Feasibility of Using Daily Home HNHF-O2 During Sleep and/or Daytime in Hypercapnic COPD Patients Following Recent (&lt 12 Wks.) Hospitalization for AECOPD for 90 Days
Phase: NA
Conditions: Pulmonary Disease, Chronic Obstructive, Hypercapnia, Hypoxia
Sponsor: Temple University

Protocol title:  
Feasibility of using daily Humidified Nasal High-flow with Oxygen during Sleep and/or Daytime in 
Hypercapnic COPD patients following recent (< 12 wks.) hospitalization for AECOPD for 90 days 
NCT03221387 
Date: 10/06/2017 

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1) Abstract of the study
Humidified Nasal High-flow with Oxygen (HNHF-O2) therapy has been reported to
have acute beneficial effects in patients with hypoxemic respiratory failure. HNHF-
O2 may be beneficial in patients with COPD and chronic impairments in gas
exchange, both hypoxemia as well as hypercapnia. HNHF-O2 may decrease work of
breathing, reduce dyspnea, improve airway humidification, and potentially stabilize
or reduce carbon dioxide levels.   However, there is limited data showing the chronic
effects of HNHF-O2 in patients with hypercapnic respiratory failure, specifically those
discharged to home following hospitalization for an acute exacerbation.   Data that
demonstrates that HNHF-O2 is well tolerated, and stabilizes or improves gas
exchange long term in patients with COPD is lacking. Similarly, data that
demonstrates that this therapeutic regimen is feasible to provide to patients in the
home environment are lacking.  This is an open-labeled pilot study of thirty patients
to determine the safety and feasibility of using the device in the outpatient
management of patients with COPD.
2) Protocol Title
Feasibility of using daily Humidified Nasal High-flow with Oxygen during Sleep
and/or Daytime in Hypercapnic COPD patients following recent (< 12 wks.)
hospitalization for AECOPD for 90 days
3) IRB Review History
Not applicable
4) Investigator
Gerard J. Criner, MD
5) Objectives
To assess the feasibility of using daily home HNHF-O2 during sleep and/or daytime
in hypercapnic COPD patients following recent (< 12 weeks) hospitalization for
AECOPD for 90 days.
6) Background
Many patients who experience a COPD exacerbation and who have received
oxygen in the hospital are candidates for home oxygen use.  Long-term oxygen use
has been shown to reduce COPD mortality.  There are a number of ways by which
oxygen can be delivered to patients in the home care setting including nasal prongs,
and a variety of mask interfaces.  In most patients with COPD oxygen flow rates of
2-4 liters per minute (lpm) are sufficient. A newer approach to oxygen delivery is
through a humidified high-flow nasal cannula. While the fraction of inspired oxygen
remains the same the flow rate can be increased to up to 60 lpm.1   The higher flow
rate of humidified oxygen has several purported benefits for the COPD patient at
home.  These include increased patient comfort, less dilution of the oxygen dose by
room air, and a slightly increased positive airway pressure that may reduce the work
of breathing and allow distal airways to participate in gas exchange (airway
recruitment).2  Additionally, HNHF-O2 leads to washout of the anatomical dead

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space of the upper airways.3  Humidification levels of HNHF-O2 have been shown to 
improve mucociliary clearance.4  High flow nasal oxygen has been studied in 
neonates, children, and adults with the greatest experience being in the neonate and 
pediatric populations.5  One of the first studies in the adult COPD patient population 
by Chatila and colleagues demonstrated that high flow nasal oxygen improved 
exercise performance and enhanced oxygenation.6  This study was conducted in 
ambulatory adult COPD patients; however most of the research since this 
publication has been directed at COPD patients who have been hospitalized where 
the goal was avoidance of intubation was the goal of therapy.1  There have been few 
studies of the use of high-flow nasal oxygen in adults with COPD in the outpatient 
setting.  Given the potential benefits on exercise tolerance and reduced work of 
breathing it would be useful to investigate this therapy in this patient population. 
 
7) Setting of the Human Research 
Potential subjects will be recruited from the pulmonary care unit located on the 5th 
floor of the Ambulatory Care Center of Temple University Hospital.  Patients will 
receive HNHF-O2 at home and will be monitored via phone calls and clinic visits 
throughout the 90 day study period. 
8) Resources Available to Conduct the Human Research 
Potential subjects will be recruited from the population of patients who are being 
managed by Temple University pulmonary physicians.  Patients are seen at the 
Temple Lung Center located on the 5th floor of the Ambulatory Care Center on the 
Health Sciences Campus as well as those who are being seen at the Temple Lung 
Center at Oaks.   Our research staff includes an administrative core that provides 
regulatory support and coordination of research activities. Importantly, 6.5 FTE 
research nurse coordinators, and 6 FTE research specialists are readily available to 
meet the needs of the variety of clinical trials in which we participate complemented 
by dedicated administrative support that includes a regulatory affairs specialist, 
grants administration office, QI and IRB regulatory oversight. Most of these 
individuals have over 15 years of clinical research experience. 
The Temple Lung Center outpatient clinic is a newly constructed 14,000 ft2 facility 
designed to create an ideal outpatient experience, integrating state of the art 
pulmonary function, exercise, and physiologic testing with physician visits. It was 
constructed to provide outpatient care, clinical research and patient and provider 
education in a state of the art setting. Patient visits, blood draws, lung function and 
exercise testing all are done in this unicenter of pulmonary research and care. The 
pulmonary function laboratory has been placed beside our outpatient practice; the 
waiting room has been designed to accommodate 50 or more persons with 
additional space to accommodate wheelchairs and/or stackable chairs.  All areas are 
wheelchair accessible. 22 recessed oxygen wall mounts capable of delivering 15 
liters per minute of supplemental oxygen are distributed within the waiting area.  The 
Temple Lung Center at Oaks is 5,500 square-foot facility is located in the Oaks 
Corporate Center on Cresson Boulevard (on Route 422, just 6 miles west of the King 
of Prussia Mall).  The site includes a patient reception/ waiting area and nine private 

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examination rooms for consultations between Temple physicians and their patients. 
To facilitate patient evaluation and treatment, full radiological, pulmonary function, 
and blood-acquisition services are available on-site.  The Sleep Center has also 
opened and is currently seeing patients. 
We treat an average of 16,000 outpatients a year; over 50% of these patients carry a 
diagnosis of advanced lung disease, including COPD, IPF, pulmonary hypertension, 
and bronchiectasis. We are a major referral center for lung volume reduction 
surgery. 
All physicians, nurses and ancillary staff members will be instructed in the details of 
this study.  
9) Prior Approvals 
Not applicable. 
10) 
Study Design 
a) Recruitment Methods 
Thirty patients hospitalized for acute exacerbation of COPD ≤ the last 12 weeks 
will be enrolled into the study. Subjects will be recruited from the Temple Lung 
Center clinical practices in Philadelphia and Oaks, PA.  
Potential subjects will be recruited during scheduled office visits to the Temple 
Lung Center offices in Philadelphia and in Oaks, PA.  Many of these patients will 
be those who have been referred to Temple.  We will also contact pulmonology 
practices in the tri-state area through direct mailings and our monthly research 
fax blast.  The Temple Lung Center also maintains an IRB-approved registry of 
patients who have agreed to be contacted to discuss participation in clinical 
research trials. 
Describe materials that will be used to recruit subjects. Include copies of these 
documents with the application. – Not applicable 
Subjects will receive compensation in the form of a $25 gift card for each 
completed visit during their participation in this study. 
b) Inclusion and Exclusion Criteria 
Consecutive patients ≥ 40 years of age or older who are admitted to the hospital 
for an acute exacerbation of COPD within the past 12 weeks. Patients will have 
COPD as the primary diagnosis and have smoked > 10 pack years. Patients 
should be receiving supplemental oxygen as part of their usual clinical care.  
Patients must be willing to give informed consent and be willing to participate in 
measurement of ABGs, brief history and physical examination and answer 
questionnaires regarding daily use of HNHF-O2 therapy. Women who are 
pregnant are excluded from this research.  Women of childbearing potential will 
have a urine pregnancy test to ensure that they are not pregnant. 
 
The main exclusion criteria are upper airway or nasal problems that prohibit the 
use of high flow oxygen and patients with any of the following will be excluded: 

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current use (≤  4 weeks of study entry) of any PAP-therapy (e.g., CPAP or 
NPPV); sleep apnea as follows: STOPBang scores ≥ 5 or STOPBang score ≥ 2 
plus BMI > 35 kg/m2; or Berlin questionnaire scores suggesting high likelihood of 
sleep apnea with increased risk of sleep-related accident (e.g., occupation as a 
commercial driver or pilot); or excessive daytime sleepiness (i.e., either of High 
(>15) score on the Epworth Sleepiness Scale or “fall asleep” accident or “near 
miss” accident in prior 12 months). 
 
c) Local Number of Subjects 
Thirty subjects will be accrued locally for this study.  
We expect few screen failures.   
d) Study-Wide Number of Subjects 
If this is a multicenter study, indicate the total number of subjects to be accrued 
across all sites. – Not applicable. 
e) Study Timelines 
• Subjects will be followed for 90 days with regular telephone follow-up and 
clinic visits throughout. 
• Subjects will be enrolled over a period of 12 months. 
• The investigators will complete the data analysis approximately 18 months 
after the first subject is enrolled. 
f) Study Endpoints 
The primary endpoints of this study are the feasibility of oxygen therapy by 
HNHF-O2 at home over a 90-day period in terms of tolerance and hours of use.   
Descriptive statistics will be used to characterize the patient population in terms 
of demographic factors and severity of airflow obstruction.  Changes in PaO2, 
PaCO2 and pH across the days will be done by analysis of variance.  The effect 
of baseline PaCO2 on change in PaCO2 with HNHF-O2 therapy will be analyzed 
as an independent effect on change in PaCO2 levels with HNHF-O2. Changes in 
respiratory rate, heart rate, blood pressure accessory muscle use will also be 
assessed by analysis of variance.  Patient tolerance and side effects will also be 
measured across days of use per patient and across days in all patients as group 
trends. Hours of use per device log and per patient diary will be independently 
analyzed and compared to one another. The impact on change in exacerbation 
frequency and severity will be analyzed. Changes in spirometry, 6MWD, GOLD 
grade and class and BODE scores prior to and after 90 days of HNHF-O2 will be 
analyzed. 
g) Procedures Involved in the Human Research 
An overview of the study is provided in the figure below. 
 

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Patients who have had a recent COPD exacerbation (<12 weeks since 
discharge) accompanied with respiratory failure who meet the above inclusion 
criteria will be considered for participation in the study.   
Once informed consent has been obtained patients will be given the opportunity 
to participate in the sleep substudy until the enrollment goal of ten subjects has 
been achieved. A separate protocol and consent form has been submitted for 
this study.  The following procedures will be performed as part of the main study:  

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Test 
Visit 1 
Visit 1a 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7  
Visit 8 
Visit 9 
Visit 10 
Visit 11 
Visit 12 
Visit 
13 
  
Screening 
Baseline 
Clinic 
Phone 
Call 
Phone 
call 
Clinic 
Phone 
call 
Clinic 
Phone 
call 
Clinic 
Phone 
call 
Clinic  
Phone 
call 
Clinic 
  
  
  
Placed 
on 
HNHF-O2 
Day 1 
Day 3 
± 3 
Day 7 
± 5 
Day 17 
± 3 
Day 28 
± 5 
Day 37 ± 
3 
Day 49 ± 
5 
Day 58 ± 
3 
Day 70 ± 
5 
Day 80 ± 
3 
Day 90 
± 5 
Screen 
X 
  
  
  
  
 
  
  
  
  
 
  
  
Informed 
Consent 
X 
  
  
  
  
 
 
  
  
  
  
 
  
  
History & 
Physical 
  
X 
  
  
  
X 
 
X 
  
X 
  
X 
 
X 
Pregnancy test 
for women of 
childbearing 
potential 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Arterial blood 
gas 
  
X 
X 
  
  
 
 
  
  
  
  
 
  
x  
Pre- and Post-
Bronchodilator 
Spirometry 
  
X 
  
  
  
 
 
  
  
  
  
 
  
X 
6 minute walk 
distance 
  
X 
  
  
  
 
 
  
  
  
  
 
  
X 
mMRC 
Questionnaire 
  
X2 
  
  
  
 
 
  
  
  
  
 
  
 
Borg 
Questionnaire 
  
X2 
X 
  
  
X 
 
X 
  
X 
  
X 
 
X 
Assess 
Accessory 
Muscle use 
  
X 
X 
  
  
X 
 
X 
  
X 
  
X 
 
X 
Assess subject 
comfort 
  
X 
X 
  
  
X 
 
X 
  
X 
  
X 
 
X 
 
 

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Test 
Visit 1 
Visit 1a 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Visit 10 
Visit 11 
Visit 
12 
Visit 
13 
  
Screening 
Baseline 
Clinic 
Phone 
Call 
Phone 
call 
Clinic 
Phone 
call 
Clinic 
Phone 
call 
Clinic 
Phone 
call 
Clinic 
Phone 
call 
Clinic 
 
 
 
Placed 
on 
HNHF-
O2 
Day 1 
Day 3 
± 3 
Day 7 
± 5 
Day 17 
± 3 
Day 28 
± 5 
Day 37 ± 
3 
Day 49 ± 5 
Day 58 ± 
3 
Day 70 ± 5 
Day 80 
± 3 
Day 
90 ± 5 
Epworth 
Sleepiness 
Scale 
X 
  
  
  
  
 
 
  
  
  
  
 
  
  
Berlin Sleep 
Questionnaire 
X 
  
  
  
  
 
 
  
  
  
  
 
  
  
STOP-Bang 
Questionnaire 
X 
  
  
  
  
 
 
  
  
  
  
 
  
  
St. George's 
Respiratory 
Questionnaire 
  
X  
  
  
  
 
 
  
  
  
  
 
  
X 
GOLD 
Category 
  
x  
  
  
  
 
 
  
  
  
  
 
  
 
BODE Index 
  
X  
  
  
  
 
  
  
  
  
 
  
X 
Daily Diary 
X 
X 
X  
  
  
X 
X 
  
X 
  
X 
X 
COPD Activity 
Test 
  
X  
  
  
  
 
 
  
  
  
  
 
  
X 
Review 
current 
medications 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Phone call 
  
  
  
X 
X 
 
X 
  
X 
  
X 
 
X  
  
Sleep substudy participants 
Insomnia 
Severity index 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Home sleep 
study 
 
X1 
 
 
 
X 
 
 
 
 
 
X 
 
 
Epworth 
Sleepiness 
 
X2 
 
 
 
X2 
 
 
 
 
 
X2 
 
 

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Scale 
1 For those subjects enrolled in the sleep substudy the acquaintance and baseline sleep studies must be completed before beginning HNHF-O2  
2 Questionnaires are done at baseline visit and repeated at home prior to the baseline, day 7, and day 70 sleep studies. 
 For ABGs, the test will be done on room air after the participant has been off the Airvo device for 20 minutes. If the participant starts to desaturate, then it can be done on 2L 
of oxygen. 

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There will be collection of demographic data including age, gender, race, current 
medications, and comorbid conditions. A patient history of duration of the nature 
and course of prehospital symptoms, past medical history of smoking, and past 
use of respiratory medications and nonpharmacological therapy for COPD will be 
elicited.   Historical collection of available clinical data including exacerbation 
history, reports of chest imaging as well as pulmonary function and/or exercise or 
cardiac data will be collected. 
 
At baseline, patients will have measurement of vital signs (heart rate, respiratory 
rate and blood pressure), dyspnea (modified Borg score, mMRC) arterial blood 
gas after 5 minutes of inspiring supplemental oxygen to keep SaO2 > 90%, and 
use of accessory muscles of ventilation. Patients will have spirometry performed 
pre-and post-bronchodilator administration. Patients will have assessment of 
their current respiratory health by completing CAT, mMRC and SGRQ 
questionnaires. A detailed history of their exacerbation frequency and severity 
will be obtained. Patients will perform a 6-minute walk test. Patients GOLD grade 
and group will be classified and patients BODE scores will be calculated. 
Patients will be queried regarding the presence and magnitude of complaints of 
cough and sputum production by using a daily electronic diary for a 2-week 
period of run in. After the 2-week run-in period the patient will be scheduled to 
return to initiate HFNC with oxygen therapy. 
 
 
 

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Patients will be seen in clinic and instructed in the use of HNHF-O2 and its 
proposed benefits. The necessity of compliance and adherence to the treatment 
plan will be emphasized. 
Following the outpatient clinic visit, patients will be set up at home using an 
established home vendor for respiratory equipment. Patients will continue to 
report their daily respiratory symptoms via the electronic diary. 
 
Post placement on optimal dose of HNHF-O2 therapy, subjects will be called the 
next day to determine if there were any problems. 
 
Patients will report to clinic at baseline and then 7 ± 2, 28 ± 5, 49 ± 5, and 70 ± 5 
days for the following assessment: 
 
• Measurements of vital signs (heart rate, respiratory rate and blood 
pressure)  
• Respiratory patient-discomfort and dyspnea assessed using an 
unmarked 100 mm visual analogic scale from “no discomfort” to 
“maximal imaginable discomfort” 
• Likert scale model indicating marked improvement (+2), slight 
improvement (+1), no change (0), slight deterioration (-1) and marked 
deterioration (-2)  
• Side effects related to high flow nasal administration: nasal dryness, 
epistaxis, nasal crusting, eye discomfort, pressure discomfort, increase 
rhinitis, decreased smell, post nasal drip, hoarseness 
• Hours of daily use of HNHF-O2 therapy 
• Daily record keeping of daily diary review 
 
At day 90 ± 2 the following will be measured: 
• Measurements of vital signs (heart rate, respiratory rate and blood 
pressure)  
• Respiratory patient-discomfort and dyspnea assessed using an 
unmarked 100 mm visual analogic scale from “no discomfort” to 
“maximal imaginable discomfort” 
• Likert scale model indicating marked improvement (+2), slight 
improvement (+1), no change (0), slight deterioration (-1) and marked 
deterioration (-2)  
• Side effects related to high flow nasal administration: nasal dryness, 
epistaxis, nasal crusting, eye discomfort, pressure discomfort, increase 
rhinitis, decreased smell, post nasal drip, hoarseness 
• Hours of daily use of HNHF-O2 therapy 
• Daily record keeping of daily diary review 
• Arterial blood gas on room air after the participant has been off the 
Airvo Device for 20 minutes.  
• Pre-and post-bronchodilator spirometry 

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• CAT, SGRQ 
• 6 Minute walk test 
• GOLD grade and group will be classified  
• BODE scores will be calculated. 
Application of HNHF-O2 therapy. During HNHF-O2, oxygen will be passed 
through a heated humidifier (myAIRVO 2, Fisher and Paykel Healthcare) and 
applied continuously through large-bore binasal prongs, with a gas flow rate of 
20-35 liters per minute (or as high as tolerated). Temperature will be adjusted 
based on patient’s comfort and range from 34-37 degrees based on prior 
experience. The fraction of oxygen in the gas flowing in the system will be 
adjusted to maintain an SpO2 of 90% or more. High-flow oxygen will be applied 
at the highest tolerated flow up to 35 lpm at home. Meter time and patient’s log of 
hours of daily use will be measured and compared. 
Hypercapnic COPD patients are encouraged to use supplemental oxygen 
therapy on a continuous basis. The use of the humidified nasal high-flow device 
in this protocol is not expected to change the total number of hours that the 
patient receives supplemental oxygen; however it will change the manner in 
which the oxygen is delivered.  Patients will be encouraged to use the device for 
oxygen delivery as many hours per day as possible.   
In order to reduce the risk of contamination and extend the life of the tubing and 
patient interface it is recommended that the user clean the device at specified 
intervals.  The patient interface should be washed in tap water and reconnected 
to the heated breathing tube.  Thereafter, the device should be run in drying 
mode.  This process takes about 90 minutes to complete and should be 
performed daily.  On a weekly basis the heated breathing tube should be 
removed along with the patient interface and both washed in warm water with a 
mild detergent.  The outside of the device should be wiped clean with a damp 
cloth.    The inside of the heated breathing tube connection port should be 
cleaned with a low-lint cloth with mild dishwashing detergent.  
The patient has the option to not receive supplemental oxygen during each of 
these cleaning procedures or to receive supplemental oxygen via a standard 
nasal cannula.  
All supplies necessary for the maintenance of the device will be provided to the 
subject at no cost to them.  
Study procedures: 
History and physical exam, vital signs.  These are all procedures routinely 
performed as standard of care. 
Lung function testing (spirometry). Pre- and post-bronchodilator testing 
(spirometry) will be performed according to ATS standards.  The bronchodilator 

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medication (albuterol) opens up the airways and will be used in lung function 
testing.  This medication is often used to treat people with COPD. Spirometry will 
be performed by experienced study personnel.   
Arterial blood gases.  Arterial blood gases will be obtained from the radial artery 
in the wrist by experienced personnel. Blood gases will be obtained on room air 
after the patient has been off the Airvo device for 20 minutes. 
6 minute walk test. Subjects will be asked to walk as far as they can for 6 
minutes while receiving supplemental oxygen. Testing will be supervised by 
experienced study personnel with access to emergency medicine such as 
sublingual nitroglycerin, aspirin and albuterol. 
Dyspnea questionnaires, accessory muscle use, and comfort assessments.  
The Borg dyspnea questionnaire and mMRC are short questionnaires that can 
be completed in a minute or two.  These questionnaires are included with this 
submission.  Use of accessory muscles requires only subject observation.  
Subject comfort assessments are also provided with this submission and can be 
completed in a minute.  
During the subject’s hospitalization various medications including 
bronchodilators, corticosteroids, and antibiotics may be administered to manage 
the COPD exacerbation.  These will be prescribed by the subject’s physician as 
standard of care. The subject’s usual maintenance medications will be prescribed 
as clinically indicated as standard of care.  Other testing and procedures (such 
as laboratory testing and radiographic imaging) may be performed.  These would 
also be standard of care. 
myAIRVO 2 device.  The myAIRVO 2 device is a humidifier with integrated flow 
generator that delivers high flow warmed and humidified respiratory gases to 
spontaneously breathing patients through a variety of patient interfaces. It is 
intended for the treatment of spontaneously breathing patients who would benefit 
from receiving high flow warmed and humidified respiratory gases. The 
myAIRVO 2 is for patients in homes and long-term care facilities. The flow may 
be from 2 – 60 L/min depending on the patient interface. There are few expected 
side effects of using the myAIRVO 2 device – if the humidification is too low, the 
subject may experience nasal/throat discomfort or epistaxis.  
Optiflow+ nasal cannula. The Optiflow+ nasal cannula is a nasal cannula 
patient interface for delivery of humidified respiratory gases. There are few 
expected side effects of using the Optiflow+ nasal cannula – some minor irritation 
or sensitivity may occur where the cannula sits on the skin. 
Telephone calls. Subjects will receive telephone calls on days 1, 3, 17, 37, 58, 
80 (after initiation of HNHF-O2) to determine vital status, assess adverse events, 
compliance with the device, and to answer any questions they may have 
regarding the study.  In addition to the scheduled telephone calls, the subject 
may receive phone calls from the monitors of the electronic daily diary if the 
subject fails to report symptoms for three consecutive days. 
 

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h) Data and Specimen Banking 
Not applicable. 
i) Data Management  
 
The primary endpoints of this study are the feasibility of oxygen therapy by 
HNHF-O2 at home over a 90-day period in terms of tolerance and hours of 
use.   Descriptive statistics will be used to characterize the patient population 
in terms of demographic factors and severity of airflow obstruction.  Changes 
in PaO2, PaCO2 and pH across the days will be done by analysis of variance.  
The effect of baseline PaCO2 on change in PaCO2 with HNHF-O2 therapy will 
be analyzed as an independent effect on change in PaCO2 levels with HNHF-
O2. Changes in respiratory rate, heart rate, blood pressure accessory muscle 
use will also be assessed by analysis of variance.  Patient tolerance and side 
effects will also be measured across days of use per patient and across days 
in all patients as group trends. Hours of use per device log and per patient 
diary will be independently analyzed and compared to one another. The 
impact on change in exacerbation frequency and severity will be analyzed. 
Changes in spirometry, 6MWD, GOLD grade and class and BODE scores 
prior to and after 90 days of HNHF-O2 will be analyzed. 
 
This is a pilot study in which the primary outcome is to determine the 
feasibility of using high-flow nasal oxygen in patients with COPD who have 
been recently discharged from the hospital with a COPD exacerbation.  As 
such it is not an efficacy trial and is powered based on the ability to detect 
safety issues or unforeseen problems.  The sample size has been estimated 
based on the method described by Viechtbauer, et.al.7   
 
The safety issue we have identified is the need to withdraw therapy because 
HNHF-O2 is not tolerated by the subject.  
The formula for this calculation is based on the probability of observing at 
least one of these events: 
𝑃(𝑥> 0) = 1 −(1 −𝜋)𝑛 where 
x = the number of events that occur across the total number of participants  
and 
π = the probability that the event will occur. 
Solving for n yields: 
𝑛= ln(1 −𝛾)
ln(1 −𝜋) 
Where γ = the confidence threshold. 
Using a 95% confidence threshold and 15% probability that an event (need to 
discontinue due to intolerance) occurs the sample size required is: 

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𝑛= 
ln(1−0.95)
ln(1−0.1)  = 28.4 subjects. 
The number of subjects has been increased to 36 to accommodate screen 
failures and dropouts and to provide evaluable data on 30 subjects. 
All data will be stored on the REDCap website and on password protected 
files on password protected computers located on the 7th floor of the Kresge 
Building.  This is an area with access restricted to study personnel. 
j) Confidentiality 
All data will be stored on the REDCap website.  The site is part 11 
compliant.  All study personnel have been trained in human subjects 
protections and good clinical practices.  Study data will only be accessible 
to study personnel via password protected websites and computer 
terminals. 
k) Confidentiality 
All data will be stored on the REDCap website.  The site is part 11 
compliant.  All study personnel have been trained in human subjects 
protections and good clinical practices.  Study data will only be accessible 
to study personnel via password protected websites and computer 
terminals. 
l) Provisions to Monitor the Data to Ensure the Safety of 
subjects 
This study utilizes an FDA-approved device for the delivery of warmed 
humidified gases for a medical indication included in the 510(k) approval 
letter.  As such, and because of the limited enrollment in this trial, there is 
no need for a data and safety monitoring board.  Monitoring of the study 
will be done by the principal investigator on a routine (monthly) basis in 
conjunction with the study sponsor and the Director of Research at the 
Temple Lung Center.  All adverse events will be reviewed with particular 
attention paid to those subjects who discontinued use of the device and 
those where oxygen therapy needed to be intensified in order to maintain 
adequate oxygenation. 
m) Withdrawal of Subjects 
Subjects may discontinue participation in the study at any point and for 
any reason.  This decision will not be held against them in any way.  If a 
subject decides to withdraw, the physician will assess their clinical 
condition and determine the best course of action for the subject.  This 
may include alternative methods of oxygen administration.  Any data that 
is collected up to the point of subject withdrawal will be retained for 
analysis. 
11) 
Risks to Subjects 

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History and physical exam, vital signs.  These are all procedures 
routinely performed as standard of care and are not associated with any 
adverse effects. 
Lung function testing (spirometry). This testing may make subjects feel 
short of breath.  On rare occasions, people feel dizzy or faint.  The 
bronchodilator medication (albuterol) opens up the airways and will be 
used in lung function testing.  This medication is often used to treat people 
with COPD.  Albuterol sometimes increases the heart rate or causes 
jitteriness or shakiness (tremors), but these effects usually disappear 
quickly.  Spirometry will be performed by experienced study personnel.   
6 minute walk test. Subjects will be asked to walk as far as they can for 6 
minutes while receiving supplemental oxygen. Subjects may feel short of 
breath as a result. Rarely, subjects may over-exert themselves and 
experience chest pain and/or faint. Testing will be supervised by 
experienced study personnel with access to emergency medicine such as 
sublingual nitroglycerin, aspirin and albuterol  
Arterial blood gases.  Arterial blood gases will be obtained from the 
radial artery in the wrist by experienced personnel.  A local anesthetic may 
be used if necessary. Blood drawing from an artery causes more pain than 
taking blood from a vein. Bruising can occur.  Very rarely, fainting, blood 
clots, or an infection at the site can occur. 
Dyspnea questionnaires, accessory muscle use, and comfort 
assessments.  The Borg dyspnea questionnaire and the CAT, mMRC 
and SGRQ questionnaires are short questionnaires that can be completed 
in a minute or two.  These questionnaires are included with this 
submission.  Use of accessory muscles requires only subject observation.  
Subject comfort assessments are also provided with this submission and 
can be completed in a minute. There are no risks associated with any of 
these procedures. 
myAIRVO device.  There are few expected side effects of using the 
myAIRVO 2 device – if the humidification is too low, the subject may 
experience nasal/throat discomfort or epistaxis. 
12) 
Potential Benefits to Subjects 
Potential benefits of study participation include the subject experiencing a 
decreased work of breathing.  It is also possible that the subject will 
experience no direct benefit. 
13) 
Privacy and Confidentiality 
The study will use or disclose protected health information.  A HIPAA 
authorization form is included with this submission. 
14) 
Compensation for Research-Related Injury 

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If a subject is injured or becomes ill as a result of this research device or a 
procedure required to be done only as a part of this research, they should 
immediately notify the research team who will arrange immediate medical 
care. There is no commitment by Temple University, Temple University 
Health System or its subsidiaries, or the study collaborator, Fisher & 
Paykel Healthcare to provide monetary compensation or free medical care 
in the event of a study-related injury. All charges will be billed to the 
subject’s insurance carrier. 
15) 
Economic Burden to Subjects 
All subjects will need supplemental oxygen as part of their clinical care.  
The only difference for this research is that the subjects will receive high-
flow oxygen.  There is no additional charge for this method of oxygen 
delivery. 
16) 
Consent Process 
• We will follow “INVESTIGATOR GUIDANCE: Informed Consent (HRP-
802).”  
 
Non-English Speaking Subjects – not applicable.  All subjects must 
be able to speak and read English. 
 
Waiver or Alteration of the Consent Process (consent will not be 
obtained, required information will not be disclosed, or the 
research involves deception) – not applicable. 
 
Subjects who are not yet adults (infants, children, teenagers) – 
Not applicable. 
 
 
Cognitively Impaired Adults – not applicable. 
 
Adults Unable to Consent – not applicable.  All subjects must be able 
to provide consent. Legally authorized representatives will not be 
approached. 
17) 
Process to Document Consent in Writing 
We will follow “INVESTIGATOR GUIDANCE: Documentation of Informed 
Consent (HRP-803).”  
18) 
Vulnerable Populations 
No vulnerable individuals will be enrolled in this study. 
19) 
Drugs or Devices 
The device that will be used for this study is the myAIRVO-2.  It and the 
high-flow nasal prongs will be provided by the manufacturer.  The device 
will be provided to outpatients enrolled in the study.  The device manual is 
submitted with this application. 

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20) 
Multi-Site Human Research 
Not applicable. 
21) 
Sharing of Results with Subjects 
There is no plan to share the results of the study with the subjects at this 
time. 
 
 

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2. Sotello D, Rivas M, Mulkey Z, Nugent K. High-flow nasal cannula oxygen in adult 
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