Oral Suction Intervention to Reduce Aspiration and Ventilator Events: NO-ASPIRATE
Phase: NA
Conditions: Respiratory Failure
Sponsor: University of Central Florida

Oral Suction Intervention to Reduce Aspiration and Ventilator Events:  NO-ASPIRATE 
NCT02284178 
August 11, 2014 

Approach 
Patients who are intubated and treated with MV are at a high risk for microaspiration of secretions,15 and 
subsequent development of VAC.36 VAC include infectious and noninfectious complications that result in 
increasing oxygenation needs after a period of stability on MV.16 Many factors contribute to microaspiration:  
gastric distention and reflux,100,101 enteral tube feeding,101-103 underinflation of the ETT cuff,104 longitudinal folds 
that develop in the ETT cuff,105 ventilator settings (low PEEP),106-108 lower head of bed position (gastric 
contents),101 sedation, and reduced level of consciousness.101 Nursing interventions that have been shown to 
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reduce the incidence of microaspiration and/or VAP in critically ill, adult patients include an aspiration risk-
reduction protocol targeting head of bed elevation, management of high residual enteral feeding volumes,19 
suctioning oral secretions prior to repositioning,23,24 and continuous suctioning of oral secretions.22 Device 
related interventions are also important, such as control of the ETT cuff pressure and insertion of the SS-
ETT.85-88,109-111 In clinical practice, we have observed that nurses are managing feedings per protocol, 
maintaining the head of bed elevation, and cleansing the mouth with antiseptics; respiratory therapists are 
maintaining the ETT cuff pressure in a targeted range; and many patients have a SS-ETT. We have also 
observed that nurses use suction swabs and tonsil suction devices for removing oropharyngeal secretions. 
Preliminary Studies:  High Resource Utilization, Large Volume of Secretions, Oral Suction Strategies 
Our preliminary work has focused on airway management of critically ill patients who require MV. We found 
that development of VAP is associated with up to $40K per case in additional costs, along with longer 
LOS.13,112 Our work has identified that frequency of oropharyngeal suction varies widely, and that the tonsil 
suction device is preferred.26-28 In a simulated laboratory setting, we determined that the oropharyngeal suction 
catheter was more effective than either a suction swab or tonsil suction device in removing oropharyngeal 
secretions.99 Two oropharyngeal suction catheters are included in oral care kits used on MV patients at the 
study site to be used concurrently with tooth brushing; however, average use is only 0.8 per day.95 Many 
patients have large volumes of oropharyngeal secretions that can be potentially aspirated.25,93,113 In preliminary 
work, we suctioned an average of 7.5 mL of secretions within a 4-hour interval, although volumes as high as 
25 mL were removed.25 Secretion removal can be achieved with < 3 suction passes with the oropharyngeal 
suction catheter over an average total duration of 48.1 seconds.25 We have not identified any issues when 
using the oropharyngeal suction catheter.25,93 In a recent pilot study of 13 critically ill subjects, we found that all 
subjects had α-amylase present in the oral secretions, and 6 (46%) had α-amylase detected in the first tracheal 
sample.93 The study was done to test α-amylase procedures and the intervention. A second specimen obtained 
one to four hours later (when ETT suctioning was needed) showed only 4 subjects (31%) with α-amylase in the 
tracheal secretions, and a lower value in those positive. The study established our ability to measure α-
amylase in the APH Specialty Diagnostic Laboratory with precision and quality controls. It also provided data 
that microaspiration frequently occurs in our study population and may be reduced with this simple 
intervention. Our co-investigator, Dr. Mehta, has studied biomarkers for microaspiration.114-118 He also provides 
oversight for the laboratory, including developing the procedures for quantifying α-amylase. These multiple 
preliminary studies informed our decision to focus on enhanced removal of oral secretions, using an 
oropharyngeal suction catheter, on a 4-hour schedule, with α-amylase as our primary outcome measure. 
Design   
A prospective, 2-group, single-blind, randomized clinical trial design is planned. The design will allow us to test 
the impact of the NO-ASPIRATE intervention on outcomes of microaspiration and VAC.  
Aims and Hypotheses 
Our primary aim is to compare the effects of the NO-ASPIRATE intervention versus usual care on 
microaspiration in critically-ill intubated patients on MV. Patients often have high volumes of oropharyngeal 
secretions, and despite existing interventions, microaspiration occurs. Regular removal of secretions that 
accumulate in the oropharynx is intended to decrease the volume or potential load, and thus reduce 
microaspiration. Our working hypotheses are that subjects in the NO-ASPIRATE group will have a reduction in 
microaspiration as measured by the percentage of tracheal specimens that are positive for α-amylase (1.1) 
and mean values of α-amylase (1.2). 
A secondary aim is to compare the effects of the NO-ASPIRATE intervention on development of VAC and 
duration of VAC-free days. By reducing the risk for microaspiration, VAC should be reduced. Our working 
hypotheses are that the subjects in the NO-ASPIRATE group will have a lower rate of VAC (2.1) and longer 
duration of VAC-free days (2.2). Another secondary aim is to explore changes in the ratio of α-amylase in the 
tracheal aspirate versus the mouth over time. Our working hypothesis is that subjects in the NO-ASPIRATE 
group will have a lower tracheal/oral α-amylase ratio over time (3.1).  
Setting and Sample 
Setting. The study will be conducted in the ICUs at Orlando Regional Medical Center (ORMC), a division of 
Orlando Health. ORMC is an 808-bed tertiary care facility that specializes in trauma, emergency care, 
cardiology, orthopedics, neurosciences, and internal medicine. The hospital serves a 5-county area in Central 
Florida area with a diverse population of 2.8 million people.119 The ICUs include Trauma (14 beds), 
Neuroscience (16 beds), Multi-System (10 beds), and Cardiac (10 beds). Nursing and respiratory care 
practices for airway management are standardized across units. The patients are managed by a team of either 
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medical or surgical intensivist physicians. Our co-investigator, Drs. Jimenez, is chief of the medical critical care 
service. Dr. Penoyer is the Director of the Center for Nursing Research, and Dr. Sole holds an appointment as 
a nurse scientist, in addition to her faculty role. The APH Pediatric Specialty Diagnostic Laboratory is part of 
Orlando Health, and will run the α-amylase assays. Dr. Mehta (co-investigator) provides leadership for the 
laboratory, and is an expert in biomarkers of microaspiration. Drs. Talbert and Xan are faculty members at 
UCF and will be involved in data management and analysis. Team members have worked together on many 
previous studies, including our R21. 
Sample. Subjects (n=560) will be enrolled if they meet the following inclusion criteria: 1) 18 years of age or 
older; 2) orally intubated with ETT and treated with MV; 3) 24 hours or less since intubation; and 4) expected to 
be intubated for at least 36 hours after enrollment. Exclusion criteria are: 1) documented aspiration at time of 
intubation; 2) intubation to treat known aspiration; 3) treatment with rescue MV therapies (high-frequency 
oscillator ventilation or extracorporeal membrane oxygenation); 4) re-intubation for any reason; 5) 
contraindications to receiving the intervention (e.g., oral injuries); 6) history of lung or head/neck cancers that 
may produce α-amylase in the lungs; 7) history of disease that affects saliva production (e.g., Sjögren's 
syndrome); and 8) prisoners. Eligible subjects are available. In fiscal year 2012, 1,641 patients were treated 
with MV on the study units (median=4 days; mean=6.2 days). On average, 28 patients are ventilated each day. 
Patients on MV are split between the medical and surgical intensivist teams, providing a diversity of diagnoses. 
We will have a large pool of patients who are highest risk:  trauma, burn, and neurological conditions.48 
Power Analysis. We used data from our pilot work and input from our consultants to estimate sample size and 
attrition. A final sample size of 400 will allow us to detect a 15% reduction in the proportion of specimens that 
are positive for α-amylase (primary aim) at an alpha level of .05 with a power of .87 (H1.1). The sample size 
will be able to detect differences in mean values of α-amylase with an effect size (d) of .25, alpha .05, and 
power of .80 (H1.2). Since VAC, our secondary aim, is a newer measure, we used data from recent studies to 
provide sample estimates. A final sample size of 400 will allow us to detect a 12.7% reduction in VAC with an 
alpha of .05 and power of .80 (H2.1). We will overenroll by 40% to account for attrition, for a targeted 
enrollment of 560 subjects.  
Procedures 
Study procedures have been developed after many of the ones we have used successfully in previous studies. 
We also incorporated procedures described by Nseir,109 Metheny,18,19 Munro (our consultant),73,80 and other 
researchers who have conducted intervention studies to prevent complications in MV patients. 
Screening and Enrollment of Subjects. A convenience sample of eligible subjects will be enrolled after ICU 
admission, within 24 hours of intubation. Our goal is to enroll subjects as soon as possible to maximize the 
effects of the intervention. Munro demonstrated the ability to recruit similar patients within 24 hours,73,120 and 
we will use her expertise as we implement the study. Nseir used a 48-hour recruitment window in a study 
testing an intervention (control of ETT cuff pressure) on microaspiration.109 We will develop a checklist to 
ensure that inclusion criteria are met at time of enrollment. The Project Director (PD) or research assistant 
(RA) will be available for 18 hours each day, 7 days per week, to facilitate enrollment. RAs will be trained 
registered nurses or respiratory therapists who have experience caring for patients on MV. The PD will 
coordinate all staffing and will develop a master schedule; flexible and variable shifts will be offered to ensure 
coverage for enrollment and delivering the intervention. We have a plan in place to ensure coverage and are 
committed to success. 
Randomization. Our biostatistician will oversee the process of randomization of subjects to either the NO-
ASPIRATE or usual care group. He will develop a blocked randomization procedure, using different sized 
blocks, to ensure balanced assignment without being able to predict group assignment.166 Because many 
subjects will be intubated with the specialized SS-ETT (about 65% from historical data), we will stratify 
randomization by type of ETT to ensure that approximately half of those with and without the SS-ETT are 
randomly assigned to each group. Stratification will help to address type of tube as a potential confounding 
variable, and will allow for secondary sub-group analysis. A member of the study team not involved in data 
collection will place group assignments for each type of ETT in numbered, sealed, opaque envelopes. Upon 
enrollment, study personnel will identify the type of ETT, and open the appropriate envelope to determine 
group assignment. Only study team members who provide the intervention will know the subjects’ assigned 
groups. ICU personnel, as well as subjects and family members, will be blinded to the assignment.  
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Principal Investigator/Program Director (Last, first, middle): Sole, Mary Lou

Figure 4. Procedures for NO-ASPIRATE and Usual Care Groups 
Figure 5.  Comparison of Suction Devices.  A, Swab; B, Suction catheter; note 
that catheter reaches the posterior oropharynx. 
A. Swab 
B. Catheter 
Intervention. Following enrollment, the 
RA will collect baseline data, implement 
the assigned intervention (NO-
ASPIRATE or usual care/sham), and 
collect specimens. The RA will then 
implement the intervention as designated 
by study arm every 4 hours. Figure 4 
summarizes the procedures for each 
group. 
To control for possible differences in 
usual oral care practices, the RA will 
perform oral cleansing and suctioning 
with a suction swab after delivering the 
NO-ASPIRATE or sham intervention 
using the hygiene components from the 
oral care kit. The RA will also perform 
tooth brushing every 12 hours. Oral antisepsis will be done after obtaining specimens for α-amylase. Some 
subjects may require additional oral suctioning for secretion management; staff will use the available tonsil 
suction device for oral suctioning in-between the scheduled interventions and document in the medical record. 
Additional necessary oral suctioning will be recorded and controlled for, if applicable.  
NO-ASPIRATE Intervention. The NO-ASPIRATE intervention involves enhanced suctioning of the mouth 
and oropharynx every 4 hours with an oropharyngeal suction catheter. The catheter is 8.25” (21 cm) long (see 
Figure 2D) and is one that we tested in the simulated setting as being most effective in removing 
oropharyngeal secretions.99 Figure 5 compares secretion removal with a suction swab (usual care) versus the 
oropharyngeal suction catheter. This length and pliability of the oropharyngeal suction catheter facilitate 
manipulation of the catheter around the ETT to reach secretions in the oropharynx. In contrast, suction swabs 
and tonsil suction devices are shorter and rigid, and do not reach secretions that pool in the oropharynx.  
During the intervention, the 
oropharyngeal suction catheter 
will be repositioned to reach both 
sides of the mouth and the 
oropharynx. Suctioning will be 
done using standard suction 
pressures until secretions are no 
longer audible or visible, for a 
duration of about 45 seconds.25 
121 We have performed this 
procedure in previous studies 
without any adverse issues, such 
as gagging or oral trauma.25,93 
However, subject response will be 
observed and the procedure will 
be stopped if intolerance is noted.  
Usual Care/Sham Intervention. A usual care/sham intervention will be delivered to those in the usual care 
group. Trained RAs will insert the suction catheter into the subject’s mouth and mimic the suction procedure for 
45 seconds without occluding the suction port. The usual care/sham intervention will be done every 4 hours. 
Data Collection. Data will be collected at enrollment and at regular intervals (Table 1), including demographic 
and physiological data to describe the sample and test equivalence between groups. We will also collect data 
related to factors that might influence microaspiration and development of VAC to assist in interpretation of 
findings and be used as possible covariates in statistical analyses. We anticipate having 4 to 6 subjects 
enrolled at a time. This estimate was based on consultation with Dr. Munro and designed to ensure adequate 
time to deliver the intervention, enroll new subjects, and record data from the medical record. Additionally, at 
this rate of accrual, laboratory will be able to regularly process the α-amylase assays.  
The PD will maintain a list of all enrolled subjects and will organize them according their geographic location. 
Approximately 20 minutes per subject will be allotted for delivering the intervention and obtaining specimens. 
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Principal Investigator/Program Director (Last, first, middle): Sole, Mary Lou

Scheduled times for the intervention will be determined (e.g., 0800, 1200, 1600 military time). The RA will 
begin the shift and deliver the intervention per study arm to the first scheduled subject. The procedure will be 
repeated until the intervention has been delivered to all subjects per schedule. Hand hygiene and infection 
prevention measures will be strictly followed. We will allow a 30-minute window before and after the scheduled 
time to deliver the intervention to account for patient care activities. If the subject is off the unit during the 
scheduled time, it will be delivered upon return to the unit. Delays or omissions in providing the intervention will 
be recorded in the study record. These data will allow us to calculate the number of scheduled interventions 
that are completed each day (dose), which may be useful in interpreting findings. 
Table 1:  Variables and Data Collection 
Variable 
Source 
When 
Purpose 
Outcome Variables 
Outcome:  Microaspiration;  
% tracheal specimens positive for 
α-amylase; mean value of α-
amylase in tracheal secretions 
Assays of α-amylase in 
tracheal aspirate 
Enrollment 
Every 12 hours  
Duration: up to 14 
days while intubated 
Aim 1—Micro-
aspiration  
 
 
Outcome: Ventilator-Associated 
Condition (VAC)—yes/no 
Subset:  Infection-Related 
Possible VAP 
Probable VAP 
Medical record data: 
 Ventilator:  PEEP, FiO2  
 Temperature 
 WBC / culture results  
 New antibiotics / duration 
Daily  
Assess for 2 days 
beyond the last 
intervention 
Aim 2—VAC  
Outcome: Ratio of α-amylase in 
tracheal and oral secretions  
 
Assays of α-amylase from 
paired tracheal and oral 
specimens 
Enrollment 
Every 12 hours  
Duration up to 14 days 
Aim 3—tracheal/oral 
ratio of α-amylase  
Demographic Data 
ETT information (time of intubation, 
type ETT, size ETT) 
Observation 
Medical Record 
Enrollment 
Describe sample 
Stratify by ETT type  
Age, gender, ethnicity, diagnoses 
Medical Record 
Enrollment 
Describe sample 
Compare groups 
Comorbidities:  COPD; immune-
compromise; chronic heart, liver, or 
renal failure 
Medical Record 
Enrollment 
Describe sample 
Compare groups 
Acuity and outcomes:  APACHE II, 
APACHE IV, SAPS, ventilator days, 
LOS 
Hospital database 
Completion of 
participation in study 
Describe sample 
Test group 
equivalence 
Physiological status:  vital signs, 
oxygen saturation, sedation level  
Medical Record 
 
Enrollment 
Daily (am) 
Describe sample 
Test equivalence 
Potential Risk Factors for Microaspiration and VAC
Backrest elevation (daily average) 
Observation 
Every 4 hours 
Test equivalence
GI data:  tubes, nutritional support; 
gastric residual, distention; vomiting 
Medical Record 
Observation 
Enrollment 
Daily (am) 
Test equivalence
ETT: min, max, mean daily cuff 
pressure; repositioning; cuff issues 
Medical Record  
Daily 
Test equivalence
Oral care: additional interventions, 
type of antiseptic 
Medical Record 
Intervention documentation 
Daily 
Test equivalence
GI medications: H2 blockers, proton 
pump inhibitors, antacids, sucralfate 
Medical Record 
Enrollment 
Daily (am) 
Test equivalence
Mobility and transport off unit 
Medical Record/observation 
Every 4 hours 
Test equivalence
Paired specimens of oral and tracheal aspirates for α-amylase. The RA will obtain an oral specimen for α-
amylase at enrollment and every 12 hours (concurrently with a tracheal aspirate) to compute the tracheal/oral 
ratio. Oral secretions will be collected into a trap during the NO-ASPIRATE or usual care/sham intervention. 
Following this procedure, a tracheal aspirate will be obtained for detection of α-amylase. Although Weiss 
detected α-amylase in BAL specimens up to 72 hours post intubation, others have suggested more frequent 
collection.46,97 Obtaining specimens every 12 hours will provide longitudinal data regarding microaspiration, 
and facilitate identification of clinical factors that contribute to its occurrence. The RA will suction the subject’s 
ETT per standard procedure (closed ETT suction with hyperoxygenation via the ventilator before the 
procedure) to retrieve tracheal secretions into a specimen trap. We tested these procedures in a preliminary 
study.93 Since ETT suctioning should be done based on identified need,121 the RA will assess the subject for 
cues identifying suctioning need before obtaining the specimen: audible crackles over the trachea, sawtooth 
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Principal Investigator/Program Director (Last, first, middle): Sole, Mary Lou

pattern on the ventilator flow waveform, cough, high peak inspiratory pressure, visible secretions, or changes 
in oxygen saturation.85,122 If suctioning is not indicated at the scheduled time, the RA will collaborate with the 
subject’s nurse to notify the RA if suctioning is clinically indicated within a 2-hour period to ensure complete 
collection of samples. Time of specimen collection (or omissions) will be noted. The usual care oral antisepsis 
done for all subjects will be done AFTER specimen collection to prevent contamination. All oral and tracheal 
specimens will be frozen to -20 C until the assays are run. A compact medical lab freezer, used solely for 
purposes of this study, will be purchased and located on or near one of the study units for easy storage. 
Specimens will be regularly transported on ice to the APH Specialty Diagnostic Laboratory.  
Endpoints. The intervention will be delivered per protocol until one of the following endpoints is met 
(whichever occurs first):  1) ETT removed (extubation); 2) tracheostomy performed; 3) 14 days of enrollment; 
or 4) other exclusion criterion met (e.g., rescue ventilation). Extending the intervention to 14 days will allow us 
a better opportunity to address the secondary aim of VAC. At the study site, the median time to tracheostomy 
is 8 days; 85% of patients on prolonged MV undergo a tracheostomy by Day 14.112 This duration of enrollment 
is longer than that reported in other intervention studies,19,73,109 and will allow us to test the effect of the 
intervention on both microaspiration and VAC prevention for an extended period. Subjects must be enrolled at 
least 36 hours to be included in analysis. Since the duration of MV varies and we want to assess the effect of 
our intervention on preventing microaspiration, we determined (with input from consultants) that a minimum 
enrollment of 36 hours would provide adequate samples to address the primary aim.  
Measurement of Primary and Secondary Outcome Variables 
Microaspiration. Assays of the biomarker, α-amylase, in paired oral and tracheal specimens will be performed 
in the APH Pediatric Specialty Diagnostic Laboratory per standard procedures (See Appendix A). Laboratory 
personnel will be blinded to study group. Alpha-amylase activity in the paired samples will be analyzed using 
the Stanbio α-amylase LiquiColor Reagent Kit. The recommended procedure was modified for a microplate 
reader. Each run of samples is accompanied by two controls, and the controls are evaluated before results are 
released. A 10 µl sample is placed in a microplate well, and 200 µl of Α-amylase LiquiColor reagent, which has 
been pre-warmed to 37C, is added to each sample and mixed. The increase in absorbance is measured at 
405nm in a spectrophotometer in 3-minute intervals for 9 minutes. The average change in absorbance is used 
to calculate a standard curve of α-amylase in µmol/min/ml, which will be converted to U/L. An α-amylase value 
of 0.6 µmol/min/ml will be considered positive. No amylase should be detected; the value 0.6 µmol/min/ml is 
the lowest possible concentration of amylase that can be detected with the method’s analytic sensitivity. After 
detection, the total values of α-amylase in secretions will be recorded. Amylase that is detected would be either 
of oropharyngeal or gastrointestinal origin; however, in this setting and location of sampling, presence from 
pancreatic source would be unlikely. Indeed the additional step of using a specific inhibitor for salivary amylase 
was shown to be not necessary in airway samples during our preliminary study. The paired oral-tracheal 
samples evaluated in the preliminary study detected large amounts of α-amylase in the oral secretions of all 
subjects, and smaller amounts in those who also had positive results in in tracheal secretions.93 
To address Aim 1 and hypothesis 1.1, total values of α-amylase will be recorded, and each tracheal aspirate 
will be coded as either positive or negative for α-amylase. Dr. Mehta, also blinded to study group, will verify the 
results of each assay. The percentage of positive specimens for the biomarker will be calculated for each 
subject. For hypothesis 1.2, the mean values of α-amylase will be calculated.  
VAC. VAC will be determined using the CDC/NHSN criteria (Figure 6, blue boxes).16 We will assess ventilator 
data (FiO2 and PEEP) daily from the medical record to assess for worsening oxygenation status. Per 
consultation with Dr. Klompas, we will assess for VAC for 2 days beyond the last intervention. To address Aim 
2 and hypotheses 2.1 and 2.2, we will record VAC as positive or negative. We will also record the time to VAC 
in days (0.1 day increments). Determination of VAC will be made by our intensivist co-investigator. The 
CDC/NHSN algorithm proceeds to determine if VAC is infection-related (grey part of algorithm).16 Our primary 
endpoint is VAC as a broad complication that includes both infectious and noninfectious etiologies; however, 
we will also report possible and probable VAP in our analyses as applicable.  
Tracheal/Oral Ratio of α-Amylase. To address Aim 3 and hypothesis 3.1, the ratio of the tracheal value to the 
oral value of α-amylase for each paired sample will be calculated.  
Training and Data Management 
Personnel Training and Fidelity. The PI will be responsible for training and will be assisted by the PD in 
ensuring that all personnel are knowledgeable in their roles. At the beginning of the study, the PI and PD will 
develop a comprehensive study Operations Manual, which will include procedures and checklists for subject 
enrollment, delivery of the NO-ASPIRATE and usual care/sham interventions, data collection, and ongoing 
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Principal Investigator/Program Director (Last, first, middle): Sole, Mary Lou

reporting related to the study (e.g., IRB and DSMB). All study personnel will complete the required CITI training 
on protection of human subjects and will sign confidentiality agreements.  
The PI and PD will train the RAs in all study-
related procedures. Initial training for the NO-
ASPIRATE intervention, the usual care/sham 
intervention, and specimen collection will be 
conducted in a simulation laboratory, followed 
by observation in the clinical setting. Inter-rater 
reliability will be established for delivery of the 
NO-ASPIRATE and usual care/sham 
interventions, and for review of the medical 
record for study-related data. A kappa of at least 
.90 will be achieved between data collectors. To 
ensure treatment fidelity, additional re-
assessment and related training will be done 
every 6 months using a standard observation 
checklist.  
Treatment fidelity and effect of usual care will be 
addressed by reinforcing existing protocols for 
head of bed elevation, daily interruption of 
sedation, and ETT cuff pressure (20-30 cm 
H2O). During our every 4 hour rounds, we will 
monitor and promote adherence, and document 
potential issues. To control for usual oral care 
practices, we will deliver oral care suctioning 
and cleansing/antisepsis interventions to both 
groups. We will also record documentation of 
additional oral suctioning interventions and 
method/tolerance of enteral feedings. Although 
random assignment of subjects to groups should 
address potential confounders, we will compare 
data between groups and control statistically if differences are noted.  
Data Management and Integrity. We will record data in electronic format, using spreadsheet or database 
software, on tablet or laptop computers that are password protected and used solely for the study. Computers 
will be stored in a locked secured area when not in use. We will use the software data validation features 
and/or filters for as many variables as possible to ensure accuracy of data entry, including missing data and 
out-of-range values. These features allow for drop down selection of findings, and specifications of parameters 
for values that are expected to be recorded. We have successfully used similar procedures in previous studies 
to ensure consistency and accuracy of data collection. Dr. Talbert will oversee data management and integrity 
for the study, and will be assisted by the PD. He has past experience in this role on NIH-funded grants, and is 
an expert at managing large databases. The PD will monitor study records to ensure completeness. Accuracy 
of the data collected from the EMR will be reviewed for 10% of subjects during the first month of the study. 
Errors will be corrected, and re-training will be done as necessary. Following the initial audit, 5% of the files will 
be audited quarterly for completeness and accuracy; we will create an audit trail to identify and correct issues 
and/or errors.123 If causes of error other than random variation are identified, we will change our procedures. 
Data Analysis   
Subjects will be randomly assigned to each of the two treatment groups at 1:1 ratio. Before analysis, data will 
be carefully examined for accuracy. Every effort will be made to avoid missing data. Subject characteristics at 
baseline will be examined to ensure a sound balance on demographic variables between the two groups. For 
continuous demographic variables, independent two-sample t tests will be used to detect differences between 
the two groups. For categorical demographic variables, the Pearson’s chi-square test will be used to examine 
differences between the two groups. If subject subsets are found to be significantly different for a demographic 
variable, then this variable will be included into the statistical models. All planned analyses will be based on the 
intent-to-treat (ITT) population, which consists of all subjects who have been randomized into the NO-
ASPIRATE or usual care group. In all analyses, an alpha level of 0.05 will be used.  
Figure 6.  Algorithm for Determining VAC
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Principal Investigator/Program Director (Last, first, middle): Sole, Mary Lou

Aim 1. To compare the effects of the NO-ASPIRATE intervention versus usual care on microaspiration 
of gastric and oral contents in critically-ill intubated patients. Hypothesis 1.1. Subjects in the NO-
ASPIRATE group will have a significantly lower percentage of tracheal secretions with α-amylase present as 
compared to those in the usual care group. Analysis 1.1. Percentages of tracheal secretions α-amylase 
present for both groups will be computed. The percentage difference between the two groups will be calculated 
along with the 95% confidence interval for the percentage difference. The logistic regression including 
covariates of interest will be used to assess the percentage difference adjusting for the prognostic covariates. 
Hypothesis 1.2. Subjects in the NO-ASPIRATE group will have a lower mean value of α-amylase in tracheal 
secretions as compared to those in the usual care group. Analysis 1.2. Values of α-amylase in tracheal 
secretions will be collected for each subject every 12 hours during study. Treatment effect based on these 
values over time will be evaluated by the generalized linear models using the generalized estimating equation 
(GEE) method.124,125 In addition, the generalized linear models with prognostic covariates of interest will be 
used to assess change in mean values of α-amylase over time adjusting for prognostic covariates. 
Aim 2. To evaluate the NO-ASPIRATE intervention versus usual care on VAC rate and time to 
occurrence. Hypothesis 2.1. Subjects in the NO-ASPIRATE group will have a significantly lower rate of VAC 
as compared to those in the usual care group. Analysis 2.1. Percentages of VAC for both groups will be 
computed. The percentage difference between the two groups will be calculated along with the 95% 
confidence interval for the percentage difference. The logistic regression including covariates of interest will be 
used to assess the percentage difference adjusting for the prognostic covariates. Hypothesis 2.2. The number 
of VAC-free days will be longer in those in the NO-ASPIRATE group as compared to the usual care group. 
Analysis 2.2. Time to VAC event for both the NO-ASPIRATE and the usual care groups will be assessed 
using the Cox proportional hazard model.126 The hazard ratio and the 95% confidence interval of the hazard 
ratio of NO-ASPIRATE group versus the usual care group will be computed. The graphical display of the 
Kaplan–Meier estimators for both groups will be presented.127 The Cox proportional hazard model with 
prognostic covariates of interest will be used to assess the difference adjusting for the prognostic covariates.  
Aim 3. To explore changes in the tracheal-to-oral α-amylase ratio between groups over time. 
Hypothesis 3.1. Subjects in the NO-ASPIRATE group will have a significantly lower tracheal/oral α-amylase 
ratio over time as compared to those in the usual care group. Analysis 3.1. Treatment effect on reducing 
tracheal/oral salivary amylase ratio over time will be assessed by the generalized linear models using the 
generalized estimating equation (GEE) method.124,125 In addition, the generalized linear models adjusting for 
prognostic covariates will be used to assess ratios over time adjusting for prognostic covariates.  
Solutions to Potential Issues 
Design. We are planning a single-blind RCT to test the NO-ASPIRATE intervention. Our goal is to blind the 
staff and subjects to the intervention group by using a sham treatment for those in the usual care group, which 
we believe to be a strength. Despite our efforts, knowledge of group membership may be identified.  
Confounding Variables. Since we know that oral suctioning and cleansing practices vary widely, we will 
assume responsibility for oral care interventions for all subjects. This will allow us to truly test the effect of the 
NO-ASPIRATE intervention versus usual care. Since we will be delivering oral hygiene, we will communicate 
well with the nursing staff to avoid duplication of procedures. Prior to the study, we will provide information 
sessions for staff (nurses and RTs) to outline roles of study team members and reinforce existing protocols. 
We will assess the medical record for additional oral suctioning done by the staff. We will use standard unit 
supplies for usual care from the oral care kit, and label components to assess if supplies are used by others. 
Additional suction swabs and catheters are not available to the staff beyond those included in the kit. If the 
patient needs additional suctioning to manage secretions, the tonsil suction device is readily available. We will 
promote adherence to existing protocols for head of bed elevation, daily interruption of sedation for weaning 
assessment, enteral feeding management, and ETT cuff pressure. We will monitor these interventions during 
rounds, reinforce adherence, and document findings. We will record information related to potential 
confounders from the EMR. We will compare equivalence between groups and control statistically if indicated. 
Standard practices to prevent microaspiration could change during the study. We will monitor for potential 
influences of any new practices, and we will include them in the analyses if warranted. Random assignment of 
subjects to groups should address potential issues. We will also use the expertise of our consultants.  
Biomarker of Microaspiration. Because our focus is on removal of oropharyngeal secretions, we are using α-
amylase as a biomarker for microaspiration because it is a specific measure of migration of oral secretions 
from the oropharynx to the lungs. We considered measuring pepsin; however, it has a short window for 
detection after aspiration and is specific to gastric contents. Although α-amylase is a newer biomarker for 
Research Strategy                                                                                             Page 89
Principal Investigator/Program Director (Last, first, middle): Sole, Mary Lou

microaspiration, the rationale for its use is strong since α-amylase is present in oral secretions and detection in 
tracheal secretions indicates aspiration. We have spoken with other researchers who have tested this 
biomarker and are confident in our decision.46 We have also specified exclusion criteria to ensure accuracy of 
findings (e.g., Sjögren's syndrome). Some researchers have used cultures of the endotracheal aspirate as a 
marker of microaspiration.15,109  However, culture results are not always precise, are expensive, and may be 
influenced by the oral care antisepsis. Using cultures only informs of microbial growth in secretions, not 
specifically aspiration of oral contents.  
VAC as an Outcome Measure. The VAE algorithm published by the CDC/NHSN will be used to determine 
VAC.16 The algorithm is a newly designated outcome measure, but it has been systematically tested and 
shown to identify events and related outcomes of mortality and length of stay.6,17,31 It is possible that the 
algorithm will be modified before the study begins. In that case, we will modify the procedures to ensure that 
we collect data to determine VAC per the algorithm that is publicly available at the start. We will also monitor 
for changes throughout the study. We will use the expertise of our consultant, Dr. Klompas, as we design the 
electronic methods for recording data to determine VAC, and in interpretation of findings. 
Staffing. We have developed a staffing plan to ensure coverage by study personnel 18 hours/day, 7 days per 
week. The PD will coordinate scheduling and develop flexible staffing options for coverage. Qualified 
individuals have offered to work as part-time RAs. We understand that the proposed project is complex; 
however, we are confident that we conduct the study as planned and will readily use our consultants’ expertise.  
Recruitment and Retention. Although unanticipated delays in subject recruitment are common in studies of 
critically ill subjects, we have been successful in enrolling subjects with similar inclusion and exclusion criteria 
in prior studies. We have a strong working relationship with the medical staff, nurse managers, and staff nurses 
on the units. We will also use the expertise of our consultant, Dr. Munro, who has conducted large NIH-funded 
clinical trials with similar populations. We have identified a conservative approach for recruitment and retention 
of subjects over 36 months during the proposed 4-year study. Our timeline has some flexibility, in that we can 
extend data collection by 3 months and achieve study goals. Other trials may be conducted at the study site 
with similar inclusion criteria for enrollment. We will collaborate with other investigators at the study site to 
facilitate enrollment in the event of competing studies. These other trials have very restrictive 
inclusion/exclusion criteria, and only 1-2 potential subjects are enrolled in other trials at a given time. The 
number of potential subjects is large, and can support needs of multiple investigators. 
Project Timeline   
We will conduct the study 
over 4 years (Table 2). 
We have allocated 6 
months to start the study, 
followed by enrollment 
over 36 months. The final 
year of the project will be 
devoted to analysis, 
dissemination of findings, 
and writing additional 
grant applications.  
Summary 
The study will add to the science related to a simple-to-implement, yet extremely important, enhanced 
oropharyngeal suction intervention to reduce microaspiration in intubated patients. Our preliminary studies 
have been logically and systematically conducted to guide this intervention study. The study has a great 
potential for improving patient outcomes and will provide data to develop evidence-based practices for 
secretion removal. Findings may also result in methods for earlier detection and treatment of potential 
aspiration. A strong multi-professional team, including internationally-known consultants, has been convened. 
Strong support for clinical research is provided by both the university and clinical setting. 
Table 2:  Project Timeline 
Activity 
Year
1 
2 
3 
4 
Quarter
1 
2 
3 
4 
1 
2 
3 
4 
1 
2 
3 
4 
1
2
3
4
Convene team; develop Operations 
Manual; purchase supplies; IRB 
approval; hire and train staff 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Consultation  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Staff training/retraining 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject enrollment, data collection, 
and management 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DSMB review (ongoing) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Data analysis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dissemination and final grant report  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Research Strategy                                                                                             Page 90
Principal Investigator/Program Director (Last, first, middle): Sole, Mary Lou

Human Subjects 
A. HUMAN SUBJECTS INVOLVEMENT, CHARACTERISTICS, AND DESIGN 
Describe the proposed involvement of human subjects in the work outlined in the Research Strategy 
section.  
The population for this study is critically ill patients who have an ETT who require mechanical ventilation (MV) 
support. Considering power analysis calculations, we propose to enroll 560 subjects to achieve a final sample 
size of 400 subjects randomized to either the NO-ASPIRATE or usual care group. Subjects will be critically ill 
patients, age 18 and older, who are admitted to one of the ICUs at Orlando Regional Medical Center (ORMC):  
Trauma, Neuroscience, Multi-System (medical-surgical), and Cardiac. Subjects will have an oral ETT, and 
require MV as part of their treatment. The project population will include: women, children (age 18-20), elderly, 
inner city and rural, low-income groups, minority populations, and those with trauma as well as chronic 
disease.  
Recent data from the study setting show that 65% of patients are male, with an average age of 53 years. Over 
half of patients admitted to the study units receive MV. Patients who are aged 18-20 represent 9% of the study 
population, and 36% are 65 years of age or older. Using similar inclusion and exclusion criteria as proposed in 
this study, we were able to enroll a diverse sample in prior studies.   
Describe and justify the sampling plan, as well as the recruitment and retention strategies and the 
criteria for inclusion or exclusion of any subpopulation.  
Subjects (n=560) will be enrolled if they meet the following inclusion criteria: 1) 18 years of age or older; 2) 
orally intubated with ETT and treated with MV; 3) 24 hours or less since intubation; and 4) expected to be 
intubated for at least 36 hours after enrollment. Exclusion criteria are: 1) documented aspiration at time of 
intubation; 2) intubation to treat known aspiration; 3) treatment with rescue MV therapies (high-frequency 
oscillator ventilation or extracorporeal membrane oxygenation); 4) re-intubation for any reason; 5) 
contraindications to receiving the intervention (e.g., oral injuries); 6) history of lung or head/neck cancers that 
may produce α-amylase in the lungs; 7) history of disease that affects saliva production (e.g., Sjögren's 
syndrome); and 8) prisoners.  
The Project Director (PD) and Research Assistants (RAs) will make rounds in the units on a regular basis (in 
between the scheduled interventions) to assess eligibility of new admissions. The PD or RA will explain the 
study and seek informed consent from patients that are able to provide their own consent, or from the legally-
authorized representative (LAR). The consent form will be available in Spanish, and translators are available at 
the Orlando Health system for those who do not read or speak English.  
Adequate subjects are available to complete the study and represent a broad cross section of critically-ill 
patients. The number of MV patients per day averages 28 across the study units. We conservatively estimate 
enrolling an average of 50 subjects per quarter. At this accrual rate, it will take 36 months for enrollment. In our 
previous studies we have had adequate representation of children (18-20 years of age), women, and 
racial/ethnic minorities. 
Our past experiences conducting research in the clinical setting with the same patient population will enhance 
our ability to recruit and retain subjects. The continued presence of the PD and RAs throughout the study 
should facilitate retention of subjects. RAs will be readily available to discuss the study and answer questions 
as they arise. We will also use our consultant, Dr. Munro, to guide us. 
Explain the rationale for the involvement of special vulnerable populations. 
We will include children ages 18-20 who meet eligibility criteria. Approximately 9% of the population is in this 
age range. In particular, younger patients are admitted to the surgical/trauma critical care service line. Patients 
with burn, trauma, and neurological injury are at highest risk for infection, and are often younger. Therefore, it 
is important to include this age group.  
We will include the elderly as they are at an increased risk for complications of MV secondary to chronic illness 
and decreased immune response, and their mortality for VAC (lung injury) is higher than younger patients.128 
We will also include pregnant women because if they require MV, oral care interventions are not any different 
for them, and the NO-ASPIRATE intervention is enhanced oral care.  
Although children less than 18 years of age are sometimes treated in the adult ICUs, we will exclude them 
because the VAC criteria specifically note applicability only to those 18 years of age and older.16  
We will exclude prisoners.  
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Principal Investigator/Program Director (Last, first, middle): Sole, Mary Lou

Describe procedures for assignment to a study group. As related to human subjects’ protection, 
describe and justify the selection of an intervention’s dose, frequency, and administration. 
Our biostatistician will oversee the process of randomization of subjects to either the NO-ASPIRATE or usual 
care group. He will develop a blocked randomization procedure, using different sized blocks, to ensure 
balanced assignment without being able to predict group assignment.166 Because many subjects (about 65% 
to 70% from historical data) will be intubated with the specialized subglottic suction ETT (SS-ETT), we will 
stratify randomization by traditional or SS-ETT to ensure that approximately half of those with and without the 
SS-ETT will be randomly assigned to each group. This will help to address type of tube as a potential 
confounding variable, and will allow for secondary sub-group analysis. A member of the study team, who will 
not be involved in data collection, will place group assignments in sequentially-numbered, sealed, opaque 
envelopes for each type of ETT. Upon enrollment, study personnel will identify the type of ETT inserted, and 
open the appropriate envelope to determine group assignment. Only study team members who provide the 
intervention will know the subjects’ assigned groups. Hospital staff members, as well as subjects and their 
family members, will be blinded to group assignment.  
The NO-ASPIRATE or usual care/sham intervention will be administered by a member of the research team 
every 4 hours. The decision for this interval was based on the volume of oral secretions measured in our 
preliminary studies,25 and non-experimental quality improvement studies that implemented oropharyngeal 
suctioning at 4- and 6-hour intervals.64,94  Concurrently with delivery of the interventions, paired specimens of 
oral and tracheal secretions will be obtained at baseline and every 12 hours for assays of α-amylase. Tracheal 
specimens will be obtained based on the subject’s need for ETT suctioning.  
List any collaborating sites where human subjects research will be performed, and describe the role of 
those sites and collaborating investigators in performing the proposed research. Explain how data 
from the site(s) will be obtained, managed, and protected. 
Subjects will be patients in one of the ICUs at Orlando Regional Medical Center. The study team has extensive 
experience conducting clinical studies in these units. Three of our co-investigators are employees at the site. 
Dr. Jimenez is chairman of the corporate Critical Care Committee, which will facilitate communication across 
units. As Director for the Center for Nursing Research, Dr. Penoyer helps to establish collaborations between 
the university and hospital. Dr. Mehta oversees the APH Specialty Diagnostic Laboratory where the α-amylase 
assays will be run. Additionally, Dr. Sole has an appointment as a Nurse Scientist at the agency, which also 
facilitates collaboration and the ability to conduct research in the setting.  
Data will be recorded in electronic means on password-protected computers. The subject’s medical record 
number will be used to retrieve study-related data from the electronic medical record (EMR). All subjects will be 
issued a unique code that will be recorded in the research files. All data will be de-identified for final analysis 
and findings will be reported in aggregate. A key, pairing the medical record number and unique identification 
code, will be kept separate from all data in a locked file in Dr. Sole’s research office at UCF. Access to this 
information will be limited and only on a “need-to-know” basis.  
B.  SOURCES OF MATERIALS  
Describe the research material obtained from living individuals in the form of specimens, records, or 
data.  
The research materials for this study include data from the subject’s medical record and observation. Oral 
secretion and sputum specimens (endotracheal aspirate) for assays of α-amylase will be obtained at baseline 
and every 12 hours for up to 14 days. Specimens will be discarded after analysis. Demographic and 
physiological data will be obtained daily from the EMR. Data to determine presence of VAC will be obtained 
daily and for 2 days after the last intervention has been delivered. VAC-related data will be obtained from the 
EMR.     
Describe any data that will be collected from human subjects for the project described in the 
application.  
At baseline (enrollment), we will collect demographic, physiological, and ventilator data (Table 1). Data include 
age, gender, ethnicity, race, diagnosis, ETT information (type of tube and time of intubation), and severity of 
illness data. Physiological data will be obtained from the medical record at time of enrollment and per schedule 
(either daily or every 4 hours):  temperature, vital signs, and sedation score. Information related to types of 
enteral tubes and nutritional support will be collected. Ventilator data will include mode of ventilation, set 
respiratory rate, positive end expiratory pressure, pressure support, and fraction of inspired oxygen. Ventilator 
data will assist in determining VAC. Temperature and results of tracheal aspirate cultures will be obtained from 
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Principal Investigator/Program Director (Last, first, middle): Sole, Mary Lou

the EMR for secondary analysis of infection or non-infection related VAC. Upon completion of the study, 
additional outcome data will include ICU length of stay, duration of mechanical ventilation and cost data from 
the hospital database for comparison of groups. 
Indicate who will have access to individually identifiable private information about human subjects.  
Study personnel who are collecting data from the EMR will have access to the medical record number to 
access study-related data. All data will be collected to meet HIPAA regulations and will be treated 
confidentially. All subjects will be issued a unique identification number so that data cannot be personally 
identified. All files (paper and electronic) will be coded with this identification number. Subjects’ medical record 
numbers will be cross-referenced to identification numbers, and will be kept separate from all data collection 
forms in a locked cabinet in one of Dr. Sole’s research offices. Access to information will be limited to the 
members of the research team on a “need to know” basis. All research team members will sign a confidentiality 
agreement and will complete mandatory CITI training for protection of human subjects. Results for presentation 
and publication will be presented in a way that individual patients cannot be identified.  
Provide information about how the specimens, records, and/or data are collected, managed, and 
protected as well as whether material or data that include individually identifiable private information 
will be collected specifically for the proposed research project. 
All data will be recorded electronically into the study database per the subject’s unique identification number. 
Demographic and other physiological data will be retrieved from the subject’s medical record. Observational 
data will be collected during the scheduled intervention times per the study protocol. Study personnel will 
record all data in electronic format using a password-protected tablet or laptop computer. Data will be backed 
up to a secure server at the College of Nursing.  
C. POTENTIAL RISKS 
Describe the potential risks to subjects (physical, psychological, financial, legal, or other), and assess 
their likelihood and seriousness to the human subjects.  
The probability of adverse consequences to participants is minimal. Removal of secretions is an independent 
nursing action that is routinely done but not per evidence-based protocol. We propose to enhance secretion 
removal through a protocol-driven procedure done every 4 hours. We do not anticipate that this frequency of 
oral suction poses a risk to subjects as nurses have the option to suction as needed with devices that they 
prefer to use, usually a suction swab or tonsil suction device. A recent study conducted in Asia tested a device 
that was kept in the mouth for continuous suction, and reported no adverse issues.22 We have observed that 
patients may awaken during oral care interventions, but that they fall back to sleep immediately after it is done. 
We have performed this procedure (NO-ASPIRATE) to obtain specimens in previous studies without any 
adverse issues, such as gagging or oral trauma.25,93 However, subject response will be observed as part of 
ongoing monitoring.  
Oral care kits are standard for each patient, with supplies for oral suction, cleansing every 4 hours, and tooth 
brushing every 12 hours. We will use the same brand of oropharyngeal catheter that is packaged in the kits on 
a scheduled every-4-hour basis to those in the NO-ASPIRATE group.  
All subjects will get usual care to prevent microaspiration, including head of bed elevation, management of 
enteral feedings, assessment of readiness to wean from MV, and management of ETT cuff pressure within 
recommended ranges. Many subjects will be intubated with the specialized subglottic suction ETT.  
Trained members of the research team will implement the NO-ASPIRATE or usual care/sham interventions 
and collect data related to the study; all RAs will be experienced practitioners in management of patients on 
MV. Education and training is scheduled before beginning data collection and regularly throughout the study.  
We will purchase all study-related supplies, including the oropharyngeal suction catheters, sputum traps, and 
materials needed to run the α-amylase assays. No additional costs will be associated with participation.  
Where appropriate, describe alternative treatments and procedures, including the risks and potential 
benefits of the alternative treatments and procedures, to participants in the proposed research. 
No alternate treatments are identified. 
D. RECRUITMENT AND INFORMED CONSENT   
Describe plans for the recruitment of subjects and the process for obtaining informed consent. If the 
proposed studies will include children, describe the process for meeting requirements for parental 
permission and child assent. 
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Subjects will be recruited from the study units at Orlando Regional Medical Center. The PI, PD, or RAs will 
review the medical records of newly admitted patients to the study units. If a potential subject meets inclusion 
criteria, the study will be explained and a request for permission to enroll will be made to the patient (if alert 
and oriented and able to give consent) or the LAR. RAs will collaborate with the staff nurses, charge nurses, 
and the intensivist teams to assist in identification of potential subjects and to receive notification when the 
LAR is available. Our goal to enroll subjects as early as possible after admission; however, we need to ensure 
that the patient has been stabilized and that the patient or LAR is able to discuss participation. 
Include a description of the circumstances under which consent will be sought and obtained, who will 
seek it, the nature of the information to be provided to prospective subjects, and the method of 
documenting consent.  
The PI, PD, or RAs will obtain consent from the patient (if competent to provide consent) or the LAR as soon 
as feasible after admission, within the designated enrollment period. Using data from previous studies, we 
expect that nearly all consents will come from the LAR. Study personnel will approach the patient or LAR, 
explain the study, and obtain consent for participation. From experience, we anticipate that 75% of LARs who 
are approached will give consent for participation. A standard script will be developed for explaining the study 
and answering study-related questions. The consent process will be available in both English and Spanish, 
and an interpreter will be available if needed through the hospital’s translation services.  
The consent form will include all required information:  purpose, number of subjects, procedures, risks and 
benefits, measures to protect confidentiality, and the organization’s required HIPAA statements. Consent will 
be documented. The patient or LAR will be given a copy of the signed consent form.  
If during the course of the study, a subject becomes alert enough to understand the study and research 
processes, and the LAR has provided initial consent for participation, we will obtain verbal assent (nodding) or 
writing (yes/no) for continuation in the study from the subject. Should the subject gain sufficient cognitive ability 
to provide consent while enrolled, the study personnel will obtain his/her signature on the consent form   
The same procedures will be used for those 18-20 years of age, who are considered children for federal 
proposals. We will follow all rules and stipulations for enrolling this age group as specified by the ORMC IRB 
procedures. The IRB treats those 18 years of age and older as adults who are able to provide their own 
consent (http://www.orlandohealth.com/pdf%20folder/IRB%20Policies%20&%20Procedures/11-14-08/400-
Children06-2008.pdf).  
E. PROTECTION AGAINST RISK 
Describe planned procedures for protecting against or minimizing potential risks, including risks to 
privacy of individuals or confidentiality of data, and assess their likely effectiveness. 
During the study, patient safety will be of highest priority and all standards of care for the ventilated patient will 
be followed. All study team members delivering the intervention will receive training in both simulated and 
clinical settings before beginning the study, and periodic re-assessment of skills is scheduled throughout the 
study. The NO-ASPIRATE or usual care intervention will be stopped if clinical signs indicate the patient does 
not tolerate the procedure. Intolerance will be assessed by a 20% or more increase in heart or respiratory rate 
or a decrease in oxygen saturation below 85%. We will train RAs in all procedures, and monitor subjects for 
any adverse responses. The assigned critical care intensivist physician will be notified immediately should any 
serious adverse events occur during the study.  
Subjects in both groups will have oral suctioning done every 4 hours. The NO-ASPIRATE group will be 
suctioned with the oropharyngeal catheter while the usual care/sham group will be suctioned with the swab. 
We will use the same type of oral hygiene equipment (catheter and swab) readily available in the oral care kits 
for the NO-ASPIRATE and usual care/sham interventions. We will regulate the suction pressure for 
oropharyngeal and ETT suction within recommended ranges. Subjects may awaken during the intervention. In 
our pilot work, 25% of subjects awakened during the procedure; however, they returned to their resting state 
immediately after the procedure. Any oral intervention has the potential to increase gagging; however, we have 
not noted that to be an issue with the oropharyngeal suction catheter in our preliminary studies.  
Paired oral and tracheal specimens will be obtained for analysis of α-amylase. Tracheal aspirates will be 
obtained every 12 hours during a scheduled NO-ASPIRATE or usual care/sham intervention if clinical 
assessment indicates that the subject needs to be suctioned through the ETT. Suctioning will be done per 
standard procedures using the closed ETT suction system and recommended suction pressures. The subject 
will be hyperoxygenated via the ventilator before the procedure. ETT suctioning is regularly necessitated by the 
intubated patient and these same standards are followed when the patient is suctioned by the nurse or 
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Principal Investigator/Program Director (Last, first, middle): Sole, Mary Lou

respiratory therapist. We have used the same procedures in preliminary studies. Oral specimens will be 
obtained during the NO-ASPIRATE or usual care/sham intervention. 
Existing standards of care to prevent microaspiration will be continued by the nursing and respiratory care 
staff. These interventions include head of bed elevation, management of enteral feedings, management of the 
subglottic suction ETT (if patient is intubated with the SS-ETT), maintaining the ETT cuff pressure within 
recommended ranges (20 and 30 cm H2O), daily assessment of readiness to extubate, and oral antisepsis.  
All data will be coded to ensure confidentiality of information. Members of the research team will be trained in 
measurement techniques and safety precautions for all interventions and related procedures. They will 
demonstrate proficiency in a simulated setting prior to initiation of the study, and on a regular basis.  
Where appropriate, discuss plans for ensuring necessary medical or professional intervention in the 
event of adverse effects to the subjects. Studies that involve clinical trials (biomedical and behavioral 
intervention studies) must include a general description of the plan for data and safety monitoring of 
clinical trials and adverse event reporting to the IRB, the NIH and others, as appropriate, to ensure the 
safety of subjects. 
The PI, Dr. Sole, will assume all responsibility for integrity and safety of the proposed study, and will provide 
close oversight of all aspects of the study. We do not anticipate adverse issues related to the study; however, 
we will be vigilant in our assessment to identify any issues and work in collaboration with our intensivist co-
investigators. The NO-ASPIRATE intervention will be stopped if clinical signs indicate the subject does not 
tolerate it. The assigned intensivist physician will be notified immediately should any serious adverse events 
occur during the study.  
At regular study team meetings, safety data will be reviewed, including compliance with the protocol, 
enrollment data, and any adverse events. Monthly meetings will be held, and will be convened more frequently 
if indicated. Should any standards of care that might influence the conduct of the study change during the 
study, meetings will be held accordingly to discuss their impact on the study. The protocol should be 
designated as no more than minimal risk; therefore, frequency of review and monitoring of data should be 
adequate. All reporting as required by the IRB will also be done per policy. All federal, state, local, university, 
and HIPAA regulations will be followed.  
An independent Data and Safety Monitoring Board (DMSB) will be established to oversee the study and 
review any adverse events. (See H.)  
F. POTENTIAL BENEFITS OF PROPOSED RESEARCH TO SUBJECTS AND OTHERS  
Discuss the potential benefits of the research to research participants and others.  
Those assigned to the NO-ASPIRATE intervention arm may have a reduced risk of microaspiration and VAC. It 
is also possible that subjects will have no direct benefit from the study. Patients in the future who are intubated 
and receiving mechanical ventilation may benefit from knowledge gained from this study. 
Discuss why the risks to subjects are reasonable in relation to the anticipated benefits to research 
participants and others. 
The NO-ASPIRATE intervention is an enhancement of existing standards of care focused on reducing the oral 
secretion load to prevent microaspiration and VAC. It will help to identify standard oral suctioning practices and 
assess the benefits. The potential benefit of the intervention to future patients is very high if it results in a 
reduced rate of microaspiration and VAC. 
G. IMPORTANCE OF THE KNOWLEDGE TO BE GAINED  
Discuss the importance of the knowledge gained or to be gained as a result of the proposed research.  
Findings will be used to inform practice and establish standards of oral suctioning that can be incorporated into 
comprehensive airway management of the mechanically-ventilated patient. Knowledge of effectiveness of the 
NO-ASPIRATE intervention in a large sample of diverse critically ill patients will have great importance in 
influencing future practice to reduce microaspiration and prevent VAC. The study will yield important data to 
guide practice, and has the potential to influence types of oral care equipment that are most effective. It may 
also provide data for earlier detection of microaspiration, and guide treatment if needed. 
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Principal Investigator/Program Director (Last, first, middle): Sole, Mary Lou

Discuss why the risks to subjects are reasonable in relation to the importance of the knowledge that 
reasonably may be expected to result. 
The study is associated with minimal risks in that all study-related procedures are considered part of the care 
of the mechanically-ventilated patient. The knowledge to be gained will help to identify effective methods and 
establish standards of practice to prevent microaspiration.  
H. DATA AND SAFETY MONITORING PLAN 
Since we are using a clinical trial approach, we will establish an independent Data and Safety Monitoring 
Board (DMSB) to oversee the study and review any adverse events. The DSMB will include an intensivist, a 
nursing manager, and a master’s or doctoral-prepared critical care nurse. None of the members will be directly 
associated with the project. The DSMB will be convened at the start of the study and will meet every 6 months 
thereafter. More frequent monitoring will be done if recommended by the DSMB or if issues are identified. 
In collaboration with the PI, Dr. Talbert (data manager) and the Project Director will prepare reports for the 
DMSB. The reports will include enrollment data and any issues or adverse events noted. The Board can 
request additional information to assist in safety monitoring. Written minutes of DSMB meetings with 
summaries of adverse events will be forwarded to the ORMC IRB and NIH according to established written 
procedures for each group. Determinations or recommendations for early stopping of the trial by the DSMB will 
be made if safety issues are identified.  
 
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Principal Investigator/Program Director (Last, first, middle): Sole, Mary Lou

Inclusion of Women and Minorities 
Inclusion of Women 
In the critical care units where patients will be enrolled, women represent 35% of patients who require 
mechanical ventilation.  In our preliminary studies, we have recruited at least this percentage of women.  We 
anticipate that enrollment in this study will be similar to the demographics of the study units.  We will monitor 
demographic data on a regular basis to assess inclusion of women in the study.  If issues are noted, we will 
identify and implement solution to ensure that women are represented.   
Inclusion of Minorities 
Patients who require mechanical ventilation represent racial and ethnic diversity.  In a recently completed 
study, we found that Hispanic or Latino patients represented 14% of the population, and non-whites comprised 
28% of the population.  This diversity will facilitate our enrolling a diverse sample.  Based on our enrollment 
calculations, we anticipate that 15% of our subjects will be Hispanic or Latino, and at least 25% will represent 
racial groups other than white.  The PI will monitor enrollment data to ensure that minority populations are 
represented.  We have achieved good diversity enrollment in previous studies conducted on the study units.    
Women &Minorities                                                                                             Page 97
Principal Investigator/Program Director (Last, first, middle): Sole, Mary Lou