Portable Oxygen Concentrator Improvements to Physical Activity, Oxygen Usage, and Quality of Life in Chronic Obstructive Pulmonary Disease Patients Using Long-term Oxygen Therapy (POC-STEP)
Phase: NA
Conditions: COPD
Sponsor: ResMed

Portable Oxygen Concentrator Improvements to Physical Activity, Oxygen Usage, and 
Quality of Life in Chronic Obstructive Pulmonary Disease Patients using Long-term 
Oxygen Therapy (POC-STEP) 
Protocol Version:  1.0; 29 Jan2018 
NCT: NCT03513068 

Clinical Study Protocol 
for 
Portable Oxygen Concentrator Improvements to Physical 
Activity, Oxygen Usage, and Quality of Life in Chronic 
Obstructive Pulmonary Disease Patients using Long-term 
Oxygen Therapy  (POC-STEP) 
Study ID: MA-16-05-02 
Sponsors: 
ResMed Corp. 
9001 Spectrum Center Blvd. 
San Diego CA  92123 
(800) 424-0737 
Inogen Inc. 
326 Bollay Dr. 
Goleta CA  93117 
(805) 562-0500 
Version:  1.0; 29 Jan2018 
Confidential Information 
Property of ResMed Corp and Inogen Inc. 
May not be used, divulged, published or otherwise disclosed 
without the consent of ResMed Corp and Inogen Inc. 

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Version 1.0 
TABLE OF CONTENTS 
 
 
SYNOPSIS .............................................................................................................................................. 4 
1 
DISEASE AND CURRENT TREATMENT ................................................................................. 7 
2 
DEVICE DESCRIPTION ............................................................................................................ 8 
2.1 
STUDY DEVICES: PORTABLE OXYGEN CONCENTRATORS (POCS) .................................................. 8 
2.2 
CONTROL DEVICE:  STANDARD OF CARE (SOC) LONG-TERM OXYGEN THERAPY ........................... 9 
3 
STUDY DESIGN ........................................................................................................................ 9 
4 
STUDY PURPOSE AND OBJECTIVES .................................................................................... 9 
4.1 
STUDY PURPOSE ......................................................................................................................... 9 
4.2 
STUDY OBJECTIVES ................................................................................................................... 10 
5 
STUDY ENDPOINTS ............................................................................................................... 10 
5.1 
PRIMARY EFFECTIVENESS ENDPOINT ......................................................................................... 10 
5.2 
SECONDARY ENDPOINTS ........................................................................................................... 10 
5.3 
EXPLORATORY ENDPOINTS ........................................................................................................ 10 
6 
INVESTIGATIONAL STUDY CENTERS ................................................................................. 10 
7 
STUDY POPULATION ............................................................................................................ 11 
7.1 
INCLUSION CRITERIA .................................................................................................................. 11 
7.2 
EXCLUSION CRITERIA ................................................................................................................ 11 
8 
INFORMED CONSENT ........................................................................................................... 11 
9 
STUDY ASSESSMENTS ......................................................................................................... 12 
9.1 
6-MINUTE WALK TEST ............................................................................................................... 12 
9.2 
ST. GEORGE’S RESPIRATORY QUESTIONNAIRE ........................................................................... 12 
9.3 
HOSPITAL ANXIETY AND DEPRESSION SCALE .............................................................................. 12 
9.4 
ACTIGRAPH .............................................................................................................................. 12 
9.4.1 Physical Activity Level (PAL) ......................................................................................... 12 
9.4.2 Steps per Day ................................................................................................................ 13 
9.4.3 Activity Intensity Level ................................................................................................... 13 
9.4.4 Average Energy Expenditure per Day ........................................................................... 13 
9.5 
OXYGEN USE - DIARIES ............................................................................................................. 13 
10 
STUDY PROCEDURES........................................................................................................... 14 
10.1 FLOW DIAGRAM AND PROCEDURES TABLE .................................................................................. 14 
10.2 SCREENING ............................................................................................................................... 15 
10.3 VISIT 1: RANDOMIZATION AND BASELINE VISIT ............................................................................ 15 
10.3.1 Baseline Data Collection ............................................................................................ 16 
10.3.2 Distribution of Study Devices ..................................................................................... 16 
10.3.3 Initializing the ActiGraph GT9X Device ...................................................................... 16 
10.4 STUDY PHONE CALLS ................................................................................................................ 17 
10.5 VISIT 2: 12-WEEKS POST RANDOMIZATION ................................................................................. 17 
10.5.1 Visit 2 Data Collection ................................................................................................ 17 
10.5.2 Data Management for the ActiGraph GT9X Device ................................................... 17 
11 
CONCOMITANT MEDICATIONS ............................................................................................ 17 
11.1 MEDICATIONS ............................................................................................................................ 17 

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12 
PATIENT COMPLETION AND WITHDRAWAL ..................................................................... 18 
12.1 PATIENT COMPLETION ............................................................................................................... 18 
12.2 PATIENT WITHDRAWAL .............................................................................................................. 18 
12.3 SCREEN FAILURES .................................................................................................................... 18 
13 
ADVERSE EVENTS ................................................................................................................ 18 
13.1 DEFINITIONS.............................................................................................................................. 18 
13.1.1 Adverse Event ............................................................................................................ 18 
13.1.2 Serious Adverse Event .............................................................................................. 18 
13.1.3 Anticipated Adverse Events ....................................................................................... 19 
13.2 ADVERSE EVENT ASSESSMENT AND REPORTING......................................................................... 19 
13.2.1 Adverse Event Assessment ....................................................................................... 19 
13.2.2 Adverse Event Reporting ........................................................................................... 20 
13.2.1 Mandatory Medical Device Reporting ........................................................................ 20 
14 
STATISTICAL ANALYSIS CONSIDERATIONS ..................................................................... 20 
14.1 ANALYSIS OF PRIMARY EFFECTIVENESS ENDPOINT ..................................................................... 21 
14.1.1 Hypotheses ................................................................................................................ 21 
14.2 SAMPLE SIZE ............................................................................................................................ 21 
14.3 ANALYSIS OF SECONDARY AND EXPLORATORY ENDPOINTS ......................................................... 21 
14.4 OTHER STATISTICAL CONSIDERATIONS ....................................................................................... 22 
15 
RISK ANALYSIS ..................................................................................................................... 22 
15.1 POTENTIAL RISKS ...................................................................................................................... 22 
15.2 MINIMIZATION OF RISKS ............................................................................................................. 23 
15.3 POTENTIAL BENEFITS ................................................................................................................ 23 
15.4 CONCLUSION............................................................................................................................. 23 
16 
STUDY DEVICES .................................................................................................................... 23 
16.1 PACKAGING AND LABELING ........................................................................................................ 23 
16.2 HANDLING AND STORAGE........................................................................................................... 23 
16.3 DEVICE ACCOUNTABILITY ........................................................................................................... 23 
16.4 DEVICE DISTRIBUTION TO/FROM PATIENTS ................................................................................. 23 
16.5 DEVICE TROUBLESHOOTING/HELP DESK .................................................................................... 24 
17 
STUDY ADMINISTRATION ..................................................................................................... 24 
17.1 INSTITUTIONAL REVIEW BOARD (IRB) APPROVAL ........................................................................ 24 
17.2 CLINICAL TRIAL AGREEMENT AND FINANCIAL DISCLOSURE .......................................................... 24 
17.3 PATIENT CONFIDENTIALITY ......................................................................................................... 24 
17.4 PATIENT COMPENSATION ........................................................................................................... 24 
17.5 INVESTIGATIONAL SITE QUALIFICATION ....................................................................................... 24 
17.6 SITE TRAINING .......................................................................................................................... 25 
17.7 DATA MANAGEMENT .................................................................................................................. 25 
17.8 INVESTIGATOR RESPONSIBILITIES ............................................................................................... 25 
17.8.1 Investigator Records .................................................................................................. 25 
17.8.2 Investigator Reports ................................................................................................... 26 
17.8.3 Investigational Site Termination ................................................................................. 26 
17.9 PROTOCOL AMENDMENTS .......................................................................................................... 26 
17.10 PROTOCOL DEVIATIONS ............................................................................................................. 26 
18 
BIBLIOGRAPHY ...................................................................................................................... 27 

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Version 1.0 
SYNOPSIS 
 
Study Title 
Portable Oxygen Concentrator Improvements to Physical Activity, Oxygen Usage, 
and Quality of Life in Chronic Obstructive Pulmonary Disease Patients using Long-
term Oxygen Therapy  (POC-STEP) 
Study ID 
MA-16-05-02 
Study Devices 
Two POCs will be used in this study:  ResMed POC and Inogen POC. Other study 
devices include the ActiGraph GT9X Link activity monitor to monitor physical 
activity.   
Control Device 
Ambulatory and non-ambulatory long-term oxygen therapy, including: 
• 
Oxygen tanks 
• 
Transfill devices 
• 
Stationary oxygen concentrators  
Study Purpose 
To evaluate changes in activity based on the use of portable oxygen concentrators 
combined with standard of care (SOC) long- term oxygen therapy versus SOC long-
term oxygen therapy alone at 12 weeks in patients with COPD who require 
continuous (24/7) long-term oxygen therapy. The study will also assess oxygen 
usage, quality of life, hospitalizations and death. 
Study Population 
Patients diagnosed with COPD who are prescribed to receive continuous (24/7) 
long-term oxygen therapy. 
Study Design 
This is a post-approval, randomized, unblinded, multicenter, parallel group design 
study with patients randomized to either control (SOC long-term oxygen therapy 
[SOC arm]) or active treatment (SOC long- term oxygen therapy plus a POC [POC 
arm]) in a 1:1 ratio. All patients will be provided with an activity monitor to wear 
continuously to monitor physical activity, and a usage diary to collect oxygen usage.  
Eligible patients have COPD and are prescribed to receive long-term oxygen 
therapy. At the enrollment/baseline visit, patients will be consented, randomized, 
receive their study devices with training (activity monitor, oxygen use diaries, and 
an assigned POC if randomized to the POC arm), and complete the Visit 1 
assessments. At Weeks 1 and 6 after the enrollment/baseline visit, they will receive 
a phone call from the site to reinforce training on study devices, oxygen usage and 
study requirements, and adverse event assessment.  At the12-week follow-up/final 
visit, they will complete an in-clinic visit to return all study devices (POC, activity 
monitor and oxygen use diaries); have activity monitor device data downloaded by 
the site; and complete the 12-week assessments. Assessments include a 6MWT, 
St. George’s Respiratory Questionnaire and HADS. Data from the activity monitor 
will be used to document changes from baseline through 12-week physical activity 
measures for primary endpoint analysis.  Patients will be assessed for adverse 
events at each encounter after signing the ICF. Study participation is complete 
when the 12-week follow-up visit is completed. Data from the ActiGraph device will 
be uploaded by the study sites for compliance assessment and statistical analyses. 
Study Centers 
Up to 20 centers in the United States will participate in this study. 

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Inclusion Criteria 
1. Patient is 40 years or older. 
2. Patient has a documented diagnosis of COPD. 
3. Patient qualifies for continuous (24/7) long-term oxygen therapy. 
4. Patient is prescribed oxygen at ≤ 5 L/min. 
5. Patient is POC-naïve, i.e., has not used a POC prior to enrolling in this study. 
6. Patient is able to tolerate pulsed oxygen therapy, i.e., oxygen delivered via a 
POC. 
7. Patient is able to fully understand study information and provide signed 
informed consent and HIPAA authorization. 
8. Patient agrees to comply with all study requirements including wearing study 
devices continuously, using oxygen as prescribed, and completing visits, 
phone calls and assessments. 
Exclusion Criteria 
1. Patient’s condition is contraindicated for the use of a POC. 
2. Patient has documented sleep-disordered breathing that is uncontrolled or 
untreated. 
3. Patient is unable to perform the 6-minute walk test. 
4. Patient has a diagnosis (within less than two weeks prior to study entry) of 
pneumonia or respiratory infection, and/or acute bronchitis requiring antibiotics, 
or new/increased dose of systemic corticosteroids. 
5. Patient has had thoracic surgery or another procedure in the six months prior 
to enrollment that is likely to cause instability of pulmonary status. 
6. Patient has an open skin ulcer or rash where the activity monitor will be worn 
on the body. 
7. Patient has a life expectancy < 1 year. 
8. Patient has non-COPD lung disease that may affect oxygenation or survival. 
9. Patient has a planned intervention(s) requiring hospitalization within the three 
months of study participation. 
10. Patient is pregnant or planning to become pregnant. 
11. Patient is participating in a clinical study of a medical product and has not 
completed the required follow-up period. 
12. Patient, in the opinion of the investigator, should be excluded from the study. 
Study Objectives 
1. To compare the effect of POC-delivered oxygen on physical activity, oxygen 
usage, and quality of life compared to non-POC oxygen therapy. 
2. To assess the effect of POC-delivered oxygen therapy on COPD mortality and 
all hospitalizations. 
Primary Effectiveness  
Endpoint 
The mean change in physical activity level from baseline at the 12 week visit 

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Secondary Study 
Endpoints 
1. Average oxygen usage/day 
2. Quality of Life 
o 
St. George’s Respiratory Questionnaire 
o 
Hospital Anxiety and Depression Scale 
3. 6MWT distance 
4. Frequency of COPD exacerbation 
5. COPD or other respiratory condition-related inpatient hospitalization ≥ 24 
hours 
6. Average number of steps taken/day (non-hospital days) 
7. Mortality due to COPD or other respiratory condition (primary cause of death) 
8. All-cause mortality 
 
Exploratory Study 
Endpoints 
1. Time to hospitalization for a COPD or other respiratory condition-related 
inpatient hospitalization ≥ 24 hours 
2. Number of days in hospital for COPD or other respiratory condition-related 
inpatient hospitalization ≥ 24 hours 
3. All-cause unplanned hospitalizations 
4. Average daily activity duration and intensity 
5. Average energy expenditure/day   
Study Management 
Center 
Regulatory and Clinical Research Institute (RCRI®) 
5353 Wayzata Blvd 
Minneapolis MN  55416 
P:  952-746-8080 
Email:  POC-STEP@rcri-inc.com 
 
 

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1 Disease and Current Treatment 
Chronic Obstructive Pulmonary Disease (COPD) is characterized by progressive airflow blockage and 
breathing-related problems.  According to the CDC, COPD was the third leading cause of death in 2014 
(Centers for Disease Control and Prevention, 2016).  Smoking is the greatest risk factor for COPD.  Other 
risk factors include exposure to air pollution, genetics, airway hyper-responsiveness, and poor lung 
growth during childhood (GOLD, 2017).  COPD severity can be stratified with the use of spirometry, which 
is a series of tests to measure the volume of air a patient can inhale, the volume of air a patient can 
exhale, and how quickly a patient can exhale.  COPD treatment options are relative to the severity of a 
patient’s condition. 
 
The economic impact of COPD is evident in direct costs including hospital stays and indirect costs such 
as missed work due to illness.  Guarascio et al. estimated the combined annual costs of COPD in the 
USA in 2010 to be $50 billion, with the most severe COPD cases resulting in the greatest expenditures.  
Twelve million Americans are known to have COPD, and expenditures related to this debilitating condition 
are expected to increase due to recent advances in screening initiatives (GOLD, 2017) (Guarascio, et al., 
2013). 
 
Therapy options for COPD symptoms include smoking cessation, pharmacologic therapy, coaching on 
inhaler technique, vaccinations against respiratory diseases, and pulmonary rehabilitation.  Long-term 
oxygen therapy (LTOT) is defined by the British Thoracic Society as ≥15 hours of oxygen use per day and 
is typically prescribed only for chronically hypoxemic patients (BTS Home Oxygen Guideline Development 
Group, 2015).  Patients with more significant COPD symptoms are expected to benefit from LTOT as it 
has been shown to improve survival, exercise, sleep and cognitive performance (GOLD, 2017) (Celli, et 
al., 2004).    
 
Patients who are prescribed LTOT for their condition have multiple options from which to choose.  
Portable Oxygen Concentrators (POCs) represent a higher level of convenience as compared to other 
ambulatory systems (e.g. liquid oxygen) and non-ambulatory oxygen systems (e.g. stationary oxygen 
tanks).  A recent crossover trial of COPD patients who were randomized to either 1) a combined system 
of a stationary continuous flow device + a portable pulsed-flow device (either a liquid oxygen system or a 
POC), or 2) a portable pulsed-flow device alone (POC), showed that 43% of patients preferred using the 
POC as a single oxygen delivery device, and 36% of patients preferred the combination of a stationary 
and a POC device.  The remaining patients expressed no preference. The fact that all patients were using 
both stationary and portable oxygen at baseline points to the perceived value of POCs from the patient 
perspective.  Furthermore, POCs offer numerous advantages over liquid oxygen, including lower cost, the 
convenience of not having to refill tanks, and relatively light weight of the system (Parker Hannafin Corp, 
2015). 
 
The purpose of this study is to explore an additional potential benefit of POCs.  Physical activity is a 
component of the “COPD vicious circle” diagrammed below.   

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Figure 1.  COPD Vicious Circle 
Source: http://hitconsultant.net/2016/07/28/powering-copd-management-with-digital-health/ 
 
Expanding upon the diagram, lower levels of physical activity in daily life are related to higher risk of 
hospital readmission and shorter survival (Pitta, et al., 2006).  It is hypothesized that the addition of a 
POC device may lead the patient to become more active compared to patients who use SOC long-term 
oxygen without a POC device therapy, and that increased activity relative to POC use may lead to better 
quality of life for patients with severe COPD. 
 
2 Device Description 
2.1 Study Devices: Portable Oxygen Concentrators (POCs) 
Two versions of commercially available POCs, one from ResMed Corp and another from Inogen Inc., will 
be used in this study to provide portable oxygen to study patients using pulsed-flow technology.  Pulsed-
dose oxygen is provided using a pre-programmed bolus amount only as the patient inhales.   
 
Both POCs have been cleared for market by FDA through the 510(k) process and are to be used in 
accordance with their respective indications for use and User Manual/Operator’s Manual. A site will only 
have one POC device available for distribution during the study. 
 
Both POCs consist of the following system components: 
• 
The main POC body/housing (with battery) 
• 
A carrying case and/or backpack for the device body 
• 
Adjustable straps to be used with the carrying case 
• 
DC power supply 
• 
AC power supply 
A nasal cannula must be used with POC and is provided separately.  An optional additional battery and/or 
battery charger may also be used with the device. 
 
The interface of both devices consists of the following features: 
• 
A power button 

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• 
A display screen 
• 
Plus/minus buttons to adjust oxygen flow 
Additional lights, symbols, and audible signals are featured on each of the POC device types to guide 
correct use of the device.  A battery symbol is included on the display screen of each device to inform the 
user of remaining battery life.  User manuals are included with each device for patient reference and full 
reference materials are in the eTMF. 
 
The POCs are to be used in accordance with their respective approved indications for use.  The POCs 
are indicated for patients who require supplemental oxygen, including COPD patients.  The POCs provide 
supplemental, high oxygen concentration to these patients.  The POCs are available via prescription only 
and may be used in home, institution, and hospital settings, as well as travel environments.   
2.2 Control Device:  Standard of Care (SOC) Long-Term Oxygen Therapy 
Long-term oxygen therapy (LTOT) is prescribed for patients whose COPD is considered to be severe.  
Oxygen is provided continuously to the patient in either a continuous-flow or pulsed delivery pattern. 
Long-term oxygen therapy can be provided to patients through stationary LTOT systems including large 
gas cylinders, large liquid oxygen cylinders, and large oxygen concentrator systems.  Some stationary 
oxygen systems also offer an ambulatory component; an example of this is a small liquid oxygen device 
which can be trans-filled from the larger container. 
For the purposes of this study, patients who are randomized to the control arm may not use a POC device 
as an ambulatory oxygen option.      
3 Study Design  
This is a post-approval, randomized, unblinded, multicenter, parallel group design study with patients 
randomized to either control (SOC long-term oxygen therapy alone [SOC arm]) or active treatment (SOC 
long -term oxygen therapy plus a POC [POC arm]) in a 1:1 ratio. All patients will be provided with an 
activity monitor to wear continuously to monitor physical activity, and an oxygen use diary to collect 
oxygen usage data.  Eligible patients have COPD and are prescribed to receive long-term oxygen 
therapy. At the enrollment/baseline visit, patients will be consented, randomized, receive their study 
devices with training (activity monitor, oxygen use diaries, and an assigned POC if randomized to the 
POC arm), and complete the Visit 1 assessments. At Weeks 1 and 6 after the enrollment/baseline visit, 
they will receive a phone call from the site to reinforce training on study devices, oxygen usage and study 
requirements, and adverse event assessment.  At the 12-week follow-up/final visit, they will complete an 
in-clinic visit to return all study devices (POC, activity monitor and oxygen use diaries); have activity 
monitor device data downloaded by the site; and complete the 12-week assessments. Assessments 
include a 6MWT, St. George’s Respiratory Questionnaire and HADS. Data from the activity monitor will 
be used to document changes from baseline through 12-week physical activity measures for primary 
endpoint analysis.  Patients will be assessed for adverse events at each encounter after signing the ICF. 
Study participation is complete when the 12-week follow-up visit is completed. 
4 Study Purpose and Objectives 
4.1 Study Purpose 
The purpose of the study is to evaluate changes in activity based on the use of POCs combined with 
SOC long- term oxygen therapy versus SOC long-term oxygen therapy alone.  The final assessment will 
be done at 12 weeks post-randomization for patients with COPD who require long-term oxygen therapy. 
The study will also assess oxygen usage, quality of life, hospitalizations and death.  

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4.2 Study Objectives 
The main study objectives are to compare the effect of POC-delivered oxygen on 1) physical activity, 2) 
oxygen usage, and 3) quality of life compared to non-POC oxygen therapy. 
 
Additional study objectives are to assess the effect of POC-delivered oxygen therapy on 1) COPD 
mortality, and 2) all hospitalizations. 
5 Study Endpoints 
5.1 Primary Effectiveness Endpoint 
The primary effectiveness endpoint is the mean change in physical activity level from baseline at the 12 
week visit.   
5.2 Secondary Endpoints 
Secondary Endpoints include: 
1. Average oxygen usage/day 
2. Quality of Life 
o 
St. George’s Respiratory Questionnaire 
o 
Hospital Anxiety and Depression Scale 
3. 6MWT distance 
4. Frequency of COPD exacerbation 
5. COPD or other respiratory condition-related inpatient hospitalization ≥ 24 hours 
6. Average number of steps taken/day (non-hospital days) 
7. Mortality due to COPD or other respiratory condition (primary cause of death) 
8. All-cause mortality 
 
5.3 Exploratory Endpoints 
Exploratory endpoints include: 
1. Time from enrollment to hospitalization for a COPD or other respiratory condition-related inpatient 
hospitalization ≥ 24 hours 
2. Number of days in hospital for COPD or other respiratory condition-related inpatient hospitalization 
≥ 24 hours 
3. All-cause unplanned hospitalizations 
4. Average daily activity duration and intensity 
5. Average energy expenditure/day  
6 Investigational Study Centers 
Up to 20 study sites in the United States will be approved to enroll patients in this study.  Minimum criteria 
for study site qualification will be explored via site completion and submission of a comprehensive 
questionnaire.  Sites which initially meet the minimum criteria may be visited by a qualified monitor to 
further discuss study details, requirements, and expectations, as well as to ascertain adequacy of site 
facilities.  Qualified sites will be provided with the study documents necessary for IRB submission.  The 
IRB approval letter and all other critical study documents will be finalized and filed electronically prior to 
enrollment of the first patient at each study site. 

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7 Study Population 
The study population includes up to 190 men and women over 40 years of age who have been diagnosed 
with COPD and who are prescribed to receive long term oxygen therapy.   
7.1 Inclusion Criteria 
An enrolled patient must meet the following inclusion criteria for enrollment; all criteria must be answered 
“yes:” 
1. Patient is 40 years or older. 
2. Patient has a documented diagnosis of COPD. 
3. Patient qualifies for continuous (24/7) long-term oxygen therapy. 
4. Patient is prescribed oxygen at ≤ 5 L/min. 
5. Patient is POC-naïve, i.e., has not used a POC prior to enrolling in this study. 
6. Patient is able to tolerate pulsed oxygen therapy, i.e., oxygen delivered via a POC. 
7. Patient is able to fully understand study information and provide signed informed consent and HIPAA 
authorization. 
7.2 Exclusion Criteria 
An enrolled patient cannot meet any of the following exclusion criteria; all criteria must be answered “no”: 
1. Patient’s condition is contraindicated for the use of a POC. 
2. Patient has uncontrolled or untreated sleep-disordered breathing that is uncontrolled or untreated. 
3. Patient is unable to complete the 6-minute walk test. 
4. Patient has a diagnosis (within less than two weeks prior to study entry) of pneumonia or respiratory 
infection, and/or acute bronchitis requiring antibiotics, or new/increased dose of systemic 
corticosteroids. 
5. Patient has had thoracic surgery or another procedure in the six months prior to enrollment that is likely 
to cause instability of pulmonary status. 
6. Patient has an open skin ulcer or rash where the activity monitor will be worn on the body. 
7. Patient has a life expectancy < 1 year. 
8. Patient has non-COPD lung disease that may affect oxygenation or survival. 
9. Patient has a planned intervention(s) requiring hospitalization within the three months of study 
participation. 
10. Patient is pregnant or planning to become pregnant. 
11. Patient is participating in a clinical study of a medical product and has not completed the required follow-
up period. 
12. Patient, in the opinion of the investigator, should be excluded from the study. 
8 Informed Consent 
Prior to any study assessments or procedures, all potential study patients must document their consent 
for study participation and authorization for use and disclosure of health information by signing the study-
specific IRB-approved Informed Consent Form (ICF).  As part of the consent process, the patient will 
have the opportunity to ask questions of, and receive answers from the personnel conducting the study. 
Patients will be considered to be enrolled in the study once they have signed the ICF, it is confirmed that 
they meet all inclusion/exclusion criteria, and they are randomized to a study arm. 

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9 Study Assessments  
9.1 6-Minute Walk Test   
The 6-Minute Walk Test (6MWT) is a commonly used test in both practice and clinical research to 
determine exercise tolerance and to predict morbidity and mortality in COPD patients.  The test measures 
the distance a patient can walk on a flat, hard surface in six minutes.  Patients will complete this test at 
the baseline and 12-week visits.  Potential study patients who are unable to complete the 6MWT at 
baseline will not be randomized (i.e., enrolled) in the study.  See the 6MWT guide in the eTMF for details 
regarding this test. 
 
9.2 St. George’s Respiratory Questionnaire 
The St. George’s Respiratory Questionnaire (SGRQ) is a validated tool that can be used to measure 
health impairment in COPD patients. (Morishita-Katsu, et al., 2016).  It is a two-part questionnaire; Part 1 
(questions 1-8) covers the patient’s recollection of their symptoms over a preceding period, and Part 2 
(questions 9-16) addresses the patient’s current state.  In this study, patients will be asked to recall their 
symptoms over the preceding 3 months for Part 1.   See the SGRQ manual in the eTMF for details 
regarding administration of the questionnaire.   See the SGRQ manual for reference in the eTMF.   
9.3 Hospital Anxiety and Depression Scale  
The Hospital Anxiety and Depression Scale (HADS) is a commonly used, validated questionnaire that 
measures anxiety and depression (Stern, 2014).  The questionnaire consists of a total of 14 questions, 
seven which pertain to anxiety and seven of which pertain to depression. 
 
Patients will complete the HADS questionnaire in a similar manner to the SGRQ at the baseline and 12-
week visits. See the HADS guide in the eTMF for details regarding administration of the questionnaire.    
9.4 ActiGraph 
For this study, activity will be measured using the ActiGraph GT9X Link.  It combines validated 
accelerometry measurement technology with a wear sensor, which can provide information on whether or 
not the device was being worn by a patient at a given time.  ActiGraph has been used to collect activity 
data in numerous research studies and is the most frequently used brand of accelerometers in the 
research field (Migueles, et al., 2017).  For this study, the ActiGraph device will be worn on the patient’s 
non-dominant wrist virtually all the time to utilize the wear detection feature and to minimize extraneous 
accelerometry measurements that may occur if it is worn on the dominant wrist.  Specific ActiGraph 
parameters that will be used in this study include physical activity level (PAL), steps per day, and activity 
intensity level.   See the eTMF for ActiGraph user guides. 
9.4.1 Physical Activity Level (PAL) 
As it relates to the primary study endpoint, PAL will be calculated using the following ratio: 
 
Total Energy Expenditure (TEE) (kcal) 
Sleep Energy Expenditure (SEE) (kcal) 
 
The TEE measurement is reported directly by ActiGraph.  The baseline calculation will use the average 
wear-filtered TEE reported within the first week of study participation.  The 12-week calculation will use 
the average wear-filtered TEE reported within the twelfth week of study participation. 
 
The baseline SEE measurement will be derived from average TEE values reported only during the 
patient’s sleep time within the first week of study participation.  The 12-week SEE measurement will be 

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derived from average TEE values reported only during the patient’s sleep time within the twelfth week of 
study participation. 
 
Note:  The TEE measurement will also be reported as a stand-alone measurement as a representation of 
average energy expenditure per day (see section 9.4.4 below). 
9.4.2 Steps per Day 
Wear-filtered steps per day will be reported by ActiGraph in daily summary reports.  The baseline steps 
per day value will be calculated from the average wear-filtered steps per day reported within the first week 
of study participation.  The 12-week steps per day value will be calculated from the average wear-filtered 
steps per day reported within the twelfth week of study participation. 
9.4.3 Activity Intensity Level 
Wear-filtered, waking physical activity level will be reported by ActiGraph and will be categorized per 
minute in the following three categories: 
 
1. 
(SVLPA) Sedentary to Very Low: VMU (sum of all three axis counts) < 3000 
2. 
(LMPA) Low to Moderate:  VMU ≥ 3000 AND vertical axis count < 1952  
3. 
(MVPA) Moderate to Vigorous: vertical axis count   ≥ 1952  
 
The baseline durations per day will be calculated from the average waking wear-filtered duration per day 
reported within the first week of study participation.  The 12-week durations per day will be calculated 
from the average waking wear-filtered durations per day within the twelfth week of study participation. 
9.4.4 Average Energy Expenditure per Day 
Wear-filtered energy expenditure will be reported in kilocalories (kcal or calories) by ActiGraph in daily 
summary reports.  The baseline estimated calories used per day will be calculated from the average 
wear-filtered calories per day reported within the first week of study participation.  The 12-week estimated 
calories used per day will be calculated from the average wear-filtered calories per day reported within 
the twelfth week of study participation. 
 
9.5 Oxygen Use - Diaries 
Patient diaries will be used to collect oxygen usage during the study.  All study patients will receive a 
diary to record their daily use of oxygen therapy.  Patients will record their usage of the SOC oxygen and 
patients assigned to the POC arm will also record use of POC oxygen.  
 
 
 

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10 Study Procedures 
10.1 Flow Diagram and Procedures Table 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screen patient for potential study participation 
Patient is not interested and/or does 
not meet study criteria 
Patient is interested and meets study criteria 
Patient is consented and signs the consent form.   
Randomize the patient to a study arm.  
Patient is enrolled. 
Update the patient screening form.  
Do not consent the patient. 
Is the patient 
able to 
perform the 
6MWT? 
No 
Yes 
Provide all study devices and train patient on 
devices. 
Patient completes baseline assessments, SGRQ 
and HADS questionnaires. 
Call patient at 1 and 6 weeks to assess for AEs 
and protocol compliance. 
Patient returns at 12 weeks for final visit and 
returns all study devices.  
Data are downloaded from ActiGraph and diaries 
collected. 
Patient completes 12-week assessments, SGRQ, 
and HADS questionnaires. 

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Figure 2. Study Flow Chart 
Table 1. Schedule of Study Procedures 
Activity 
Visit 1 
Enrollment/Baseline/ 
Randomization 
 
Phone Calls 
Week 1 and Week 6 
± 3 days* 
Visit 2 
Week 12 ± 7 
days 
Follow-up* 
Informed Consent 
X 
 
 
Demographics and  medical history 
X 
 
 
Modified physical exam 
X 
 
 
Vital signs 
X 
 
X 
Inclusion/exclusion criteria 
X 
 
 
PaO2 at rest 
X 
 
X 
Randomization 
X 
 
 
ActiGraph and oxygen usage diary 
distribution 
X 
 
 
POC distribution^ 
X 
 
 
Device training 
X 
X 
 
ActiGraph set-up and initialization 
X 
 
 
ActiGraph data download 
 
X 
Usage diary collected 
 
 
X 
St. George’s Respiratory  
Questionnaire 
X 
 
X 
HADS 
X 
 
X 
6MWT 
X 
 
X 
Concomitant meds† 
X 
X 
X 
Adverse events 
X 
X 
X 
Return all study devices** 
 
 
X 
*After Visit #1 
^ for patients assigned to the POC arm 
† Respiratory condition-related medications only 
** Patients will have the option to purchase their POC device used in the study 
10.2 Screening  
Trained site study personnel will screen patients for study participation by two methods: 
1) review COPD patient medical records for existing LTOT users who appear to meet study criteria 
to approach them about their interest in study participation;   
2) Ask COPD patients who are prescribed LTOT for the first time during the study enrollment phase 
and who appear to meet study criteria about their interest in study participation. 
10.3 Visit 1: Randomization and Baseline Visit 
After a potential study patient has 1) completed the initial informed consent process and signed the study-
specific informed consent form, 2) successfully completed the baseline 6MWT, and 3) been determined to 
meet all inclusion criteria and none of the exclusion criteria, the patient will be randomized in a 1:1 ratio to 
either SOC long-term oxygen therapy only (control arm) or SOC long- term oxygen therapy plus a POC 
(treatment arm).  Randomization will be stratified by site and will be implemented via small permuted 
blocks.  Randomization assignments will be assigned through the electronic study database and will be 
obtained by trained site personnel.  A patient is considered enrolled at the time of randomization. Patients 
will be given all study devices relevant to their study arm assignment and will receive training on all 
devices at the baseline visit.  Patients will be instructed to contact their site study staff with any questions 
pertaining to the study. 

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10.3.1 Baseline Data Collection 
The following information will be collected at baseline: 
• 
Inclusion and exclusion criteria confirmation 
• 
Demographics  
• 
Medical history  
• 
Modified physical exam 
• 
Vital signs (temperature, pulse, respiratory rate, and blood pressure) 
• 
PaO2 at rest 
• 
SGRQ questionnaire 
• 
HADS questionnaire 
• 
6MWT results 
• 
Concomitant medications* 
• 
Adverse events 
• 
Protocol deviations 
*Respiratory condition-related medications only 
10.3.2 Distribution of Study Devices 
During the baseline visit, all patients will receive the following devices: 
• 
ActiGraph activity monitor 
 
In addition to the above devices, treatment arm patients will also receive one POC device. 
Patients will be trained on the use of all study-related devices during the baseline visit and will be 
provided with the associated device instructions/guides for reference.  All patients will be instructed to 
complete oxygen use diaries each day. 
10.3.3 Initializing the ActiGraph GT9X Device 
The following components of the ActiGraph GT9X device will be used for this study.  Items in bold will be 
distributed and explained to the patient by a trained research team member. 
 
• 
ActiGraph Link 
• 
Link Wrist Band 
• 
Single Dock 
• 
CentrePoint (CP) Data Hub 
• 
USB Cables 
• 
AC Wall Plug 
 
A trained member of the study team will install the ActiSync software on a designated computer in 
advance of enrolling the first study patient.  Study personnel will be emailed invitations to the CentrePoint 
platform.  The battery for each patient’s ActiGraph device will be fully charged (for approximately three 
hours) in anticipation of enrollment.  The ActiGraph device will be programmed using applicable 
instructions found in the ActiGraph GT9X Link + CentrePoint Quick Start Guide and/or the ActiGraph Site 
User Guide (in the eTMF) during the baseline visit.  Additional ActiGraph GT9X device programming and 
use instructions will be provided during the Site Initiation Visit.   

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10.4  Study Phone Calls 
A trained member of the site research team will call patients at 1 week (±3 days) and 6 weeks (±3 days) 
after study enrollment.  The purposes of the phone calls are to: 
• 
Assess for previously unreported adverse events 
• 
Obtain updates on any ongoing adverse events 
• 
Obtain any updates on respiratory condition-related concomitant medications 
• 
Assess patient protocol compliance, i.e., use of ActiGraph devices, oxygen usage diaries, POC 
usage (if randomized to the treatment arm) 
• 
Answer any study-related questions the patient may have 
• 
Address any study-related concerns the patient may have 
• 
Provide additional study device training and support as needed 
Phone calls will be documented on a standardized study worksheet for source documentation. 
10.5  Visit 2: 12-Weeks Post Randomization 
Patients will return all study devices at the 12-week visit and will continue with their prescribed COPD 
care plan, including LTOT.  Patients will have the option to purchase their POC device used in the study. 
10.5.1 Visit 2 Data Collection 
The following information will be collected 12 weeks ±7 days post-randomization: 
• 
Vital signs  
• 
PaO2 at rest 
• 
SGRQ questionnaire 
• 
HADS questionnaire 
• 
6MWT results 
• 
Oxygen usage diary 
• 
Concomitant medications 
• 
Adverse events 
• 
Protocol deviations 
10.5.2 Data Management for the ActiGraph GT9X Device 
A trained member of the study team will plug the device into the designated computer at the 12-week visit 
by following the instructions in the ActiGraph GT9X Link + CentrePoint Quick Start Guide and/or the 
ActiGraph Site User Guide (in the eTMF).  The data will be automatically uploaded to the CentrePoint 
platform.   
Additional data download instructions may be provided during study initiation and/or throughout the study 
as necessary.  After data have been uploaded from the ActiGraph device, a trained study team member 
who uploaded the data should submit the data for data management and analysis as instructed in study 
training materials. 
11 Concomitant Medications  
11.1 Medications 
Only respiratory condition-related concomitant medications taken at baseline and during the study, 
including changes, will be recorded on the Concomitant Medication eCRF.  There are no prohibited 
medications for this study. 

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12 Patient Completion and Withdrawal 
12.1  Patient Completion 
A patient’s participation in this study is considered complete after the 12-week follow-up visit is 
completed.  
12.2  Patient Withdrawal 
A patient may withdraw (or be withdrawn) from the study prematurely for the following reasons: 
• 
Withdrawal of consent by patient 
• 
Withdrawal of patient by investigator 
• 
Lost to follow-up 
• 
Termination of study by the sponsor 
• 
Death 
• 
Other (to be specified). 
The reason for termination will be recorded on the appropriate eCRF.  In the event that a patient 
withdraws from the study, a final study visit should be conducted in person.  At a minimum, the patient will 
return all study-related devices and accessories during the final study visit.  If the patient wishes to 
purchase their study POC, they may do so upon study withdrawal.  Other final study-related activities 
(e.g. questionnaire completion) may be conducted at the investigator’s discretion and with the patient’s 
agreement.   
12.3  Screen Failures 
Screen failures are those patients who have signed the informed consent but are then determined to be 
ineligible for randomization to a study arm.  A log of all study screen failures will be maintained by each 
investigational site.  The reason(s) for screening failure will be recorded on the log.  
13 Adverse Events 
13.1 Definitions 
13.1.1 
Adverse Event 
For the purposes of this study, an adverse event (AE) is defined as any undesirable/unusual medical 
experience that occurs to a patient during the study, whether or not it is considered to be device related, 
including (but not limited to) those events that result from the use as stipulated in the protocol.   If an 
investigator is unsure about whether to report a finding as an adverse event, s/he should report the event 
on the AE eCRF. 
 
13.1.2 
Serious Adverse Event 
A serious adverse event is an adverse event that:  
• 
Leads to death, or 
• 
Leads to serious deterioration in the health of a patient that: 
o 
results in a life-threatening illness or injury, 
o 
results in permanent impairment of a body structure or body function, 
o 
requires inpatient hospitalization ≥ 24 hours or prolongation of existing hospitalization, 

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o 
results in medical or surgical intervention to prevent permanent impairment to a body 
structure or a body function. 
13.1.3 
Anticipated Adverse Events 
Warnings, contraindications, and hazards are outlined in the User/Operator Manual for the POCs and 
should be reviewed with patients when they receive their study device(s).  All study devices are to be 
used in accordance with their respective approved, current instructions found in the manual.  Anticipated 
adverse events include events that are reasonably expected to occur as a result of the patient’s disease 
state or treatment. 
 
COPD-related Anticipated Adverse Events:   
• 
COPD exacerbation and related symptoms including: 
o 
Cough 
o 
Dyspnea (shortness of breath) 
o 
Excessive mucus production 
o 
Wheezing 
o 
Chest tightness 
o 
Cyanosis 
o 
Respiratory infections 
o 
Headache 
o 
Fever 
o 
Confusion 
o 
Chest pain 
• 
Lack of energy (fatigue) 
• 
Unintended weight loss 
• 
Swelling in ankles, feet, or legs 
• 
Death 
LTOT-related Anticipated Events: 
Anticipated adverse events associated with LTOT include, but are not limited to, the following: 
• 
Fires 
• 
Burns 
• 
Nosebleed 
• 
Dry mouth 
• 
Dry throat 
• 
Headache 
• 
Tripping/falling over equipment 
• 
Electrical shock and damage 
• 
Noise irritation 
• 
Low oxygen level due to improper equipment use, improper accessory use, or device malfunction 
13.2 Adverse Event Assessment and Reporting 
13.2.1 
 Adverse Event Assessment 
Adverse event information will be collected on all patients.  At every patient encounter throughout the 
study, the investigator will inquire about adverse events since the last encounter.  Patient medical records 

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will be reviewed throughout the study and at study completion to specifically look for AEs and AE 
updates.  Study staff will ask specific questions during the 1- and 6-week phone calls to assess for AEs. 
13.2.2 
Adverse Event Reporting 
Adverse events (AEs) are to be reported in the electronic study database on an AE eCRF as soon as 
possible after discovery by the site and are to be updated with new information and upon final resolution 
of the event.  Supporting source documents for SAEs may be requested by RCRI; if requested, these 
documents are to be de-identified, labeled with the patient’s study ID number, and promptly provided via 
email to RCRI or uploaded to the electronic study database.  Adverse events will be evaluated by the 
investigator and classified for seriousness (as defined in Section 13.1.2), relatedness, and severity:  
 
Relatedness 
Adverse events will be judged by the Investigator as to their relatedness to the study device or procedure 
using the following classifications:  
• 
Unrelated: The event is due to the underlying disease state or concomitant medication or therapy 
not related to the study-specific devices or procedures. 
• 
Probably Not Related:  The event had no significant temporal relationship to the study-specific 
devices or procedures and/or a more likely alternative etiology exists. 
• 
Possibly Related: The event had a strong temporal relationship to the study-specific devices or 
procedures and alternative etiology is equally or less likely compared to the potential relationship 
to the study-specific devices or procedures.  
• 
Probably Related: The event had a strong temporal relationship to the study-specific devices or 
procedures and another etiology is unlikely. 
• 
Unknown:  Relationship of the event to the study-specific devices or procedures and alternative 
etiology is unknown. 
 
Severity 
Adverse events will be categorized by the Investigator as mild, moderate, or severe, depending on the 
event’s impact on the subject’s daily activity level: 
• 
Mild:  Usually transient, requiring no special treatment; does not interfere with the subject’s daily 
activities. 
• 
Moderate:  Low-level inconvenience or concern to the subject; may interfere with daily activities, 
usually resolved by simple therapeutic non-interventional methods. 
• 
Severe: Interruption in subject’s daily activity requiring systemic drug therapy or other treatment.   
 
13.2.1 Mandatory Medical Device Reporting  
Manufacturers are required to report to the FDA via an electronic equivalent of Form 3500A when they 
learn that any of their devices may have caused or contributed to a death or serious injury or has 
malfunctioned and the malfunction would be likely to cause or contribute to a dearth or serious injury if it 
were to recur (key terms are defined in 21 CFR 803.3.).   Manufacturers must also report to the FDA 
when they become aware that their device has malfunctioned and would be likely to cause or contribute 
to a death or serious injury if the malfunction were to recur.  Should such an event occur during this study, 
the appropriate device manufacturer will file Form 3500A with FDA’s Center for Devices and Radiological 
Health as required by law. 
14 Statistical Analysis Considerations 
Following is a summary of the Statistical Analysis Plan for this study.  Please refer to the separate SAP 
for detailed information.  

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14.1 Analysis of Primary Effectiveness Endpoint 
The primary endpoint is the mean change in PAL from baseline at the 12 week visit.  The PAL is 
calculated as the ratio of total daily energy expenditure to sleep energy expenditure, as described in 
Section 9.4.1. The study will be considered successful if the mean change in PAL is assessed for both 
study arms.  In addition, in the event of a successful study, the following hypothesis test will also 
performed.   
14.1.1 Hypotheses 
The hypotheses associated with the primary endpoint are defined as follows: 
 
H0: µt - µc = 0 
H1: µt - µc ≠ 0 
 
where µt is the mean change in PAL for the test patients (patients assigned to the POC arm) and  µc is 
the mean change in PAL for control patients.  If the null hypothesis is rejected, i.e., the conclusion of 
inequality is achieved, and the observed difference between the mean sample changes in PAL, 𝑥𝑥̅𝑡𝑡−𝑥𝑥̅𝑐𝑐 , 
is greater than 0, then higher physical activity level by the test group, as compared to the control group, 
will be considered demonstrated.  For accuracy, non-wear time data will be excluded from analysis. 
14.2 Sample Size 
The following assumptions were used to determine the sample size for the primary endpoint of mean 
change in PAL from baseline at 12 weeks: 
 
• 
Patients will be assigned to either the test or control treatment group 
• 
The primary analysis is an inequality comparison of the test treatment to the control treatment 
• 
The standard deviation for both test and control treatments is 0.22. 
• 
A difference between treatment groups of ≥ 0.1 is considered clinically significant (i.e., the 
minimal desired detectable difference between treatment groups) 
• 
The difference between the treatment groups is expected to be 0 
• 
Greater than 80% power is considered sufficient 
• 
Statistical test will be performed with a two-sided 5% significance level 
To maintain at least 80% power to detect a difference between treatment groups of 0.1 with a common 
standard deviation of 0.22, 77 patients per treatment group would be required for a total of 154 patients.  
Adjusting for potential 20% attrition, 93 patients per treatment group will be required for a total of 186 
patients.  An additional four patients will be enrolled in order to provide more data for the success 
calculation, thereby bringing the total sample size to 190. 
14.3 Analysis of Secondary and Exploratory Endpoints 
The full list of all secondary and exploratory endpoints can be found in Section 5.3.  The mean changes 
from baseline in continuous secondary and other endpoints will be compared between treatment groups 
via independent samples t-tests, or a non-parametric equivalent as appropriate.  General Linear Modeling 
will be used to assess the impact of potentially influential covariates.   
 
For comparisons of categorical variables, a chi-square test (if appropriate) or Fisher’s exact test will be 
used.  Standard logistic regression will also be fit to these endpoints to include center effects and relevant 
covariates.   
 

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For certain variables associated with only one treatment arm, such as POC usage, summaries and 
estimation, including 95% confidence intervals, may be provided, with no formal hypothesis test 
performed. 
 
The frequencies of each individual type of adverse event will be summarized along with a 95% exact 
binomial upper confidence bound.  Adverse events, including UADEs, will also be summarized based 
upon seriousness, severity and relation to the procedure and the device.  Individual adverse events will 
be listed for both groups, including time to event and resolution.   
14.4 Other Statistical Considerations 
Analysis Data Sets 
At a minimum, two distinct analysis sets will be used for the evaluation of primary and secondary 
effectiveness endpoints.  The intent-to-treat analysis set will include all randomized patients enrolled in 
the study.  The per protocol analysis set will only include patients with complete primary effectiveness 
endpoint data and no major protocol violations.  The safety evaluation will be based on the intent-to-treat 
analysis set only. 
 
Justification of Pooling Data across Centers 
A formal analysis will be conducted to determine the appropriateness of pooling data across the study 
centers.  This will include constructing a linear regression model for the primary effectiveness endpoint 
with three factors: center, treatment and center by treatment interaction.  Furthermore, “super-centers” 
may be constructed from centers with small numbers of enrolled patients to be entered into models as 
fixed effects. 
 
Verification of Randomization Procedure 
In order to verify the success of the randomization procedure, the distribution of each baseline and 
demographic variable of interest will be summarized by treatment group.  Continuous variables will be 
summarized via mean, median, standard deviation, and range.  Categorical variables will be summarized 
via counts and frequency distributions. 
 
Missing Data 
A sensitivity analysis will be performed for each endpoint to assess the potential impact of missing data 
on the results.  A detailed description of all planned sensitivity analyses can be found in in the Statistical 
Analysis Plan together with the analysis of the relevant endpoints.  Missing values will be ignored for the 
summaries of baseline characteristics, other summaries and safety endpoints. 
 
Standard Statistical Methods 
Unless otherwise stated, all P-values will be considered significant at a two-sided significance level of 
0.05.  Summary statistics will be generated for all relevant variables.  In the comparison of continuous 
variables, distributions will be tested for the normality assumption. If standard parametric techniques are 
found to be inadequate, an appropriate non-parametric technique or a Box-Cox transformation will be 
used.  No corrections will be made for multiple testing procedures. All analyses will be conducted using 
SAS® version 9.1 or higher. 
. 
15 Risk Analysis 
15.1 Potential Risks 
Refer to Section 14.1.3 for a list of potential risks.      

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15.2 Minimization of Risks 
This study involves the use of FDA-cleared, Class II medical devices that deliver oxygen therapy with no 
greater than minimal risk to study patients.  All study devices will be used in accordance with their 
respective approved indications and instructions. The selection of qualified investigators and the provision 
of study training to site personnel prior to each site’s study initiation constitute additional efforts to 
minimize risk.   
 
In this study, patients will be contacted at 1-week and 6-weeks and will return for a final study visit at 12-
weeks post-randomization, allowing for the assessment of adverse events.   
15.3 Potential Benefits 
Patients may be inclined to increase their physical activity level by participating in this study; however, it is 
possible that patients will not experience any benefits from study participation.  The results of this study 
may guide the future treatment of patients with COPD. 
15.4 Conclusion 
The study sponsors firmly believe that the value of the knowledge to be gained by conducting this clinical 
study to demonstrate the potential of POC devices to positively influence physical activity level in COPD 
patients outweighs any potential risks posed to participating patients.    
16 Study Devices 
16.1 Packaging and Labeling 
Labeling describing relevant contraindications, hazards, adverse effects, interfering substances or device, 
warnings, and precautions are provided in the ActiGraph GT9X Link + ActiLife Quick Start Guide, 
ResMed POC User Manual, and the Inogen POC User Manual.  Study devices (POC, ActiGraphs) will be 
sent to the sites from Sherpa Clinical Packaging. See the eTMF for logistical information on device 
shipment/returns and Sherpa Clinical Packaging contact information. 
16.2 Handling and Storage 
The investigator must ensure that all study devices are stored in a secure location until issued to a study 
patient.  All supplies are to be used only for this study and not for any other purpose.  The investigator 
must return all devices to the sponsor(s) at the conclusion of the study. 
16.3 Device Accountability 
The investigator is responsible for study device accountability, reconciliation and record maintenance.  
The investigator must maintain study device accountability records throughout the course of the study.   
16.4 Device Distribution to/from Patients  
Upon being randomized to a study arm, all patients will receive an activity monitor and a diary to record 
oxygen usage.  Patients who are randomized to the treatment arm will also receive the POC device 
assigned for distribution by his/her specific study site.  At the time of device distribution, patients will be 
informed that they must return all study devices at the end of study participation. Patients are required to 
return all study devices (POC [if applicable], ActiGraph) to the site at the 12-week visit (or at study 
termination, if earlier).  Sites will return the study devices to Sherpa Clinical Packaging in a bulk shipment 
at the end of the study. Patients will have the option to purchase their POC device used in the study. 

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16.5 Device Troubleshooting/Help Desk  
Study patients will be provided with contact information for trouble-shooting all study devices (POCs, 
ActiGraph).  
17 Study Administration 
17.1 Institutional Review Board (IRB) Approval 
The study must be reviewed and approved by the site’s IRB before patient enrollment begins at the site.   
A signed copy of the IRB approval letter and IRB-approved ICF/HIPAA form must be submitted to RCRI.  
Investigators are responsible for submitting and obtaining initial approval and continuing approval from 
the IRB and forwarding copies of the approval letters and ICF/HIPAA forms to RCRI.  The investigator will 
notify RCRI within five (5) working days in the event of withdrawal of IRB approval.  
17.2 Clinical Trial Agreement and Financial Disclosure 
The investigator agrees to be responsible for conducting this study in accordance with the signed clinical 
trial agreement and this protocol, including study team oversight/management, reporting and record-
keeping requirements and controlling the study devices.  In addition, the investigator is responsible for 
ensuring that proper informed consent is obtained from each patient prior to participating in the study as 
well as protecting the rights, safety and welfare of participating patients. 
 
All investigators will be required to sign a financial disclosure form, which certifies the investigator’s and 
his/her immediate family’s financial interest in the study sponsors and study outcomes.  Investigators 
must inform RCRI of any changes related to financial disclosure throughout the course of the study and 
for a period of two years after the study is terminated. 
17.3 Patient Confidentiality 
All information and data sent to RCRI, the study sponsors and/or their designees concerning patients and 
their participation in this study are considered confidential by RCRI, the study sponsors and their 
designees (subcontractors or contract research organization).  Only authorized RCRI and sponsor 
personnel or approved contracted agents will have access to some portions of these confidential files and 
will act in accordance with applicable regulations as required by HIPAA.  The IRBs also have the right to 
inspect and copy all records pertinent to this study.   
17.4 Patient Compensation  
Patients will receive compensation from the sponsors for their participation in the study upon completion 
of the 12-week visit.  Compensation is also contingent upon the return of all study devices and will be 
provided to the patient by the investigational site. The compensation amount will be specified in the 
Informed Consent Form and the Clinical Trial Agreement.   
17.5 Investigational Site Qualification 
Investigational site qualification visits or phone calls will be conducted by RCRI prior to acceptance of a 
site into this study.  As part of the study site selection criteria, investigators will be familiar with the use of 
POC devices and LTOT.  The site qualification visit/call will be scheduled to include time with the 
investigator, co-investigators, study coordinator and other study personnel.  Topics of discussion will 
include a review of personnel qualifications, investigator qualifications, adequacy of potential patient pool, 
clinical study experience, study-specific requirements for procedures and equipment, and a review of 
staffing and equipment availability and appropriateness.  A written report of the qualification visit/call will 
be drafted by RCRI.  Resolution of any concerns and/or completion of any necessary activities identified 
during the visit/call will be documented and submitted to the investigator.   

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17.6 Site Training 
Study-specific training of study personnel is the responsibility of RCRI and the investigator.  Study training 
will occur before first enrollment.  To ensure protocol compliance as well as accurate data collection, site 
training will include a detailed review of the protocol, eCRF completion, study-specific procedures, study 
devices, and monitoring logistics. Product-specific training will be provided for the POC device to be 
distributed by the site, the activity monitor (and associated software) and the oxygen diaries during the 
site initiation visit. 
 
17.7 Data Management 
Study-specific eCRFs will be used to enter study data into the EDC system.  The PI or designated study 
personnel at each site is responsible for entering data into the CRFs.  Queries/corrections will be 
managed within the EDC system via electronic queries.   Prior to final database lock, the investigator will 
electronically sign each eCRF; this responsibility cannot be delegated to another person.   
 
Data and eCRFs will be reviewed by study monitors at regular intervals throughout the study as outlined 
in the study monitoring plan.  Data clarification requests (DCFs or queries) may be generated by a 
monitor during a monitoring visit and/or during remote data review.  Data management, including DCFs, 
will be conducted in accordance with the study’s Data Management Plan. 
17.8 Investigator Responsibilities 
The investigator is responsible for ensuring that the study is conducted according to the Clinical Trial 
Agreement, the protocol, IRB requirements and HIPAA.  Specific responsibilities are listed in the Clinical 
Trial Agreement and this protocol.  
 
Records and reports must remain on file at the investigational site for a minimum of two years after the 
completion/termination of this study.  They may be discarded only upon written approval from ResMed 
and Inogen.  The investigator must contact ResMed and Inogen before destroying any records and 
reports pertaining to the study to ensure that they no longer need to be retained.  In addition, RCRI must 
be contacted if the investigator plans to leave the site to ensure that arrangements for a new investigator 
or records transfer are made prior to investigator departure.  
17.8.1 
Investigator Records  
Records to be maintained by the investigator include: 
 
• 
Protocol and all amendments 
• 
Signed Clinical Trial Agreement 
• 
Signed Financial Disclosure Forms 
• 
IRB approval letter including consent and HIPAA authorization form(s) 
• 
IRB Membership list or Letter of Assurance 
• 
All correspondence relating to the study between the site and study sponsors and/or RCRI 
• 
CVs and professional licenses for all investigators 
• 
Site personnel signature and responsibility list 
• 
Clinical monitor sign-in log 
• 
Patient screening log 
• 
The following records will be maintained for each patient enrolled in the study: 
o 
Patient-signed ICFs and HIPAA forms  
o 
Compete, accurate and current source documentation for CRFs 
o 
Adverse event reports and any supporting documentation 
o 
Protocol deviations 
o 
Complete medical records relative to the study 

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o 
Records pertaining to patient death during the study (including death records, death 
certificate, and autopsy report if performed). 
 
The study sponsors reserve the right to secure data clarification and additional medical documentation on 
patients enrolled in this study at any time.  
17.8.2 
Investigator Reports 
Investigators are required to prepare and submit reports to their respective IRB in accordance with the 
IRB’s requirements.  
17.8.3 
Investigational Site Termination 
The sponsors reserve the right to terminate an investigational site for any of the following reasons: 
• 
Failure to secure patient informed consent or HIPAA authorization prior to enrollment 
• 
Failure to properly report adverse events 
• 
Repeated protocol violations 
• 
Repeated failure to appropriately complete eCRFs 
• 
Failure to enroll an adequate number of patients 
• 
Loss of or unaccounted for study product inventory 
• 
Administrative decision by the company 
17.9 Protocol Amendments 
Investigators may not modify this protocol without obtaining written concurrence of RCRI, the sponsors, 
and the IRB 
17.10 Protocol Deviations 
Any deviations from this protocol undertaken to protect the life or physical well-being of a patient in an 
emergency situation must be reported to RCRI within five working days of occurrence, and the respective 
IRB as soon as possible but in no event later than five working days after the emergency occurs. All 
protocol deviations must be reported on Protocol Deviation eCRF. 
 
 

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18 Bibliography 
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