Comparison of Oxygenation Between Nasal Positive Airway Pressure (PAP) Versus Standard Care During Propofol-based Sedation for Endoscopic Ultrasound in an Ambulatory Surgical Setting: a Prospective Randomized Control Trial
Phase: NA
Conditions: Endoscopic Ultrasound
Sponsor: Indiana University

 
 
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Comparison of oxygenation between nasal positive airway pressure (PAP) versus standard care during 
propofol-based sedation for endoscopic ultrasound in an ambulatory surgical center: a prospective 
randomized controlled trial. 
 
 
 
 
 
 
Principal Investigator: John DeWitt, M.D. 
 
Co-PI: Mohammad Al-Haddad, M.D., Benjamin Bick, M.D., Mark Gromski, M.D. and Beth Traylor, M.D. 
 
Statistician: James E Slaven, M.S.  
 
 
Contacts: 
 
John DeWitt, M.D. 
 
 
 
 
Address: Indiana University Medical Center 
550 North University Blvd, UH 4157 
Indianapolis, IN 46202 
Phone: 317-944-0880 
Email: jodewitt@iu.edu 
 
Michael Pedro, M.D., VP, Medical Director  
 
 
 
 
 
 
Vyaire Medical 
26125 North Riverwoods Blvd. 
Mettawa, IL 60045 
Phone: 339.293.9211 
Email:  michael.pedro@vyaire.com 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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SUMMARY TABLE 
 
Title 
Comparison of oxygenation between nasal positive airway pressure (PAP) 
versus standard care during propofol-based sedation for endoscopic 
ultrasound in an ambulatory surgical center: a prospective randomized 
controlled trial. 
Project Office 
 
Study Size (# of patients) 
124 patients 
Study Design 
Prospective randomized controlled single site trial. 
Primary Outcome 
Compare the incidence, duration, and severity of oxygen desaturation 
(oxygen saturation below 90% for ≥15 seconds). 
Secondary Outcome 
1. Compare the amount of propofol administered during induction 
and total dose administered for procedure 
2. Compare Modified Observer's Assessment of Alertness/Sedation 
Scale (MOAAS) scores immediately prior to endoscopic intubation 
and during the procedure 
3. Compare the length of time from induction to endoscopic insertion 
4. Compare the incidence and duration of procedural interruptions 
(ie: number of times and length of time the endoscope is removed 
from the patient)  
5. Compare the incidence, duration, and reason for airway 
maneuvers  
6. Compare the length of time for the procedure (ie: length of time 
from procedure start to procedure end) 
7. Compare recovery times 
a. Ready to discharge 
b. Actual discharge 
8. Compare patient satisfaction scores (visual analog scale (VAS)) 
immediately after procedure 
a. Overall experience 
b. Quality of sedation  
c. Pain experienced during procedure 
d. Pain after the procedure 
e. Nausea after awakening 
f. Vomiting after awakening 
g. Dizziness after awakening 
h. Recollection of scope insertion 
i. 
Recollection of scope removal  
j. 
Awake during the procedure 
k. Could drive at discharge if permitted 
l. 
Would work at discharge if permitted  

 
 
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9. Compare patient satisfaction scores 48 hours later 
a. Overall experience 
b. Quality of sedation  
c. Pain experienced during procedure 
d. Pain after the procedure 
e. Nausea after awakening 
f. Vomiting after awakening 
g. Dizziness after awakening 
h. Recollection of scope insertion 
i. 
Recollection of scope removal  
j. 
Awake during the procedure 
k. Could drive at discharge if permitted 
l. 
Would work at discharge if permitted 
m. Time spent sleeping in the 24 hours after the procedure 
n. Time could have driven after the procedure 
10. Compare patient tolerance to SuperNO2VA™EtCO2 compared to 
control (ie: nasal cannula at 10LPM) 
11. Compare endoscopist satisfaction scores for 
a. Overall experience 
b. Rating of sedation 
c. Difficulty of patient to sedate 
d. Quality of the procedure 
e. Difficulty of intubation 
12. Compare anesthesiologists satisfaction scores 
a. Overall experience 
b. Rating of sedation  
c. Difficulty of patient to sedate 
13. Compare the incidence of cardiac complications  
 
 
Inclusion Criteria 
1. Age 18 years of age or older 
2. Patients undergoing upper endoscopic ultrasound 
3. American Society of Anesthesiology (ASA) Physical Status I-III  
4. BMI ≥35 kg/m2 or documented Obstructive Sleep Apnea 
5. Has provided written informed consent 
Exclusion criteria 
1. Inpatient status 
2. Active Congestive Heart Failure Exacerbation 
3. Untreated ischemic heart disease 
4. Acute exacerbation of respiratory disorders, including COPD and 
asthma 
5. Emergent procedures 
6. Pregnancy 
7. Previous enrollment in this study 
8. Inability to provide informed consent 

 
 
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9. Additional medical testing planned for the same day 
10. History of allergic reaction to Propofol 
11. Tracheostomy 
12. Supra-glottic or sub-glottic tumor 
13. Gastrointestinal tract obstruction or delayed transit (including 
delayed gastric emptying, gastric bezoar, achalasia, toxic 
megacolon). 
 
Study Procedures 
 
Pretreatment Evaluation 
N/A 
On-Study Visits 
N/A 
Follow-up Visits 
Patient will complete a mail-in survey after 48 hours. 
End of Study Visit 
N/A 
Brief Analysis Plan 
Based on the literature the incidence of hypoxemia (ie: oxygen 
saturation < 90% for > 15 seconds) in using supplemental oxygen with 
nasal cannula is as high 43%. (Patel et. al.) Thus we expect the 
complication rate of hypoxemia in the SuperNO2VA™EtCO2 group to be 
13%, we need 62 patients per group (112 patients in total) to detect this 
expected difference with 80% power at 0.05 two-sided level of 
significance. To adjust for 10% missing rate, we need approximately 124 
patients in total. 
 
 
 
1. OBJECTIVES 
 
Primary Objective 
The primary objective of the study is to prospectively and randomly compare the incidence, duration, and 
severity of oxygen desaturation between a nasal mask with nasal positive airway pressure (PAP) versus standard 
care (nasal cannula) during propofol-based sedation for endoscopic ultrasound in an ambulatory surgical center 
(ASC) in patients considered high risk for hypoxia (ie: BMI ≥35 kg/m2  or documented Obstructive Sleep Apnea.  
 
Endpoints of Interest 
1. Compare the amount of propofol administered during induction and total dose administered for 
procedure 
2. Compare Modified Observer's Assessment of Alertness/Sedation Scale (MOAAS) scores immediately 
prior to endoscopic intubation and during the procedure 

 
 
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3. Compare the length of time from induction to endoscopic insertion 
4. Compare the incidence and duration of procedural interruptions (ie: number of times and length of time 
the endoscope is removed from the patient)  
5. Compare the incidence, duration, and reason for airway maneuvers  
6. Compare the length of time for the procedure (ie: length of time from procedure start to procedure end) 
7. Compare recovery times 
8. Compare patient satisfaction scores (visual analog scale (VAS)) immediately after procedure 
9. Compare patient satisfaction scores 48 hours later 
10. Compare patient tolerance to SuperNO2VA EtCO2 compared to control (ie: nasal cannula at 10LPM) 
11. Compare endoscopist satisfaction scores for 
12. Compare anesthesiologists satisfaction scores 
13. Compare the incidence of cardiac complications  
 
Study Design 
This is a prospective randomized controlled single site trial. 
 
2. BACKGROUND  
Endoscopic ultrasound is a common procedure performed in ambulatory surgical centers in the U.S. Most 
patients undergoing endoscopy require sedation to have an acceptable experience.1-2 In endoscopic 
ultrasound (EUS), sedation is a necessity because the ability to interpret images and perform therapeutic or 
diagnostic procedures are dependent on the subjects cooperation.  Reliable imaging cannot be obtained if 
the patient is not cooperative. Propofol is a commonly used sedative that has been used in several studies 
for endoscopic procedures and is associated with low complication rates in healthy patients (ie: ASA I and 
II).3-5 However, recent prospective studies have shown that hypoxemia frequently occurs during endoscopic 
procedures in patients with a BMI > 30kg/m2 or have a history of OSA 6-9 and the mortality rate for sedation 
in the endoscopy suite is significantly higher than that of the comparable cases performed in operating 
room.10 Although the cause of the high mortality in GI suite has yet to be determined, it seems to be related 
to hypoxia and/or hypercarbia due to respiratory depression and upper airway obstruction from sedation.10  
 
Continuous positive airway pressure (CPAP), applied nasally or via facemask, has been shown to be more 
effective at minimizing hypoxia than other devices under sedation or general anesthesia.11-12 However, it 
requires a special mask and CPAP machine with high-fresh gas flows which may not be routinely equipped in 
GI endoscopy suites due to space and cost constraints.13 Therefore, a simplified CPAP system could be a 
surrogate for a conventional CPAP machine for procedures requiring sedation or general anesthesia with 
spontaneous breathing via a natural airway. Recently, a simple, novel CPAP device was developed, which 
includes a sealed nasal mask and disposable, flow-inflating hyperinflation bag (SuperNO2VA Et™ Satellite Set, 
Revolutionary Medical Devices, USA).14 A small pilot study by Ghebremichael, et al. demonstrated safety and 
efficacy with the use of the SuperNO2VA Et™ device for nasal mask ventilation (NMV) in anesthetized and 
paralyzed patients.14 The objective of our study is to compare oxygenation in spontaneously ventilating 
obese patients or those with diagnosed or undiagnosed OSA undergoing endoscopic ultrasound under 
propofol based sedation in an ambulatory surgical center between the SuperNO2VA Et™ nasal positive 
airway pressure (PAP) device and routine care with nasal cannula for O2 supply.  In a simulated patient 
setup, the SuperNO2VA ET CO2Nasal mask are accurate for measurements of end tidal carbon dioxide 
(etCO2).  
 
 

 
 
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3. DISCUSSION OF SUBJECT POPULATION 
3.1. Subject Characteristics 
The study population for this investigation is all adults who have a BMI > 35 kg/m2 or documented OSA 
scheduled to receive Propofol based sedation for Endoscopic Ultrasound. 
 
3.2. Inclusion and Exclusion Criteria 
 
a) Inclusion Criteria:   
1. Age 18 years of age or older 
2. Patients undergoing upper endoscopic ultrasound 
 
3. American Society of Anesthesiology (ASA) Physical Status I-III  
4. BMI ≥35 kg/m2 or documented Obstructive Sleep Apnea 
5. Has provided written informed consent 
 
b) Exclusion Criteria:  
1. Inpatient status 
2. Active Congestive Heart Failure Exacerbation 
3. Untreated ischemic heart disease 
4. Acute exacerbation of respiratory disorders, including COPD and asthma 
5. Emergent procedures 
6. Pregnancy 
7. Previous enrollment in this study 
8. Inability to provide informed consent 
9. Additional medical testing planned for the same day 
10. History of allergic reaction to Propofol 
11. Tracheostomy 
12. Supra-glottic or sub-glottic tumor 
13. Gastrointestinal tract obstruction or delayed transit (including delayed gastric emptying, 
gastric bezoar, achalasia, toxic megacolon). 
 
3.3. Discussion of Subject Population:  
Patients with either a BMI ≥35 kg/m2 or a documented Obstructive Sleep Apnea scheduled for Endoscopic 
Ultrasound with Propofol sedation at are increased risk for severe hypoxemia intra-operatively and post-
operatively due to Propofol’s relaxant effect on muscle of the upper airway.  In addition patients with OSA 
usually fall into three scenarios. Those that are diagnosed with OSA and are using their CPAP, those that 
are diagnosed with OSA but do not use CPAP, and the undiagnosed OSA patient. Therefore, more patients 

 
 
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than not are at risk for cardiopulmonary morbidity intra-operatively and immediately after Propofol based 
sedation.  
 
 
4. SUBJECT IDENTIFICATION, RECRUITMENT AND CONSENT 
 
4.1.  
Method Of Subject Identification And Recruitment 
Subject consenting will take place at the GLES immediately prior to the procedure by key research 
personnel such as PI, Co-PIs, and/or study coordinators. Subject initials and/or study identification 
number will refer to the subjects. 
 
4.2.  
Consent Process 
Subjects deemed eligible to participate in the study will be explained in detail the purpose, nature and 
procedures of the study, as well as the potential risks, benefits and alternatives. They will be given a 
consent form to read and if they so choose, to discuss with friends, family, and other clinicians. They 
will be invited to ask questions and, after all questions are answered to their satisfaction, invited to 
sign the consent form. The Principal Investigator (with proper delegation of authority) will participate 
in the consenting process to ensure the subject has full understanding of the procedure and risks. No 
study-specific procedure will be performed before the consent form is signed. 
 
Subject participation in this investigation is voluntary. Written informed consent is required from all 
subjects prior to the subject's participation in the investigation. Also, an obtained permission of the 
faculty anesthesiologist, in charge of the patient’s anesthesia care, must also be granted for subject 
participation. If the subject is illiterate or unable to adequately read the informed consent form, a 
witness' signature and a cross mark or a fingerprint of the subject is required. In accordance with FDA 
regulation 21 CFR Part 50, informed Consent shall be obtained prior to any study procedure. The 
original of the signed consent will be retained at the investigational site. A signed copy of the consent 
will be given to the subject. While not anticipated, Sponsor will report any failure to obtain subject 
consent to the IRB within 5 days of learning of such an event, as required by regulation. 
 
Prior to participating in this investigation, the site will be required to have an IRB-approved Informed 
Consent Document. Any modifications to the consent must be approved by Sponsor and by the IRB of 
record. The Principal Investigator at each study site is responsible for obtaining and maintaining the 
approved informed consent and forwarding an IRB-stamped copy to Sponsor. 
  
4.3. Costs to the Subject 
None 
 
4.4.  
Payment for Participation 
None 
 
4.5. Return of Individual Research Results 
Not Applicable. 
 
5. METHODS AND STUDY PROCEDURES 
 
5.1   Instruments 

 
 
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The SuperNO2VA™EtCO2 (Nasal Oxygenating Ventilating Apparatus) mask is indicated to deliver gas, 
create a seal, and provide positive pressure while placed over a patient’s nose and connected to either an 
anesthesia circuit or hyperinflation bag during respiratory, anesthesia, and resuscitation procedures. The 
SuperNO2VA™EtCO2 mask is also intended to facilitate simultaneous oxygenation and ventilation during 
intubation, as the mask covers only the patient’s nose, leaving the clinician with an unobstructed view of 
the airway. 
 
5.2   Methods:  
This study involves the oxygenation, continuous positive airway pressure, and ventilation of a subject via 
nasal mask and oxygenation via a closed facemask. The interventions directly related to this study are that 
of supplement oxygen, bag-mask ventilation, and continuous nasal CPAP intra-operatively and in the Post 
Anesthesia Care Unit. 
 
Patients will be randomized in groups of ten to one of two groups using a random number table. Group 
A: Standard care with a nasal cannula. Group B: SuperNO2VA™EtCO2.  
 
For each anesthetic case, a preoperative history and physical and intraoperative record will be 
documented (table 1).  
 
Table 1: General Patient characteristics 
  
Age (years) 
  
Gender (M/F) 
  
Height (cm) 
  
Weight (kg) 
  
BMI (kg/m2) 
  
ASA classification (I-III) 
  
Diagnosed OSA on home CPAP 
 
Diagnosed OSA not on home CPAP 
 
STOP-BANG Score 
 
Patient Co-morbidities* 
 
 
*Co-morbidities include any history of: hypertension, diabetes, coronary disease, valvular disease, 
arrhythmia, cerebrovascular disease, active cancer, tobacco use, pulmonary disease, renal disease, liver 
disease. 
 
Once in the endoscopy suite, the patients will have continuous monitoring of heart rate, end tidal CO2 
(EtC02), O2 saturation, and every 2-minute BP monitoring.  Patients randomized to group A, the 
anesthesia provider will supply oxygen via nasal cannula at 10LPM. Patients randomized to group B, the 
anesthesia provider will attach the SuperNO2VA™ EtCO2’s circuit port to the hyperinflation bag with the 
oxygen flow rate to 10 L/min, and the APL valve completely closed.   Initial dosing bolus 0.5-1.0 mg/kg 
actual body weight of Propofol will be administered for sedation and MOAA/S scores will be assessed. 
Nursing or the research assistant will then record the patient’s MOAA/S score. If the patient’s MOAA/S 
score is ≥ 4, additional 10-20mg boluses will be administered every 30 – 90 seconds until a MOAA/S score 
of <4 reached. Once a MOAA/S score of < 4 is reached the endoscopist will perform endoscopic intubation 
and the goal will be to maintain a MOAA/S score of <4 until the procedure is over. If the patient’s MOAA/S 
score ≥4, additional 10 – 40mg bolus of propofol will be administered every 30-90 seconds until the 

 
 
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MOAA/S is <4.   The measurements that will be made are the following: the incidence, severity, and time 
of oxygen desaturation, number of airway maneuvers performed, duration of airway maneuvers, reason 
for performing the airway maneuver, the onset time of administration of sedation, the duration of the 
procedure, the total dosage of the medication, vital signs - blood pressure, heart rate, and oxygen 
saturation, the time to full recovery, and patient cooperation.  Nursing or the research assistant will 
document their patient’s depth of sedation, cooperation with procedure, and safety.   Patients will recover 
in the endoscopy suite.  The patients will have continuous monitoring of heart rate, end tidal CO2 (EtC02), 
O2 saturation, and every 5-minute BP monitoring and MOAAS Score.  The time to discharge will be 
obtained for each patient.  Patients will also complete a satisfaction and pain questionnaire before they 
are discharged.  Patients will also be asked to complete  another questionnaire within 48 hours concerning 
their satisfaction and their subjective degree of impairment due to the sedation either with a paper form 
and self-addressed envelope or electronically sent via e mail.  If the patients do not complete their 
questionnaire, someone will contact them by telephone to collect the data.  A statistician using student 
T-test, Fishers exact test, and other statistical methods they deem appropriate will analyze the collected 
data. 
 
5.3 Definitions of Events  
• 
Airway maneuver: consists of either airway maneuvers such as chin lift, jaw thrust, submental 
pressure, mask ventilation, pushing downward on the mask, tightening of the strap, flexing the head 
forward or the insertion of a nasal or oral airway, supraglottic device, or ETT 
• 
Oxygen desaturation: SpO2 ≤ 90% for ≥ 15 seconds 
• 
Cardiac complications is defined by a change in either SBP or DBP > 25% from baseline, a change in 
heart rate > 25% from baseline, arrhythmias, and ST-changes on EKG (ST depression or elevation). 
• 
Full recovery is defined as the time from endoscope withdrawal until a MOAA/S score of 5 was 
achieved and the patient could drink liquids and ambulate independently. 
• 
Full recovery until actual discharge is defined as the interval from full recovery until the patient 
exited the recovery room. 
• 
Induction to full sedation is the time from initial administration of intravenous sedative or analgesic 
to the insertion of the endoscope 
• 
Intraprocedural period was defined as the time of first scope insertion until the last scope removal. 
• 
Procedural interruption is defined as the removal of the endoscope due to a respiratory 
complication 
• 
Modified Observer's Assessment of Alertness/Sedation Scale (MOAAS) from 1 – 5 
MOAAS:   
0 No response after painful trapezius squeeze 
1 Responds only after painful trapezius squeeze 
2 Responds only after mild prodding or shaking 
3 Responds only after name is called loudly and/or repeatedly 
4 Lethargic response to name spoken in normal tone 
5 Responds to name spoken in normal tone 
 
5.4 Crossover to Other Group After Randomization 

 
 
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Patients in either Group A or Group B will be eligible for crossover to the other group at the discretion of 
the anesthesiologist in order to safely complete the procedure and minimize the likelihood of future 
adverse events.  
 
Group A (Standard care with a nasal cannula) to Group B (SuperNO2VA™EtCO2) group will occur when 
during the procedure either: 1) two or more simultaneous or non-synchronous adverse events related to 
changes in SBP, Sp02 or HR that do not respond to typical maneuvers to reverse these or; 2) any of the 
following two occur: a) any change in heart rhythm other than sinus bradycardia or sinus tachycardia or; 
b) ST changes appear on EKG occur. 
 
Group B to Group A: If any of the following occur:  1) patient refusal to wear the mask once placed due 
to claustrophobia, poor fit or discomfort or any other reason;  2) two or more simultaneous or non-
synchronous adverse events related to changes in SBP, Sp02 or HR that do not respond to typical 
maneuvers to reverse these or; 3) any of the following two occur: a) any change in heart rhythm other 
than sinus bradycardia or sinus tachycardia or; b) ST changes appear on EKG occur. 
6. SUBJECT WITHDRAWALS 
Subjects may be withdrawn from the study for the following reasons: 
1. Unacceptable adverse events (safety or tolerability) 
2. The subject’s may withdraw from the study at any time and for any reason 
3. Clinician decision that it is in the best interest of the subject to withdraw from the study 
 
7. SAFETY AND REPORTABLE EVENTS 
 
7.1. Adverse Event Definition 
Adverse Event (AE): An Adverse Event is any undesirable clinical event occurring to the subject during 
clinical study, whether or not it is considered related to the investigational product. This includes a 
change in a subject's condition or laboratory results, which has or could have a deleterious effect on the 
subject's health or well-being. An Adverse Event that is related to the investigational device may be 
referred to as an Adverse Device Effect (ADE). 
 
Adverse Events 
For study conduct purposes, adverse events will be categorized at the investigative site into two groups: 
Serious Adverse Events, and Non-Serious Adverse Events. The Investigator as either related to the device 
or its deployment, or not related to the device or its deployment will assess the causal relationship of 
each adverse event. Each Adverse Event assessed as being related to the device or its deployment will 
also be assessed by the Investigator as being anticipated or unanticipated. 
 
An adverse event does not include: 
• 
Medical or surgical procedures; the condition that leads to the procedure is not an adverse event 
• 
Pre-existing disease, conditions, or laboratory abnormalities present at the start of the study that do not 
worsen in frequency or intensity 
• 
Situations where an untoward medical occurrence has not occurred (e.g., hospitalizations for cosmetic 
or elective surgery or social/convenience admissions) 
• 
Expected ICU course 

 
 
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7.2. Unanticipated Adverse Device Effect (UADE) 
Any device related adverse event, the nature or severity of which is not consistent with or listed in the 
applicable product information (e.g., instructions for use, subject informed consent document, subject 
information brochure [if applicable], promotional literature) or any other unanticipated serious 
problem associated with a device that relates to the rights, safety, or welfare of subjects. 
 
 
7.3. Responsibilities for Reporting Serious Adverse Events 
All adverse events, whether observed by the Investigator, elicited from or volunteered by the subject, 
should be documented. Each adverse event will include a brief description of the experience, the date 
of onset, the date of resolution, the duration and type of experience, the severity, the relationship to 
investigational product (i.e., drug or device), contributing factors, and any action taken with respect to 
the study drug/device. 
 
Investigators and research coordinators will be instructed that all AE and corresponding relevant 
information should be recorded on the Adverse Event Form. In addition, the clinical site will be 
responsible for notifying Sponsor within 24 hours of any UADE. All relevant information regarding an 
UADE should be recorded on the Adverse Event Form and reported to Sponsor via Fax within 24 hours 
of the event. In addition to the event form, copies of adverse device effect related source documents 
should be forwarded to the Sponsor. 
 
The Principal Investigator is responsible for reporting AEs to the IRB of record in accordance with IRB 
procedures. The Sponsor is responsible for informing the appropriate regulatory authorities and other 
Investigators of any UADEs that have occurred. 
 
The Principal Investigator will record all serious adverse experiences that occur during the study 
period in the appropriate source documents and/or AE log as applicable. 
 
8. RISK/BENEFIT ASSESSMENT 
 
8.1. Potential Risks 
As with use of all medical devices, complications may occur. Recognized risks associated with the use of 
the study intervention include, but are not limited to, the following: 
 
• 
Allergic reactions: although the materials being used are hypoallergenic and the risk is small, there 
remains a risk for an allergic reaction that may result in hives, swelling, or anaphylaxis. 
• 
Ocular injury: although the SuperNO2VA Et™ Mask was designed to contour away from the eyes, 
mishandling of the mask or accidental slippage from its intended position may result in contact with 
the subject’s eye, resulting in a corneal abrasion and/or other ocular injury. 
• 
Pressure ulcer: although the clinical protocols states to remove the SuperNO2VA Et™ after successful 
placement of an invasive airway, if the SuperNO2VA Et™ is mistakenly left on the subject for an 
extended period of time it can lead to a pressure ulcer. 
 
8.2.  Risks Minimization 

 
 
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• 
To minimize the risk of allergic reactions the SuperNO2VA Et™ has undergone and successfully passed 
biocompatibility testing. However, there is still a very small risk for an allergic reaction that may result 
in hives, swelling, or anaphylaxis. 
• 
To minimize the risk of an ocular injury, it is recommended that all clinicians be properly trained on 
how to use the SuperNO2VA™EtCO2 and be familiar with the Instructions For Use (IFU). 
• 
To minimize the risk of a pressure, it is recommended that all clinicians be properly trained on how to 
use the SuperNO2VA™EtCO2, be familiar with the Instructions For Use (IFU), and monitor the subject’s 
face for redness every 30 minutes that the SuperNO2VA™ EtCO2 is secured to the subject. 
 
 
8.3. Potential Benefits to Subjects 
• 
Improved oxygen delivery, administration, and oxygenation 
• 
Potentially able to reduce post-op respiratory complications 
 
8.4. Alternatives to Participation 
The alternative for not participating in this study is not using the SuperNO2VA™ EtCO2 for gastrointestinal 
endoscopy.  
 
9. CONFIDENTIALIATY OF DATA AND INFORMATION STORAGE  
All study participants will be assigned a study number.  The PI will maintain the key to the study number and 
medical record number in a password locked Indiana University computer.  Information about study subjects 
will be kept confidential and managed according to the requirements of the Health Insurance Portability and 
Accountability Act of 1996 (HIPAA).  Patient data will be entered into a password protected electronic 
spreadsheet and online database (i.e. REDCap).  Only the investigators, who have been invited to participate 
in the study and who are registered with the IRB, as well as have documented completion of all IRB and HIPAA 
regulations will have access to patient data, but not the medical record key.  
 
Electronic records will be stored for 5 years after study conclusion on the institution’s password protected 
computer, after which time they will be deleted. If there is a breach in confidentiality or violation of IRB and 
HIPAA regulations, the IRB will be notified in a timely manner (within 7 days) and appropriate actions taken 
thereafter.  All data used in the analysis and reporting of this investigation will be de-identified.   
 
In order to ensure compliance with the Health Insurance Portability and Accountability Act (HIPAA), all 
subjects enrolled in the study will be required to provide authorization to disclose Protected Health 
Information (PHI). This authorization will be included in the informed consent document as required by the 
IRB. In all study reports and in any resulting publications, subjects will not be referred to by their initials and/or 
study identification number. 
 
The co-PIs will monitor for safety. Data safety will be ensured by having all patient consents and information 
stored in the REDCaps system. After randomization patient and study data outside the REDCaps system will 
only be identified by study number. Any recruitment data and randomization tables will be stored as a single 
copy in a locked cabinet in a PI’s secured Faculty office. 
 
10. SAMPLE SIZE DETERMINATION AND DATA ANALYSIS  
 
10.1. Sample Size Determination 
Power analyses were performed for the three primary objectives, using a power level of 0.80 and an alpha 

 
 
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level of 0.05.  Based on the literature the incidence of hypoxemia (ie: oxygen saturation < 90% for > 15 
seconds) in using supplemental oxygen with nasal cannula is as high 43%. (Patel et. al.) Thus we expect the 
complication rate of hypoxemia in the SuperNO2VA Et™ group to be 13%, we need 62 patients per group (124 
patients in total). This sample size will allow us to detect this expected difference with 80% power at 0.05 two 
sided level of significance. To adjust for 10% missing rate, we need approximately 124 patients in total. 
 
10.2. Randomization 
A random number generator program will be used to assign sequential qualified study cases to control group 
(N = 62) or SuperNO2VA™EtCO2 group (N = 62) before collection of additional demographic information and 
before anesthetic and surgical care. After study group assignment, baseline data will be collected, including 
age, gender, height, weight, and BMI. 
 
10.3. Planned Statistical Analysis 
Although randomization into treatment groups should minimize differences between the groups, basic 
bivariate analyses will be performed to determine if there are any clinical or demographic differences, using 
the data collected in table 1.  Logistic regression models will be performed to determine if there are significant 
differences between the groups for both incidence and severity.  Student’s t-tests will be performed to 
determine if there is a significant difference between groups for duration, with Wilcoxon non-parametric tests 
being performed if the data are non-linear.  If significant differences in clinical or demographics characteristics 
were found, multivariable models will be performed to adjust for these possible confounding variables using 
logistic regression and ANCOVA models (with GEE models being used to model non-linear data with the 
appropriate exponential family distribution).  All analytic assumptions will be verified and all analyses 
performed with SAS v9.4, SAS Institute, Cary, NC), analyzing the data as both per-protocol and intention-to-
treat. 
        
 
A Data Safety and Monitoring Board (DSMB) will be convened once half the necessary study population 
has been enrolled, to discuss the current status of primary endpoints and adverse events, all of which will be 
tabulated throughout the study.  If effect sizes are larger than originally planned and there is a statistically 
significant decrease in the primary event at this halfway mark, the study will end at this time. 
 
11. ETHICS 
Institutional Review Board (IRB) 
Prior to participating in this investigation, the site will be required to obtain approval from its governing IRB. 
The Principal Investigator is responsible for obtaining and maintaining IRB approval to participate in this 
investigation. Prior to subject enrollment, a signed copy of the IRB approval letter addressed to the 
Investigator certifying study approval must be submitted to the Sponsor. The IRB for this study is the local 
IRB at Indiana University Hospital. The Investigator will report to the Sponsor immediately if, for any reason, 
the approval to conduct the investigation is withdrawn. This report will include a complete description of the 
reason(s) for which approval was withdrawn. 
  
12. DATA MONITORING 
 
Data Review 
The Sponsor will review all CRFs for completeness and clarity upon receipt. Missing or unclear data will be 
requested as necessary throughout the study. The Sponsor will request further documentation such as 
physician procedure notes when UADEs and/or malfunctions are observed and reported. 
 

 
 
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The Sponsor will provide clinical monitoring including comparison of CRFs to source documentation for 
accuracy and appropriateness, review of/for adverse events, prompt evaluation of UADE, and site 
compliance. To this end, the Principal Investigator will permit inspection of the study files and subject CRFs 
by Sponsor representatives and/or responsible government agencies. 
 
Prior to initiation of the study, sites will be trained on the clinical protocol, accepted clinical practices and 
Federal regulations pertaining to clinical research. Study sites will receive interim monitoring, as needed, 
and a final visit prior to study closure. 
 
 
Compliance and Deviations 
It is expected that sites (Investigators, study coordinators, ancillary site personnel, and study subjects) will 
be compliant with the study protocol. Should it be determined that the site is non-compliant, reasonable 
efforts will be made to secure compliance. These efforts/actions shall be documented in writing and 
maintained within the study administration file at the Sponsor’s location. 
 
Should the site continue to remain non-compliant, the study Sponsor may restrict device availability and/or 
notify the governing IRB. Should efforts to bring the site into compliance fail, the site may be suspended 
from study participation until the noncompliance is resolved. Federal regulations require the Sponsor to 
report non-compliances in the study to the appropriate regulatory authorities. Therefore, in the event of an 
Investigator or site suspension, the governing IRB and other appropriate regulatory authorities shall be 
notified. 
 
Protocol Deviations 
Protocol Deviations (PDs) will be documented on a Protocol Deviation Case Report Form. PDs are reportable 
to the institution's governing IRB and regulatory agencies during the annual reporting process, unless 
otherwise directed by the individual governing IRB requirements or as the specific circumstance dictates. 
Every attempt shall be made to adhere to the study protocol. However, should an Investigator be required 
to deviate from the protocol to protect the life or physical well-being of a study subject in an emergent 
circumstance, such notice shall be given to the study Sponsor as soon as possible, but no more than 5 
working days from the date the event occurred. With the exception of an emergent circumstance, prior 
approval from Sponsor and the appropriate regulatory authorities is required for any change in, or deviation 
from, the study protocol as such changes may affect the soundness of the investigation or the rights, safety, 
and welfare of study subjects. 
 
Data Safety Monitoring 
     Two gastroenterologists (Thomas Imperiale, MD and Nicholas Rogers, MD), who are not a part of the study, 
will review adverse events, serious adverse and protocol deviations at the Indiana University site.  These events 
and deviations will also be reported to the IU IRB as required.  They will review all serious adverse events within 
24 hours of their occurrence.  Once 62 participants have been randomized, an interim analysis will be completed 
to  review efficacy of primary endpoint, adverse events, serious adverse and protocol deviations.  A final safety 
review will be performed once all the subjects complete the study. 
 
Investigator Reports and Responsibilities 
Investigators are responsible for ensuring the investigation is conducted in accordance with the study 
protocol and applicable Federal regulations (21 CFR, Part 812, Subpart E).  
 

 
 
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Investigators are also responsible for: 
• 
Obtaining IRB approval for study conduct and re-approval as applicable (if more than one Investigator is 
participating in the study at a site, the Principal Investigator shall be responsible for the IRB approval 
and re- approvals) 
• 
Obtaining informed consent of study subjects prior to enrollment into the clinical study 
• 
Protecting the subject rights, safety, and welfare 
• 
Maintenance of subject records and confidentiality 
• 
Record retention as defined in Federal regulations 21 CFR, Part 812.140 (a), (d), and (e) 
• 
Management of investigation and study related activities according to the Clinical Investigator 
Agreement and the Study Research Agreement 
• 
Submission of site-specific study closure report to governing IRB within 3 months of notification from 
study Sponsor (if more than one Investigator is conducting the study, the Primary Investigator is 
responsible for submission of the study closure report) 
• 
Return of any unused investigational product to the study Sponsor upon request or at the conclusion of 
the clinical study 
 
In addition: 
• 
An Investigator shall report to the Sponsor, within 5 working days, a withdrawal of approval by the 
reviewing IRB of the Investigator's part of an investigation 
• 
If an Investigator uses a device without obtaining informed consent, the Investigator shall report such 
use to the Sponsor and the reviewing IRB within 5 working days after the use occurs 
• 
An Investigator shall, upon request by a reviewing IRB or regulatory agency official, provide accurate, 
complete, and current information about any aspect of the investigation 
 
Sponsor Reports and Responsibilities 
The study Sponsor is responsible for ensuring the study is conducted in accordance with the study protocol 
and applicable federal regulations (21 CFR, Part 812, Subpart C). Further, the study Sponsor is responsible 
for the following: 
• 
Selecting qualified Investigators and providing Investigators with appropriate information for study 
conduct 
• 
Ensuring review and approval process for governing IRB is obtained 
• 
Training all clinical investigators in the study  
• 
Appropriate monitoring of the clinical study 
• 
Prompt notification to the appropriate regulatory and all Investigators of UADE 
• 
Record maintenance and retention per Federal regulations (21 CFR, Part 812.140 (b), (d), and (e) 
• 
Submission of final study closure report that details cumulative study experience to the appropriate 
regulatory authorities, governing IRBs, and Investigators within 6 months of completing the clinical 
investigation in addition to fulfilling annual reporting requirements 
 
In addition: 
• 
A Sponsor who conducts an evaluation of an UADE shall report the results of such evaluation to all 
reviewing IRBs and participating Investigators within 10 working days after the Sponsor first receives 
notice of the effect. Thereafter the Sponsor shall submit such additional reports concerning the effect as 
an IRB request 

 
 
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• 
A Sponsor shall notify all reviewing IRBs and participating Investigators of any withdrawal of approval of 
an investigation or a part of an investigation by a reviewing IRB within 5 working days after receipt of 
the withdrawal of approval 
• 
At regular intervals, and at least yearly, a Sponsor shall submit progress reports to all reviewing IRBs. In 
the case of a significant risk device, a Sponsor shall also submit progress reports to the regulatory 
authority 
• 
A Sponsor shall notify all reviewing IRBs of any request that an Investigator return, repair, or otherwise 
dispose of any units of a device. Such notice shall occur within 30 working days after the request is made 
and shall state why the request was made 
• 
In the case of a significant risk device, the Sponsor shall notify the IRB within 30 working days of the 
completion or termination of the investigation and shall submit a final report to all reviewing IRBs and 
participating Investigators within 6 months after completion or termination. In the case of a device that 
is not a significant risk device, the Sponsor shall submit a final report to all reviewing IRB's within 6 
months after termination or completion 
• 
A Sponsor shall submit to the IRB a copy of any report by an Investigator of use of a device without 
obtaining informed consent, within 5 working days of receipt of notice of such use 
• 
If an IRB determines that a device is a significant risk device, and the Sponsor had proposed that the IRB 
consider the device not to be a significant risk device, the Sponsor shall submit to the appropriate 
regulatory agency a report of the IRB's determination within 5 working days after the Sponsor first 
learns of the IRB's determination 
• 
A Sponsor shall, upon request by a reviewing IRB, provide accurate, complete, and current information 
about any aspect of the investigation 
 
Study Termination 
The Sponsor may terminate the study at any time. If terminated, the Sponsor will promptly notify the 
Investigator to cease enrollment of subjects. The study will also be terminated when the objectives have 
been fully met and all of the designated data collected. 
 
Study Registration 
The study will be listed at www.clinicaltrials.gov. 
 
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