjects will receive standard opioid therapy (oral oxycodone/acetaminophen 5/325 mg 60 min. prior and IV morphine 4-12 mg or hydromorphone IV 0.5-1.5 mg 5 to 10 min. prior and buccal fentanyl 400 mcg as needed during burn wound care) and can receive bolus supplemental sedative medications (benzodiazepines) as ordered by Drs. Jones or Bailey if needed in the judgment of the burn-care nurse. Subjects will be monitored closely by research personnel during the first burn wound care session from 1 hour prior to 1 hour after completion of burn wound care. Every heart rate and blood pressure recordings will be abstracted from the medical record from 1 hour prior to through 1 hour after completion of the daily burn wound dressing changes for days 1 through 5. Alert adverse events will be reported by research personnel or the patient-care nurse to first the attending physician and then to the safety monitor.

Nurse alert parameters to notify the attending physician and independent safety monitor include: heart rate (HR) \< 55 beats per min sustained for \> 10 min; systolic BP \< 90 mm Hg or \>140 mm Hg sustained for \>10 minutes; diastolic BP \< 50 mm Hg or \>90 mm Hg sustained for \>10 minutes, respiratory rate \< 10 breaths per minute sustained for \>10 minutes or oxygen saturation \<92% sustained for \>10 minutes; or persistent inability to understand rationale for triggering the PCA device despite education and demonstration.

If the study subject has evidence of sustained hemodynamic instability (HR\<60 bpm, SBP \<90 mmHg or DBP \< 50 mmHg) during the daily pre-procedure assessment, the patient will not be eligible to receive study drug on that day. For that day the patient will receive standard of care as appropriate instead of the study intervention. The patient will then be reassessed prior to the subsequent study days to determine eligibility for study drug up through day 5.

Data Collection Measures and Procedures Study entry demographic and descriptive data: Data to be recorded includes: age, gender, race, ethnicity, admission weight, severity of burn injury, burn etiology, total body surface area burned and depth of injury, and all home and hospital medications.

Daily Measures on Protocol. The following will be obtained from enrolled patients each day by a member of the research team.

Overall anxiety and pain. The abbreviated Burn Specific Anxiety and Pain Scale (BSAPS) on day 1, 1 hour prior to the first burn dressing change.

Procedural Anxiety. Anxiety, defined as a state marked by apprehension, agitation, increased motor activity, arousal, and fearful withdrawal will be obtained from subjects. Patients will evaluate current anxiety level 1 hour before and 1 hour after each burn dressing change using a 100-mm Visual Analogue scale-anxiety (VAS-A). Subjects will be asked to rate their current level of anxiety on the VAS-A in response to, "How anxious are you feeling today?" A 100-millimeter vertical line will be anchored on each end by statements 'not anxious at all' to 'the most anxious I have ever been'. The VAS-A will have a vertical orientation, as it is more sensitive and easier for subjects to use, particularly for those with a narrowed visual field or when under stress. Subjects will be asked to mark their current anxiety level on the vertical line. Scores will be derived by the distance in millimeters from the bottom anchor to the mark placed by the subject, yielding interval level data. Reason(s) for not obtaining a daily anxiety assessment will be recorded. The proportion of those assessments completed and reasons for non-completion will be used to inform strategies to minimize missing data for our planned randomized clinical trial.

Procedural Pain. Patients' will evaluate current pain level 1 hour before and 1 hour after each burn dressing change using a 100-mm Visual Analogue Scale-Pain. Patients will be asked to rate their current level of pain on the VAS-P in response to "How much pain are you having right now?" A 100-millimeter vertical line will be anchored on each end by statements of 'no pain at all' to 'the most pain I have ever experienced'. As with the VAS-A, the vertical orientation has been chosen due to increased sensitivity and ease of use for patients.Subjects will be asked to mark their current pain level on the vertical line. Scores will be derived by the distance in millimeters from the bottom anchor to the mark placed by the subject, yielding interval level data. Reason(s) for not obtaining the pain assessments will be recorded. The proportion of those assessments completed and reasons for non-completion will be used to inform strategies to minimize missing data for our planned randomized clinical trial.

Protocol adherence. A checklist will be completed daily to monitor the number of days subjects are able to use the PCA device for up to 5 days. A checklist will also be used to monitor the ability of the burn-nurses to adhere to the PCA protocol per instructions.

Daily adverse event monitoring. Research staff will record and report the presence of hypotension, bradycardia (known adverse effects of dexmedetomidine), and protocol deviations related to drug, pump or both. Heart rate and blood pressure will be abstracted from the medical record. Research team staff or burn-nurses caring for PCA-DEX subjects will alert the attending physician and the safety monitor for HR \< 55 bpm sustained for \> 10 min; systolic BP \< 90 mm Hg or \>140 mm Hg sustained for \>10 minutes; diastolic BP \< 50 mm Hg or \>90 mm Hg sustained for \>10 minutes, respiratory rate \< 10 breaths per minute sustained for \>10 minutes or oxygen saturation \<92% sustained for \>10 minutes during the period 1 hour prior through 1 hour after completion of burn wound dressing change on days 1-5 for any necessary intervention or protocol withdrawal.

Post-PCA-DEX Acceptability Survey. Upon completion of the PCA-DEX protocol, we will query subjects and nurses about their satisfaction with self-administration of medication to manage anxiety, ease of medication administration, and the resulting level of relaxation.

Arms:
arm 1: Prior to the burn dressing changes PCA-DEX patients will receive a bolus of dexmedetomidine (Precedex®) 0.25 mcg/kg administered over 10mins by nurse staff, followed by a continuous infusion of Precedex® at 0.4 mcg/kg/hr via a standard infusion pump (LifeCare PCA). Patients will self-medicate as needed for anxiety self-management by self-administering a bolus of Precedex® 0.1 mcg/kg.

Interventions: intervention 1: Dexmedetomidine
Intervention descriptions: intervention 1: Prior to the burn dressing changes PCA-DEX patients will receive a bolus of dexmedetomidine (Precedex®) 0.25 mcg/kg administered over 10 minutes by nursing staff, followed by a continuous infusion of Precedex® at 0.4 mcg/kg/hr via a standard infusion pump (LifeCare PCA). Patients will self-medicate as needed for anxiety self-management by self-administering a bolus of Precedex® 0.1 mcg/kg. This dosage is within the FDA-approved package insert parameters. Heart rate, blood pressure and oxygen saturation will be closely monitored by a staff RN already trained to provide care in the procedure room. 1 hour prior to- and after completion of the burn dressing change each day using a 100-mm visual analog scale. Patients will both rate their satisfaction with PCA-DEX for anxiety management after each completion of the burn dressing change.

Protocol document:
Prot_SAP_000.pdf: 
Revised Research Protocol December 10, 2015 
2015H0019: Safety, Feasibility, and Acceptability of Patient-Controlled Anxiolysis with 
Dexmedetomidine (PCA-DEX) for Burn-Care Dressing Changes 
 
Regulatory Sponsor/PI: 
Larry M. Jones, MD 
Associate Professor of Surgery - Clinical 
Director, Burn Center 
 
 
 
 
The Ohio State University Wexner Medical Center 
 
 
 
 
410 W. 10th Avenue 
 
 
 
 
Columbus, OH 43210 
 
Sub-Investigators: 
 
 
 
 
 
Claire Murphy, PharmD 
 
 
 
 
Rebecca Coffey, MSN, CNP 
 
 
 
 
J. Kevin Bailey, MD 
 
 
 
 
 
 
 
 
 
Kristin Calvitti, MS, RN, ACNSBC, CMSRN 
 
 
 
 
 
 
 
 
 
Mahmoud Abdel-Rasoul, MAS 
 
 
 
 
 
Funding Sponsor: 
 
The Ohio State University Center for Clinical &  
Translational Science (CCTS) 
 
 
Study Products: 
 
Dexmedetomidine:  Precedex® 
 
 
 
 
 
Version / Date: 
 
 
Version 3/20 April 2018 
 
 
CONFIDENTIAL 
 
This document is confidential and the property of The Ohio State University Wexner 
Medical Center.  No part of it may be transmitted, reproduced, published, or used by other 
persons without prior written authorization from the study sponsor. 


Study Summary 
Title 
Safety, Feasibility, and Acceptability of Patient-Controlled Anxiolysis 
with Dexmedetomidine for Burn-care Dressing Changes 
Short Title 
Patient-Controlled Anxiolysis. 
Protocol Number 
The standard protocol number used to identify this study.   
Phase 
Phase II 
Methodology 
Study design is an open label, pilot study of patient controlled 
anxiolysis with dexmedetomidine (PCA-DEX) 
Study Duration 
Estimated duration for the study is 1 year. 
Study Center(s) 
The study will involve a single site: 
The Ohio State University Wexner Medical Center 
410 W. 10th Avenue 
Columbus, OH 43210 
Objectives 
The primary aim of this pilot study is to establish the safety and 
feasibility of PCA-DEX during burn care dressings for patients with 
burn injury. The secondary aim is to determine the acceptability of 
PCA-DEX for anxiety symptom management by patients with burn 
injury and nursing staff caring for these patients. 
Number of Subjects 
20 
Diagnosis and Main 
Inclusion Criteria 
Study subjects will be recruited from patients admitted for initial 
management of burn injury with >1% total body surface area burn who 
are able to operate the PCA infusion pump and do not have conditions 
that could be worsened by dexmedetomidine (e.g., bradycardia, high 
degree heart block, or hypotension). 
Study Product, 
Dose, Route, 
Regimen 
Dexmedetomidine (Precedex®) loading dose of 0.25 mcg/kg 
intravenously over 10 minutes, initiated 10 minutes prior the start of 
burn dressing change, followed by a continuous infusion rate of 0.4 
mcg/kg/hr by the Alaris® PCA Module.  Throughout the dressing 
change, study patients may self-administer mini-doses (0.1 mcg/kg 
with a 10 minute pump lock-out).  All patients will continue to receive 
standardized opioid therapy for dressing changes. 
Duration of 
administration 
Up to 5 days during burn wound care procedures only 


Statistical 
Methodology 
Descriptive statistics will be carried out on categorical demographic, 
clinical, safety and feasibility data will be summarized as frequencies 
and percents. Continuous demographic, clinical, procedural pain and 
procedural anxiety data will be summarized as means and standard 
deviations. Repeated measurements over time will be summarized at 
each relevant time point.  
 
 
 


1. Introduction 
This document is a protocol for a human research study.  This study will be conducted 
according to US and international standards of Good Clinical Practice (FDA Title 21 part 
312 and International Conference on Harmonization guidelines), applicable government 
regulations and Institutional research policies and procedures. 
 
1.1 
Background 
Pain associated with burn injury is usually high intensity pain and can be extremely 
challenging for clinicians to adequately manage. In order to improve burn care-
related outcomes such as wound closure rates, length of stay, total cost of care, 
patients are subjected to incredibly painful procedures including debridement, 
wound care, and physical and occupational therapy. Current practice guidelines 
recommend early analgesic intervention with a standardized approach for the 
management of pain associated with burn-care treatments.(Faucher et al, 2006)  
The impact of inadequate control of procedural pain has been associated with 
psychological complications including increases in anxiety, background pain, and 
future procedural pain.(Summer et al, 2007) The psychological responses of 
sustained anxiety associated with anticipation of heightened procedural pain or 
exacerbation of background pain, is associated with an increase in sympathetic 
activation resulting in the release of catecholamines and changes in local blood flow 
which lower the nociceptive threshold and sensitize the wound. (Chapman et al, 
1986; Zimmerman, 1984) Additionally, muscle tension in the area of burn injury 
can occur with anxiety to an extent that local nociceptors are activated. Anxiety can 
also potentiate the perception of pain through triggering of higher brain centers and 
memories of the previous trauma.(Meyer et al, 2002) These psychological and 
physiological factors associated with sustained and significant anxiety intensify in a 
positive feedback phenomenon known as the “wind-up phenomenon”, contributing 
to the immense challenges of providing adequate pain management and ultimately 
decreasing quality of life in patients experiencing burn care interventions.(Chapman 
et al, 1986)  Multiple dressing changes and treatments over the course of the burn 
patients recovery can increase fear and anxiety. Patients report feelings of 
helplessness, and loss of control.(Esfahlan et al, 2010) To date, only two studies 
guide benzodiazepine based anxiolysis during burn dressing changes with 
inconclusive evidence of effectiveness.(Bidwell et al, 2012; Patterson et al, 1997)  
A limitation of this current practice is that medications are administered at the 
nurses’ discretion based on subjective observations of a patient’s anxiety. There is 
no opportunity for patients to engage in anxiety self-management. Clearly, 
innovative interventions are needed that are safe and feasible to implement that 
effectively manage the significant anxiety in patients undergoing burn-care dressing 
changes.   


 
 
Numerous studies have demonstrated that patient controlled analgesia in burn 
patients is beneficial given the patient can self-titrate medication need according to 
individual requirements that are not controlled by the clinician. (Prakash et al, 
2004; Kinsella et al, 1988) The wide variations associated with clinician-delivered 
opioid therapy and the over- and under-treatment of pain can be avoided with this 
strategy. (Prakash et al, 2004; Kinsella et al, 1988)However, there have been no 
previous investigations of providing patients with the opportunity to self-manage the 
significant anxiety experienced prior to and during burn-care treatments and dressing 
changes.  One medication that might be ideal for anxiety self-management is 
dexmedetomidine. Dexmedetomidine (Precedex®) is an α2-agonist FDA-approved 
for surgical sedation or procedures. Chlan and colleagues have previously 
demonstrated the benefits of patient controlled sedation with dexmedetomidine for 
mechanically ventilated patients’ anxiety self-management.(Chlan et al, 2010) 
There is, however, limited examination in of dexmedetomidine the burn population, 
and there is not known if patient controlled administration of dexmedetomidine is 
beneficial for burn patients to self-manage their anxiety during painful and 
distressful burn care treatments. 
 
1.2 
Investigational Agents 
Dexmedetomidine (Precedex®) is a selective alpha-2 adrenergic agonist with both 
sedative and analgesic properties.  The pharmacokinetic profile has a rapid onset and 
short duration of action, producing light sedative properties.  Dexmedetomidine has 
no active metabolites, does not diminish respiratory drive, and has minimal effects 
on cognitive function.  Subjects receiving dexmedetomidine for sedation can be 
easily awakened without stopping the infusion.  Precedex® was originally approved 
in 1999 (NDA 021038) for sedation of initially intubated and mechanically 
ventilated patients during treatment in an intensive care setting, not to exceed 24 
hours; the indication for sedation of non-intubated patients prior to and/or during 
surgical and other procedures was approved later in 2008. 
 
The Alaris® PCA Module with Guardrails® Suite MX Software is an 
electromechanical infusion pump that uses a stepper motor that exerts pressure on an 
inserted syringe to control the infusion into a patient.  The PCA module is connected 
to the Alaris®PC unit which  is pole-mounted.  The PCA module includes an 
attached patient dose request cord that allows a patient to self-administer medication 
within physician-prescribed, programmed parameters that include delivery mode, 
PCA dose, lockout interval (5-120 min in 1 min increments) and/or 1 or 4 hour dose 
limits.  The Alaris®PCA Module with Guardrails® Suite MX Software is indicated 
for accurate, volumetric, infusion of drugs by continuous or patient-demanded (PCA) 


intravenous administration.The Alaris®PCA Module allows patients to self-
administer drug within clinician programmed limits and/or hospital-defined 
medication limits.   
 
2. Study Objectives 
2.1 
Primary Objective: 
The primary aim of this pilot study is to establish the safety and feasibility of patient-
controlled anxiolysis with dexmedetomidine (PCA-DEX) during burn care dressings 
for patients with burn injury.  
 
Feasibility will be defined by: 
a) Number and proportion of patients who consent to enrollment 
b) Proportion of eligible subjects enrolled prior to first dressing change 
c) Number of days on protocol that patients successfully use the PCA device 
d) Ability of burn nurses to adjust the pump and adhere to the infusion rates of the 
PCA-DEX protocol. 
 
Safety will be assessed by: 
The proportion of patients successfully completing the pilot trial without adverse 
effect which include significant hypotension, bradycardia, or agitation from 
uncontrolled anxiety. Detailed safety monitoring parameters clearly alert the research 
and burn-nurses of the guidelines for contacting independent physician safety 
monitors at each site.  Hemodynamic compromise (e.g., bradycardia, hypotension), 
unresolved agitation or inability of any study patient to safely participate in the PCA-
DEX protocol are specified reasons the physician safety monitor can stop the 
protocol and/or remove any subject from the study.  The number of patients who 
develop any of these adverse effects and/ or who require removal from the protocol 
will be reported. 
 
2.2 
Secondary Objectives: 
Secondary objectives for the study include: 
a) Patient Acceptability: Patients will evaluate PCA-DEX in regards to their 
willingness to use PCS-DEX prior to and during burn dressing changes to self-
manage anxiety and their satisfaction ratings with anxiety self-management.  
b) Nurse Acceptability: The nursing staffs’ acceptability of the PCA-DEX protocol 
for patients’ to self-manage anxiety surrounding burn care dressing changes will 
also be evaluated. 
 
3. Study Design 
3.1 
General Study Design 
The study design will be an open label, single arm, pilot study with all patients 
receiving standardized opioid therapy plus patient controlled anxiolysis with 


dexmedetomidine for burn care dressing changes.  The protocol will last up to five 
days or until the patient exits the study.  After 5 days the regimen for burn care 
dressing changes reverts to usual care with drug choice by the attending physician.   
 
3.2 
Primary Study Endpoints 
The primary endpoints to be reported in this study includes establishing the 
feasibility of subject recruitment and protocol adherence to a protocol for  PCA-DEX 
for burn care dressing changes in patients admitted for initial burn care management.  
Feasibility will be determined by the number and proportion of patients who consent 
to enrollment, the proportion of eligible subjects enrolled prior to first dressing 
change, number of days on protocol that patients successfully use the PCA device, 
and ability of burn nurses to adjust the pump and adhere to the infusion rates of the 
PCA-DEX protocol. 
 
3.3 
Secondary Study Endpoints 
The secondary endpoints to be analyzed in this study include evaluation patient and 
nursing acceptability of the PCA-DEX protocol. 
 
 
3.4 
Primary Safety Endpoints 
Potential adverse events associated with PCA-DEX will be monitored 1 hour before 
through 1 hour after each dressing change. The primary safety endpoints to be 
measured include the following: 
a) 
Proportion of subjects adverse effects (systolic blood pressure < 90 mmHg, 
diastolic < 50 mmHg, heart rate < 50 beats/min or respiratory rate <10 
breaths/minute) and require protocol suspension or eventual removal for safety 
reasons from the study for these reasons prior to day 5. 
b) 
Proportion of days with protocol violations related to the drug, pump, or both. 
 
4. Subject Selection and Withdrawal 
4.1 
Inclusion Criteria 
Subjects may be included in the study if all of the following conditions exist: 
1. 
Patients ages 18- 89 years admitted for initial management of thermal burn 
injury (flame, scald, contact) 
2. 
Presentation to The Ohio State University Wexner Medical Center Burn Center 
within 48 hours of burn injury 
3. 
Initial assessment of thermal burn size greater than 1% total body surface area 
4. 
Expected stay of  at least 3 days 
5. 
Read, write and speak English 
6. 
Subject is capable of providing informed consent 
 
4.2 
Exclusion Criteria 
Subjects will be excluded from the study if any of the following conditions exist: 


1. 
Positive pregnancy test or lactation 
2. 
incarcerated  
3. 
Active alcohol withdrawal  
4. 
Current hemodynamic instability (current hypotension systolic blood pressure 
<100 mmHg, sustained heart rate < 60 beats/min without a pacemaker, 
symptomatic bradycardia, or second or third degree heart block based on a 6-
second electrocardiogram (ECG) waveform verified by two members of the 
healthcare team proficient in ECG interpretation)  
5. 
Paralysis of other condition preventing patient ability to operate PCA device  
6. 
Acute hepatitis or liver failure  
7. 
Acute stroke or acute, uncontrolled seizures 
8. 
Acute myocardial infarction  
9. 
Severe cognition or communication difficulties (e.g., coma, deafness without 
signing literacy, dementia, non-English speaking)  
10. Chemical or electrical burn. 
11. Any condition precluding inclusion at the discretion of the burn surgeons 
  
4.3 
Study Exit Criteria 
Subjects will exit from the study if any of the following conditions exist: 
1. 
Subject completes protocol 
2. 
Subject voluntarily withdraws from the study 
3. 
Subject death 
4. 
Subject experiences a serious persistent adverse event such as unexplained  
rash or sustained adverse effect such as systolic blood pressure < 90 mmHg, 
diastolic < 50 mmHg, heart rate < 50 beats/min or respiratory rate <10 
breaths/minute. 
 
4.4 
Subject Recruitment and Screening 
Subjects will be recruited from the Burn Center within The Ohio State University 
Wexner Medical Center (OSUWMC). OSUWMC is the only central Ohio hospital 
with a commitment to the management of adult burn patients with a 22-bed Burn 
Center verified by the American Burn Association. Patients range in age from 16- 
89+ and include injuries from flame, scald, contact, chemical, and electrical 
mechanisms. The Burn Center admits about 300 patients per year with an average 
length of stay of 6.3 days (range 1-64).  
 
Informed Consent will be obtained from the patient only. A member of the research 
team (Coffey, Murphy, Calvitti, Uribe) will review the patient census on the Burn 
Center each morning with the unit’s charge nurse to determine if there are any 
patients who meet the study inclusion criteria. All of these individuals are employed 
at the OSUWMC. If any patient on the Burn Center meets the inclusion criteria, the 
responsible member of the research team listed above will then discuss the 
potentially eligible patient with either Dr. Jones or Dr. Bailey, who will make the 


final determination about the patient’s eligibility. If Dr. Jones or Dr. Bailey 
determines the patient is study eligible, he/she will then be approached for consent 
and potential enrollment into the study. Given all patients are in-patients on the Burn 
Center, recruitment will take place in the privacy of the hospital room before any 
scheduled burn care dressing changes in the procedure room.   
 
If a patient is willing to hear more information about the study, the responsible 
member of the research team will explain to the patient that a study is being 
conducted to examine whether a medication administered by patients’ themselves to 
manage anxiety during the burn care dressing changes is feasible, safe and 
acceptable to patients. Patients who decide to participate in the study will self-
administer dexmedetomidine (Precedex ©), a medication approved by the Food and 
Drug Administration (FDA) to help manage anxiety during medical procedures. Our 
study is interested in examining whether patients themselves can and will self-
administer this medication during the burn care dressing changes. Patients will be 
told that the nurses caring for them on the Burn Center will continue to provide pain 
medication per the routine physician orders on the unit. Patients will be told that the 
decision whether or not to participate in the study will not affect their care on the 
Burn Center in any way. If the patient is interested in participating in the study, a 
copy of the consent form will be provided to the patient prior to the scheduled burn 
care dressing change. Patients will be asked to read the consent form, ask any 
questions they may have about the study with the responsible member of the 
research team. Ample time will be given for any patient to consider study 
participation prior to the scheduled time for the first dressing change in the 
procedure room on the Burn Center. Given the study inclusion criteria, patients will 
only be approached once for study participation given our aim is to examine PCS-
DEX beginning with the first burn care dressing change, up to 5 days on the Burn 
Center. If the patient provides consent, the HIPAA form will next be presented to 
allow the research team to collect information from the patient and from the medical 
record. If the patient declines to participate in the study, he/she will be thanked for 
their time and will not be approached again during hospitalization on the Burn 
Center.  
 
 
4.5 
Early Withdrawal of Subjects 
Subjects will be withdrawn if any of the Exit Criteria listed in Section 4.3 are 
present.  If subjects are withdrawn prior to hospital discharge, they will be 
transitioned to standard regimen for burn care dressing changes at the discretion of 
the attending burn surgeon.  Any patient who elects to withdraw from the PCA-DEX 
protocol or is withdrawn prior to completing of the 5 day protocol will be closely 


monitored for an additional 24 hours for any adverse events.  All data will be 
considered for analysis regardless of length of time on protocol. 
 
5. Study Drug 
5.1 
Description 
Dexmedetomidine (Precedex®) is a selective alpha-2 adrenergic agonist with both 
sedative and analgesic properties.  The pharmacokinetic profile has a rapid onset and 
short duration of action, producing light sedative properties.  Dexmedetomidine has 
no active metabolites, does not diminish respiratory drive, and has minimal effects 
on cognitive function.   
 
5.2 
Treatment Regimen 
We will utilize a dosing algorithm consisting of a loading dose (0.25 mcg/kg) 
administer over 10 minutes, initiated 10 minutes prior to the start of burn wound 
care, followed by a continuous basal infusion of 0.4 mcg/kg/hr with 6 allowable 
patient-controlled self-boluses per hour (0.1 mcg/kg) each with a 10-minute lock-out.  
The Lifecare PCA® Infusion System is the infusion pump used at OSUWMC for 
patient controlled analgesia.  The pump will be utilized in the PCA + continuous 
mode.  Flow rates based on a 30 mL syringe range from 0.1-650 ml/hr (0.1-9.99 
ml/hr in 0.1 ml/hr increments, 10-99.9 ml/hr in 0.1 ml increments and 100-650 ml/hr 
in 1 ml increments. Delivery accuracy is ± 2% of full scale plunger travel not 
including syringe variation.  Settings, dose delivery times and aggregate dosing are 
recorded by the pump for later retrieval. 
 
5.3 
Preparation and Administration of Study Drug 
Dexmedetomidine will be stored, prepared and dispensed from the Investigational 
Drug Service (IDS# M-1429) within OSUWMC.  When study drug is requested for a 
subject, IDS will coordinate the preparation and dispensing of dexmedetomidine 
using a supply designated for this study.  Required paper work will be completed.   
 
 For patients weighing up to 88 kg, under strict aseptic technique, 200 µg/2 ml will 
be added to 28 ml of 0.9% sodium chloride; this will yield a concentration of 200 
µg/30 ml (or 6.7 µg/ml).  Dexmedetomidine will be delivered via a pharmacy-
prepared 30 ml syringe for use with the Alaris®PCA Module as described above.  
Preparation date and time will be recorded.   
 
For patients weighing more than 88 kg, under strict aseptic technique, 400 µg/4 ml 
will be added to 26 ml of 0.9% sodium chloride; this will yield a concentration of 
400 µg/30 ml (or 13.3 µg/ml).  Dexmedetomidine will be delivered via a pharmacy-
prepared bar-coded syringe manufactured for use with the Alaris®PCA Module as 


described above.  Preparation date and time will be recorded.   
 
All dexmedetomidine preparation will be performed in accordance with USP 797 
standards. 
 
 
 
5.4 
Receipt of Drug Supplies 
Upon receipt of the of the study treatment supplies, an inventory will be performed 
and a drug receipt log filled out and signed by the person in the IDS accepting the 
shipment.  The designated study staff will count and verify that the shipment 
contains all the items noted in the shipment inventory.  Any damaged or unusable 
study drug in a given shipment will be documented in the study files.   
 
5.5 
Storage 
Dexmedetomidine will be controlled by the Investigational Drug Service, a secure 
pharmacy service at OSUWMC.  The study drug will be stored in a secure, limited 
access location separate from commercial drug supplies. The investigational 
dexmedetomidine supply will be stored at a controlled room temperature not 
exceeding 25 °C (77 °F) with excursions allowed between 15 to 30 °C (59 to 86 °F).  
The study drug is not light sensitive and requires no additional special storage 
conditions.  Each dose will be signed out of the IDS log with the lot number of each 
200 µg/2 ml clear glass vial used to prepare the syringe for the study patient.  Vials 
are intended for single-use only. 
 
5.6 
Study Drug Accountability 
Study drug accountability will be performed to document activity dates, drug 
receipt,  dose and number of vials of drug dispensed, subject initials and subject ID 
number  to whom drug dispensed, running inventory and disposition of expired or 
unused drug.  Accountability will be accomplished by using institutional drug 
accountability forms and/or an electronic accountability system. 
 
 
6. Study Procedures 
Dexmedetomidine PCA Protocol:  The PCA-DEX dosing algorithm will consist of a 
loading dose (0.25 mcg/kg) given intravenously over 10 minutes, administered 10 minutes 
prior to the start of burn wound care, followed by a continuous basal infusion of 0.4 
mcg/kg/hr with 6 allowable patient-controlled self-boluses per hour (0.1 mcg/kg) each with 
a 10-minute lock-out.  Drs. Larry Jones and J. Kevin Bailey or their designate will write 
the PCA-DEX medication orders.  Subjects will receive standard opioid therapy (oral 
oxycodone/acetaminophen 5/325 mg 60 min. prior and IV morphine 4-12 mg or 
hydromorphone IV 0.5-1.5 mg 5 to 10 min. prior and buccal fentanyl 400 mcg as needed 


during burn wound care) and can receive bolus supplemental sedative medications 
(benzodiazepines) as ordered by Drs. Jones or Bailey if needed in the judgment of the 
burn-care nurse.  Subjects will be monitored closely by research personnel during the first 
burn wound care session from 1 hour prior to 1 hour after completion of burn wound care.  
Every heart rate and blood pressure recordings will be abstracted from the medical record 
from 1 hour prior to through 1 hour after completion of the daily burn wound dressing 
changes for days 1 through 5.  Alert adverse events will be reported by research personnel 
or the patient-care nurse to first the attending physician and then to the safety monitor.  
 
Nurse alert parameters to notify the attending physician and independent safety monitor 
include:  heart rate (HR) < 55 beats per min sustained for > 10 min; systolic BP < 90 mm 
Hg or >140 mm Hg sustained for >10 minutes; diastolic BP < 50 mm Hg or >90 mm Hg 
sustained for >10 minutes, respiratory rate < 10 breaths per minute sustained for >10 
minutes or oxygen saturation <92% sustained for >10 minutes; or persistent inability to 
understand rationale for triggering the PCA device despite education and demonstration. 
 
If the study subject has evidence of sustained hemodynamic instability (HR<60 bpm, SBP 
<90 mmHg or DBP < 50 mmHg) during the daily pre-procedure assessment, the patient 
will not be eligible to receive study drug on that day.  For that day the patient will receive 
standard of care as appropriate instead of the study intervention. The patient will then be 
reassessed prior to the subsequent study days to determine eligibility for study drug up 
through day 5. 
 
Data Collection Measures and Procedures  
Study entry demographic and descriptive data:  Data to be recorded includes:  age, 
gender, race, ethnicity, admission weight, severity of burn injury, burn etiology, total body 
surface area burned and depth of injury, and all home and hospital medications. 
 
Daily Measures on Protocol. The following will be obtained from enrolled patients each 
day by a member of the research team. 
 
Overall anxiety and pain. The abbreviated Burn Specific Anxiety and Pain Scale 
(BSAPS) on day 1, 1 hour prior to the first burn dressing change. (Taal et al, 
1999) 
 
Procedural Anxiety. Anxiety, defined as a state marked by apprehension, agitation, 
increased motor activity, arousal, and fearful withdrawal will be obtained from 
subjects.  (McCartney et al, 1994) Patients will evaluate current anxiety level 1 
hour before and 1 hour after each burn dressing change using a 100-mm Visual 
Analogue scale-anxiety (VAS-A). (McCartney et al, 1994; Hornblow et al, 1976)  


Subjects will be asked to rate their current level of anxiety on the VAS-A in 
response to, “How anxious are you feeling today?”  A 100-millimeter vertical line 
will be anchored on each end by statements ‘not anxious at all’ to ‘the most anxious 
I have ever been’.  The VAS-A will have a vertical orientation, as it is more sensitive 
and easier for subjects to use, particularly for those with a narrowed visual field or 
when under stress.  (Cline et al, 1992; Gift, 1989) Subjects will be asked to mark 
their current anxiety level on the vertical line. Scores will be derived by the distance 
in millimeters from the bottom anchor to the mark placed by the subject, yielding 
interval level data. (Bergbom-Engberg et al, 1989; Knebel et al 1994)    Reason(s) 
for not obtaining a daily anxiety assessment will be recorded.  The proportion of 
those assessments completed and reasons for non-completion will be used to inform 
strategies to minimize missing data for our planned randomized clinical trial. 
 
Procedural Pain.  Patients’ will evaluate current pain level 1 hour before and 1 hour 
after each burn dressing change using a 100-mm Visual Analogue Scale-Pain. 
(McCartney et al, 1994) Patients will be asked to rate their current level of pain on 
the VAS-P in response to “How much pain are you having right now?” A 100-
millimeter vertical line will be anchored on each end by statements of ‘no pain at all’ 
to ‘the most pain I have ever experienced’. As with the VAS-A, the vertical 
orientation has been chosen due to increased sensitivity and ease of use for patients. 
(Cline et al, 1992; Gift, 1989) Subjects will be asked to mark their current pain 
level on the vertical line. Scores will be derived by the distance in millimeters from 
the bottom anchor to the mark placed by the subject, yielding interval level data. 
(Bergbom-Engberg et al, 1989; Knebel et al 1994)  Reason(s) for not obtaining the 
pain assessments will be recorded.  The proportion of those assessments completed 
and reasons for non-completion will be used to inform strategies to minimize 
missing data for our planned randomized clinical trial. 
 
Protocol adherence.  A checklist will be completed daily to monitor the number of 
days subjects are able to use the PCA device for up to 5 days.  A checklist will also 
be used to monitor the ability of the burn-nurses to adhere to the PCA protocol per 
instructions.  
 
Daily adverse event monitoring.  Research staff will record and report the presence 
of hypotension, bradycardia (known adverse effects of dexmedetomidine), and 
protocol deviations related to drug, pump or both. Heart rate and blood pressure will 
be abstracted from the medical record.  Research team staff or burn-nurses caring for 
PCA-DEX subjects will alert the attending physician and the safety monitor for HR 
< 55 bpm sustained for > 10 min; systolic BP < 90 mm Hg or >140 mm Hg sustained 
for >10 minutes; diastolic BP < 50 mm Hg or >90 mm Hg sustained for >10 minutes, 
respiratory rate < 10 breaths per minute sustained for >10 minutes or oxygen 
saturation <92% sustained for >10 minutes during the period 1 hour prior through 1 


hour after completion of burn wound dressing change on days 1-5 for any necessary 
intervention or protocol withdrawal.   
 
Post-PCA-DEX Acceptability Survey.  Upon completion of the PCA-DEX protocol, we 
will query subjects and nurses about their satisfaction with self-administration of 
medication to manage anxiety, ease of medication administration, and the resulting level 
of relaxation.  
 
7. Statistical Plan 
Statistical analysis will be carried out on categorical demographic, clinical, safety and 
feasibility data will be summarized as frequencies and percents. Continuous demographic, 
clinical, procedural pain and procedural anxiety data will be summarized as means and 
standard deviations. Repeated measurements over time will be summarized at each 
relevant time point. 
 
8. Safety and Adverse Events 
8.1 
Definitions 
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 
will 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 a 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 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.  
 
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 30 
days 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 will 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 will 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 will also be 
recorded and documented as an adverse event.  
 
Post-study Adverse Event 
All unresolved adverse events will 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 will 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 will 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 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. 
 
8.2 
Assessment of Severity and Causality for Adverse Events 
 
Each adverse event will be assessed for severity based on the criteria below. 
 
Severity Grading for Assessment of Adverse Events 
Vital Signs 
Mild 
(Grade 1)  
Moderate 
(Grade 2)  
Severe 
(Grade 3)  
Potentially Life  
Threatening (Grade 4) 
Bradycardia 
- beats per  
minute  
50 – 54  
45 – 49  
< 45  
Requirement 
intervention (e.g. pacer 
or atropine), emergency 
rapid response 
activation or transfer to 
a higher level of care 
(e.g. intensive care unit 
or progressive care 
unit) 
Hypertension 
(systolic) -  
mm Hg  
141 – 
150  
151 – 155  
> 155  
Requirement for 
medication for 
hypertension as 
assessed by burn 
physician or transfer to 
a higher level of care 
(e.g. intensive care unit 
or progressive care 
unit) 
 
 


Hypertension 
(diastolic) -  
mm Hg  
91 – 95  
96 – 100  
> 100  
Requirement for 
medication for 
hypertension as 
assessed by burn 
physician or transfer to 
a higher level of care 
(e.g. intensive care unit 
or progressive care 
unit)  
Hypotension 
(systolic) –  
mm Hg  
85 – 89  
80 – 84  
< 80  
Requirement for 
intravenous fluids, 
vasopressor agents 
rapid response 
activation or transfer to 
a higher level of care 
(e.g. intensive care unit 
or progressive care 
unit)  
Hypotension 
(diastolic) –  
mm Hg 
45-49 
40-44 
<40 
Requirement for 
intravenous fluids, 
vasopressor agents 
emergency rapid 
response activation or 
transfer to a higher 
level of care (e.g. 
intensive care unit or 
progressive care unit) 
Respiratory 
Rate – 
breaths  
per minute  
12-17  
8-12 
<8 
Requirement for 
reversal agent (e.g. 
naloxone), rapid 
response activation or 
intubation  
Oxygen 
saturation, % 
85-91 
80-85 
<80 
Requirement for 
reversal agent (e.g. 
naloxone), emergency 
rapid response 
activation or intubation 
 
 
 
 


In addition, all adverse events will be assessed for causality using the World Health 
Organization-Uppsala Monitoring Center (WHO-UMC) standardized case causality 
assessment system as indicated below: 
 
 
8.3  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 will 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 will be 
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 will 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. 
 
8.4 
Reporting of Serious Adverse Events 
8.4.1 Study Sponsor Notification by Investigator 
A serious adverse event must be reported to the study sponsor by telephone 
within 24 hours of finding out of the event.  A Serious Adverse Event (SAE) 
form must be completed by the investigator and faxed to the study sponsor 
within 24 hours.  The investigator will keep a copy of this SAE form on file at 
the study site.  Report serious adverse events by phone and facsimile to: 
 
Larry M. Jones, MD 
614-293-5710 office  
 
 
 
 
614- 293-3472 fax 
 
At the time of the initial report, the following information should be provided: 
• 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 
 
Within the following 48 hours, the investigator must provide further 
information on the serious adverse event in the form of a written narrative.  
This should include a copy of the completed Serious Adverse Event form, and 
any other diagnostic information that will assist the understanding of the event.  
Significant new information of ongoing serious adverse events should be 
provided promptly to the study sponsor. 
 
8.4.2 IRB Notification by Investigator 
Reports of all serious adverse events (including follow-up information) must 
be submitted to the IRB within 10 working days if it falls under the UPIRTSO 
guidelines.  Copies of each report and documentation of IRB notification and 
receipt will be kept in the Clinical Investigator’s binder. 


 
8.4.3 FDA Notification by Sponsor 
The study sponsor shall notify the FDA by telephone or by facsimile 
transmission of any unexpected fatal or life-threatening experience associated 
with the use of the drug as soon as possible but no later than 7 calendar days 
from the sponsor’s original receipt of the information. 
 
If a previous adverse event that was not initially deemed reportable is later 
found to fit the criteria for reporting, the study sponsor will submit the adverse 
event in a written report to the FDA as soon as possible, but no later than 15 
calendar days from the time the determination is made. 
 
Agency 
Criteria for 
Reporting 
Timeframe 
Form to 
Use  
Submission 
address/fax 
numbers  
OSU 
IRB 
SAE: fatal, life-
threatening or 
serious, 
unexpected, at 
least possibly 
related  
Within 48 
hours for 
SAE 
resulting in 
death 
 
Within 7 days 
for SAE that 
are life-
threatening 
and 
unanticipated. 
Event 
Reporting 
Form 
version 3.2 
Online 
submission 
FDA 
SAE: fatal, life-
threatening, 
unexpected, at 
least possible 
related 
7 calendar 
days  
FDA 
prefers 
MedWatch 
3500a 
Form but 
alternative 
formats are 
acceptable 
(e.g. 
summary 
letter) 
Fax: 1 
(800) FDA 
- 0178 
SAE: serious, 
unexpected, at 
least possibly 
related 
15 calendar 
days 


 
8.5 
Stopping Rules  
Initial protocol suspension rules are as follows for an individual subject’s 
participation in the study: 
• 
Sustained (>30 min.) adverse effects defined by systolic blood pressure < 90 or 
> 180 mmHg, diastolic blood pressure < 50 or > 100 mmHg; heart rate < 50 or 
> 120 beats/min. or respiratory rate <10 breaths/min. 
• 
Persistent inability to understand rationale for triggering the PCA device 
despite education and demonstration 
 
Any subject who experiences any of the above will first be evaluated by the 
attending physician (or his/her designate) and then the safety monitor.  The safety 
monitors will communicate their findings to Dr. Jones and their opinion of any 
event(s) regarding the suitability of an individual subjects to continue on the study 
protocol.  Dr. Jones will review the circumstances and will decide whether to restart 
the protocol or withdraw the subject from the protocol.  
 
Stopping rules for the study (not for individual subjects) will be determined by an 
independent DSMB after final review of the protocol.  Since this is a feasibility pilot 
study with no comparator arm, study stopping criteria would likely be focused on 
adequate rates of recruitment, rates of study withdrawal due to subjects not being 
able to use the PCA device and differences in serious adverse event rates (but setting 
the level of significance to a stringent level because of the small sample size).  
 
8.6 
Medical Monitoring 
It is the responsibility of the Principal Investigator to oversee the safety of the study 
at the study site.  This safety monitoring will include careful assessment and 
appropriate reporting of adverse events as noted above, as well as the construction 
and implementation of a site data and safety-monitoring plan (see section 9 Auditing, 
Monitoring and Inspecting).  Medical monitoring will include a regular assessment 
of the number and type of serious adverse events. 
 
8.7 
Independent Data and Safety Monitoring Board 
A Data Safety Monitoring Board will be established for this study by Dr. Jones and 
Dr. Chlan.  The Board will consist of a minimum of 4 individuals, including a 
physician/surgeon, pharmacist, nurse-researcher, and statistician.  All members will 
be independent of the study protocol and research team.  
 
We will constitute an independent Data Safety Monitoring Committee for this 
study. Members include the following: 
 


David Evans, MD 
DSMC Chair and Surgeon 
Wexner Medical Center 
Michele Balas, PhD, RN, BC-NP, CCRN 
Associate Professor, College of Nursing 
Tony Gerlach  
Pharmacist, Surgical ICU 
Wexner Medical Center 
Larry Jones, MD,  
ex officio, non-voting 
Director, Burn Unit 
Wexner Medical center 
The Ohio State University 
Principal Investigator and IND Sponsor 
Kevin Bailey, MD,  
ex officio, non-voting 
Burn Surgeon  
Wexner Medical center 
The Ohio State University 
Investigator 
Linda Chlan, PhD, RN, FAAN,  
ex officio, non-voting 
Professor, College of Nursing 
Co-Principal Investigator 
Claire Murphy, Pharm D,  
Ex officio, non – voting  
Pharmacist  
Wexner Medical Center  
The Ohio University  
Investigator 
Rebecca Coffey, MSN, RN, CNP 
Ex officio, non-voting 
Nurse coordinator 
Wexner Medical Center 
The Ohio State University 
Investigator 
 
 Data Safety Monitoring Committee (DSMC) 
At predetermined intervals during the course of the trial, the DSMC responsibilities 
are the following: 
 
1.  Review the clinical protocol, informed consent documents and plans for data and 
safety monitoring; 
2.  Evaluate the progress of the study, including periodic assessments of data quality 
and timeliness, participant recruitment, accrual and retention, participant risk versus 
benefit, and other factors that can affect study outcome; 
3.  Consider factors external to the study when relevant information becomes 
available, such as scientific or therapeutic developments that may have an impact on 
the safety of the participants or the ethics of the study; 
4.  Review, make recommendations and assist in the resolution of problems reported 
by the PI; 
5.  Protect the safety of the study participants: 
6.  Report on the safety and progress of the study; 


7.  Make recommendations to the PI, FDA, and/or the IRB concerning continuation, 
termination or other modifications of the study based on the observed beneficial or 
adverse effects of PCS-DEX; 
8.  Ensure the confidentiality of the study data and the results of monitoring; 
9.  Assist the PI by commenting on any problems with study conduct, enrollment, 
sample size, and/or data collection. 
 
The DSMC will be comprised of one independent OSUMC physician, College of 
Nursing faculty, and SICU PharmD.  Each will have one vote.  One will be named 
Chair of the Committee (Dr. Evans).  The PI, IND holder (Dr. Jones), and members 
of the research team from The Ohio State University will be ex officio non-voting 
member.  The Chair of the committee is responsible for documenting decisions to 
continue and is responsible for issuing meeting minutes.  
 
For this study, 20 subjects will be enrolled.  The DSMC will review the outcomes 
including the safety data after each group of 5 subjects.  The DSMC will review 
safety data collected in each group at a quarterly Safety Review Meetings (SRM).  
At each meeting, the DSMC members will discuss the safety data. These discussions 
will include, but are not limited to, details of any adverse events of clinical relevance 
that raise concern about next cohort, any clinically significant changes in subject 
vital signs. The DSMC will decide if the study will continue. The decision will be 
based on consideration of the clinical significance of all relevant endpoints. 
Authorization to proceed will be obtained in a document signed and dated by the 
Chair of the DSMC and maintained in the study files.  If the safety profile is 
unacceptable, no new subjects will be enrolled.  In this case, the DSMC Chair will 
document the scientific rationale for the decision based on the safety data and 
recommendations of the DSMC. The Investigators will review the documentation 
and provide written agreement not to proceed with the trial.  If there are no safety 
concerns after each review, the study may proceed.  The decision to proceed must be 
by unanimous favourable vote. 
 
Process of safety monitoring 
Meetings of the SRC will take place after quarterly or after each group of 5 subjects 
are available. The Chair may call ad hoc DSMC meetings. 
 
Safety Evaluation 
The group safety review data will consist of data collected from Screening until Day 
5 inclusive. The following data will be presented:   
 
Adverse Events 
 
Vital signs 


 
Safety data (adverse events and vital signs data) will be provided to DSMC members 
by the PI as soon as it becomes available.  
 
If any SAE(s) occurred in the group under review, the SAE forms and narrative 
summaries will be presented as well; the SAE documentation will be provided by the 
PI for distribution to other committee members. All voting members of the DSMC 
must be present at the meeting. A negative vote on going forward by any of the 
voting members of the DSMC will place the study on hold pending further review 
and discussion or terminate the study.  
 
The Chair of the DSMC will prepare meeting minutes summarizing the discussion 
and detail the outcome of the vote pertaining to the continuation of the study. The 
minutes will specify the decision of each individual member of the DSMC and the 
overall decision of the DSMC. A copy of the minutes will be distributed to all 
members of the DSMC within one working day of the meeting.  
 
Immediately following the DSMC meeting (i.e., within one day of the meeting) the 
Chair will send the report to the PI for distribution to all members of the DSMC as 
well as the IRB and FDA, as appropriate. At the end of the study all DSMC 
documents will be forwarded to the PI for inclusion in the study files. 
 
All SAEs will be reported immediately (within 24 hours of their occurrence). This 
can be done by faxing a completed SAE Fax Cover Sheet and SAE CRF and by 
direct telephone communication to the CCTS, IRB, or FDA.  A completed SAE Fax 
Cover Sheet and SAE CRF will follow all telephone reports within 24 hours.  
 
Any SAEs, including death due to any cause, which occurs to any patient entered 
into this study, whether or not considered related to the investigational product, will 
be reported within 24 hours to the Sponsor (CCTS) or their representative. A 
completed SAE Fax Cover Sheet and SAE CRF will follow all telephone reports 
within 24 hours.  All patients with SAEs will be followed up for outcome by Ms. 
Coffey.   
 
9. Data Handling and Record Keeping 
9.1 
Confidentiality 
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. 
 
9.2 
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. 
 
Data generated by the methods described in the protocol will be recorded in the 
subjects' medical records and/or study progress notes.  Data may be transcribed 
legibly on CRFs supplied for each subject or directly inputted into an electronic 
system or any combination thereof. 
 
9.3 
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. 


 
9.4 
Records Retention 
The Investigator will retain study records including source data, copies of case report 
forms, consent forms, HIPAA authorizations and all study correspondence for at 
least 5 years after the study file has been closed with the IRB. 
 
10. Study Monitoring, Auditing, and Inspecting 
10.1 Study Monitoring Plan 
This study will be monitored by the OSU Center for Clinical and Translational Science 
(CCTS) Study Monitoring Service in accordance with the Standard Operating Procedures 
(Appendix 5-B).  The investigator will allocate adequate time for such monitoring activities 
which are to promote study participant safety, regulatory and protocol compliance, and data 
integrity. The extent of these activities will be commensurate with the level of risk and 
complexity that the study poses. In order for these activities to occur, the Investigator will 
also ensure that the monitor or other compliance or quality assurance reviewer is given 
access to all the above noted study-related documents and study related facilities (e.g. 
pharmacy, diagnostic laboratory, etc.), and has adequate space to conduct the monitoring 
visit. 
 
10.2 Auditing and Inspecting 
The investigator will permit study-related monitoring, audits, and inspections by the 
IRB, the sponsor, 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. 
 
11. 
Ethical Considerations 
This study is to be conducted according to US and international standards of Good Clinical 
Practice (FDA Title 21 part 312 and International Conference on Harmonization 
guidelines), applicable government regulations and Institutional research policies and 
procedures. 
 
This protocol and any amendments will be submitted to a properly constituted independent 
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.  The investigator should 
provide a list of IRB members and their affiliate to the sponsor. 
 
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.  The 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 is submitted to any study 
procedure.  This consent form must be signed by the subject, and the investigator-
designated research professional obtaining the consent.  
 
12. Study Finances 
12.1  
Funding Source 
This study is financed through a pilot grant from The Ohio State University Center 
for Clinical & Translational Science. 
 
12.2  
Conflict of Interest 
Any investigator who has a conflict of interest with this study (patent ownership, 
royalties, or financial gain greater than the minimum allowable by their institution, 
etc.) must refer to the Regents Policies on Individual Conflict of Interest Policy or 
Institutional Conflict of Interest Policy. These policies require University Faculty 
and staff to report external professional activities and business and significant 
financial interests related to his or her University activities by submitting a COI 
(Conflict of Interest) at least once per year. Faculty and staff should also update their 
COI when substantial changes in business or financial interests occur, when an 
activity that presents a potential conflict of interest is anticipated, or when submitting 
an application for research support or technology transfer, submitting research 
protocols to the IRB, or receiving financial contributions. All OSUWMC and OSU 
investigators will follow the University conflict of interest policy. 
 
12.3  
Subject Stipends or Payments 
Subjects will receive no payment or stipend for participation in this study. 
 
13. Publication Plan 
Neither the complete nor any part of the results of the study carried out under this protocol, 
nor any of the information provided by the sponsor for the purposes of performing the 
study, will be published or passed on to any third party without the consent of the study 
sponsor.  Any investigator involved with this study is obligated to provide the sponsor with 
complete test results and all data derived from the study.