Randomized Controlled Trial of Inferior Vena Cava Ultrasonography in the Management and Disposition of Pediatric Patients Undergoing Evaluation for Sepsis and Dehydration
Phase: NA
Conditions: Sepsis, Gastroenteritis, Dehydration
Sponsor: Icahn School of Medicine at Mount Sinai

Randomized Controlled Trial of Inferior Vena Cava Ultrasonography in the 
Management and Disposition of Pediatric Patients Undergoing Evaluation 
for Sepsis and Dehydration
PI: Dr. James Tsung
NCT02568189
Document Date: 5-26-2015

Protocol Name: 
Randomized Controlled Trial of Inferior Vena Cava 
Ultrasonography in the Management and Disposition of 
Pediatric Patients Undergoing Evaluation for Sepsis and 
Dehydration   
Principal Investigator: 
Elizabeth Haines 
516-946-9742
ejhaines@gmail.com or elizabeth.haines@mssm.edu
Primary Contact 
Name/Contact Info: 
Elizabeth Haines 
516-946-9742
Date Revised: 
2/10/2015 
Study Number: 
IF1733382 
1 
Revised 11/21/11 
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Instructions: 
1. Prepare a document with the following sections. Note that, depending on the nature of your research,
certain sections below may not be applicable. Indicate N/A as appropriate, explaining where possible.
2. For any items described in the sponsor’s protocol, grant application or other source documents
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Brief Summary of Research (250-400 words): 
1) Objectives:
    The primary objective of this study is to assess the utility of early versus delayed ultrasonography 
of the inferior vena cava in pediatric patients undergoing emergency department evaluation of 
sepsis and dehydration 
2) Background
Ultrasound is a widely accepted and highly useful clinical tool.  It carries the additional advantage 
of being rapid, painless and non-radiating. It has long been used to assess cardiac output and 
vascular pathologies.  More recently emergency and trauma clinicians have been using it to assess 
hydration status, shock/sepsis states and fluid responsiveness (nguyen).   Using sonography to 
look at the inferior vena cava gives clinician a rapid view of vascular collapsibility that has been 
previously demonstrated to correlate with MAP and CVP (Sinonson/schiller, Stone/Huang). 
Previously Jones et. al. completed an RCT in adults greater than age 17 evaluating the goal 
directed utility of early versus delayed inferior vena cava sonography for patients presenting with 
non traumatic hypotension to the emergency department.  This  study found improved outcomes 
and more accuracy in diagnostic etiology of in those undergoing immediate IVC imaging.  

Protocol Name: 
Randomized Controlled Trial of Inferior Vena Cava 
Ultrasonography in the Management and Disposition of 
Pediatric Patients Undergoing Evaluation for Sepsis and 
Dehydration   
Principal Investigator: 
Elizabeth Haines 
516-946-9742
ejhaines@gmail.com or elizabeth.haines@mssm.edu
Primary Contact 
Name/Contact Info: 
Elizabeth Haines 
516-946-9742
Date Revised: 
2/10/2015 
Study Number: 
IF1733382 
2 
Revised 11/21/11 
3) Setting of the Human Research- The Emergency Department of Mount Sinai Hospital
4) Resources Available to Conduct the Human Research –
Internal resources from the Department of Emergency Medicine. 
5) Study Design – A randomized controlled trial of IVC Ultrasonography in pediatric patients 0-21
year of age.
a) Recruitment Methods
All patients, regardless of age or gender, who present to the Emergency Department who trigger triage 
STOP SEPSIS ALERT (based on triage vital signs and chief complaint), vomiting requiring zofran or 
diarrhea with concern for dehydration/hypovolemia , whom the treating physician believes would 
benefit from intravenous fluids will be eligible for inclusion into this study. The “treating physician” 
refers to one of the Pediatric Emergency Medicine attendings or fellows, all of whom are listed as co-
investigators on the application form submitted with this protocol. Only if and when a patient or 
parent expresses interest in participating in the study, the Attending or Fellow caring for the patient 
will determine if the patient is eligible.  If the patient is eligible, and has no criteria that would exclude 
them from the study, written informed consent will be obtained from the guardian and assent will be 
obtained in children > 7 years old. The patient will be enrolled in the study and randomized to either 
the immediate ultrasonography group (US of the IVC first with before the clinician fully assesses the 
patient and places rehydration orders) or the control group (Ultrasonography at 15 minutes into the 
assessment and management of the patient). 

Protocol Name: 
Randomized Controlled Trial of Inferior Vena Cava 
Ultrasonography in the Management and Disposition of 
Pediatric Patients Undergoing Evaluation for Sepsis and 
Dehydration   
Principal Investigator: 
Elizabeth Haines 
516-946-9742
ejhaines@gmail.com or elizabeth.haines@mssm.edu
Primary Contact 
Name/Contact Info: 
Elizabeth Haines 
516-946-9742
Date Revised: 
2/10/2015 
Study Number: 
IF1733382 
3 
Revised 11/21/11 
b) Inclusion and Exclusion Criteria
Inclusion criteria for enrollment in study:  
All patients, regardless of age or gender, who present to the Emergency Department who: 
A. Trigger triage STOP SEPSIS ALERT (based on triage vital signs and chief complaint)
And/OR
B. Present with vomiting requiring Zofran
And/OR
C.
Present with diarrhea with concern for dehydration/hypovolemia
whom the treating physician believes would benefit from intravenous fluids will be eligible for 
inclusion into this study.  
Exclusion criteria for enrollment in study: 
(1) Unstable patients with life-threatening injuries who require ongoing resuscitation.
(2) Patient undergoing traumatic resuscitation
c) Number of Subjects
Using the following equation to calculate sample size for proportional outcomes in randomized
controlled trials and using data from a 2012 study by Paul et. al. citing a 58% overall compliance
with PALS severe sepsis target times:
where     c is set at 7.9 for a power of 80% 
1 is current percent success rate on standard protocol
2 is the current percent success plus the anticipated treatment effect percent
We have calculated the total number of subjects in the sepsis arm to be: 82 per group or 
164 total patients for a power of 80% and a type I error set at 5% 
For the gastroenteritis and dehydration arm we have established a sample size using a the 
following power calculation for continuous (time) outcomes 

 
Protocol Name: 
Randomized Controlled Trial of Inferior Vena Cava 
Ultrasonography in the Management and Disposition of 
Pediatric Patients Undergoing Evaluation for Sepsis and 
Dehydration   
Principal Investigator:  
Elizabeth Haines 
516-946-9742  
ejhaines@gmail.com or elizabeth.haines@mssm.edu 
Primary Contact 
Name/Contact Info: 
Elizabeth Haines 
516-946-9742 
Date Revised: 
2/10/2015 
Study Number: 
IF1733382 
 
4 
Revised 11/21/11 
 
 
where     c is set at 7.9 for a power of 80%  
 
 2 is set for a 10% size treatment effect (reduction in time) 
We would need 200 subjects per group or a total of 400 patients in the gastroenteritis arm 
of the study. 
 
 
 
 
d) Study Timelines 
Currently the Mount Sinai Pediatric Emergency Department sees approximately 30,500 
patients on an annual basis.  Of this total census about 200 trigger the Stop Sepsis alert 
upon registration.  Based on this we have set the enrollment period over 12 months.  
 
Current census data predicts approximately 3000 Mount Sinai annual emergency 
department visits for vomiting and dehydration requiring antiemetic therapy. In order to 
collect a convenience sample of 400 patents and adjust for seasonal variability, the study 
period will enroll over a six month period between June 2015 and November 2015.  
 
 
e) Study Endpoints 
For the Sepsis arm endpoints include: 
Primary 
• 
Secured second vascular access point- type (IO, second IV, CV access) within 15 min of physician 
evaluation 
• 
Inotrope/Vasopressor use 
• 
Antibiotic within 60 min 

 
Protocol Name: 
Randomized Controlled Trial of Inferior Vena Cava 
Ultrasonography in the Management and Disposition of 
Pediatric Patients Undergoing Evaluation for Sepsis and 
Dehydration   
Principal Investigator:  
Elizabeth Haines 
516-946-9742  
ejhaines@gmail.com or elizabeth.haines@mssm.edu 
Primary Contact 
Name/Contact Info: 
Elizabeth Haines 
516-946-9742 
Date Revised: 
2/10/2015 
Study Number: 
IF1733382 
 
5 
Revised 11/21/11 
• 
60 ml/kg Normal Saline bolus administered within 60 minutes 
 
Secondary 
• 
Disposition- PICU, Floor, Discharge 
• 
Length of ED stay (from sepsis alert to admission/discharge order entry) 
• 
Return ED Visit for same illness 
• 
Survival to hospital discharge 
• 
30 day mortality 
• 
Left ventricular function 
• 
Source of sepsis 
 
For the Gastroenteritis/Dehydration arm endpoints include: 
Primary 
 Type of rehydration: oral versus intravenous 
 Total amount of fluids given (ml amount) 
 Total ED length of stay from triage time to disposition time (order to admit/discharge) 
 
 
 
f) Procedures Involved in the Human Research 
Allocation of patients to intervention and control arms will be accomplished by a computer generated 
randomization application Sherlock MD©.  Randomization will be separate for sepsis cohort and 
gastroenteritis cohort. Within sepsis and gastroenteritis cohorts, subjects will be stratified by disease 
severity.  Specifically they will meet criteria for severe sepsis or  meet criteria for severe dehydration 
based on standard clinical severity scoring (e.g. SIRS criteria, Clinical Dehydration Score). 
Subjects randomized to either arm will receive diagnostic imaging of the inferior vena cava with 
ultrasound. Subjects randomized to the investigational arm will undergo IVC ultrasound immediately 

 
Protocol Name: 
Randomized Controlled Trial of Inferior Vena Cava 
Ultrasonography in the Management and Disposition of 
Pediatric Patients Undergoing Evaluation for Sepsis and 
Dehydration   
Principal Investigator:  
Elizabeth Haines 
516-946-9742  
ejhaines@gmail.com or elizabeth.haines@mssm.edu 
Primary Contact 
Name/Contact Info: 
Elizabeth Haines 
516-946-9742 
Date Revised: 
2/10/2015 
Study Number: 
IF1733382 
 
6 
Revised 11/21/11 
upon arrival and clinician evaluation. Those subjects randomized to the control arm will undergo IVC 
ultrasound after a timed 15 minute delay. The IVC will be scanned in both longitudinal and transverse 
planes.  All study clinicians will undergo brief  20 minute standardized training session to review 
which images to obtain.. Still and dynamic images will be recorded and saved.    Imaging procedure 
involves a credentialed ultrasound clinician using an ultrasound machine to visualize the inferior vena 
cava in order to assess the collapsibility and respiratory variation.  This vessel is visualized by placing 
the ultrasound probe on the subxiphoid area of the abdomen using transducer gel.  Images will be 
obtained in two axes (transverse and sagittal). Images/video will be recorded and stored using a 
unique study subject number to assure that health information remains confidential and de-identified.  
Treatment and management decisions will be at the discretion of the treating clinician.  The enrolling 
clinician will be responsible for obtaining consent, randomization and completing the data collection 
forms.  As indicated by the study inclusion criteria, all participants who have triggered the electronic 
Severe Stop Sepsis notification or have clinically suspected dehydration due gastroenteritis or 
vomiting will be screened and consented by the enrolling clinician. Given the published data that 
suggests inferior vena cava ultrasound may help clinicians more effectively and efficiently treat sepsis 
and dehydration, the main objective of this study is to see if it can reliably improve outcomes as well 
as improve compliance with targeted treatment goals. We believe that clinical care of subjects who 
undergo Inferior vena cava US is unlikely to be altered in a negative way.  
 
 
 
 
g) Specimen Banking 
     Not applicable 
 
h) Data Management and Confidentiality 
During the process of data collection, patient identifiers will be collected (first and last name, MR#, 
age, birth date, date of visit.  This identifying information is necessary for US will be located on only 
1 form.  This form will be kept in a locked file cabinet in a locked office remaining on the medical 
campus of Mount Sinai Hospital at all times.   
Data forms will be kept in a secure locked file. HIPAA-sensitive Personal Health Information (PHI) 
will not be reused or disclosed to any other person or entity, except as required by regulation and law 
or for authorized oversight of the research project. 
 

 
Protocol Name: 
Randomized Controlled Trial of Inferior Vena Cava 
Ultrasonography in the Management and Disposition of 
Pediatric Patients Undergoing Evaluation for Sepsis and 
Dehydration   
Principal Investigator:  
Elizabeth Haines 
516-946-9742  
ejhaines@gmail.com or elizabeth.haines@mssm.edu 
Primary Contact 
Name/Contact Info: 
Elizabeth Haines 
516-946-9742 
Date Revised: 
2/10/2015 
Study Number: 
IF1733382 
 
7 
Revised 11/21/11 
The ultrasound images and clips are not saved in the permanent medical record in EPIC.  However, all 
images are saved in an ultrasound archive supported and secured by Mount Sinai Medical Center IT 
Department and is HIPAA compliant.  
 
 
i) Provisions to Monitor the Data to Ensure the Safety of subjects 
In order to ensure that adequate provisions are in place for monitoring the data to ensure the safety of 
subjects, ultrasound image review for quality assurance (QA) will occur weekly during the 
study.  Images will be reviewed to determine the presence or absence of total inferior vena collapse 
and presumed severe dehydration (as well as other pathology).  If the 2nd (QA) interpretation is 
positive for pathology.  The EPIC record will be reviewed to see if the patient was treated with 
appropriately given the QA read findings.   If there are any discrepancies or pathological findings 
noted on the image review, there is a procedure in place to contact patients and institute any changes 
in treatment, if necessary.  Previous studies site good interobserver agreement with a Cohen’s Kappa 
= 0.64. In accordance we anticipate that a discrepancy between ultrasound interpretations will happen 
rarely.  
 
 
A DSMB will be formed from personnel not participating in this trial. This board will include a senior 
scientist and an ethicist.  To monitor for safety problems, adverse events will be reported to the 
DSMB.  An interim data analysis is planned when study enrollment reaches (25% enrollment) 40 
patient in the sepsis arm and 100 in the gastroenteritis arm to ensure no excess rates of adverse events 
are observed in the intervention group compared with the control group. 
 
The primary responsibility of the DSMB is to ensure the safety of the patients. None of the members 
will be investigators in the study.  
 
The DSMB may meet in person or by telephone conference. Routine business may also be addressed 
via email. The work of the DSMB, however, will be conducted in complete isolation from any of the 
investigators of this study. Breaches of this confidence by any member of the DSMB that might 
impair investigator blinding will be strictly avoided.  
 
 
 
 
 
 

 
Protocol Name: 
Randomized Controlled Trial of Inferior Vena Cava 
Ultrasonography in the Management and Disposition of 
Pediatric Patients Undergoing Evaluation for Sepsis and 
Dehydration   
Principal Investigator:  
Elizabeth Haines 
516-946-9742  
ejhaines@gmail.com or elizabeth.haines@mssm.edu 
Primary Contact 
Name/Contact Info: 
Elizabeth Haines 
516-946-9742 
Date Revised: 
2/10/2015 
Study Number: 
IF1733382 
 
8 
Revised 11/21/11 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MSSM Principal Monitor:  Elizabeth Haines, DO and James Tsung, MD 
Indicate whether this person is the PI, a Team Member, or is Independent: Co PI

 
Protocol Name: 
Randomized Controlled Trial of Lung Ultrasound to Replace Chest X-Ray 
in the Emergency Department 
Principal Investigator:  
James Tsung, MD, MPH 
Primary Contact 
Name/Contact Info: 
Brittany Pardue, MD  brittanypardue@gmail.com 212-241-6272 
Date Revised: 
April 1, 2012 
Study Number: 
HS# 12-00153, GCO# 12-048(0001)(01) ED 
 
9 
Revised 11/7/11 
DSMB chair: 
 
Name: Richardson 
First Name: Lynne 
Academic Title: Associate Professor of Emergency Medicine, Vice Chair for Academic, Research, 
and Community Programs 
Department: Emergency Medicine 
Mailing Address: 
, New York, NY 10029 
Phone: 212-824-8066 
Fax: 212-426-1946 
E-mail: lynne.richardson@mssm.edu 
 
Dr, Richardson is a nationally recognized Emergency Medicine health services researcher; her areas of 
interest are access and barriers to care, and improving effective utilization of health care resources. She is 
actively involved in several NIH funded trials and holds a vast number of publications and research based 
advocacy roles. She has a commitment to patient safety and equality, she is well equipped to assess risk to 
the research subject’s health and well being.  In monitoring this study she will  
 
 Monitor for adverse outcomes, poor outcomes and subject withdraw rates 
The committee will meet to review results at when 25% enrollment has occurred  to ensure no 
excess rates of adverse events are observed in the intervention compared with the control group. 
 If excess rates of adverse events (e.g. higher frequency of unscheduled healthcare visits, longer 
length of stay, higher admission rates) are observed in the intervention compared with the control 
group, the DSMB may interrupt or alter the study design. 
 This study does not involve medications. Dose selection procedures do not apply. 
 During the process of data collection patient identifiers will be collected (first and last name, 
MR#, age, birth date, date of visit, notes regarding medication and fluid orders).  This identifying 
information is necessary for US will be located on only 1 form.  This form will be kept in a locked 
file cabinet in a locked office within Mount Sinai Hospital at all times 
 Should adverse events be noted by the oversight board a suspension of this study will occur and 
the PPHS and IRB will be fully informed immediately of such occurrence. 
 
MSSM Additional DSMB Member: 
Indicate whether this person is the PI, a Team Member, or is Independent: Independent

 
Protocol Title: 
Randomized Controlled Trial of Inferior Vena Cava 
Ultrasonography in the Management and Disposition of 
Pediatric Patients Undergoing Evaluation for Sepsis and 
Dehydration   
Principal Investigator 
Name/Contact Info:  
Elizabeth Haines 
516-946-9742 ejhaines@gmail.com or 
elizabeth.haines@mssm.edu 
Primary Contact 
Name/Contact Info 
Elizabeth Haines 
516-946-9742 
Date Revised: 
2/10/2015 
Study Number: 
IF1733382 
 
10 
Revised  9/2/14 
Last Name: Newman 
First Name: David 
Academic Title: Associate Professor of Emergency Medicine 
Department: Emergency Medicine 
Mailing Address: 1 Gustave Levy Place, Box 1620, New York, NY 10029 
Phone: 212-824-8065 
Fax: 212-426-1946 
E-mail: davidnewman@mountsimai.org 
 
 
j) Withdrawal of Subjects 
If a patient or parent expresses that they unable to tolerate the procedure, the 
ultrasound exam will be stopped immediately and the patient will be removed 
from the study.  There are no infectious risks from the use of ultrasound in this 
study. The machine will be cleaned per routine procedure after each examination.   
 
6) Risks to Subjects 
There are no known risks to ultrasound, with no reports of adverse events in over 65 
years of clinical use.  The use of ultrasound is painless by avoiding contact of the 
ultrasound probe with the body part (solely maintaining contact with the ultrasound 
gel).  The ability of patients to tolerate ultrasound without pain, is well documented in 
the literature.   
 
7) Provisions for Research Related Injury 
None 
8) Potential Benefits to Subjects 
More accurate diagnosis of dehydration and severe sepsis requiring emergent fluid 
resuscitation 
 
9) Provisions to Protect the Privacy Interests of Subjects 
Potential subjects will be approached in the privacy of the ED exam room, in which 
all personal, private, and sensitive information will be kept confidential as during any 

 
Protocol Title: 
Randomized Controlled Trial of Inferior Vena Cava 
Ultrasonography in the Management and Disposition of 
Pediatric Patients Undergoing Evaluation for Sepsis and 
Dehydration   
Principal Investigator 
Name/Contact Info:  
Elizabeth Haines 
516-946-9742 ejhaines@gmail.com or 
elizabeth.haines@mssm.edu 
Primary Contact 
Name/Contact Info 
Elizabeth Haines 
516-946-9742 
Date Revised: 
2/10/2015 
Study Number: 
IF1733382 
 
11 
Revised  9/2/14 
routine doctor-patient exchange. The subject can decline participation at any point in 
the study. 
 
 
10) 
Economic Impact on Subjects 
There is no additional cost to the patient nor to the hospital.   There is no 
charge for the performed inferior vena cava US to the patient.  
 
11) 
Payment to Subjects 
none 
12) 
Consent Process 
Consent will be obtained either from the potential participant if age 18 years or 
greater or the parent/guardian of the potential participant aged less than 18 years. 
Consent will be obtained in a private setting in the examination room of the 
Emergency Department prior to performing the ultrasound. The person providing 
consent will be allowed to consider the request free of time constraints and sense of 
obligation or white coat pressure.  They will be given the opportunity to review the 
consent document and discuss it with whomever they like.  Assent will be obtained 
for all potential participants greater than or equal to age 7 years and will be 
documented on the last page of the child consent form. 
 
13) 
Process to Document Consent in Writing 
Written consent with a paper based form will use basic language that is easy to 
understand (5th grade level.  To ensure that the subject understands, they will be asked 
to reiterate in their own words the purpose of the research, what they will need to do 
as participants in the study, and what the potential risks and alternatives are. 
 
 
14) 
Vulnerable Populations 

Protocol Title: 
Randomized Controlled Trial of Inferior Vena Cava 
Ultrasonography in the Management and Disposition of 
Pediatric Patients Undergoing Evaluation for Sepsis and 
Dehydration   
Principal Investigator 
Name/Contact Info:  
Elizabeth Haines 
516-946-9742 ejhaines@gmail.com or
elizabeth.haines@mssm.edu
Primary Contact 
Name/Contact Info 
Elizabeth Haines 
516-946-9742
Date Revised: 
2/10/2015 
Study Number: 
IF1733382 
12 
Revised  9/2/14 
The population of interest in this study includes patients < 18 years old (i.e vulnerable 
subjects).  All efforts will be made to protect these children during this study.  As 
previously listed, ultrasound emits no radiation and is a painless procedure; therefore 
this study presents no risk to these patients.  If the patient/child or parent expresses 
any discomfort from the ultrasound or procedure, the procedure will be immediately 
discontinued and the patient will be removed from the study. 
When subjects with diminished mental capacity are to be enrolled, there will be an 
independent assessment of capacity to sign consent. If a potential participant does not 
have the capacity to sign consent, permission of a surrogate and assent of the 
potential participant if aged 7 years or greater will be obtained. If permission of the 
surrogate is not obtained, the potential participant will not be enrolled in the study.   It 
is important that persons with diminished capacity be included in this study. 
Dehydration is clinically important and common morbidity in young children with 
diminished capacity (e.g. those with mental retardation/cerebral palsy). This 
population is particularly vulnerable to sepsis and moderate to severe dehydration 
requiring resuscitation and should be allowed to participate in the study.  
Assent from the potential participant will be obtained for all potential participants 
greater than or equal to age 7 years. Consent will be obtained from parents/guardians 
of potential participants who are younger than 18 years of age.  
15)
Multi-Site Human Research (Coordinating Center)
Not applicable in this study
16)
Community-Based Participatory Research
Not applicable in this study
17)
Sharing of Results with Subjects
Relevant information and findings from the ultrasound imaging studies will be
shared as per standard of care in the Emergency Department
18)
IRB Review History
Primary application- no applicable history

Protocol Title: 
Randomized Controlled Trial of Inferior Vena Cava 
Ultrasonography in the Management and Disposition of 
Pediatric Patients Undergoing Evaluation for Sepsis and 
Dehydration   
Principal Investigator 
Name/Contact Info:  
Elizabeth Haines 
516-946-9742 ejhaines@gmail.com or
elizabeth.haines@mssm.edu
Primary Contact 
Name/Contact Info 
Elizabeth Haines 
516-946-9742
Date Revised: 
2/10/2015 
Study Number: 
IF1733382 
13 
Revised  9/2/14 
19)
Control of Drugs, Biologics, or Devices
Note: The IDS has its own forms that must be completed and a review process
that must be followed before the IDS representative will sign off on Appendix B
for submission to the PPHS.
***Please see attached FDA 510-approved device brochure- specific to the 
ultrasound equipment used in this study