Clinical trial NCT04042727
Conditions: Rapid Atrial Fibrillation Heart Rate Control
Keywords: Dexmedetomidine Critical Care Atrial Fibrillation
Sponsor: Stony Brook University
Start date: 2019-08-21; Completion date: 2021-12-31
Enrollment: 13 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to assess the effects of Dexmedetomidine (DEX), on heart rate control in patients with rapid atrial fibrillation (AF) through a pragmatic, randomized, double blinded study comparing the addition of Dex or placebo to standard of care (SOC) treatment.

Detailed description:
Dexmedetomidine is a commonly used sedative/anxiolytic agent in the ICU with sympatholytic properties that can cause a decrease in heart rate. Eligible patients will be randomized into one of two groups: SOC plus Dex arm or SOC plus placebo (normal saline) arm. Study drug infusion will be administered at an infusion rate of 1μg/kg/hr via IV, and will not include a loading dose. Four 6-second telemetry rhythm strips will be collected per hour, starting one hour prior to study drug infusion, during the eight hour infusion period, and two hours post infusion cessation). Degree of heart rate control and time to heart rate control for both groups will be analyzed.

Arms: arm 1: Dexmedetomidine hydrochloride infusion will be prepared by the investigational pharmacy and administered intravenously at a rate of 1mcg/kg/hr for a duration of 8 hrs to patients in rapid Afib in addition to the usual standard of care as deemed necessary by patient's ICU team. arm 2: Normal Saline solution will be prepared by investigational pharmacy and administered intravenously at a rate of 1mcg/kg/hr for a duration of 8 hrs to patients in rapid Afib in addition to the usual standard of care as deemed necessary by patient's ICU team.
Interventions: intervention 1: Dexmedetomidine Hydrochloride intervention 2: Normal Saline
Intervention descriptions: intervention 1: Six vials of Dexmedetomidine hydrochloride 100mcg/ml (2ml per vial) will be added to a 250mL bag of normal saline by the investigational pharmacy to prepare for infusion by patient's bedside nurse. Infusion rate will be 1mcg/kg/hr. intervention 2: 0.5% sodium chloride (NaCl). The investigational pharmacy will prepare the normal saline placebo 250mL bag for infusion by patient's bedside nurse. Infusion will be 1mcg/kg/hr.

Protocol documents:
Prot_SAP_000.pdf: 
PROTOCOL TITLE:   
Controlling Rapid Atrial-Fibrillation with Dexmedetomidine (C-RAD) Randomized Double-Blind Controlled 
Trial 
 
 
PROTOCOL VERSION/AMENDMENT: 0.01 
NCT04042727 
DATE: 9/21/2020 
STUDY PERSONNEL: 
 
 
 
Andreas Kalogeropoulos, MD MPH PhD  
Associate Professor, Department of Medicine (Cardiology) 
 
 
Elliott Bennett-Guerrero, MD (Co-I) 
Professor and Vice Chair for Clinical Research (Dept of 
Anesthesiology) 
 
Ibrahim Almasry, MD (Co-I) 
Cardiac Electrophysiology Attending (Div of Cardiology/Dept of 
Medicine) 
 
Roberto Thomas Sanchez, BS (Co-I)  
 
Jamie Romeiser, MPH (Co-I)  
 
Study datamanager and statistician 
 
Brittney Ayala, MS   
 
 
Clinical Research Coordinator 
 
 
1.1 OBJECTIVES 
 
1.2 Describe the purpose, specific aims, or objectives of this research. Specifically, explain why it is important to do the 
study. 
 
The purpose of this trial is to assess the ability of Dexmedetomidine (Dex), a commonly used sympatholytic, to 
improve heart rate control in patients with rapid Atrial Fibrillation (AF) through a pragmatic, randomized, 
double blind study comparing the addition of Dexmedetomidine or placebo to standard of standard of care 
(SOC) treatment.  
 
This trial is the first of its kind to use bradycardia, a common side effect of Dexmedetomidine, for therapeutic 
purposes in an attempt to control heart rate in rapid Atrial Fibrillation.  The aim is to study whether 
Dexmedetomidine can help improve rate control for patients with rapid-AF in the critical care setting – a setting 
in which the management of AF is often challenging due to co-morbidities and organ dysfunction. 
 
1.2 State the hypothesis to be tested, if applicable. NOTE:  A hypothesis is a specific, testable prediction about what you 
expect to happen in your study that corresponds with your above listed objectives. 
Addition of Dexmedetomidine administration to patients with atrial fibrillation already receiving standard of 
care results in improved heart rate control compared to the standard of care plus placebo arm. 
 
2.0 SCIENTIFIC/SAFETY ENDPOINTS 
 
2.1  
Describe the scientific endpoint(s), the main result or occurrence under study.  NOTE:  Scientific endpoints are 
outcomes defined before the study begins to determine whether the objectives of the study have been met and to draw 


conclusions from the data.  Include primary and secondary endpoints.  Some example endpoints are:  reduction of 
symptoms, improvement in quality of life, or survival.  Your response should not be a date.   
Primary Endpoints:  
The primary end point will be to assess the degree of heart rate control (mean ventricular heart rate <100 bpm), 
in the Dexmedetomidine plus SOC arm compared to the placebo plus SOC arm. Heart rate will be calculated 
from 6-second rhythm strips obtained every 15-minutes from the hospital’s electronic medical record. Heart rate 
will be recorded 1-hour prior to the study drug administration, for 8-hours during study drug infusion and for 2-
hours post cessation of the study drug infusion (a total of 44 rhythm strips).   
 
Key Secondary Endpoints: 
1) Time to heart rate control (HR <100 bpm) in the Dexmedetomidine plus SOC arm vs. Placebo plus SOC arm. 
2) Percentage of rhythm strips with heart rate <100 bpm. 
3) Percentage of rhythm strips with conversion to sinus rhythm. An attending cardiologist (Dr. Almasry- CoI), 
who is blinded to study drug assignment, will adjudicate all rhythm strips for determination of heart rhythm. 
 
Exploratory Endpoints: 
Descriptive assessment of rate control, and vasoactive medications used in both arms during the 8-hour study 
drug infusion. 
 
Safety Endpoints: 
1) Percentage of patients requiring pausing or discontinuation of study drug. 
2) Episodes of hypotension defined as two consecutive values of SBP <90 mm Hg requiring intervention. 
3) Episodes of bradycardia requiring cessation of infusion (persistent heart rate <50 bpm). 
 
 
3.0 BACKGROUND AND RATIONALE: 
 
3.1  
Provide the scientific or scholarly background, rationale, and significance of the research based on the existing 
literature and how it will contribute/fill in gaps to existing knowledge.  
Atrial fibrillation (AF) is the most common arrhythmia, affecting nearly 2.2 million Americans1-7. 
Approximately 25% of men and women over 40 will develop AF in their lifetime7. AF is characterized by a 
rapid irregular atrial activation, or “quivering”, resulting in loss of atrial systole, ineffective ventricular filling 
and a lack of distinct P-waves with repetitive RR-interval patterns on electrocardiogram (ECG). Rapid, irregular 
ventricular contraction rates can develop in AF and result in decreased cardiac output, increase myocardial 
oxygen demand, and atrial appendage thrombus formation1,8-12. AF can result in decompensated heart failure13, 
myocardial infarction (MI)14-17, systemic embolization18, and increased overall morbidity19 and mortality13,18,20-
25. AF increases cardiovascular-associated mortality26,27 and acute myocardial infarction (AMI) risk increases 2-
fold14,15. AF management strategies initially require a rapid reduction in ventricular rate in order to prevent 
these complications and improve symptoms. Long term strategies usually revolve around rate control +/- 
rhythm control. 
 
 
Initiation and maintenance of AF is affected by the autonomic nervous system (ANS)28 and may be 
promoted by heightened vagal and sympathetic tone29,30. Excessive adrenergic stress has been implicated in 
adverse events including direct myocardial damage31,32.  Since excessive sympathetic drive is implicated in the 
development of rapid AF, then the use of a sympatholytic-agent may have a role in the treatment of rapid AF in 
the acute setting.  
 


 
Dexmedetomidine, a centrally acting alpha-2 agonist (sympatholytic), was approved by the FDA in 
1999 for anxiolysis and sedation in both intubated and non-intubated patients33-40. It is one of the most 
commonly used medications in ICUs, therefore, there is extensive knowledge about its safety profile.  It is 
generally regarded as a safe drug. Common side effects of Dexmedetomidine are bradycardia and 
hypotension33, yet it causes less hypotension than other sedatives such as Propofol, and benzodiazepines34. 
 
Several studies have suggested a role for Dexmedetomidine with ventricular arrhythmias26,35-39. The role 
of Dexmedetomidine for patients with rapid atrial tachyarrhythmias remains unknown. Our proposed study is 
the first of its kind to evaluate whether Dexmedetomidine, an anxiolytic/sedative agent, can be used to lower the 
heart rates of patients with AF. We hypothesize that its sympatholytic properties will lead to improved rate 
control over standard of care management. We believe this study could have important clinical therapeutic 
implications for use in patients with rapid AF and expand the armamentarium available for treating rapid AF in 
the critical care setting.  
 
3.2  
Include complete citations or references:  
1. 
Perula-de-Torres LA, Martinez-Adell MA, Gonzalez-Blanco V, et al. Opportunistic detection of atrial 
fibrillation in subjects aged 65 years or older in primare care: a randomised clinical trial of efficacy. 
DOFA-AP study protocol. BMC family practice. 2012;13:106. 
2. 
Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national 
implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in 
Atrial Fibrillation (ATRIA) Study. Jama. 2001;285(18):2370-2375. 
3. 
Furberg CD, Psaty BM, Manolio TA, Gardin JM, Smith VE, Rautaharju PM. Prevalence of atrial 
fibrillation in elderly subjects (the Cardiovascular Health Study). The American journal of cardiology. 
1994;74(3):236-241. 
4. 
Curry SJ, Krist AH, Owens DK, et al. Screening for Atrial Fibrillation With Electrocardiography: US 
Preventive Services Task Force Recommendation Statement. Jama. 2018;320(5):478-484. 
5. 
Welton NJ, McAleenan A, Thom HH, et al. Screening strategies for atrial fibrillation: a systematic 
review and cost-effectiveness analysis. Health technology assessment (Winchester, England). 
2017;21(29):1-236. 
6. 
England PH. Atrial Fibrillation Prevalence Estimates in England: Application of Recent Population 
Estimates of AF in Sweden. London: Public Health England. 2015. 
7. 
Lloyd-Jones DM, Wang TJ, Leip EP, et al. Lifetime risk for development of atrial fibrillation: the 
Framingham Heart Study. Circulation. 2004;110(9):1042-1046. 
8. 
Pritchett EL. Management of atrial fibrillation. The New England journal of medicine. 
1992;326(19):1264-1271. 
9. 
Atrial fibrillation: current understandings and research imperatives. The National Heart, Lung, and 
Blood Institute Working Group on Atrial Fibrillation. Journal of the American College of Cardiology. 
1993;22(7):1830-1834. 
10. 
Lip GY, Metcalfe MJ, Rae AP. Management of paroxysmal atrial fibrillation. The Quarterly journal of 
medicine. 1993;86(8):467-472. 
11. 
Disch DL, Greenberg ML, Holzberger PT, Malenka DJ, Birkmeyer JD. Managing chronic atrial 
fibrillation: a Markov decision analysis comparing warfarin, quinidine, and low-dose amiodarone. 
Annals of internal medicine. 1994;120(6):449-457. 
12. 
Jonas DE, Kahwati LC, Yun JDY, Middleton JC, Coker-Schwimmer M, Asher GN. Screening for Atrial 
Fibrillation With Electrocardiography: Evidence Report and Systematic Review for the US Preventive 
Services Task Force. Jama. 2018;320(5):485-498. 
13. 
Benjamin EJ, Wolf PA, D'Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation 
on the risk of death: the Framingham Heart Study. Circulation. 1998;98(10):946-952. 


14. 
Soliman EZ, Safford MM, Muntner P, et al. Atrial fibrillation and the risk of myocardial infarction. 
JAMA internal medicine. 2014;174(1):107-114. 
15. 
Smolina K, Wright FL, Rayner M, Goldacre MJ. Incidence and 30-day case fatality for acute myocardial 
infarction in England in 2010: national-linked database study. European journal of public health. 
2012;22(6):848-853. 
16. 
Schmitt J, Duray G, Gersh BJ, Hohnloser SH. Atrial fibrillation in acute myocardial infarction: a 
systematic review of the incidence, clinical features and prognostic implications. European heart 
journal. 2009;30(9):1038-1045. 
17. 
Garg RK, Jolly N. Acute myocardial infarction secondary to thromboembolism in a patient with atrial 
fibrillation. International journal of cardiology. 2007;123(1):e18-20. 
18. 
Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the 
Framingham Study. Stroke. 1991;22(8):983-988. 
19. 
Lee S, Shafe AC, Cowie MR. UK stroke incidence, mortality and cardiovascular risk management 1999-
2008: time-trend analysis from the General Practice Research Database. BMJ open. 2011;1(2):e000269. 
20. 
Corley SD, Epstein AE, DiMarco JP, et al. Relationships between sinus rhythm, treatment, and survival 
in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study. 
Circulation. 2004;109(12):1509-1513. 
21. 
Andersson T, Magnuson A, Bryngelsson IL, et al. All-cause mortality in 272,186 patients hospitalized 
with incident atrial fibrillation 1995-2008: a Swedish nationwide long-term case-control study. 
European heart journal. 2013;34(14):1061-1067. 
22. 
Raju NC, Hankey GJ. Dabigatran etexilate in people with atrial fibrillation. BMJ. 2010;341:c3784. 
23. 
Hannon N, Sheehan O, Kelly L, et al. Stroke associated with atrial fibrillation--incidence and early 
outcomes in the north Dublin population stroke study. Cerebrovascular diseases (Basel, Switzerland). 
2010;29(1):43-49. 
24. 
Friberg L, Hammar N, Pettersson H, Rosenqvist M. Increased mortality in paroxysmal atrial fibrillation: 
report from the Stockholm Cohort-Study of Atrial Fibrillation (SCAF). European heart journal. 
2007;28(19):2346-2353. 
25. 
Stewart S, Hart CL, Hole DJ, McMurray JJ. A population-based study of the long-term risks associated 
with atrial fibrillation: 20-year follow-up of the Renfrew/Paisley study. The American journal of 
medicine. 2002;113(5):359-364. 
26. 
Chrysostomou C, Sanchez-de-Toledo J, Wearden P, et al. Perioperative use of dexmedetomidine is 
associated with decreased incidence of ventricular and supraventricular tachyarrhythmias after 
congenital cardiac operations. The Annals of thoracic surgery. 2011;92(3):964-972; discussion 972. 
27. 
Chen LY, Sotoodehnia N, Buzkova P, et al. Atrial fibrillation and the risk of sudden cardiac death: the 
atherosclerosis risk in communities study and cardiovascular health study. JAMA internal medicine. 
2013;173(1):29-35. 
28. 
Workman AJ. Cardiac adrenergic control and atrial fibrillation. Naunyn-Schmiedeberg's archives of 
pharmacology. 2010;381(3):235-249. 
29. 
Herweg B, Dalal P, Nagy B, Schweitzer P. Power spectral analysis of heart period variability of 
preceding sinus rhythm before initiation of paroxysmal atrial fibrillation. The American journal of 
cardiology. 1998;82(7):869-874. 
30. 
Coumel P. Autonomic influences in atrial tachyarrhythmias. Journal of cardiovascular 
electrophysiology. 1996;7(10):999-1007. 
31. 
Singer M. Catecholamine treatment for shock--equally good or bad? Lancet (London, England). 
2007;370(9588):636-637. 
32. 
Dunser MW, Hasibeder WR. Sympathetic overstimulation during critical illness: adverse effects of 
adrenergic stress. Journal of intensive care medicine. 2009;24(5):293-316. 
33. 
Research CfDEa. Precedex Approval Package. 2010. 
34. 
Hoy SM, Keating GM. Dexmedetomidine: a review of its use for sedation in mechanically ventilated 
patients in an intensive care setting and for procedural sedation. Drugs. 2011;71(11):1481-1501. 
35. 
Ling X, Zhou H, Ni Y, Wu C, Zhang C, Zhu Z. Does dexmedetomidine have an antiarrhythmic effect on 
cardiac patients? A meta-analysis of randomized controlled trials. PloS one. 2018;13(3):e0193303. 


36. 
Herr DL, Sum-Ping ST, England M. ICU sedation after coronary artery bypass graft surgery: 
dexmedetomidine-based versus propofol-based sedation regimens. Journal of cardiothoracic and 
vascular anesthesia. 2003;17(5):576-584. 
37. 
Ren J, Zhang H, Huang L, Liu Y, Liu F, Dong Z. Protective effect of dexmedetomidine in coronary 
artery bypass grafting surgery. Experimental and therapeutic medicine. 2013;6(2):497-502. 
38. 
Corbett SM, Rebuck JA, Greene CM, et al. Dexmedetomidine does not improve patient satisfaction 
when compared with propofol during mechanical ventilation. Critical care medicine. 2005;33(5):940-
945. 
39. 
Shehabi Y, Grant P, Wolfenden H, et al. Prevalence of delirium with dexmedetomidine compared with 
morphine based therapy after cardiac surgery: a randomized controlled trial (DEXmedetomidine 
COmpared to Morphine-DEXCOM Study). Anesthesiology. 2009;111(5):1075-1084. 
40. 
Zientara A, Mariotti S, Matter-Ensner S, et al. Fast-Track Management in Off-Pump Coronary Artery 
Bypass Grafting: Dexmedetomidine Provides Rapid Extubation and Effective Pain Modulation. The 
Thoracic and cardiovascular surgeon. 2018. 
 
 
4.0 STUDY DESIGN 
 
4.1  
Describe and explain the study design (e.g. case-control, cross-sectional, ethnographic, experimental, 
interventional, longitudinal, and observational). Indicate if there is randomization, blinding, control group, etc. If 
randomizing, explain how this will be achieved. 
 
Prospective, randomized, controlled, double-blind placebo controlled study.   
5.0 LOCAL NUMBER OF SUBJECTS 
5.1 
Indicate the total number of subjects who will be enrolled or records that will be reviewed through Stony Brook.  
This is a single center pilot study designed to enroll 60 subjects, 30 per arm. 
 
5.2 
If this study is only being conducted through Stony Brook, provide statistical justification (i.e. power analysis) for 
the number of subjects provided in 5.1 above.  If qualitative research, so state, and provide general justification for the 
total number of subjects proposed. 
Based on prior clinical experience, we anticipate the average heart rate in the Standard of Care (SOC) treatment 
plus placebo arm will be higher (mean ventricular rate of about 100 bpm), with more relative variability 
(standard deviation of 20).  We believe the SOC plus Dexmedetomidine group will have a lower average heart  
rate (mean ventricular heart rate of about 85 bmp) with less variability (standard deviation of 15). Because of 
the uncertainty in these estimates, a range of power estimations were calculated by using a target goal of 60 
participants (30 per group) [see table below].  The power estimations were carried out using PASS 12 Software 
(Kaysville, Utah).  Using a two sample t-test allowing for unequal variance, and a range of standard deviations, 
we will have between 81.5% - 99.4% power to detect a difference between the two groups.  
Numeric Results for Two-Sample T-Test Allowing Unequal Variance 
Alternative Hypothesis: H1: δ = μ1 - μ2 ≠ 0 
Power 
N1 
N2 
N 
δ 
σ1 
σ2 
Alpha 
0.99395 
30 
30 
60 
15 
15 
10 
0.05 
0.96771 
30 
30 
60 
15 
15 
15 
0.05 
0.89745 
30 
30 
60 
15 
15 
20 
0.05 
0.94849 
30 
30 
60 
15 
20 
10 
0.05 
0.89745 
30 
30 
60 
15 
20 
15 
0.05 


0.81497 
30 
30 
60 
15 
20 
20 
0.05 
 
 
5.3 
If applicable, indicate your screen failure rate, i.e., how many subjects you expect to screen to reach your target 
sample 
We anticipate a screen failure rate of approximately 10-15%, which is reasonable for a trial of this type. 
Therefore, we expect to screen ~70 patients. 
5.4 
Justify the feasibility of recruiting the proposed number of eligible subjects within the anticipated recruitment 
period. For example, how many potential subjects do you have access to? What percentage of those potential subjects do 
you need to recruit? 
There are approximately 65 adult Critical Care beds at Stony Brook University Hospital. Patients in adult ICUs 
or ICRs who meet the eligibility criteria below will be screened daily for entry into the study by study personnel 
with the help of the PIand Dr. Bennett-Guerrero, a Co-I, who is an intensivist in the CTICU. We anticipate that 
5%-10% of the daily ICU population will be in AFIB. We plan to enroll approximately 1 patient each day to 
achieve our target of 60 patients. 
 
We will also consider enrolling patients - who are not in need of life support - in the Medical ICR and the 
CACU, as they can also present rapid AF in these critical care settings while bearing fewer comorbidities. They 
are less sick than patients in the ICUs, the nurse to patient ratio in these units is 4:1, arterial lines (A-lines) are 
the standard for patient heart rate (HR) and blood pressure (BP) monitoring, and we believe that these patients 
may also benefit from being included in this study.  
      
 
6.0 INCLUSION AND EXCLUSION CRITERIA 
 
6.1 Inclusion Criteria:  
● Adult patients in a Stony Brook University Hospital ICU or ICR with rapid atrial fibrillation (with 
ventricular rates >100 bpm) 
● Patients with and without capacity to consent will be screened. Consent will be acquired either from the 
patient directly or from the Legal Authorized Representative when the patient is not able to consent, as 
is consistent with most ICU studies.  
● Patients that are mechanically ventilated as well as those that are not.  
 
 
6.2 Exclusion Criteria:  
● <18 years of age. 
● Anticipated ICU or ICR length of stay of less than 11-hours. 
● Patients with a permanently paced heart rhythm. 
● Patients with known 2nd and 3rd degree heart blocks, junctional rhythms 
● Known pregnancy 
● Patients with known allergy to Dexmedetomidine. 
● Patients receiving Dexmedetomidine prior to onset of study 
● Non-intubated patients with a Glasgow Coma Scale (GCS) <8. 
● Patients who weigh more than 400 pounds (182 kg) (protocol dosing restriction). 
● Patients with untreated, symptomatic hypotension (sustained SBP <90 mm Hg). 
● Patients who have received amiodarone, lidocaine, or mexiletine within 4-hours prior to consent. 
 
 


6.3 
Describe how individuals will be screened for eligibility.  Upload all relevant screening documents with your 
submission (screening protocol, script, questionnaire). Identify who will certify that subjects meet eligibility requirements.  
Dr. Kalogeropoulos, Associate Professor Department of Medicine, Dr. Bennett-Guerrero (a Co-I, who is an 
intensivist in the CTICU), and other study personnel will make rounds in the various ICUs and ICRs throughout 
the day to determine if there are patients who are potentially eligible for the trial. In addition, clinicians (RNs, 
MDs) will also be encouraged to refer patients with rapid-AF to our attention for consideration. Study personnel 
will use the IRB approved inclusion/exclusion checklist to determine and confirm eligibility. 
 
6.4 
Indicate whether you are specifically recruiting or targeting any of the following special populations in your study 
using the checkboxes below. (You will be asked for additional information in Section 7 if you check any of these boxes)  
 N/A 
 
 
6.5 
Indicate if you will include minorities (American Indians, Alaskan Native, Asian, Native Hawaiian, Pacific Islander, 
Black [not of Hispanic origin] and Hispanic) as Federal mandates require that you include minorities unless you can justify 
their exclusion 
☒ 
Yes 
☐ 
No, Justify:  
6.6 
Indicate whether you will include non-English speaking individuals in your study.  Provide justification if you will 
specifically exclude non-English speaking individuals. Review http://research.stonybrook.edu/human-subjects-standard-
operating-procedures/policy-non-english-speakers-research-subjects for SBU policy on inclusion of non-English speakers. 
Upload any translated materials (consent, questionnaires, etc).  
We will not include individuals who do not speak English in this study.  
 
7.0 Vulnerable Populations 
7.1 
For research that involves pregnant women, review, complete and upload Supplemental Form A:  Pregnant 
Women, Fetuses, Non-Viable Neonates, or Neonates of Uncertain Viability. 
☐ 
Confirmed 
☒ 
N/A:  This research does not involve pregnant women. 
7.2 For research that involves neonates of uncertain viability or non-viable neonates, review, complete and upload 
Supplemental Form A:  Pregnant Women, Fetuses, Non-Viable Neonates, or Neonates of Uncertain Viability. 
☐ 
Confirmed 
☒ 
N/A:  This research does not involve non-viable neonates or neonates of uncertain viability. 
 
7.3 
For research that involves prisoners, review, complete and upload Supplemental Form H: Prisoners  
☐ 
Confirmed 
☒ 
N/A:  This research does not involve prisoners. 
 
7.4 
For research that involves minors (under 18 years), review, complete and upload Supplemental Form F: Minors 


☐ 
Confirmed 
☒ 
N/A:  This research does not involve persons who have not attained the legal age for consent to treatments or 
procedures (“children”). 
 
7.5 
For research that involves adults who cannot consent for themselves, you will be asked additional information in 
Section 25 (“Informed Consent”) 
☒ 
Confirmed 
☐ 
N/A 
 
7.6 
Consider if other specifically targeted populations such as students, employees of a specific firm, or educationally 
or economically disadvantaged persons are vulnerable.  Provide information regarding their safeguards and protections, 
including safeguards to eliminate coercion or undue influence. 
vulnerable populations will be targeted.  
☒ 
N/A 
 
8.0 Eligibility Screening  
8.1 
Describe screening procedures for determining subjects’ eligibility.  Screening refers to determining if 
prospective participants meet inclusion and exclusion criteria.  
Include all relevant screening documents with your submission (e.g. screening protocol, script, questionnaires) as 
attachments.  
Dr. Kalogeropoulos, Associate Professor Department of Medicine, and other study personnel will make rounds 
in the various ICUs and ICRs throughout the day to determine if there may be patients who are potentially 
eligible for the trial. In addition, if clinicians (RNs, MDs) bring patients with rapid-AF in an adult ICU or ICR 
to our attention, these patients will also be screened for eligibility. The patient’s medical record, telemetry 
monitoring and ECGs (when available) will be reviewed to ascertain that the patient is in fact in rapid-AF. 
Study personnel will use the IRB approved inclusion/exclusion checklist to determine and confirm eligibility. 
 
☐ 
N/A:  There is no screening as part of this protocol. 
 
9.0 Recruitment Methods 
☐ 
N/A:  This is a records review only, and subjects will not be recruited.  NOTE:  If you select this option, please 
make sure that all records review procedures and inclusion/exclusion screening are adequately described in other 
sections, including date range for records that will be reviewed. 
 
9.1 
Describe source of subjects: When, where, and how potential subjects will be recruited.  
NOTE:  Recruitment refers to how you are identifying potential participants and introducing them to the study. These 
may include, but are not limited to: ResearchMatch.org, physician referral, Office of Clinical Trials database, West 


Campus departmental pools, reviewing medical charts, Research Participant Groups/help groups, advertising companies, 
call centers, in person announcements / presentations 
Dr. Kalogeropoulos, Associate Professor Department of Medicine, and other study personnel will make rounds 
in the various ICUs and ICRs throughout the day to determine if there may be patients who are potentially 
eligible for the trial. In addition, if clinicians (RNs, MDs) bring patients with rapid-AF in an adult ICU or ICR 
to our attention, these patients will also be screened for eligibility. The patient’s medical record, telemetry 
monitoring and ECGs (when available) will be reviewed to ascertain that the patient is in fact in rapid-AF. 
Study personnel will use the IRB approved inclusion/exclusion checklist to determine and confirm eligibility. If 
a patient appears to be eligible we will discuss the study with them or with their LAR. 
 
9.2 
Describe how you will protect the privacy interests of prospective subjects during the recruitment process.  NOTE:  
Privacy refers to an individual’s right to control access to him or herself. This is NOT asking about confidentiality of data.   
We will speak to patients or their LAR in a private setting.  
9.3 
Identify/describe any materials that will be used to screen/recruit subjects and upload copies of these documents 
with the application. They may include, but are not limited to Telephone scripts for calling, flyers, Questionnaires, 
Posters,  Letters or written material to be sent or emailed, pamphlets, posted advertisements, email invitations.  
N/A 
10.0 RESEARCH PROCEDURES  
Provide a detailed description of all research procedures or activities being performed on the research subjects. This 
should serve as a blueprint for your study and include enough detail so that another investigator could pick up your 
protocol and replicate the research.  For studies that have multiple or complex visits or procedures, consider the addition 
of a schedule of events table in in your response. Be sure to include: 
● Procedures being performed to monitor subjects for safety or to minimize risks.  
● All drugs and devices used in the research and the purpose of their use, and their regulatory status 
ROUTINE CARE: All patients (ie in both study arms) will receive routine standard of care (SOC) treatment of 
their atrial fibrillation per the discretion of their treating physicians. This typically includes correction of 
electrolyte abnormalities (K+, Mg2+) and administration of beta blockers, calcium channel blockers, and 
Digoxin, etc. in order to achieve rate control and prevent complications associated with rapid ventricular rates. 
Our trial will record details of this care but does not control nor limit what SOC is used in the treatment of the 
patient’s rapid-AF. 
SUMMARY OF RESEARCH PROCEDURES: From the perspective of the subject, the only additional 
aspects of the trial that are not routine will be the following:  
      1) Patient’s rhythm will be confirmed by reviewing telemetry and available ECGs. Patients deemed  
          to be in rapid-AF will be consented and randomized in a 1:1 fashion to receive placebo (normal saline 
infusion), 
          or the study drug Dexmedetomidine. A patient who is no longer in rapid-AF at time of consent will be 
screen failed 
          (see Statistical Methods section for details). 
      2) An order for the study drug will be entered into the Electronic Medical Record (EMR) as a  
          Therapeutic Non-Formulary (TNF) request per Stony Brook’s Investigational Pharmacy’s standard  
          operating procedure.  The Investigational Pharmacy will prepare the blinded study drug  
          with appropriate labeling as either 250 mL of normal saline (placebo) or  


          Dexmedetomidine (1200 µg/250 mL).  The study drug will be delivered to the patient’s  
          bedside.  The patient’s nurse will scan the medication using the hospital’s routine bar code  
          technology and administer the drug via infusion pump. 
 
 
Study drug administration and monitoring: 
 
      a.   Study drug will be infused at 1 µg/kg/hr with maximum rate of 150 µg/hr for a  
            period of 8 hours from the initial start of study drug administration.  This              
            dosing regimen is consistent with routine use of Dexmedetomidine at  
            Stony Brook and in numerous clinical studies 
            (see RISKS section). 
 
      b.   Heart rate will be continuously monitored via telemetry, as is routine in ICU patients. Per the 
study  
                        protocol, blood pressure will be measured every 15 minutes during study drug  
                        administration either non-invasively by cuff  or via an indwelling arterial catheter (placed for 
routine care).  
 
      c.   If HR is < 50 bpm, SBP < 80 mm Hg, or RASS< -2 for non-intubated patients,  
or a patients clinically decompensates, the study drug infusion will be  paused for 1 hour. The 
study drug will then be restarted at half the dose (i.e. 0.5 µg/kg/hr) once the patient is stable and 
no longer hypotensive or bradycardic. If the infusion is not restarted then the patient will be 
assessed hourly to determine if it is safe to resume the infusion once the above pausing criteria 
have been resolved. 
 
      3) Concomitant medications: The study prohibits the use of Dexmedetomidine during the study drug 
administration period for  
           sedation.  
4) As described in Endpoints, rhythm strips will be printed from the hospital EMR every 15 minutes for 
assessment of cardiac rhythm and rate. 
      5) Routinely collected demographic and patient related variables (e.g. date of birth, age, race, ethnicity, sex, 
height, weight, medical history, comorbidities:  type 2 diabetes, smoker; pre-existing conditions:  coronary 
artery disease, congestive heart failure, chronic kidney disease, chronic obstructive pulmonary disease; 
APACHE 3 variables:  AaDO2 or PaO2, temperature, MAP, pH arterial, heart rate, respiratory rate, sodium 
(serum), potassium (serum), creatinine, hematocrit, white blood cell count, Glasgow Coma Scale; date and time 
of ICU admission, admitting diagnosis, RASS score, mechanical ventilation, systolic and diastolic blood 
pressure, heart rate, date of last echocardiogram, left ejection fraction, left atrial size, concomitant medications 
(e.g. vasopressors, beta-blockers)) will be recorded from the EMR. 
 
10.1 
Describe what data, including long-term follow-up, will be collected.  NOTE:  For studies with multiple data 
collection points or long-term follow up, consider the addition of a schedule or table in your response. 
As described above, we will collect rhythm strips 1-hour before and 2-hours after the study drug administration 
period, and during the 8-hour study drug administration period. The investigational team will print out 4 rhythm 
strips per hour- amounting to a total of 44 rhythm strips. This information will be included and ordered 
sequentially into the patients study’s folder. An attending cardiologist (Dr. Almasry- CoI), who is blinded to 
study drug assignment, will adjudicate all rhythm strips for determination of heart rhythm. 
Routinely collected demographic and patient related variables (e.g. date of birth, age, race, ethnicity, sex, 
height, weight, medical history, comorbidities:  type 2 diabetes, smoker; pre-existing conditions:  coronary 
artery disease, congestive heart failure, chronic kidney disease, chronic obstructive pulmonary disease; 
APACHE 3 variables:  AaDO2 or PaO2, temperature, MAP, pH arterial, heart rate, respiratory rate, sodium 
(serum), potassium (serum), creatinine, hematocrit, white blood cell count, Glasgow Coma Scale; date and time 
of ICU admission, admitting diagnosis, RASS score, mechanical ventilation, systolic and diastolic blood 


pressure, heart rate, date of last echocardiogram, left ejection fraction, left atrial size, concomitant medications 
(e.g. vasopressors, beta-blockers)) will be recorded from the EMR. 
 
List, 
and upload, any instruments or measurement tools used to collect data (e.g. survey, scripts, questionnaire, 
interview guide, validated instrument, data collection form).   
 
10.2 
Describe any source records that will be used to collect data about subjects (e.g. school records, electronic 
medical records) and include the date range for records that will be accessed. 
Electronic medical records will be used to collect demographic information, patient related variables (e.g. date 
of birth, age, race, ethnicity, sex, height, weight, medical history, comorbidities:  type 2 diabetes, smoker; pre-
existing conditions:  coronary artery disease, congestive heart failure, chronic kidney disease, chronic 
obstructive pulmonary disease; APACHE 3 variables:  AaDO2 or PaO2, temperature, MAP, pH arterial, heart 
rate, respiratory rate, sodium (serum), potassium (serum), creatinine, hematocrit, white blood cell count, 
Glasgow Coma Scale; date and time of ICU admission, admitting diagnosis, RASS score, mechanical 
ventilation, systolic and diastolic blood pressure, heart rate, date of last echocardiogram, left ejection fraction, 
left atrial size, concomitant medications (e.g. vasopressors, beta-blockers)) will be recorded from the EMR. 
 
Additionally, heart rate (HR) will be calculated from 6-second rhythm strips obtained every 15-minutes. Heart 
rate will be recorded 1-hour prior to the study drug administration, during the 8-hours of the study drug infusion 
and for 2-hours post cessation of the study drug infusion (a total of 44 rhythm strips). An attending cardiologist 
(Dr. Almasry- CoI), who is blinded to study drug assignment, will adjudicate all rhythm strips for determination 
of heart rhythm. 
 
10.3 
Indicate whether or not the results for individual subjects, such as results of investigational diagnostic tests, 
genetic tests, or incidental findings will be shared with subjects or others (e.g., the subject’s primary care physician) and 
if so, describe how these will be shared. 
 
Not applicable as no results will be shared during the course of the study. 
 
10.4 
Indicate whether or not generalized study results will be shared with subjects or others, and if so, describe how 
these will be shared. 
We plan to disseminate study results in a published manuscript.  
 
11.0 Study Timelines 
11.1 
Describe the anticipated duration of the study needed to enroll all study subjects. 
It is expected to take approximately 3 months to enroll all study subjects. 
 
11.2 
Describe the duration of an individual subject’s participation in the study. Include length of study visits, and 
overall study follow-up time. 
The duration of an individual subject’s participation in the study will be approximately 11-hours. This is to 
ensure the collection of heart rate data which will be recorded for 1-hour prior to the study drug administration, 
for 8-hours during the study drug infusion, and for 2-hours post cessation of the study drug infusion. 


 
11.3 
Describe the estimated duration for the investigators to complete this study (i.e. all data is collected and all 
analyses have been completed). 
Full study completion is expected within 6 months.  
 
12.0 Research Setting 
12.1 
Describe all facilities/sites/locations where you will be screening and conducting research procedures.  
Include a description of the security and privacy of the facilities (e.g. locked facility, limited access, privacy 
barriers).  Facility, department, and type of room are relevant.  Do not abbreviate facility names.   
Example: “A classroom setting in the Department of Psychology equipped with a computer with relevant 
survey administration software,” “The angiogram suite at Stony Brook University Hospital, a fully 
accredited tertiary care institution within New York State with badge access,” 
Adult Intensive Care Units and ICRs at SBU Hospital are secure and private facilities within the hospital.  
 
12.2 
For research procedures being conducted, for this study, external to SBU and its affiliates (e.g., in schools, 
out-of-state, internationally, etc.) describe:  
● Site-specific regulations or customs affecting the research 
● The composition and involvement of any community advisory board 
● Local scientific and ethical review structure outside the organization. 
● Local issues affecting the research and rights of research subjects.  
NOTE:  This question is not referring to multi-center research.  If this research is being conducted 
internationally, Supplemental Form C must be completed and uploaded.  
N/A 
☒ 
N/A:  This study is not conducted outside of SBU or its affiliates. 
13.0 Resources and Qualifications 
 
13.1 
The Principal Investigator (PI) must confirm, in consultation with Chair and Dean as applicable, that 
adequate resources are present to conduct and complete the study compliantly and safely. Specifically: 
☐ NO ☒YES 
 The proposed subject population(s) are available in sufficient numbers to meet the study 
requirements. 
☐ NO ☒YES 
 Sufficient funds are available to conduct and complete the study compliantly and safely. 
☐ NO ☒YES 
 The PI and study team have sufficient time to conduct and complete the study compliantly and 
safely. 
☐ NO ☒YES 
 The PI has determined that the named study team is qualified to conduct the research 
compliantly and to monitor the safety and welfare of the enrolled research subjects effectively. 


☐ NO ☒YES 
 The PI ensures that the study team is fully aware of his/her involvement in this study and the 
details of the study protocol.  
☐ NO ☒YES The PI ensures that the study teams will only be involved in research procedures for which they 
have been trained, and are currently certified and/or licensed, if required. 
 
13.2 
Describe the availability of medical or psychological resources that subjects might need as a result of 
anticipated consequences of the human research, if applicable. (e.g, “on-call availability of a counselor or 
psychologist for a study that screens subjects for depression”). 
Patients will be continuously monitored in an ICU or ICR setting, with bedside nurses and physicians 
immediately available should the need arise due to unanticipated consequences.   
13.3 
Describe your process to ensure that all study team members are updated on the progress of the 
research and the regulatory requirements (including enrolled subjects, unanticipated problems etc.)  
The study team will have regular (e.g. weekly) meetings to discuss and review any issues that may arise.  
14.0 Other Approvals 
14. 
 List approvals that will be obtained prior to commencing the research (e.g., University Hospital sign-offs 
per the UH Application, Cancer Center Scientific review, school, external site, funding agency, laboratory, 
Radiation Safety, IBC, SCRO, IACUC, RDRC). 
Investigational Pharmacy: We have already consulted with Stony Brook’s Investigational Pharmacy (Richard 
Connor, RPh). He has been extremely helpful and given us guidance on randomizing patients in the pharmacy, 
purchasing the study drug, setting up the procedures to order the study drug, and having the pharmacy prepare 
the study-drug, all of which have been incorporated into our study design. The IRB application will be sent to 
the Department of Medicine for approval as per routine. 
☐ 
N/A:  This study does not require any other approvals. 
 
15.0 Provisions to Protect the Privacy Interests of Subjects 
15.1 
Describe how you will protect subjects’ privacy interests during the course of this research and any steps 
you will take to make the subject feel at ease. 
NOTE:  Privacy refers to an individual’s desire/right to control access to or to place limits on whom they interact 
with or whom they provide personal information.  Privacy applies to the person.  Confidentiality refers to how 
data collected about individuals for the research will be protected by the researcher from release.  Confidentiality 
applies to the data.   
Examples of appropriate responses include:  “participant only meets with a study coordinator in a private office 
setting where no one can overhear”, or “the participant is reminded that they are free to refuse to answer any 
questions that they do not feel comfortable answering.”   
All meetings with participants, or their LAR, and study personnel will occur in private settings where no one 
can overhear these discussions of patient information. 


 
 
16.0 Data Management and Analysis 
 
16.1 
Describe the data analysis plan, including any statistical procedures.  This section applies to both 
quantitative and qualitative analysis.  
All statistical procedures/analyses will be performed by the trial’s biostatistician using SAS 9.4 (SAS Institute 
Inc., Cary, NC).  
Randomization: Randomization lists will be generated by the study’s statistician using block randomization 
with random permuted block sizes of 2 and 4 will be used to ensure a similar number of patients in each group 
over time.  Patients will be stratified at randomization on 2 factors (mechanically ventilated yes/no, receiving an 
inotropic agent, i.e. dopamine, dobutamine, epinephrine, or milrinone yes/no). From these 4 randomization lists 
4 sets of sealed envelopes will be created with randomization assignments to maintain allocation concealment, 
and the Investigational Pharmacy will store and open these sealed envelopes consecutively to randomize each 
patient.  All eligible patients who are consented, randomized, and received the treatment/placebo will be 
included in the analyses, consistent with a modified intent-to-treat (mITT) principle. 
Data management:  
Collection of CRF documents and rhythm strips values will occur on paper forms as source documents. These 
documents will be stored in a locked office and the transferred/matched/merged to the electronic data capture 
system (Redcap) for complete record storage.  
Sample size/Power Calculation:  
Based on prior clinical experience, we anticipate the average heart rate in the Standard of Care treatment 
(placebo) will be higher (mean ventricular rate of about 100 bpm), with more relative variability (standard 
deviation of 20).  We believe the Dexmedetomidine group will have a lower average heart (mean ventricular 
heart rate of about 85 bmp) with less variability (standard deviation of 15). Because of the uncertainty in these 
estimates, a range of power estimations were calculated by using a target goal of 60 participants (30 per group) 
[see table below].  The power estimations were carried out using PASS 12 Software (Kaysville, Utah).  Using a 
two sample t-test allowing for unequal variance, and a range of standard deviations, we will have between 
81.5% - 99.4% power to detect a difference between the two groups.  
 
 
Numeric Results for Two-Sample T-Test Allowing Unequal Variance 
Alternative Hypothesis: H1: δ = μ1 - μ2 ≠ 0 
Power 
N1 
N2 
N 
δ 
σ1 
σ2 
Alpha 
0.99395 
30 
30 
60 
15 
15 
10 
0.05 
0.96771 
30 
30 
60 
15 
15 
15 
0.05 
0.89745 
30 
30 
60 
15 
15 
20 
0.05 
0.94849 
30 
30 
60 
15 
20 
10 
0.05 
0.89745 
30 
30 
60 
15 
20 
15 
0.05 
0.81497 
30 
30 
60 
15 
20 
20 
0.05 
 


Primary Endpoints:  
The primary end point will be the difference in mean ventricular heart rate between the Dexmedetomidine plus 
SOC arm compared to the placebo plus SOC arm during the last 4-hours of study drug administration. Each 
individual will have a total of 16 mean ventricular heart rate measures taken during the last 4-hours of study 
drug administration. These measures will be averaged for each person. Using this measure, the two groups will 
be compared using independent t-tests.  
  
To further understand variability in heart rate between the two groups, a 
standard deviation will be calculated for each individual’s 16 measurements. 
Multivariable linear regression will be used to model the outcome of SD, with 
the primary predictor of randomization group. We will control for the subject’s 
mean value in this analysis. These analyses will be performed at the p ≤ 0.05 
level. 
 
Key Secondary Endpoints: 
Time to heart rate control (HR <100 bpm) in the Dexmedetomidine plus SOC arm vs.  Placebo plus SOC arm 
will be analyzed using an exact stratified log-rank test (i.e., a time to event survival analysis). An exploratory 
analysis, cox’s proportional hazard model may be used to compare time to event after adjusting possible 
confounding factors that might be imbalanced between the two groups.  
 
Percentage of rhythm strips with heart rate <100 bpm (last 4-hours) and 
percentage of rhythm strips with conversion to sinus rhythm  (last 4-hours) 
will be calculated for each individual.  Wilcoxon Rank Sum tests will be used to 
assess differences in these two outcomes between the two study groups. 
Secondary analyses will be performed at the p ≤ 0.025 level.   
 
 
 
16.2 
If applicable, provide a power analysis.   
NOTE:  This may not apply to certain types of studies, including chart/records reviews, survey studies, or 
observational studies.  This question is asked to elicit whether the investigator has an adequate sample size to 
achieve the study objectives and justify a conclusion.  
Please see above. 
 
17.0 Confidentiality 
   A. Confidentiality/Security of Study Data 
Describe the local procedures for maintenance of security and confidentiality of study data and any records that 
will be reviewed for data collection.   
17.1 
Where and how will all data and records be stored?  Include information about:  password protection, 
encryption, physical controls, authorization of access, certificates of confidentiality, and separation of identifiers 
and data, as applicable.  Include physical (e.g. paper) and electronic files. 
All paper study documents will be stored in a locked room, e.g. the research coordinators office. 


We will use a Stony Brook SBMIT RedcAP database to store study data.  Only study personnel will have log in access to 
this study specific RedcAP database. Additional study data, e.g. Master Log, will be stored on a study specific folder 
created by SBMIT on the “w” drive of the Department of Anesthesiology, and similar to all our other studies only study 
personnel will have access (granted by SBMIT) to this study specific folder. 
 
17.2 
How long will the data be stored? 
Data will be stored for 6 years. 
17.3 
Who will have access to the data? 
Only study personnel will have access to the data. All study personnel will provide evidence of their appropriate CITI 
training certifications. 
17.4 
Who is responsible for receipt or transmission of the data? 
Not applicable for this study. 
 
17.5 
How will the data be transported/transmitted? 
Not applicable for this study. 
 
B. Confidentiality of Study Specimens 
Describe the local procedures for maintenance of confidentiality of study specimens.   
☒ 
N/A:  No specimens will be collected or analyzed in this research.   
(Skip to Section 18.0) 
17.6 
Where and how will all specimens be stored?  Include information about:  physical controls, 
authorization of access, and labeling of specimens, as applicable.   
Response: N/A 
17.7 
How long will the specimens be stored? 
Response: N/A 
17.8 
Who will have access to the specimens? 
Response: N/A 
17.9 
Who is responsible for receipt or transmission of the specimens? 
Response: N/A 
17.10 How will the specimens be transported? 
Response: N/A 
 
18.0 Provisions to Monitor the Data to Ensure the Safety of Subjects  


☐ 
N/A:  This study is not enrolling subjects OR is limited to records review procedures only OR is a minimal risk 
study 
18.1 
Describe the plan to evaluate the data periodically regarding both harms and benefits to determine 
whether subjects remain safe. The plan might include establishing a data safety monitoring committee and a 
plan for reporting data monitoring committee findings to the IRB and the sponsor. 
The study’s PI and its Independent Safety Monitor (see below) will review all Safety Endpoints (see below) and study 
related AEs on an ongoing basis. Given the extensive use and knowledge of this drug (approved by FDA in 1999) and the 
short duration of exposure (only 8 hours), the lack of bolus dosing, and the provision to lower the dose if needed, we 
believe this is an appropriate strategy. 
18.2 
Describe what data are reviewed, including safety data, untoward events, and efficacy data. 
Safety Endpoints: 
1) Percentage of patients requiring pausing or discontinuation of study drug. 
2) Episodes of hypotension defined as two consecutive values of SBP <90 mm Hg requiring  
    intervention. 
3) Episodes of bradycardia requiring cessation of infusion (persistent heart rate <50 bpm). 
4) Any study related AEs. 
18.3 
Describe any primary or secondary safety endpoints. 
Safety Endpoints: 
1) Percentage of patients requiring pausing or discontinuation of study drug. 
2) Episodes of hypotension defined as two consecutive values of SBP <90 mm Hg requiring  
    intervention. 
3) Episodes of bradycardia requiring cessation of infusion (persistent heart rate <50 bpm). 
4) Any study related AEs. 
18.4 
Describe how the safety information will be collected (e.g., with case report forms, at study visits, by 
telephone calls with participants). 
Case Report Forms with data entered into a RedcAP database. 
 
 
18.5 
Describe the frequency of safety data collection, including when safety data collection starts. 
Safety data collection starts after initiation of study drug since there is no risk related to study procedures, e.g. printing out 
baseline rhythm strips, that occur before this time. 
18.6 
Describe who will review the safety data. 
The PI  and Dr. Aaron Sasson, an attending physician at Stony Brook and its Chief of Surgical Oncology, who will 
independently review and monitor the data for safety and will review all serious adverse events that may be related to the 
study on an ongoing basis. 
18.7 
Describe the frequency or periodicity of review of cumulative safety data. 
The study’s PI and Independent Safety Monitor will review all Safety Endpoints (see below) and study related AEs on an 
ongoing basis and at least on a monthly basis. 
18.8 
Describe the statistical tests for analyzing the safety data to determine whether harm is occurring. 
Given the small size of this pilot study (only 30 subjects per arm) there are no formal test for analyzing the safety data 
consistent with most clinical trials of this size. 


18.9 
Describe any conditions that trigger an immediate suspension of the research. 
No specific conditions. 
19.0 Withdrawal of Subjects 
☐ 
N/A:  This study is not enrolling subjects.  This section does not apply. 
19.1 
Describe anticipated circumstances under which subjects may be withdrawn from the research without 
their consent. 
Before a subject is randomized if they are no longer in AF then we will screen fail them. If the patients do not tolerate the 
study drug, we have procedures to pause it and if necessary, terminate the study drug infusion. 
]19.2 
Describe any procedures for orderly termination.   
NOTE:  Examples may include return of study drug, exit interview with clinician.  Include whether additional 
follow up is recommended for safety reasons for physical or emotional health. 
Response: N/A 
19.3 
Describe procedures that will be followed when subjects withdraw from the research, including retention 
of already collected data, and partial withdrawal from procedures with continued data collection, as applicable. 
Response: As there is nothing sensitive collected in this study, we will continue to confidentially store the available study 
data until the study is concluded, and all data are destroyed per Stony Brook IRB guidelines on maintenance of study 
records.  
19.4 
Describe what will happen to data already collected.  
Response: We will continue to confidentially store the available study data until the study is concluded, and all data are 
destroyed. 
 
 
20.0 Risks to Subjects 
20.1 In your opinion, what is the overall risk (physical and nonphysical) to research subjects in this study 
(minimal, greater than minimal or unknown)  
More than minimal risk. 
20.2 Describe if any subjects are withdrawn from therapeutic procedures or drugs (e.g., washout periods) prior 
to, or during, their participation in the study.   
N/A 
20.3 List the reasonably foreseeable risks, discomforts, hazards, or inconveniences to the subjects related to their 
participation in the research. Consider physical, psychological, social, legal, and economic risks.  Include a 
description of the probability, magnitude, duration, and reversibility of the risks.  
NOTE:  Breach of confidentiality is always a risk for identifiable subject data. 


The table found below is part of the original FDA labeling document for Dexmedetomidine HCl describing the adverse 
reactions associated with the drug: 
                                 
 
The following table is part of the 2016 FDA labeling for Dexmedetomidine HCL which includes postmarketing adverse 
reactions: 


                                                
 
We consider the first table to be more applicable to the study that we have designed given the dosing algorithm that we 
have created, the absence of a bolus or loading dose, and the reduced timeframe of the study drug infusion (far shorter 
than the infusion timeframe of 15.9 hours seen in the latter table of adverse effects).  
Dexmedetomidine, approved by the FDA in 1999, is used commonly in the ICU setting. The most common side effects 
associated with Dexmedetomidine use (>2%) are hypotension, bradycardia, and dry mouth1. For that reason, 
Dexmedetomidine should only be administered to patients who are in a continuously monitored setting such as in an 
intensive care unit. Treatment of hypotension and bradycardia may necessitate decreasing or stopping the 
Dexmedetomidine infusion, intravenous fluid administration, and the use of pressors. The intravenous administration of 
anticholinergic agents (e.g. glycopyrrolate or atropine) can also be administered to modify vagal tone.  
To test the maximum safely tolerated dose of Dexmedetomidine, a study used doses 13 times greater than the upper limit 
of Dexmedetomidine’s therapeutic range. In this case, the most significant effects were seen in two patients who received 
the highest doses of Dexmedetomidine. The first patient presented first-degree atrioventricular (AV) block- which showed 
no hemodynamics compromise- while the other patient presented a second-degree heart block- which was resolved in one 
minute2.  Within this same study, it was noted that giving patients twice the recommended loading dose of 


Dexmedetomidine (2µg/kg/hr for the first 10 minutes) did not present any adverse symptoms for the majority of subjects 
in the Dexmedetomidine cohort. However, two of the patients did experience bradycardia and hypotension.  
Other researchers have determined the importance of avoiding the initial bolus/ loading dose of Dexmedetomidine. 
Notably when Jakob et al. avoided the provision of a loading dose and did not exceed the 1.5µg/kg/hr dose of 
Dexmedetomidine, SAEs were seen in equivalent frequencies when comparing the SOC and the Dexmedetomidine 
cohorts1. Therefore, many clinicians support the implementation of this safety administration measure, which ensures a 
reduction in bradycardia and hypotension Dexmedetomidine-associated SAEs3.  
Transient hypertension has been occasionally described, primarily during the loading dose.  Owing to the peripheral 
vasoconstrictive effects of Dexmedetomidine. Treatment of the transient hypertension has generally not been necessary in 
studies, although reduction of the loading infusion rate may be considered. 
Dexmedetomidine does not cause bradypnea the way Propofol, benzodiazepines or opiates do. It however, can cause 
decreases in respiratory rate as part of its sympatholytic/anxiolytic mechanism of action. As such, Precedex is used 
frequently and safely used in non-intubated patients in conjunction with benzodiazepines without concern for respiratory 
compromise4-20. 
Rare side effects that have been reported with infusions > than 24 hrs include ARDS, respiratory failure, agitation, sinus 
arrest and death.  Bradycardia and hypotension are more frequently observed in patients with high vagal tone, or those 
receiving prolonged infusions, with high doses and with bolus administration. 
Dexmedetomidine infusion in this study will run for only 8 hrs and be well within the FDA’s recommended 24 hrs 
infusion limit. The maximum dosage in this study will be 1µg/kg/hr, which is significantly less than the 1.5µg/kg/hr 
infusion maximum allowed by standard dosing regimens. No bolus will be given in this study to further decrease the risks 
of hypotension. Blood pressures will be checked manually every 15 minutes non-invasively or continuously in patients 
who have arterial catheters. 
 
References:  
1. 
Jakob SM, Ruokonen E, Grounds RM, et al. Dexmedetomidine vs midazolam or propofol for sedation 
during prolonged mechanical ventilation: two randomized controlled trials. Jama. 2012;307(11):1151-
1160. 
2. 
Research CfDEa. Precedex Approval Package. 2010. 
3. 
Dasta JF, Kane-Gill SL, Durtschi AJ. Comparing dexmedetomidine prescribing patterns and safety in 
the naturalistic setting versus published data. The Annals of pharmacotherapy. 2004;38(7-8):1130-1135. 
4. 
Herr DL, Sum-Ping ST, England M. ICU sedation after coronary artery bypass graft surgery: 
dexmedetomidine-based versus propofol-based sedation regimens. Journal of cardiothoracic and 
vascular anesthesia. 2003;17(5):576-584. 
5. 
Ren J, Zhang H, Huang L, Liu Y, Liu F, Dong Z. Protective effect of dexmedetomidine in coronary 
artery bypass grafting surgery. Experimental and therapeutic medicine. 2013;6(2):497-502. 
6. 
Zientara A, Mariotti S, Matter-Ensner S, et al. Fast-Track Management in Off-Pump Coronary Artery 
Bypass Grafting: Dexmedetomidine Provides Rapid Extubation and Effective Pain Modulation. The 
Thoracic and cardiovascular surgeon. 2018. 
7. 
Ostermann ME, Keenan SP, Seiferling RA, Sibbald WJ. Sedation in the intensive care unit: a systematic 
review. Jama. 2000;283(11):1451-1459. 
8. 
MD CVZ. Fibrilación auricular: -Guías Clínicas. Fisterra. http://www.fisterra.com/guias2/fa.asp. 
Published 2009. Accessed. 
9. 
Testa LD, Tobias JD. Pharmacologic drugs for controlled hypotension. J Clin Anesth. 1995;7(4):326-
337. 
10. 
Zhang YH, Zhu J, Song YC. Suppressing sympathetic activation with clonidine on ventricular 
arrhythmias in congestive heart failure. International journal of cardiology. 1998;65(3):233-238. 


11. 
Virtanen R, Savola JM, Saano V, Nyman L. Characterization of the selectivity, specificity and potency 
of medetomidine as an alpha 2-adrenoceptor agonist. European journal of pharmacology. 1988;150(1-
2):9-14. 
12. 
Khalil MA, Abdel Azeem MS. The impact of dexmedetomidine infusion in sparing morphine 
consumption in off-pump coronary artery bypass grafting. Seminars in cardiothoracic and vascular 
anesthesia. 2013;17(1):66-71. 
13. 
Tsujikawa S, Ikeshita K. Low-dose dexmedetomidine provides hemodynamics stabilization during 
emergence and recovery from general anesthesia in patients undergoing carotid endarterectomy: a 
randomized double-blind, placebo-controlled trial. Journal of anesthesia. 2019;33(2):266-272. 
14. 
Ederle J, Dobson J, Featherstone RL, et al. Carotid artery stenting compared with endarterectomy in 
patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of 
a randomised controlled trial. Lancet (London, England). 2010;375(9719):985-997. 
15. 
Stoneham MD, Thompson JP. Arterial pressure management and carotid endarterectomy. British journal 
of anaesthesia. 2009;102(4):442-452. 
16. 
Gertler R, Brown HC, Mitchell DH, Silvius EN. Dexmedetomidine: a novel sedative-analgesic agent. 
Proceedings (Baylor University Medical Center). 2001;14(1):13-21. 
17. 
Talke P, Chen R, Thomas B, et al. The hemodynamic and adrenergic effects of perioperative 
dexmedetomidine infusion after vascular surgery. Anesthesia and analgesia. 2000;90(4):834-839. 
18. 
Guler G, Akin A, Tosun Z, Eskitascoglu E, Mizrak A, Boyaci A. Single-dose dexmedetomidine 
attenuates airway and circulatory reflexes during extubation. Acta anaesthesiologica Scandinavica. 
2005;49(8):1088-1091. 
19. 
Tufanogullari B, White PF, Peixoto MP, et al. Dexmedetomidine infusion during laparoscopic bariatric 
surgery: the effect on recovery outcome variables. Anesthesia and analgesia. 2008;106(6):1741-1748. 
20. 
McCutcheon CA, Orme RM, Scott DA, Davies MJ, McGlade DP. A comparison of dexmedetomidine 
versus conventional therapy for sedation and hemodynamic control during carotid endarterectomy 
performed under regional anesthesia. Anesthesia and analgesia. 2006;102(3):668-675. 
 
 
20.4 Describe procedures performed to minimize the probability or magnitude of risks, including procedures 
being performed to monitor subjects for safety. 
There are numerous procedures to minimize risks to study subjects including: 
1) The Investigational Pharmacy will prepare the study drug, and an order for the study drug will be entered into the 
Electronic Medical Record (EMR) as a Therapeutic Non-Formulary (TNF) per Stony Brook’s Investigational Pharmacy’s 
standard operating procedure.  The patient’s nurse will scan the medication using the hospital’s routine bar code 
technology. 
2) We will not bolus study drug, which is most associated with adverse events with this drug.  
3) Heart rate is already continuously monitored in ICU and ICR patients. Per the study protocol blood pressure will be 
measured every 15 minutes during study drug administration either by an indwelling arterial catheter (placed for routine 
care) or non-invasively by cuff. 
4) If HR is < 50 bpm, SBP < 80 mm Hg, or RASS< -2 for non-intubated patients, or the patients shows significant 
evidence of decompensation, the study drug infusion will be  paused for 1 hour, and then restarted at half the dose (i.e. 0.5 
µg/kg/hr) if none of the pausing criteria still exist.   
5) We will only enroll patients who are already in an ICU where there is immediate availability of supportive care.  
6) We will monitor pre-specified Safety Endpoints on an ongoing basis: 
Safety Endpoints: 


1) Percentage of patients requiring pausing or discontinuation of study drug. 
2) Episodes of hypotension defined as two consecutive values of SBP <90 mm Hg requiring  
    intervention. 
3) Episodes of bradycardia requiring cessation of infusion (persistent heart rate <50 bpm). 
4) Any study related AEs. 
 
 
20.5 If applicable, indicate which procedures may have risks to the subjects that are currently unforeseeable. 
Administration of study drug (Dexmedetomidine) may have other (ie unforeseen) risks. 
20.6 Indicate which research procedures, if any, may have risks to an embryo or fetus should the subject be or 
become pregnant. 
 
☒ 
N/A 
 
20.7 If you responded to 20.6 that there are such risks, how will you minimize the risk of a pregnancy occurring 
during the course of the study?  (Select all that apply) 
 
☐ 
Counseling on birth control and /or abstinence 
☐ 
Pregnancy test during the study 
☐ 
Pregnancy test prior to initiation of the study 
☐ 
Other   _____ 
☒ 
N/A    
20.8 If applicable, describe possible risks to others who are not subjects. 
N/A 
 
21.0 Potential Benefits to Subjects 
21.1 
Describe the potential benefits that individual subjects may experience by taking part in the research.  
Include the probability, magnitude, and duration of the potential benefits.   
The potential benefit of Dexmedetomidine use in patients with rapid-AF is better and faster heart rate control.  
 
21.2 
Indicate if there is no direct benefit.   
NOTE:  Compensation cannot be stated as a benefit. 
 
Indicate if there is a potential benefit to others, future science or society.    
There is a need for improved methods of heart rate control in patients with rapid-AF so learning if Dexmedetomidine is 
usefull for this could potentially benefit others. 


 
22.0 Compensation for Research-Related Injury 
☐ 
N/A:  The research procedures for this study do not present risk of research related injury. This section does not 
apply.   
22.1 
If the research procedures carry a risk of research related injury, describe the available compensation to 
subjects in the event that such injury should occur.   
None per standard Stony Brook approved IRB approved investigator initiated research. 
 
22.2 
Provide a copy of contract language, if any, relevant to compensation for research related injury. 
NOTE:  If the contract is not yet approved at the time of this submission, submit the current version here.  If the 
contract is later approved with different language regarding research related injury, you must modify your 
response here and submit an amendment to the IRB for review and approval. 
N/A 
23.0 Economic Burden to Subjects 
23.1 
Describe any costs that subjects may be responsible for because of participation in the research.   
NOTE:  Some examples include transportation or parking. 
There are no additional financial costs to the subject. The study team will pay for the study drug.  
☐ 
N/A:  This study is not enrolling subjects, or is limited to records review procedures only.  This section does not 
apply. 
24.0 Compensation for Participation 
☒ 
N/A:  There is no compensation for participation.  This section does not apply.  
24.1 
Describe the amount/nature and timing/scheduling of any compensation to subjects, including 
monetary, course credit, or gift card compensation. Describe any prorated payments based on participation. 
N/A 
24.2 
Justify the amount and scheduling of payments described above to ensure that they are reasonable and 
commensurate with the expected contributions of the participant. If multiple visits are involved payments should 
be prorated. 
Note: If using West Campus Departmental pools, participation in studies may be offered for credit in class but 
students MUST be given other options for fulfilling the research component that are comparable in terms of time, 
effort, and education benefit.  Please list alternative activities 
N/A 
25.0 Informed Consent 
25.1   
Will you be obtaining consent from subjects?   


☒ 
Yes 
(If yes, Provide responses to each question in this Section, and upload your consent documents 
where indicated in the electronic submission system) 
☐ 
No 
(If no, Skip to next section) 
25.2 
Describe how the capacity to consent will be assessed for all subjects. Review for guidance 
http://research.stonybrook.edu/human-subjects-standard-operating-procedures/determining-potential-adult-
subjects-ability-consent: 
We will be enrolling patients who have capacity to consent as evidenced by their ability to provide consent for routine 
medical care in the ICU and in the ICR and knowledge that the subject understands the following: 1) that the activity is 
research, not standard treatment, 2) the risks and benefits of a study, 3) the alternatives that are available if s/he does not 
participate; and 4) that, if s/he chooses not to participate, this decision will be accepted without penalty, i.e., without 
jeopardizing clinical care.  
In addition, consistent with most ICU studies, we will also enroll patients without capacity to consent through their 
Legally Authorized Representative.  
 
25.3 
Describe the consent process that will be conducted to ensure that subject is fully informed regarding 
study details and subject rights. Include where the consent process will take place, with consideration of the need 
to protect the subject’s right to privacy.  
The study will be discussed in a private setting or in the patient’s hospital room. Subjects (or their LAR) will be provided 
with enough time to have their questions answered, and discuss the study with family members if appropriate.  
25.4 
Describe how you will ensure that subjects are provided with sufficient time to consider taking part in the 
research study.  Detail if there is there any time period expected between informing the prospective subject and 
obtaining the consent.   
NOTE:  It is respectful to the prospective subject to ensure that sufficient time is given to have their questions 
answered and to consider their participation 
Same as above. 
25.5 
Describe the process to ensure ongoing consent, defined as a subject’s willingness to continue 
participation for the duration of the research study.   
If a subject (or LAR) voices any concern about continued participation in the study, they will be reminded that they have 
the ability to withdraw from the study.  
Non-English Speaking Subjects  
☒ 
N/A:  This study will not enroll Non-English speaking subjects.   
 
25.6 
Indicate which language(s) other than English are likely to be spoken/understood by your prospective 
study population or their legally authorized representatives. 
 N/A 
25.7 
If subjects who do not speak English will be enrolled, describe the process to consent the subjects, as well 
as the process to be used to ensure their understanding of research procedures throughout the conduct of the 
study. Review SOP’s section 17.8 for important policies in this regard: http://research.stonybrook.edu/human-


subjects-standard-operating-procedures/policy-non-english-speakers-research-subjects for SBU policy on 
inclusion of non-English speakers.  
N/A 
Adults Unable to Consent  
☐ 
N/A:  This study will not enroll adults unable to consent.  
 
25.8 
Justify why it is necessary to include adult subjects who are unable to consent. 
Consistent with most ICU studies, we will also enroll patients without capacity to consent through their Legally 
Authorized Representative. This is necessary since many patients in the ICU do not have capacity to consent so studies in 
ICU patients cannot be practically done without the option for using an LAR approach. 
25.9 
Describe how you will identify Legally Authorized Representatives (LAR) for the subjects that will be 
consistent with the NYS Family Health Care Decisions Act (FHCDA; see http://research.stonybrook.edu/human-
subjects-standard-operating-procedures/definitions-2).  Indicate why it is necessary to include subjects who are 
unable to consent. 
Note:  For research conducted outside of New York State, provide information that describes which individuals 
are authorized under applicable law to consent on behalf of a prospective subject to their participation in the 
research.   
We will confirm through review of the medical chart and discussion with medical staff who the subjects LAR is. 
Consistent with most ICU studies, we will enroll patients without capacity to consent through this LAR. This is necessary 
since many patients in the ICU do not have capacity to consent so studies in ICU patients cannot be practically done 
without the option for using an LAR approach. 
25.10 Describe the process for obtaining assent from the adult subjects 
Indicate whether assent will be obtained from all, some, or none of the subjects.  If some, indicate which adults 
will be required to assent and which will not. 
No assent will be obtained. 
If assent will not be obtained from some or all subjects, provide an explanation of why not. 
Assent is usually not required for ICU studies in patients who lack capacity due to the affects of critical illness and/or 
ongoing sedation. 
25.11 Describe whether assent of the adult subjects will be documented and the process to document assent.   
Response: N/A 
25.12 Describe how you will obtain consent from a subject to use their data if they later become capable of 
consent.  How will competence be assessed and by whom?  
Given the short duration of this study (less than 12 hours), we do not see how a patient without capacity is likely to 
develop capacity during this short period. 
26.0 Waiver or Alteration of Consent Process 
Complete this section if: 


● Informed consent will not be obtained at all 
● Informed consent will be obtained, but not documented, or 
● consent will be obtained, but not all required information will be disclosed (e.g., in deception research) 
☒ N/A:  A waiver or alteration of consent is not being requested. 
 
26.1 
Review, complete, and upload SUPPLEMENTAL FORM G: Consent Waivers  
☐  
 Confirmed 
26.2 
If the research involves a waiver of the consent process for planned emergency research, please contact 
the Office of Research Compliance for guidance regarding assistance in complying with federal regulations 
governing this activity (see: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=50.24)  
 
27.0 Multi-Site Research (Multisite/Multicenter Only) 
☒ N/A:  This study is not a multi-site study.  This section does not apply. 
27.1 
If this is a multi-site study where SBU is the lead site and/or the IRB of record, describe the processes to 
ensure communication among sites. Include:  
● All sites have the most current version of the IRB documents, including the protocol, consent document, 
and HIPAA authorization. 
● All required approvals have been obtained at each site (including approval by the site’s IRB of record). 
● All modifications have been communicated to sites, and approved (including approval by the site’s IRB of 
record) before the modification is implemented. 
● All engaged participating sites will safeguard data as required by local information security policies. 
● All local site investigators conduct the study appropriately. 
● All non-compliance with the study protocol or applicable requirements will be reported in accordance 
with local policy. 
N/A 
27.2 
Describe the method for communicating to engaged participating sites: 
● Problems 
● Interim results 
● Study closure 
N/A 
27.3 
Indicate and statistically justify the total number of subjects that will be enrolled or records that will be 
reviewed across all sites. 
N/A 
 
28.0 Banking Data or Specimens for Future Unspecified Use 
☒ 
N/A:  This study is not storing data or specimens for research outside the scope of the present protocol.  
This section does not apply. 


IMPORTANT: If you are proposing to bank specimens for future use, you may be subject to licensure 
requirements under the NYS Department of Health, and must be covered under the SBU license. See SOPs at 
http://research.stonybrook.edu/human-subjects-standard-operating-procedures/data-tissue-registries-banks 
28.1 
If data will be banked for research outside of the scope of the present protocol, describe where the data 
will be stored, how long they will be stored, how will they be accessed, and who will have access to the data  
NOTE:  Your response here must be consistent with the information provided to subjects in your Consent 
Documents  
N/A 
28.2 
If specimens will be banked (stored) for research outside of the scope of the present protocol, describe 
where the specimens will be stored, how long they will be stored, identifiers that will be associated with each 
specimen, how will they be accessed, and who will have access to the specimens  
NOTE:  Your response here must be consistent with the information provided to subjects in your Consent 
Documents 
N/A 
28.3 
Describe the procedures to release banked data and/or specimens for future uses, including: the process 
to request a release, approvals required for release, who can obtain data or specimens, and the data to be 
provided with specimens. 
N/A 
29.0 Drugs and Devices 
☐ 
N/A:  This study does not involve drugs or devices.  This section does not apply. 
29.1 
Does this study involve use of radiopharmaceuticals? ☐ Yes  ☒ No 
29.2 
For investigational devices (including marketed devices being used off label), Provide the following 
information below: 
Where will the device(s) be stored? Note that the storage area must be within an area under the PI’s control     
Describe the security of the storage unit/facility      
Provide full detail regarding how the dispensing of the device(s) will be controlled (accountability of 
removal/return of used devices, and disposition of remaining devices at the conclusion of the investigation) and 
documented (accounting records/logs)    
The Investigational Pharmacy will store, prepare, and dispense the study drug using their routine procedures. Per FDA 
guidance our study meets all criteria for IND exemption. 
29.3 
For investigational drugs (including humanitarian use devices, and marketed drugs being used off label), 
will the services of the Investigational Drug Pharmacy be used for storage, dispensing, accounting the drug 
(required for research conducted at UH, HSC, Cancer Center, and Ambulatory Surgery Center)?  
☒  
Yes   
☐ 
No →PI Provide the following information below:  


● Where will the drugs/biologics be stored? Note that the storage area must be within an area under the 
PI’s control       
● Describe the security of the storage unit/facility:       
● Provide full detail regarding dispensing of the drugs(s), how labeled, controlled (accountability, 
disposition of unused drug at the conclusion of the investigation)  and documented (accounting 
records/logs):        
N/A 
 
 
30.0 Sharing of Results with Subjects    
30.1 
Describe whether results (study results or individual subject results, such as results of investigational 
diagnostic tests, genetic tests, or incidental findings) will be shared with subjects or others (e.g., the subject’s 
primary care physicians) and if so, describe how it will be shared.