Noninvasive NAVA Versus NIPPV in Low Birthweight Premature Infants
Phase: NA
Conditions: Noninvasive Ventilation, Low Birth Weight
Sponsor: Virginia Commonwealth University

 
 
Title: Noninvasive NAVA Versus NIPPV in Low Birthweight Premature Infants 
 
NCT #: NCT03137225 
 
Document approval date: 09/08/2016 
 
Document Type: Protocol and Statistical Analysis Plan 
 
 
 

Date: Thursday, September 08, 2016 12:49:46 PM
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ID: HM20005575
View: SF - Study Identification
Study Identification
1. * Select the Principal Investigator:
Henry Rozycki 
2. * Study Title:
Noninvasive NAVA Versus NIPPV in Low Birthweight Premature Infants 
3. * Is this a student or trainee project in which activities will be carried out by that individual under your supervision:
Yes
No
4. Select any associated VCU IRB protocols:
ID
PI
There are no items to display
5. Select all individuals who are permitted to edit the IRB protocol and should be copied on communications (study staff will be
entered later).  These individuals will be referred to as protocol editors:
Last Name
First Name
E-Mail
Phone
Mobile
ID: HM20005575
View: SF - Student/Trainee Investigator Contact
ID: HM20005575
View: SF - Research Determination
Research Determination
1. * Select one of the following that applies to the project:
Research Project or Clinical Investigation
Exception from Informed Consent for Planned Emergency Research
Humanitarian Use of Device for Treatment or Diagnosis
Humanitarian Use of Device for Clinical Investigation
Emergency Use of Investigational Drug, Biologic or Device
Treatment Use (Expanded Access to Investigational Product for Treatment Use)
Center or Institute Adminstrative Grant Review
ID: HM20005575
View: SF - Federal Regulations
Federal Regulations
1. * Is this a Clinical Trial:
Yes
No
2. Is this an Applicable Clinical Trial that must be registered and reported to clinicaltrials.gov:
Yes
No
3. * Is this a FDA regulated study:
Yes
No
4. * Is this study supported by the Department of Defense (DoD):
Yes
No
5. * Check if any of the following funding sources apply to this research:
None of the above
ID: HM20005575
View: SF - Personnel

  
Personnel
1. * Indicate all VCU/VCUHS personnel, including the PI, who will be engaged in this study:
 
Name Roles
Roles
-
Other
Responsibilities Responsibilities
- Other
QualificationsQualifications
- Other
COI
Investigator
 
 
 
 
 
 
 
 
 
 
 
 
 Identify all non-VCU personnel who will be engaged in this study AND who DO NOT have IRB approval for this study from their
own institution.
 NameRolesRoles -
Other
Responsibilities Responsibilities -
Other
QualificationsQualifications
- Other
COI
Investigator
There are no items to display
3. CV/Biosketch:  (required for PI, Medically/Psychologically Responsible Investigators and Student/Trainee Investigators)
 
ID: HM20005575
View: SF - Conflict of Interest
  
Conflict of Interest
1. * To the best of your knowledge, do you (as PI) or any other engaged individual hold a financial conflict of interest related to
this study?
  
Yes
No
2. If Yes, provide:
Name(s) of the engaged conflicted individual(s)
Brief description of the financial conflict of interests
3. * Describe any potential non-financial conflicts of interest for members of the research team that could impact the conduct of
the study (if None, please state "None"):
None
4. Describe any institutional conflict of interest with this research that you or any member of the research team may be aware of:
None
 
ID: HM20005575
View: SF - Communication Plan for Research Team
  
Communication Plan for Research Team
1. * Describe the process that will be used to ensure that all persons at all involved sites assisting with the research are
adequately informed about the protocol and their research related duties and functions:
Investigators will brief and inform clinical personnel of study design by poster in break room, email and personal interactions before first
enrollment; however, clinical personnel will be not be performing any research related duties. Members of the research team will meet
after each subject to review protocol, data acquisition and to go over any problems identified.

  
ID: HM20005575
View: SF - IRB Panel Setup
  
IRB Panel Setup
1. * To which IRB is this study being submitted for review:
 
VCU IRB
Western IRB
NCI Central IRB
Other IRB (Request to Defer to Another Institution)
  
ID: HM20005575
View: SF - Review Setup
  
Review Setup
1. * Does this study involve greater than minimal risk:
  
Yes 
No
2. * Review Type Requested: (subject to IRB approval)
 
Full Board
Expedited
Exempt
 
  
ID: HM20005575
View: SF - Research Description
  
Research Description
1. * Describe the study hypothesis and/or research questions.  Use lay language whenever possible.
We hypothesize that in very low birth weight infants who require respiratory support via noninvasive ventilation, that synchronizing the
ventilator breath with the baby's breath using neurally adjusted ventilatory assist (NAVA) will reduce the number and/or severity of
apnea/bradycardia/desaturation episodes compared to nasal intermittent positive pressure ventilation (NIPPV). 
2. * Describe the study's specific aims or goals.  Use lay language whenever possible.
The specific goal is to measure the number and severity of cessation of breath/low heart rate/low blood oxygen level events (ie,
apnea/bradycardia/desaturation events) in a 4 hour period while receiving one of the two types of non-invasive ventilation modes (either
NIPPV or NAVA) currently used in very low birthweight infants.
3. * Describe the study's background and significance, including citations, or upload a citation list in document upload.  Use lay
language whenever possible.
Very low birthweight (VLBW) premature infants in the NICU frequently require respiratory support for prolonged periods of time. Invasive
mechanical ventilation (which requires intubating the baby with a tube to provide breaths) can lead to ventilator-induced lung injury.
Because of this, noninvasive respiratory support has become increasingly popular, as this form of ventilation has been shown to reduce
the incidence of permanent lung injury. (1)
There are several methods to provide non-invasive support. The gentlest is continual flow of air and oxygen via nasal cannula. However,
premature infants often develop apnea, either becasue the signals from their immature brain are not yet sufficient or because the
muscles in the back of their throat do not get enough nerve signals to maintain suffiicient opening. As a result, babies on nasal cannula
often develop clinical apnea/bradycardia/desaturations. Before putting these babies back on invasive ventilation, clinicians often try to
provide the baby with machine breaths while still on non-invasive ventilation. This method is called nasal intermittent positive pressure
ventilation and studies have demonstrated that this method reduces the need for re-intubation in VLBW infants (1) and reduces the rate
of apneic events. 
A newer method of non-invasive breathing support that has been FDA approved and used in VLBW infants, synchronizes the machine
generated breath with the patient's own breath. Neurally adjusted ventilatory assist (NAVA) does this by replacing the standard
nasogastric tube with a nasograstric tube that has sensors which detect the baby's natural diaphragm activity, which signal the ventilator
to breath in synchronization with the baby. Studies have shown that the efficacy of nasal ventilation is significantly enhanced when the
machine breath is synchronized with the patient breath (2). Synchronization also reduces diaphragmatic dysfunction (3). It can improve
gas delivery, reduce work of breathing, and make patients demonstrably more comfortable (4). 
Neurally Adjusted Ventilatory Assist (NAVA) is a mode of partial support. NAVA can be 
used both in intubated patients (invasive NAVA) as well as in extubated patients who 
require noninvasive positive pressure ventilation (noninvasive NAVA) (5). Invasive 
NAVA has been shown to deliver equivalent ventilation while requiring lower peak 
inspiratory pressure, as well as reduced respiratory muscle load, compared to 
conventional pressure support ventilation. 
Currently, the choice of using NIPPV or NAVA is at the clinician's discretion. Both are regularly and frequently used in the VCU Health
System's NICU. There are no studies that have examined 
whether NAVA triggered synchronized ventilation is more effective than non-
synchronized NIPPV. In addition, there is limited data on the synchronicity and 
mechanics of non-invasive NAVA in VLBW infants. Information comparing clinical and 
lung mechanical outcomes between NIPPV and NIV NAVA would significantly benefit 
VLBW care providers and, consequently, their patients in getting the best evidenced-
based therapy.
1. Tang S, Zhao J, Shen J, Hu Z, Shi Y. Nasal intermittent positive pressure ventilation versus nasal continuous positive airway pressure
in neonates: a systematic review and meta-analysis. Indian Pediatr. 2013 Apr;50(4):371-6.
2. Gizzi C, Montecchia F, Panetta V, Castellano C, Mariani C, Campelli M, Papoff 
P, Moretti C, Agostino R. Is synchronised NIPPV more effective than NIPPV and 
NCPAP in treating apnoea of prematurity (AOP)? A randomised cross-over trial. 
Arch Dis Child Fetal Neonatal Ed. 2015 Jan;100(1):F17-23.
3. Petrof B, Jaber S, Matecki S. Ventilator-induced diaphragmatic dysfunction. Current opinion in critical care 2010; 16(1): 19-25 
4. Stein H, Firestone K. Application of neurally adjusted ventilatory assist in neonates. Seminars in Fetal and Neonatal Medicine 2014;
19(1): 60-69.
5. Moerer O, Beck J, Brander L, Costa R, Quintel M, Slutsky AS, et al. Subject-
ventilator synchrony during neural versus pneumatically triggered non-invasive 

helmet ventilation. Intensive Care Med 2008; 34:1615-23.
4. * Briefly describe the study design, including all interventions or interactions with research participants and access to
identifiable data.  Use lay language whenever possible.
STUDY DESIGN
a. Subjects
Subjects: VLBW (< 1501 grams birthweight) infants in the VCU Health System NICU who are receiving either NPPV or non-inasive
NAVA therapy as ordered by their clinical providers. Investigators are clinicians who work in the NICU and will therefore be able to
identity eligible subjects. 
NAVA and NIPPV are different modes for the way non-invasive ventilation breaths are triggered. Both utilize the same delivery system,
ventilator, cannula, etc. In NIPPV, the ventilator breaths are triggered by time, i.e. the ventilator sends a breath to match the prescribed
rate like one every 3 seconds for a rate of 20 breaths per minute, no matter whether the patient is inhaling or exhaling. In NAVA, the
normal feeding tube is replaced by a special tube that has a sensor located around where the diaphragm surrounds the esophagus. The
sensor picks up the electrical signal of the diaphragm muscle contracting, and this mark of the beginning of inhalation is used to trigger a
machine breath, so the machine and the patient are coordinated. Aside from the catheter connection, all other procedures are the same.
b). Randomization - the order of modes will be assigned based on a random number table using a 5 block design to match the DSMB
reporting needs. c) The change from one mode to the next involves activating a switch on the ventilator. There are no procedures that
need to be done to the subject. They will remain in their current environment, connected to all the routine and study-related monitoring
equipment. d) During the study, which involves both modes, the subjects will be monitored as routine by the staff, as well as one of the
study faculty (Rozycki or Moores). In the event that one of us needs to step away briefly, an attending neonatologist and a neonatal
fellow are on site in the NICU
As part of routine care, infants on either mode have a nasograstric tube in place. Those subjects who are receiving NIPPV will have their
nasogastric tubes replaced by a NAVA nasograstric tube. The subject will then be randomized to one of the two modes (NIPPV or non-
invasive NAVA). After a one hour stabilization period, during which small adjustments to the non-inasive settings can be made to
clinically optimize the settings, the study will begin. A Nellcor pulse oximeter probe will be placed on an extremity to provide a continuous
non-invasive downloadable measure of saturation (blood oxygen level) and heart rate. Data from the ventilator will be downloaded in
real-time to a laptop. These data will be recorded for 4 hours continuously. After that, the ventilator will be switched to the other mode
(NIPPV to NAVA or NAVA to NIPPV), at the same PEEP and respiratory rate. Again, one hour will be allowed to adjust the ventilator
settings. Data will then be collected for 4 hours on the second ventilation mode. At that time, the clinician will be informed if either mode
was significantly better and the clinician will decide which mode the patient will return to.We will not know which mode is better until the
data are analyzed in aggregate. We're concerned about safety perspective where the subject is on Mode A as chosen by the clinician,
and we find that during the time they are on Mode A, they have far more events than when we have them on Mode B. This would be
valuable information, since the choice of NPIIV vs. NAVA is currently not clearly indicated. To address this, we will provide the clinician
with the results that are available at the time of the study. This will be number of events that are routinely measured clinically, i.e. events
that cause alarms such as apnea or bradycardia or desaturations outside the clinical limits. These are objective measures that the
clinician can incorporate into their decision making if they so choose. 
Data to be collected will include heart rate, saturations from the pulse oximeter, and respiratory rate, expired tidal volume, peak pressure
and synchronization from the ventilator. 
Clinical data will include: birthweight, gestational age, age at study (days of life) and pre-study ventilator settings, Data will be kept in a
secure HIPAA compliant database and only study investigators will have access to it.
Analysis: The simultaneous recordings will be scored for: a) Apnea ( cessation of breath resulting in no airflow for > 20 seconds or for >
5 seconds if accompanied by bradycardia [HR < 100 bpm] or desaturation [Oximetry < 85%]) b) Bradycardia (hr < 100 bpm for > 5
seconds) c) Desaturation (< 85% for > 5 seconds) d) Synchronicity, measured as average triggering and cycling-off delays for each
modality, and total wasted patient respiratory efforts for each modality.
Primary outcome: The number of isolated apneas, bradycardias and desaturations and the number of combined events will be
compared by mode of ventilation. 
Secondary outcome: a) Synchronicity from the ventilator at the time of an event. This will be analyzed to determine whether
asynchronicity is related to increased number of events during the study. b) Overall asynchronicity counts will be determined by
ventilator data that can be uploaded and analyzed with software supplied by the manufacturer. c) average mean airway pressure and
peak inspiratory pressures required in each mode of ventilation.
There are no well-characterized tools to measure premature infant 'comfort'. There are semi-subjective pain scores that the nursing staff
use but we are more likely to have irritation or discomfort from the probe. Thus, this will be an ongoing assessment of a) the infant's
state - quiet sleep, quiet awake, agitated, restless, etc. b) new onset tachycardia or tachypnea coincident with applying the probes. c)
facial grimaces that are different than baseline as assessed by the nurse caring for the patient
The threshold for an adverse event will be dependent on the baseline level. If the baseline rate is, say, 4-6 events an hour, a 25%
increase is 1 event, which is within the patient's variance. On the other hand, in one having no events, just one event is a 100%
increase. We have 2 criteria - 1) An event that requires intervention with breathing support such as with more breaths or a bag and
mask, 2) an increase from baseline of at least 4-5 events/hr. from baseline
5. Upload any supporting tables or documents:
ID: HM20005575
View: SF - Study Activities
  
Study Activities
1. * Select which study type best describes the majority of the study. Your response will help determine which IRB panel should
review this.
 
Bio-Medical
Qualitative - Social/Behavioral/Education (SBE)
Quantitative - SBE
Mixed Method - SBE
Mixed Method - Biomedical
2. * This study will involve (check all that apply):
 
procedures such as surveys, interviews, field studies, focus groups, educational tests, deception, psycho-physiological testing, any
other similar data collection
secondary data analysis: procedures such as analysis of information collected for non-research purposes (includes both
retrospective and prospectively collected information), or analysis of data previously collected for a prior research study
drugs, devices, experimental interventions, biohazards, radiation, other medical or surgical procedures
 
ID: HM20005575
View: SF - Bio-Med Project Details
  
Bio-Med Project Details
1. * Select all details that apply:

 
Drugs, Biologics, Supplements, and/or Other Compounds
Placebo
Washout Period
Device Evaluation
Bio-Hazards, Other Toxins, Recombinant DNA/Gene Transfer
Radiation Exposure and/or Scans involving radiation (PET, MRA)
Stem Cells
Expanded Access - Treatment Use of an Investigational Product
Other Medical or Surgical Procedures
Protected Health Information (PHI)
 
ID: HM20005575
View: SF - Bio-Med Device Evaluation Details
  
Bio-Medical Device Evaluation Details
1. * Select the type of device evaluation this study will involve:
 
Marketed Medical Device (including 510k device)
Investigational Medical Device
New Use for Marketed Medical Device
Other Devices
2. * List devices this study will involve:
Device
Manufacturer
IDE
IDE Holder
Doc
Servo-i Ventilator
Maquet
N/A
Not Required
Servo-i (0.01)
Servo-i NAVA
Maquet
N/A
Not Required
NAVA brochure(0.01)
3. * Documents required for upload: 
If the IDE is held by a sponsor-investigator, upload at least one of the following documents for verification of the IDE
number:
Study Protocol including IDE number
Communication from the FDA with verification of the IDE
If the IDE is held by the sponsor, upload at least one of the following documents for verification of the IDE number
(required if IND held by sponsor):
Sponsor protocol
Communication from the sponsor verifying the IDE number
Communication from the FDA verifying the IDE number
If evaluating an approved device, upload documentation of the approved use(s).
 
ID: HM20005575
View: SF - Data Collection Details
  
Data Collection Details
1. * Select all involved in the study:
 
Specimen/Biologic Sample Collection
Protected Health Information (PHI)
Audio/Video
Existing Data or Specimens Not From a Registry or Repository
Use of Internet for Data Collection
Registries/Repositories (Includes Accessing, Contributing or Creating)
None of the Above
2. * Select all identifiers that will be collected as part of this study (including for recruitment, data gathering, data analysis, etc.),
even if the data will eventually be anonymized:
 
Names
Geographic Locators Below State Level
Social Security Numbers
Dates (year alone is not an identifier)
Ages >89
Phone Numbers

 
Facsimile Numbers
E-mail Addresses
Medical Record Numbers
Device Identifiers
Biometric Identifiers
Web URLs
IP Addresses
Account Numbers
Health Plan Numbers
Full Face Photos or Comparable Images
License/Certification Numbers
Vehicle ID Numbers
Other Unique Identifier
No Identifiers
Employee V#
3. If "Other Unique Identifier" was selected above, describe the identifiers:
4. * Will participants be able to withdraw their data (paper, electronic, or specimens) from the study if they no longer wish to
participate:
  
Yes
No
5. If yes above, describe how participants will be able to withdraw their data:
  
ID: HM20005575
View: SF - HIPAA
  
HIPAA
1. * Describe the protected health information that will be obtained or used in this research:
MRN, birth dates, date of study. The only data that are needed from the EMR are: gestational age, birth-weight, age at study,
medications while on study, ventilator mode and settings at time of study, gender and Apgar scores and head ultrasound results.
2. * Describe the source(s) of the protected health information:
VCU's electronic medical record system
3. * Explain how the PHI collected or used in this research is the minimum necessary to accomplish this research:
The above mentioned data will be needed to evaluate the role of maturity on the outcomes. These variables are either standard clinical
descriptors of a neonatal research population (birth-weight, gestational age, gender, Apgar Scores) to inform any reader of an
aggregated data publication about whether the study sample is representative of the relevant population, or ones that can influence the
outcome variable (medications, ventilator history, evidence of brain bleeds)
4. * Select all pathways this research will employ to use or access PHI:
 
De-Identified Data
Limited Data Set
Waiver of Authorization
Partial Waiver of Authorization
Signed Authorization Combined with Consent Form
Signed Authorization as Stand-Alone Form
 
ID: HM20005575
View: SF - Data Confidentiality and Storage
  
Data Confidentiality and Storage
1. * Confidentiality refers to the way private, identifiable information about a participant or defined community is maintained and
shared.  Describe all of the precautions that will be used to maintain the confidentiality of identifiable information, samples or
specimens:
Subjects will have a study number unique to the subject. The key linking the study number to the patient will be kept in a separate
comouter file stored in a password protected computer and file. All other data will be stored in VCU RedCap files.
The data on the laptop is non-identifiable. It will consist of real-time data from the ventilator and apnea monitor, without any identifiers. It
will be analyzed for events, without identifiers. Only the event numbers (number and duration of apneas, bradycardias, etc. and
synchronicity) will be linked to the subject when stored in VCU Redcap files.The signed consent form will be stored in a locked filing
cabinet in a locked office in the VCU Children's Pavilion.
2. * Who will have access to study data:
Named investigators  
3. * If applicable, describe the process for assigning codes to the data including :
- how codes will be assigned
- whether there will be a key linking identifiable information to the data
- where the key will be stored
- who will have access to the key
- when the key will be destroyed
Each subject will get a study number (1, 2, 3, etc) as they are identified/consented to the study. The code will be kept separately as
above and access limited to study investigators. The key code will be destroyed upon completion of tfe study and analysis. The key
linking the study number to the patient will be kept in a separate computer file stored in a password protected computer and file. Only the
4 investigators named in this study (Moores, Xu, Sirota and Rozycki) will have access to the key.
4. * Will the sponsor or investigator obtain a certificate of confidentiality for this study:

 
No - CoC will not be Obtained
Yes - CoC has been Obtained
Yes - CoC Request is Pending
Yes - Plan to Submit CoC Request
5. If the Certificate of Confidentiality has been obtained by the PI, upload it here:
6. * What will happen to the research records when the research has been completed:
 
Stored indefinitely with identifiers removed
Stored indefinitely with identifiers attached
Destroyed at the end of study once the minimum time required for data retention has been met per VCU Data Retention
Policy and/or sponsor retention requirements
Destroyed when notified by sponsor but not less than the minimum time required for data retention per VCU Data Retention Policy
Other
7. If Other, explain:
8. If "stored indefinitely with identifiers attached", explain why identifiers are necessary:
ID: HM20005575
View: SF - Types of Sites
  
Types of Sites
1. * Select which of the following accurately describes this study:
 
Not Multicenter Study
Multicenter Study - VCU Lead
Multicenter Study - Non-VCU Lead
2. * Select all sites where study interventions or interactions will occur and/or identifiable data will be held:
 
VCU Site
Non-VCU Site (VCU Investigators are conducting/overseeing the conduct of the study)
3.  * Is there a community partner in this research study:
  
Yes
No
  
ID: HM20005575
View: SF - VCU Site Details
  
VCU Site Details
1. * Select all VCU sites that will be utilized in this study:
 
Clinical Research Services Unit (CRSU)
Massey Cancer Center
VCU Health System
VCU Qatar
Other VCU Site
2. * Provide details regarding each VCU Site including:
- what clinics / facilities will be used
- resources that are available for the conduct of this study:
Site - NICU on CCH6
Study involves normal care practices - normal care and monitoring by personnel will continue during the study period.
 
ID: HM20005575
View: SF - VCU Health System
  
VCU Health System
1. * The PI has reviewed and agrees to comply with the Conduct of Clinical Research in VCU Health System Patient Care Areas
policy:
  
Yes
No
2. * Explain how you will notify and obtain support from patient care providers in the units where the study will be conducted:
Investigators will brief and inform clinical personnel of study design by poster in break room, email and personal interactions before first
enrollment.
  
ID: HM20005575
View: SF - Study Funding
  
Study Funding

1. * Have you applied for funding:
  
Yes
No
  
2. If so, is this study already funded:
  
Yes
No
  
ID: HM20005575
View: SF - Study Population
  
Study Population
1. * Provide the total number of participants you expect to enroll in this study under the VCU IRB:
15
2. If this is a multi-Center Project, what is the total anticipated number of subjects across all sites:
3. * Provide justification for the sample size:
Sample Size
Based on published data, monitored events occur at an average frequency of 9.2 over a 4-hour period. The degree of variability is not
known but assuming an SD of 50%, a sample size of 10 subjects would have an 0.8 power for a 50% reduction in events at an alpha of
0.05. A similar study to ours comparing NIPPV and flow-synchronized NIPPV (2) had 19 participants and achieved statistically significant
differences between the two modalities. Based on this, we are anticipating a need for 15 subjects
4. * List the study inclusion criteria:
1. < 1501 grams (VLBW infant)
2. Patient must be receiving daily caffeine therapy for apnea
3. On non-invasive ventilation, either NIPPV or non-invasive NAVA
5. * List the study exclusion criteria:
1. No concerns for acute sepsis (i.e., blood cultures, if drawn, have been negative 
for 48 hours, and no active signs/symptoms of sepsis).
2. No history of meningitis or seizures
3. No signs of increased intracranial pressure, including bulging fontaneIle, presence of ventricular shunt device, or ventriculomegaly by
most recent ultrasound. 
4, Presence of Grade III or IV intraventricular hemorrhage
5. No cyanotic heart defects or clinically significant congenital heart disease. Will allow PDA, PFO, and mild to moderate ASD/VSD as
determined by pediatric cardiology.
6. Non-English speaking legal representatives (parents)
6. * Check all participant groups that are likely to be involved in this study. If it is possible that a regulated vulnerable population
(children, pregnant women, prisoners) COULD BE involved in the study, be sure to check them:
 
Healthy Volunteers
Children
Emancipated Minors
Pregnant Women
Fetuses, Neonates, Fetal Material or In-Vitro Fertilization
Prisoners
Decisionally Impaired Adults
When cancer is integral to the research - cancer Patients, Family Members, Healthcare Providers or Prevention
VCU Health System Patients
Non-VCU Patients
VCU/VCUHS Students or Trainees
VCU/VCUHS Employees
Individuals with Limited English Proficiency
Active Military Personnel
When researching in a K-12 environment - populations Within School Districts or Other Learning Environments
7. If you are either targeting, or excluding, a particular segment of the population / community, provide a description of the
group/organization/community and provide a rationale:
The decreased ability to explain the technical aspects of the study to LEP parents through either medically-approved translation service
or a medically-certified informed consent form in other languages makes it difficult for these parents to be fully informed to make a
decision in the best interests of their child.
8. * Select the age range(s) of the participants who may be involved in this study:
 
< 1 Year
1 - 6 Years
7 - 12 Years
13 - 17 Years
18 - 20 Years
21 - 65 Years
> 65 Years
 
ID: HM20005575
View: SF - Children
  
Children

1. * Check all of the childrens categories that apply to the study:
 
45
CFR
46.404
Research involving no greater than minimal risk to children, with adequate provisions for soliciting the assent of the
children and permission of their parents or guardians, as set forth in Sec. 46.408
45
CFR
46.405
Research involving greater than minimal risk but presenting the prospect of direct benefit to individual
participants
45
CFR
46.406
Research involving greater than minimal risk and no prospect of direct benefit to individual participants, but likely to yield
generalizable knowledge about the participantଛs disorder or condition
45
CFR
46.407
Research not otherwise approvable which presents an opportunity to understand, prevent or alleviate a serious problem
affecting the health or welfare of children. (Research in this category must be reviewed and approved by the Secretary
of the Department of Health & Human Services)
2. * Will this study involve participants who could be wards of the state:
  
Yes
No
3. * Describe how children will be assented to participate in the study:
Not applicable - this study is recruiting newborn infants only
4. * Describe how you plan to obtain permission of parents or guardians:
Parents of stable infants receiving non-invasive ventilation will be approached in their private single patient NICU rooms and presented
with layman-term information about the study. They will be given a copy of the consent form, all of their questions will be answered and
they will have the opportunity to take the information home to review.
  
ID: HM20005575
View: SF - Children: Direct Benefit [45 CFR 46.405]
  
Children: Direct Benefit [45 CFR 46.405]
1. * Explain briefly how the risk is justified by the anticipated benefit to participants:
While both modes of non-invasive ventilation are currently approved and used in the US and in the VCU NICU, it is not known which
may be better. Hence, there is a possibilty that one mode may be inferior to the other. Currently, a clinician picks one mode and then
watches for clinical signs to determine if they picked the right one. By participating in this study, the subject gets exposed to both in a
brief period of time, and the efficacy and superiority of one over the other can be assessed. In normal care, this side by side assessment
is not done.
2.  * Explain briefly how the relation of the anticipated benefit to the risk is at least as favorable to the participants as that
presented by available alternative approaches:
The alternative approach is to not participate. Study participants will be far more intensely monitored for how the ventilation mode is
working than non-participants. Non-participants depend on nursing observation (a nurse may have 1-2 other patients) and historic data
from the monitor. Participants will have an investigator watching their respiratory status continuously for four hours on each mode, so be
better able to assess which one is better for the subject. This information will be shared with the clinical team who may use it to
potentially select a better mode of non-invasive ventilation for that patient.
  
ID: HM20005575
View: SF - Pregnant Women, Fetuses, Neonates and Post-Delivery Material
  
Pregnant Women, Fetuses, Neonates and Post-Delivery Material
1. * Check all of the following categories that apply to this research:
 
45 CFR 46.204 Research involving pregnant women or fetuses.
45 CFR
46.205(a) and
(b)
Research involving neonates of uncertain viability.
45 CFR
46.205(a) and
(c)
Research involving nonviable neonates
45 CFR
46.205(d)
Research involving viable neonates.
45 CFR 46.206 Research involving, after delivery, the placenta, the dead fetus, or fetal material.
45 CFR 46.207 Research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious
problem affecting the health or welfare of pregnant women, fetuses, or neonates.
  
ID: HM20005575
View: SF - Neonates: Viable [45 CFR 46.205d]
  
Neonates: Viable [45 CFR 46.205d]
If research data is collected on a neonate (newborn, after delivery) that is VIABLE, the regulations for special protections for
children apply (Subpart D).  Therefore,  in addition to selecting Viable neonates here, Children must be selected in Study
Population.
If research data is collected on pregnant women, or the viability of the neonate is questioned, other sections may apply.
 
ID: HM20005575
View: SF - Potential Subject Identification and Recruitment
  
Potential Subject Identification and Recruitment
1. * Choose all recruitment methods that may be used: 
 
E-mail Campaign
Phone Solicitation
Flyers, Letters or Newspaper/TV/Radio Ads

 
Website
Direct Contact
Psychology Research
Participant Pool (SONA)
VCU TelegRAM announcement
Word of Mouth
Other
2.  If Other, please describe:
3. * Select the methods used to obtain names and contact information for potential subjects:
 
Pre-Existing Relationship with Participants
Selected from Pre-Existing VCU Records
Selected from Pre-Existing Non-VCU Records
Selected from Publicly Available Records
Referred by Health Care Provider or Other Health Professional
Recruited from Database or Registry
Identified through Community Based Organization (Schools, Church Groups, etc.)
Self Referred (Flyer/Ad)
Other
4. If Other, please describe:
5. * Describe specific details for identifying and recruiting participants, including but not limited to:
- Specific locations where recruitment materials will be displayed
- How contact information is obtained for any direct contact with potential participants
- Who will approach and/or respond to potential participants:
Inpatient babies in the Neonatal Intensive Care Unit (NICU) will be screened for inclusion and exclusion criteria by investigators, who
work in the NICU.
Families of potential subjects will be approached by one of the investigators for consent.
6. Describe any special recruitment procedures for vulnerable populations:
7. Upload all recruitment materials including ads, flyers, scripts, letters, email invitations, TelegRAM announcements, and
postcard reminders:
8. * Before potential participants consent to the study, will screening questions be asked or will any screening procedures/tests
be done that would not otherwise be done as standard of care:
No
9. If Yes, will identifiable information about individuals be recorded during screening:
  
Yes
No
ID: HM20005575
View: SF - Privacy
  
Privacy
1. * Privacy is an individualଛs right to control how others view, record, or obtain information about them.  When privacy is
violated it can involve such things as being asked personal questions in a public setting; being publicly identified as having a
particular characteristic or diagnosis; being photographed, videotaped or observed without consent; or disclosing personal
information. 
Describe how participants' privacy will be protected during:
- identification,
- recruitment,
- screening,
- the consent process,
- conduct of the study, and 
- data dissemination:
The NICU is a single bed room design. All work including obtaining consent, and performing the study will be done in the private single
bed room.
Data will only be reported in aggregate, not by individuals. No data will be linked to any information that could identify the subject
  
ID: HM20005575
View: SF - Costs to Participants
  
Costs to Participants
1. Select all categories of costs that participants or their insurance companies will be responsible for:
 
Participants will have no costs associated with this study
Study related procedures that would be done under standard of care
Study related procedures not associated with standard of care
Administration of drugs / devices
Study drugs or devices
Other

2. If Other, explain:
3. * Provide details of all financial costs to the participant, other than time and transportation. Additional details regarding
standard of care costs will be requested on another screen, if applicable.
None
4. If applicable, upload a Cost Analysis form here:
ID: HM20005575
View: SF - Compensation
  
Compensation
1. * Describe any compensation that will be provided including:
- items such as parking/transportation
- total monetary amount
- type (e.g.,  gift card, cash, check, merchandise, drawing, extra class credit)
- how it will be disbursed:
None
2.  If compensation will be pro-rated, explain the payment schedule:
  
ID: HM20005575
View: SF - Risks, Discomforts, Potential Harms and Benefits
  
Risks, Discomforts, Potential Harms and Benefits
1. * Describe the risks to participants associated with this study:
- physical, psychological, social, legal, financial, and other risks
- seriousness of given risks
- probability or likelihood of given risks
1. For some participants, the nasograstric tube may need to be replaced before the study begins. There is very very small risk of trauma,
bleeding or a transient drop in heart rate when a new tube is placed. Note that tubes are placed and replaced routinely in this population.
2. Even though both modes of non-invasive ventilation are currently used clinically, it is possible that one mode will not be as well
tolerated as the other, or that it will take longer than one hour to adjust the settings. The subject might have more
apnea/bradycardia/desaturation events. While these are common and are, in fact, why the patient is being treated clinically with one of
the two modes under investigation, a significant increase in the events. If this occurs, the study will be stopped and the clinical team
notified. Any needed interventions will be under the direction of the clinical team. The most likely outcome will be to place the subject
back on the ventilation mode that he/she was on prior to the study. 
3. The adverse events are the outcomes that will be affected by/measured for the interventions. Both NIPPV and NAVA are used to
treat/prevent these events. The study is seeking to answer which mode is better at preventing them. Since we don't know this yet, it is
possible that one of the modes will be worse, which is why it will be monitored as an adverse event, and if one mode does cause more
events, the study will be stopped. Plus this info will be given to the clinician to use when selecting a mode for the patient in the future.
2. * Describe how the risks / harms will be minimized:
1. The nasogastric tubes will be placed by experienced NICU personnel who place nasogastric tube every day.
2. The subjects will be monitored contiuously by: cardiorespiratory monitor, 2 pulse oximeters and by direct observation by study
personnel during the set-up phase and each four hour observations. If , during the first trial, the event number or severity increases
beyond what which would be considered safe in normal clinical care, the mode will be considered a failure. The clinical team will be
informed and the clinical team (not the investigators) will decide if, in their judgment, the alternate mode should be used for the second
trial. If the increased event number or severity occurs during the second trial, the mode will be considered a failure, the clinical team will
be informed and the clinical team will determine further care decisions. 
3. The events are ones that are monitored as part of the usual care, and this will continue during the study period. These babies are
always connected to monitors which are linked to nursing phones as well as central telemetry. The investigator doing the study will be
present to assess/intervene, and as back-up, the clinical team will provide their routine care for such events.
3. If the disclosure of any of the information obtained during the study would place the individual at risk for harm (legal,
reputation, emotional etc.) and the information will be recorded so that the individual could be identified, explain the
protections that will be put in place to decrease the risk of disclosure:
Not applicable
4. * The Code of Virginia requires that most medical personnel and all employees of institutions of higher education report
suspected child/elder abuse or neglect. Is it likely investigators could discover information that would require mandatory
reporting by the investigators or staff:
  
Yes
No
5. * Is it likely investigators could discover a participant's previously unknown condition (eg disease, suicidal thoughts, wrong
paternity) or if a participant is engaging in illegal activities:
  
Yes
No
6. If yes, explain how and when such a discovery will be handled:
7. * Describe any potential risks or harms to a community or a specific population based on study findings:
None anticipated
8. * Describe criteria for withdrawing an individual participant from the study; such as safety or toxicity concerns, emotional
distress, inability to comply with the protocol, etc.:
If, between consent and study, the subject no longer meets inclusion criteria or does meet exclusion criteria.
If the number/severity of events becomes a clinically relevant safety concern, the study mode will be considered a failure. The clinical
team will be informed and they will have the authority to stop the study.
9.  * Summarize any pre-specified criteria for stopping or changing the study protocol due to safety concerns:
The exact number/severity of events that might define a safety concern is subject dependent based on prior event history. A subject who
normally has 0-1 events an hour may have a clinical safety concern at 4-5 events/hr while in one who is normally having 3-4 events/hr,
the same rate of 4-5 events would not be significant. Clinically, a change in event rate is judged against baseline rate. However, events
that require significant intervention, i.e. mechanical breathing support from ventilator or bag and mask, will be an absolute stopping
indication. 
The threshold for an adverse event will be dependent on the baseline level. If the baseline rate is, say, 4-6 events an hour, a 25%
increase is 1 event, which is within the patient's variance. On the other hand, in one having no events, just one event is a 100%
increase. We have 2 criteria - 1) An event that requires intervention with breathing support such as with more breaths or a bag and
mask, 2) an increase from baseline of at least 4-5 events/hr. from baseline.
10. Where appropriate, discuss provisions for ensuring necessary medical, professional, or psychological intervention in the
event of adverse events to the subjects:
Current protocols in place in NICU.
11. * Describe any potential for direct benefits to participants in this study:
Observational results will be shared with the clinical team. These may include infant's comfort level on each mode of non-invasive
ventilation; pressure levels on each mode, general frequency of apnea/bradycardia/desaturation events. Based on this information, the
clinical team may choose to change the mode of ventilation. 
There are no well-characterized tools to measure premature infant 'comfort'. There are semi-subjective pain scores that the nursing staff
use but we are more likely to have irritation or discomfort from the probe. Thus, this will be an ongoing assessment of a) the infant's
state - quiet sleep, quiet awake, agitated, restless, etc. b) new onset tachycardia or tachypnea coincident with applying the probes. c)
facial grimaces that are different than baseline as assessed by the nurse caring for the patient.
12. * Describe the scientific benefit or importance of the knowledge to be gained:
Information derived from analysis of study data may determine which mode of non-invasive ventilation is better in short term use for
VLBW infants by examining outcome data with more depth and precision than is currently done clinically. This will help clinicians to
better choose the optimal mode.

13. If applicable, describe alternatives (research or non-research) that are available to potential participants if they choose not to
participate in this study:
They will be maintained on their current clinically chosen mode of ventilation
14. * Indicate if this study will have a Data Safety Monitoring Board (DSMB) or a Data Safety Monitoring Plan (DSMP): [Required for
all Full Review studies]
 
DSMB Review Required
DSMP Required
Not Required
 
ID: HM20005575
View: SF - DSMP Details
  
DSMP Details
1. * Describe your Data Safety Monitoring Plan for monitoring the data collected to ensure the safety of participants:
At 5 subject intervals, data on the number of failures, and the frequency/severity of events will be provided to Dr. Karen Hendricks-
Munoz, MD, MPH who is Chair of Neonatal Medicine at VCU. She will assess the study for safety. Her opinion about whether the study
should continue is final.
The DMSP is the chief of the service. We will submit outcomes and adverse event data to her after every 5 subjects. It is an expectation
that the DMSP assessment of whether to stop or continue will be made in writing to the PI within 28 days, and a copy will be forwarded
to the other investigators, the device sponsor and the IRB each time.
 
ID: HM20005575
View: SF - Consent Qualifiers
  
Consent Qualifiers
1. * Are you submitting your study as exempt and therefore no consent is required:
  
Yes
No
  
ID: HM20005575
View: SF - Consent Groups
  
Consent Groups
1. * List all consent groups:
Group
Types
Waivers
Roles
Roles
-
Other
Consent
Coercion
Decision
Status
Change
VLBW
infants on
non-
invasive
ventilation
Written/Signed
Consent by
Parent/Guardian
(for child) or
Legally
Authorized
Representative
(for adult)
No
Waivers
Requested
Principal
Investigator
Co/Sub-
Investigator
Trainee/Student
 
In the subject's
private room
when the
parents/guardians
are visiting
Preference will
be given to
having one of
the investigators
not currently
caring for the
potential subject
as person to
obtain consent.
The alternative
of not
participating,
with no effect on
care, will be
emphasized
during review of
the consent form
Several of the
investigators
take one week
turns on the
clinical service
where the study
participants will
be cared for.
Since only the
investigators will
be obtaining
consent, it is
very likely that
an investigator
who is not
directly caring
for the patient
will be available
to explain the
study and obtain
consent. Since
the subjects are
usually in the
NICU for weeks,
during which
they often meet
the criteria to
participate, it
would be very
unusual for the
clinician caring
for the subject to
need to get
consent
Parents/guardians
may have up to
24 hours to
consent. This may
be renewed if the
subject continues
to receive non-
invasive
ventilation
 
2. Upload any consent / assent documents:
ID: HM20005575
View: SF - Documents
  

Documents
 
 
ID: HM20005575
View: SF - Protocol Complete
  
 
   
 
Section Complete:
SUMMARY
 
 
End of Application:
IRB HUMAN SUBJECTS STUDY
 
Click Continue Below
 
  
  
  
 
 

 
 
  
ID: HM20005575
View: Bio-Med Devices
  
Bio-Medical Devices
1. * Name:
Servo-i Ventilator  
2. * Manufacturer:
Maquet
3. * Provide the IDE number for any investigational devices or new use of a marketed device:
N/A
4. * Select who holds the Investigational Device Exemption for the device:
 
External to VCU Sponsor or Investigator
VCU Sponsor-Investigator
VCU Sponsor who is not the Investigator
Not Required
5. If evaluating an approved device, upload documentation of the approved uses:
Servo-i (0.01)
 Describe use of the device in the methods section.
ID: HM20005575
View: Bio-Med Devices
  
Bio-Medical Devices
1. * Name:
Servo-i NAVA  
2. * Manufacturer:
Maquet
3. * Provide the IDE number for any investigational devices or new use of a marketed device:
N/A
4. * Select who holds the Investigational Device Exemption for the device:
 

 
External to VCU Sponsor or Investigator
VCU Sponsor-Investigator
VCU Sponsor who is not the Investigator
Not Required
5. If evaluating an approved device, upload documentation of the approved uses:
NAVA brochure(0.01)
 Describe use of the device in the methods section.