Registry of Stable Hypercapnic Chronic Obstructive Pulmonary Disease Treated With Non-Invasive Ventilation Amendment: Home Tele-Monitoring of Non-Invasive Ventilation in Chronic Obstructive Pulmonary Disease
Conditions: Chronic Obstructive Pulmonary Disease
Sponsor: ResMed

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 1 of 34 
Home Tele-Monitoring of Non-Invasive Ventilation in 
Chronic Obstructive Pulmonary Disease – HOmeVent Connect 
Prospective, non-interventional, observational multicentre study 
 
Title 
Home Tele-Monitoring of Non-Invasive Ventilation in 
Chronic Obstructive Pulmonary Disease 
Acronym 
HOmeVent Connect 
Type of study 
Non-interventional, observational, prospective, European, multicentre 
clinical study on marketed medical devices 
Relevant regulatory document: ISO 14155 (as far as possible in NIS) 
Protocol version identifier 
Version no. 2.0 dated 2020-01-10 (replaces previous version 160422) 
Medicinal product(s) 
ResMed non-invasive ventilation (NIV) devices and tele-monitoring 
solution for home care use available in clinical routine care 
Product reference 
CE 161c, 122, 125, 129, 161b, 161a,167b, ResMed connectivity 
module: CE 169a 
Registry number 
NCT02811588 
Sponsor 
ResMed Germany Inc, Martinsried, Germany 
CRO 
CRI – The Clinical Research Institute, Munich, Germany 
Countries of study 
European countries (e.g. Germany, Spain, UK) 
Research question and 
objectives 
Primary Objective 
 
Incidence of unplanned all-cause hospitalisations in routine clinical 
care in patients treated with NIV therapy who are continuously 
monitored by telemetric data 
 
Secondary Objectives 
 
Incidence of unplanned COPD-caused hospitalisations 
 
Predictors of unplanned all-cause hospitalisations 
 
Predictors of unplanned COPD-caused hospitalisations 
 
Predictors of compliance and persistence to NIV therapy 
 
 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 2 of 34 
Marketing authorisation of devices 
Marketing authorisation holder(s) ResMed Ltd,1 Elizabeth Macarthur Drive, Bella Vista, NSW 2153 
Australia 
Legal representative in Europe: ResMed Germany Inc., 
Fraunhoferstr. 16, 82152 Martinsried, Germany 
Phone: +49 (0) 89 99 01-001 
Fax: +49 (0) 89 99 01-10 08 
MAH contact person 
Katrin Pucknat 
ResMed Germany Inc., 
Fraunhoferstr. 16, 82152 Martinsried, Germany 
Email: Katrin.Pucknat@resmed.de 
 
 
 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 3 of 34 
1. Table of contents 
1. 
Table of contents ............................................................................................................................. 3 
2. 
List of abbreviations ......................................................................................................................... 5 
3. 
Responsible parties ......................................................................................................................... 6 
3.1 
Signatures .............................................................................................................................. 7 
4. 
Synopsis ........................................................................................................................................... 8 
5. 
Amendments and updates ............................................................................................................. 11 
6. 
Milestones ...................................................................................................................................... 14 
7. 
Rationale and background ............................................................................................................. 14 
8. 
Research question and objectives ................................................................................................. 15 
9. 
Research methods ......................................................................................................................... 15 
9.1 
Study design ........................................................................................................................ 15 
9.1.1 
Type / design of study .................................................................................................. 16 
9.1.2 
Primary Outcomes ....................................................................................................... 16 
9.1.3 
Secondary Outcomes................................................................................................... 16 
9.2 
Study settings ...................................................................................................................... 17 
9.2.1 
Study sites .................................................................................................................... 17 
9.2.2 
Study population .......................................................................................................... 17 
9.2.3 
Study duration .............................................................................................................. 18 
9.2.4 
Withdrawal from consent of use of medical data ......................................................... 18 
9.3 
Study Visits .......................................................................................................................... 18 
9.3.1 
Pre-Screening and check of eligibility .......................................................................... 18 
9.3.2 
Prescription of treatment .............................................................................................. 19 
9.3.3 
Screening and enrolment visit ...................................................................................... 19 
9.3.4 
Initiation of treatment ................................................................................................... 20 
9.3.5 
Follow-up visits............................................................................................................. 20 
9.3.6 
Follow-up questionnaires ............................................................................................. 20 
9.3.7 
Visit table ...................................................................................................................... 21 
9.4 
Variables .............................................................................................................................. 21 
9.5 
Data sources ........................................................................................................................ 21 
9.5.1 
Data documented by study sites .................................................................................. 21 
9.5.2 
Data obtained from patients ......................................................................................... 21 
9.5.3 
Data transferred from NIV devices ............................................................................... 22 
9.6 
Study size ............................................................................................................................ 22 
9.7 
Data management ............................................................................................................... 22 
9.7.1 
Electronic case reporting form ..................................................................................... 22 
9.7.2 
Personal Data and Data Protection ............................................................................. 22 
9.7.3 
Completion of Case Report Forms .............................................................................. 23 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 4 of 34 
9.8 
Data analysis ....................................................................................................................... 23 
9.9 
Quality control ...................................................................................................................... 23 
9.9.1 
Source Data ................................................................................................................. 23 
9.9.2 
Source Documents ...................................................................................................... 24 
9.9.3 
Access to Source Data/Document ............................................................................... 24 
9.9.4 
Direct Access ............................................................................................................... 24 
9.9.5 
Audits ........................................................................................................................... 24 
9.10 Limitations of the research methods .................................................................................... 24 
9.11 Other aspects ...................................................................................................................... 24 
10. Protection of human subjects......................................................................................................... 25 
11. Management and reporting of Adverse Events/Adverse Reactions .............................................. 25 
11.1 Recording and reporting Adverse Events/Adverse Device Effects ..................................... 27 
12. Plans for disseminating and communicating study results ............................................................ 27 
12.1 Publication policy ................................................................................................................. 27 
13. References ..................................................................................................................................... 28 
 List of stand-alone documents ............................................................................................. 29 
Annex 1.
 SRI questionnaire ................................................................................................................ 30 
Annex 2.
 CAT questionnaire ............................................................................................................... 34 
Annex 3.
 
 
 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 5 of 34 
2. List of abbreviations 
AE 
Adverse Event 
ADE 
Adverse Device Effect 
CAT 
COPD Assessment Test™ questionnaire 
CDISC 
Clinical Data Interchange Standards Consortium 
CTMS 
Clinical Trial Management System 
CFR 
Code of Federal Regulations 
COPD 
Chronic Obstructive Pulmonary Disease 
CRF 
Case Report Form 
CRO 
Contract Research Organisation 
e-CRF 
Electronic Case Report Form 
e-TMS 
Electronic Trial Management System 
EDC 
Electronic Data Capture 
ERC 
Endpoint Review Committee 
FU 
Follow-Up 
GCP 
Good Clinical Practice 
HMV 
Home Mechanical Ventilation 
IFU 
Instruction For Use of a medical device 
NIV 
Non-Invasive Ventilation 
PID 
Patient unique identifier in the e-TMS 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SOP 
Standard Operating Procedure 
SRI 
Severe Respiratory Insufficiency 
USADE 
Unexpected Serious Adverse Device Effect 
 
 
 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 6 of 34 
3. Responsible parties 
 
Steering Committee Members: 
Professor Michael Dreher, MD 
University Hospital RWTH Aachen, Department for Pneumology, and Intensive Care Medicine- 
Pauwelsstr. 30, 52074 Aachen, Germany 
 
Dr Claudio Rabec 
University Hospital Dijon, Department of Pneumology and Respiratory Critical Care 
14 rue Paul Gaffarel, 21079 Dijon, France 
 
Professor Nicholas Hart, MD 
Lane Fox Respiratory Service, St Thomas Hospital, Guy`s & St Thomas NHS Foundation Trust 
Westminster Bridge Road, London, SE1 7EH, UK 
 
Representative of the sponsor: 
Katrin Pucknat 
President, ResMed Germany Inc., 
Fraunhoferstr. 16, 82152 Martinsried, Germany 
 
 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 7 of 34 
3.1 
Signatures 
The undersigned have read this protocol and agreed to conduct this study in accordance with all stipulations of 
the protocol and in accordance with the Declaration of Helsinki. 
 
Date 
Signature 
 
 
_____________________ 
_______________________________________ 
Professor Michael Dreher 
(International Chief Investigator and chair of Steering Committee) 
 
 
_____________________ 
_______________________________________ 
Dr Claudio Rabec 
 
 
_____________________ 
_______________________________________ 
Professor Nicholas Hart 
 
 
_____________________ 
_______________________________________ 
Katrin Pucknat (sponsor representative) 
 
 
_____________________ 
_______________________________________ 
Janina Haug (study statistician) 
 
 
 
 
 
_____________________ 
_______________________________________ 
Signature of Principal Investigator  
 
 
_______________________________________ 
(Name of Principal Investigator in block letters) 
 
 

HOmeVent Connect
Confidential
Version no. 2.0 dated 2020-01-10
HomeVent Connect Protocol_v 2.0_200110.docx
Page 7 of 34
3.1 
Signatures
The undersigned have read this protocol and agreed to conduct this study in accordance with all stipulations of
the protocol and in accordance with the Declaration of Helsinki.
Date
Signature
_____________________
_______________________________________
Professor Michael Dreher
(International Chief Investigator and chair of Steering Committee)
_____________________
_______________________________________
Dr Claudio Rabec
_____________________
_______________________________________
Professor Nicholas Hart
_____________________
_______________________________________
Katrin Pucknat (sponsor representative)
_____________________
_______________________________________
Janina Haug (study statistician)
_____________________
_______________________________________
Signature of Principal Investigator
_______________________________________
(Name of Principal Investigator in block letters)
15.01.2020

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 8 of 34 
4. Synopsis 
Title 
Home Tele-Monitoring of Non-Invasive Ventilation in 
Chronic Obstructive Pulmonary Disease – HOmeVent Connect 
Prospective, non-interventional, observational multicentre study 
Rationale and 
Background 
There is robust scientific evidence that non-invasive ventilation (NIV) therapy 
is an effective option for most COPD patients hospitalised with acute 
hypercapnic respiratory failure secondary to an acute disease exacerbation 
[3]. More recently, NIV has been shown to significantly improve survival and 
quality of life in COPD patients with chronic stable hypercapnic disease [4] 
and in patients with persistent hypercapnia after an acute chronic respiratory 
failure [11]. Over the past two decades, the utilisation of NIV has become one 
of the most important developments in the field of mechanical ventilation. 
However, unsuccessful NIV was found to be independently associated with 
death [5] and poor NIV compliance was associated with higher risk of repeat 
acute NIV use [6]. There is a paucity of useful predictors of poor patient 
compliance and the performance of conventional algorithms for detecting 
COPD exacerbations is still weak. Detection of NIV failure is crucial in patient 
management in view of its negative effect on quality of life and prognosis and 
the fact that it often leads to hospitalisation. In addition, 70% of COPD-related 
healthcare costs are consequences of emergency and hospital stays for the 
treatment of exacerbations [7]. 
Recently, tele-monitoring emerged and unfolded differently among various 
healthcare organisations and countries. Evidence regarding its impact on the 
management of COPD patients is still insufficient to draw firm conclusions. 
Assumption has been made that remote monitoring of home NIV treatment 
could help to identify novel predictors of the early detection of NIV failure and 
deteriorations in patients with COPD. 
The incidence in routine clinical care of unplanned all-cause and COPD-
caused hospitalisations in patients treated with NIV therapy who are 
continuously monitored by telemetric data in several European countries 
needs evaluation. In addition, predictors of unplanned all-cause and COPD-
caused hospitalisations as well as of compliance and persistence to NIV 
therapy should be assessed in this patient population with special respect to 
continuous tele-monitoring. 
Research questions 
and objectives 
Primary Objective 
 
Incidence of unplanned all-cause hospitalisations in routine clinical care in 
patients treated with NIV therapy who are continuously monitored by 
telemetric data 
Secondary Objectives 
 
Incidence of unplanned COPD-caused hospitalisations 
 
Predictors of unplanned all-cause hospitalisations 
 
Predictors of unplanned COPD-caused hospitalisations 
 
Predictors of compliance and persistence to NIV therapy 
Study design 
Non-interventional, observational, prospective, European, multicentre clinical 
study on marketed medical devices 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 9 of 34 
Population 
 
Inclusion criteria: 
 
Age ≥18 years 
 
COPD eligible for NIV treatment (according to applicable medical 
guidelines and local policy in routine clinical care) 
 
Prescription of an adequate ResMed NIV device with tele-monitoring 
option (according to Annex 1, 3.) as part of routine clinical care 
 
Acceptance of tele-monitoring and corresponding data handling 
 
Naive to long-term NIV treatment with initiation of NIV either ≤7 days 
before or after enrolment into study 
 
Able to fully understand information on data protection and provide written 
informed consent for use of corresponding medical and telemetric data. 
Exclusion criteria: 
 
Invasive ventilation therapy 
 
Another life-threatening disease with estimated survival < 12 months (other 
than COPD, e.g. cancer) 
 
Further exclusion criteria according to IFU of the device intended and 
prescribed. 
Variables 
All clinical variables are documented in a web-based e-CRF. Study relevant 
data available in routine clinical care will be entered into the e-CRF by 
adequate site staff members: demographic data, medical and treatment 
history and co-morbidities, physical status, and current medication as well as 
data on the aetiology of COPD, diagnosis parameters to determine the 
reasons for NIV therapy prescription. The patient will be asked to fill out SRI 
and CAT questionnaires. 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 10 of 34 
Data sources 
Data documented by study sites: 
Data will be derived from routine clinical care records and findings, 
observations or other sources (e.g. hospital records, clinical and office charts, 
electronic patient records, laboratory notes, recorded data from automated 
devices, patient files, laboratories and medico technical departments). In 
cases where data are collected while speaking to the patient, the e-CRF is the 
source document (if the patient’s answer is documented there without prior 
documentation in other media). 
Data obtained from patients: 
Baseline and follow-up data derived from quality of life questionnaires SRI and 
CAT. 
Every six months of follow-up short questionnaires asking for hospitalisations 
and other potential SAEs since last contact will be sent by mail to all patients 
Data imported from devices: 
All ResMed devices to be used for NIV therapy within this study (refer to 
Annex 1, 3.) are CE-certified, marketed devices. All are used for NIV treatment 
in line with the corresponding instruction for use. Tele-monitoring data of the 
devices will be sent remotely to a central tele-monitoring server managed by 
an independent certified health data hosting service provider, located in 
France. Pre-defined technical and usage monitoring data will subsequently be 
transferred to the CRO as coded (pseudonymised) data for scientific analysis 
together with data derived from the e-CRF. 
Study size 
About 25 NIV expert centres in several European countries, e.g. Germany, 
Spain, UK are expected to participate in the study. In addition, data of 
comparable patients included by NIV expert centres in France in the “Cohorte 
de l'ANTADIR” (ANTADIR registry) will be used for joined analysis. 
Approximately 550 adult female and male patients with COPD eligible for NIV 
treatment will be enrolled, out of which 231 patients have been enrolled within 
the phase 1 of the study. 
Data analysis 
Data from all sites will be pooled for analysis. Standard statistical methods will 
be used to analyse all data. Continuous variables will be summarised using 
the number of observations, mean, median, standard deviation, minimum and 
maximum values. Categorical variables will be summarised using the number 
of observations and percentages. Two-sided, 95% confidence intervals will be 
used to characterise the major parameters. Demographic variables will be 
tabulated and summarised using descriptive statistics. 
 
 
 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 11 of 34 
5. Amendments and updates 
Amendment no. 1, dated 2019-12-30 
After 231 patients being enrolled within 1.5 years in this observational study (phase 1) a review of feasibility was 
performed by the Steering Committee. As a consequence, modifications to protocol for subsequent phase 2 have 
been made primarily for the following aspects: 
 
Focus on NIV treatment and the use of tele-monitoring device data 
 
In- and exclusion criteria slightly broader according to routine clinical care 
 
More concise definition of primary and secondary endpoints 
 
Extension to study sites in other European countries 
Details of the amendment: 
Section of study protocol 
Amendment or update 
Reason 
Marketing Authorisation Holder 
(MAH) 
MAH contact person modified 
New contact person nominated by 
MAH. 
3. Responsible parties and 
representatives of the sponsor 
List and addresses modified 
Updated 
6. Milestones 
Milestone dates adapted 
Updated to new planned schedules 
7. Rationale and background 
Text adapted to modified major 
aspects of the study, like tele-
monitoring data, and to recent 
literature 
Wording updated according to 
latest published references 
8. Research question and 
objectives 
The objectives have been adapted 
to modified major aspects of the 
study, like tele-monitoring data, and 
to a more concise definition 
Adaptation to more concise and 
tele-monitoring focused objectives, 
also ensuring higher level of 
feasibility of the study in phase 2 
9.1. Study design 
Use of more up-to-date terms with 
reference to routine clinical care 
and IFU. 
Routine clinical care should be the 
major factor for definition of the 
study design. 
9.1.1 Type / design of study 
Enrolment to the study clarified 
(NIV centres only) and HMV 
definition adapted. Flowchart 
adapted to study visits (e.g. 
inclusion of pre-screening) and 
procedures (e.g. informed consent 
for telemetric monitoring). 
Procedures should reflect routine 
clinical care processes in all 
potentially participating countries, 
therefore, office-based 
pulmonologists will not be part of 
phase 2. Improved consistency 
with regulatory wording regarding 
pre-screening. 
9.1.2. Primary Outcome 
Primary outcome has been 
adapted to modified major aspects 
of the study and to the more 
concise definition “all-cause 
Hospitalisations” 
Adaptation to more concise 
objectives, also ensuring higher 
level of feasibility of the study in 
phase 2 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 12 of 34 
Section of study protocol 
Amendment or update 
Reason 
9.1.3 Secondary Outcomes 
Secondary outcomes have been 
adapted to modified major aspects 
of the study, like tele-monitoring 
data, and to more concise 
definitions 
Adaptation to more concise 
objectives, also ensuring higher 
level of feasibility of the study in 
phase 2 
9.2.1. Study sites  
Study will be conducted in several 
countries in Europe and in NIV 
sites, only. 
Cooperation with French ANTADIR 
registry is defined. 
A higher level of feasibility should 
be ensured and a better 
representation of routine clinical 
care in different European 
countries. 
A clinical study structure in this field 
of indication is existing in France, 
thus, this study will cooperate with 
the existing ANTADIR registry to 
avoid doubled infrastructure with 
competing efforts 
9.2.2. Study population 
Total number of patients defined in 
addition to those already enrolled in 
phase 1. 
Use of tele-monitoring added as 
prerequisite and corresponding 
process of informed consent 
defined. 
Maximum of data from ANTADIR 
registry defined 
In- and exclusion criteria slightly 
broader defined according to 
routine clinical care 
Definition of patients still to be 
enrolled in phase 2 and limitation of 
those coming from the French 
ANTADIR registry. 
Adaptation of definitions and 
procedures to routine clinical care 
situation regarding usage of these 
devices. 
9.2.3. Study duration 
Extension of end of study and 
estimate of individual follow-up 
period added. 
Adaptation according to new 
planned schedules in phase 2. 
9.2.4. Withdrawal from consent of 
use of medical data 
Reference to ISO 14155 and 
information on use of data before 
withdrawal added. 
Editorial changes. 
9.3. Study visits 
More detailed description of visit 
procedures and data items added. 
Several patient questionnaires 
deleted. 
Updated in accordance with the 
requirements of the GDPR. 
Improvement with respect to 
feasibility. 
9.3.1 Pre-Screening and check of 
eligibility 
More detailed description of visit 
procedures added. 
Updated in accordance with the 
requirements of the GDPR. 
9.3.2. Prescription of treatment 
Definition on diagnosis, prescription 
of therapy and use of devices with 
referenced to IFU added. 
Adaptation to routine clinical care 
and clarification of procedures in 
this observational study. 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 13 of 34 
Section of study protocol 
Amendment or update 
Reason 
9.3.3 Screening and enrolment 
visit 
Consenting to the study elaborated. 
More detailed description of visit 
procedures and data items added. 
Updated in accordance with the 
requirements of the GDPR. 
9.3.4 Initiation of treatment 
Reference to medical guidelines 
added. 
Adaptation to routine clinical care 
and clarification of procedures in 
this observational study. 
9.3.5 Follow-up visits 
More detailed description of visit 
procedures and data items added. 
Adaptation to routine clinical care 
and clarification of procedures in 
this observational study. 
Updated in accordance with the 
requirements of the GDPR. 
9.3.6 Follow-up questionnaires 
Detailed description of procedures 
for FU questionnaires and 
corresponding exceptions added. 
Updated in accordance with the 
requirements of the GDPR. 
Exception for data from France 
necessary to meet feasible 
processes there. 
9.3.7 Visit table 
Visit table adapted. 
Update to modified procedures and 
schedules. 
9.4 Variables 
More precise definition and 
description added. 
Updated in accordance with the 
requirements of the GDPR. 
9.5 Data sources 
Editorial changes 
More concise wording. 
9.5.2 Data obtained from patients 
Editorial changes 
More concise wording. 
9.5.3 Data transferred from NIV 
devices 
Detailed description of data transfer 
processes from devices. 
Updated in accordance with the 
requirements of the GDPR. 
9.6 Study size 
Adaptation of number of patients 
and sites to new definitions. 
Updated in accordance with the 
content of the protocol. 
9.7 Data management 
Editorial changes 
More concise wording. 
9.8 Data analysis 
Editorial changes 
More concise wording. 
9.9 Quality control 
Editorial changes 
More concise wording. 
9.9.4 Direct Access 
Editorial changes. 
No copy of the signed informed 
consent form has to be send to the 
CRO 
More concise wording. 
Updated in accordance with the 
requirements of the GDPR. 
9.10 Limitations of the research 
methods 
Editorial changes 
More concise wording. 
9.11 Other aspects 
Details on funding added. 
Updated in accordance with 
requirements of ISO 14155. 
10. Protection of human subjects 
Reference to ISO 14155 added and 
editorial changes. 
More concise wording. 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 14 of 34 
Section of study protocol 
Amendment or update 
Reason 
11. Management and reporting of 
Adverse Events/Adverse 
Reactions 
Definitions updated to meet 
wording of the ISO 14155. 
Adverse Events of Special Interest 
no longer defined. 
To reflect ISO 14155 requirements. 
13. References 
Editorial changes 
For consistency with updated 
protocol. 
Annexes 
Editorial changes 
For consistency with updated 
protocol. 
6. Milestones 
Milestone 
Planned date 
Start of enrolment of phase 1, i.e. start of data collection 
September 2016 
End of enrolment of phase 1 
June 2017 
End of follow-up of phase 1 
Mar 2018 
Check of feasibility of phase 1, i.e. end of data collection phase 1 
Sept 2018 
Start of enrolment of phase 2, i.e. start of data collection 
March 2020 
End of enrolment of phase 2 
March 2021 
End of follow-up of phase 2 
March 2022 
7. Rationale and background 
The prevalence of chronic respiratory disease continues to increase in industrialised countries, mainly because of 
tobacco use and improved overall survival.[1, 8] Currently it is estimated that 65 million people globally are 
affected by moderate-to-severe COPD, and over the next decade deaths from COPD are projected to increase by 
more than 30% resulting in COPD becoming the third leading cause of death worldwide by 2030.[2] In addition to 
being an important cause of mortality, COPD is also associated with significant morbidity. The symptom burden of 
COPD is similar to that of cancer,[9] and the negative impact of COPD on health status is greater than that of self-
reported cardiovascular disease or diabetes.[10] In addition, the chronic nature of COPD and associated 
morbidities mean that this disease is associated with significant disease-related economic and healthcare 
costs.[7] 
There is robust scientific evidence that non-invasive ventilation (NIV) therapy is an effective option for most COPD 
patients hospitalised with acute hypercapnic respiratory failure secondary to an acute disease exacerbation [3]. 
More recently, NIV has been shown to significantly improve survival and quality of life in COPD patients with 
chronic stable hypercapnic disease [4] and in patients with persistent hypercapnia after an acute chronic 
respiratory failure [11]. Over the past two decades, the utilisation of NIV has become one of the most important 
developments in the field of mechanical ventilation. However, unsuccessful NIV was found to be independently 
associated with death [5] and poor NIV compliance was associated with higher risk of repeat acute NIV use [6]. 
There is a paucity of useful predictors of poor patient compliance and the performance of conventional algorithms 
for detecting COPD exacerbations is still weak. Detection of NIV failure is crucial in patient management in view of 
its negative effect on quality of life and prognosis and the fact that it often leads to hospitalisation. In addition, 70% 
of COPD-related healthcare costs are consequences of emergency and hospital stays for the treatment of 
exacerbations [7]. 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 15 of 34 
Recently, tele-monitoring emerged and unfolded differently among various healthcare organisations and 
countries. Evidence regarding its impact on the management of COPD patients is still insufficient to draw firm 
conclusions. Assumption has been made that remote monitoring of home NIV treatment could help to identify 
novel predictors of the early detection of NIV failure and deteriorations in patients with COPD. 
The incidence in routine clinical care of unplanned all-cause and COPD-caused hospitalisations in patients 
treated with NIV therapy who are continuously monitored by telemetric data in several European countries needs 
evaluation. In addition, predictors of unplanned all-cause and COPD-caused hospitalisations as well as of 
compliance and persistence to NIV therapy should be assessed in this patient population with special respect to 
continuous tele-monitoring. 
8. Research question and objectives 
The study will determine in several European countries the incidence in routine clinical care of unplanned all-
cause and COPD-caused hospitalisations in patients treated with NIV therapy who are continuously monitored by 
telemetric data. Clinical and telemetric predictors of unplanned all-cause and COPD-caused hospitalisations and 
of NIV therapy compliance and persistence will be assessed in those patients. 
The study will target adult individuals with COPD eligible for home NIV therapy according to applicable medical 
guidelines who agree to continuous telemetric monitoring. Medical data from routine clinical care will be 
documented in an electronic case report form (e-CRF), e.g. patient demographics, diagnostic information 
(including primary diagnosis and quality of life), and blood gas analysis at baseline and in follow-up. Telemetric 
data on NIV treatment (e.g. type of ventilator, modes and settings, usage times, usage profiles) will be added to e-
CRF medical data. 
 
Primary Objective 
 
Incidence of unplanned all-cause hospitalisations in routine clinical care in patients treated with NIV therapy 
who are continuously monitored by telemetric data 
 
Secondary Objectives 
 
Incidence of unplanned COPD-caused hospitalisations 
 
Predictors of unplanned all-cause hospitalisations 
 
Predictors of unplanned COPD-caused hospitalisations 
 
Predictors of compliance and persistence to NIV therapy 
9. Research methods 
9.1 
Study design 
Non-interventional, observational, prospective, European, multicentre clinical study on marketed medical devices. 
The study protocol does not define any specific study procedure for enrolled patients. Therapies and procedures 
during the course of this study will be performed according to the individual decision of the treating physician 
based on current applicable medical guidelines and on local policy in clinical routine care. This includes the 
indication and the use of the NIV device and possible follow-up examinations according to routine clinical care. All 
devices will be prescribed and used according to the corresponding Instruction for Use (IFU), only. 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 16 of 34 
9.1.1 
Type / design of study 
This clinical study is a prospective observational study. 
Patients will be diagnosed and evaluated for eligibility of NIV therapy by NIV expert centres and will be 
consecutively enrolled into the study provided that all inclusion and exclusion criteria are met and written consent 
is given to use their clinical routine data according to data privacy regulations. 
NIV therapy refers to the application of ventilatory assistance without the use of an invasive airway. Home 
mechanical ventilation (HMV) is defined as NIV administered daily, primarily delivered in the user's home or other 
long-term care facility (not a hospital). It does not include treatment of patients with obstructive sleep apnea alone, 
or those with a tracheostomy not requiring mechanical ventilation. 
Further follow-up of the patient according to clinical routine care will be performed by the NIV expert centre and by 
health care provider. 
9.1.2 
Primary Outcomes 
 
Rate of unplanned all-cause hospitalisations in the study population normalised to one year of FU 
9.1.3 
Secondary Outcomes 
 
Rate of unplanned COPD-caused hospitalisations in the study population normalised to one year of FU 
 
Prediction model with all-cause hospitalisation as independent variable and medical and telemetric data of the 
NIV devices as depending variables 
 
Prediction model with COPD-caused hospitalisation as independent variable and medical and telemetric data 
of the NIV devices as depending variables 
Follow-up by 
Health Care Providers 
Pre-screening of eligible COPD patients 
Signed consent for use of medical data (enrolment) 
Initiation of NIV either ≤7 days 
before or after enrolment into 
study
Informed consent for 
telemetric monitoring - 
AirView® “on” 
Follow-up in NIV expert centre 
according to routine clinical care 
Tele-monitoring 
follow up 
+ 
patient questionnaires 
Pre-screening and 
Enrolment phase 
Observation phase 
Initiation of NIV either ≤7 days before or after enrolment into study 
Figure 1: Flowchart of study visits and procedures 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 17 of 34 
 
Prediction models with mean hours of device usage (compliance) and percentage of days with device usage 
related to total number of days potentially under therapy (persistence) as independent variables and medical 
and telemetric data of the NIV devices as depending variables 
9.2 
Study settings 
9.2.1 
Study sites 
About 25 NIV expert centres in several European countries, e.g. Germany, Spain, UK are expected to participate 
in the study. In addition, data of comparable patients included by NIV expert centres in France in the “Cohorte de 
l'ANTADIR” (ANTADIR registry) will be used for joined analysis. 
NIV expert centres are defined as those with any hospital or outpatient and/or co-ordinated HMV services, i.e. 
clinics having expertise in prescribing, initiating and monitoring HMV. NIV expert centres in the defined countries 
will be identified by the Steering Committee members and will be invited to participate to the study. 
The prospective, non-interventional, observational study titled “Cohorte de l'ANTADIR - Database of Patients 
Registered as Treated With Respiratory Support in a Multicentre Homecare Federation for Patients With 
Respiratory Problems” (NCT01181869) is currently being conducted in France under sponsorship of ANTADIR 
(Association Nationale pour les Traitements A Domicile, les Innovations et la Recherche). Data set, basic 
procedures and in- and exclusion criteria of a cohort of COPD patients will be comparable to the settings of the 
HOmeVent Connect study for the period when both studies are running in parallel. It was agreed between 
ResMed and ANTADIR not to establish another observational study in France with focus on comparable patients 
but to join data of comparable patient cohorts for joined analysis. Adequate data of patients in France treated with 
corresponding ResMed devices will be transferred to CRI as coded (pseudonymised) data. These data will be 
joined with data of patients of the HOmeVent Connect study and analysed as part of a joined analysis to increase 
patient sample size, power of analysis and reliability of the results. Details will be given in a Statistical Analysis 
Plan (SAP). 
9.2.2 
Study population 
Approximately 550 adult female and male patients with COPD eligible for NIV treatment will be enrolled, out of 
which 231 patients have been enrolled within the phase 1 of the study. Patients’ written informed consent to use 
their routine clinical data according to data privacy standards must be obtained prior to documentation of patients’ 
data in the e-CRF.  
With regard to tele-monitoring as a pre-requisite in phase 2 the patient is also required to consent on the handling 
of the tele-monitoring data.  
If a patient is enrolled into the study but is never using the prescribed device (i.e. refusal of prescribed therapy) 
he/she will be replaced. 
If a patient, who has already started NIV therapy, is enrolled, the start of therapy must not be longer than 7 days 
before enrolment. 
All patients using the device will be followed during routine clinical practice and will visit a site only in the course of 
their routine clinical care. No treatment or medical examinations additional to routine clinical care will be 
performed. 
Within this study population, data of a maximum of about 100 patients will be added by the French ANTADIR 
registry in line with in- and exclusion criteria of this observational study. 
 
 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 18 of 34 
Inclusion criteria: 
 
Age ≥18 years 
 
COPD eligible for NIV treatment (according to applicable medical guidelines and local policy in routine clinical 
care) 
 
Prescription of an adequate ResMed NIV device with tele-monitoring option (according to Annex 1, 3.) as part 
of routine clinical care 
 
Acceptance of tele-monitoring and corresponding data handling 
 
Naive to long-term NIV treatment with initiation of NIV either ≤7 days before or after enrolment into study 
 
Able to fully understand information on data protection and provide written informed consent for use of 
corresponding medical and telemetric data. 
Exclusion criteria: 
 
Invasive ventilation therapy 
 
Another life-threatening disease with estimated survival < 12 months (other than COPD, e.g. cancer) 
 
Further exclusion criteria according to IFU of the device intended and prescribed 
9.2.3 
Study duration 
The duration of the study is scheduled to be about 2 years with an enrolment phase of about 12 months after 
initiation of the first site in the first country as competitive enrolment in all participating countries. After about 12 
months of follow-up of the last patient enrolled and subsequent final data cleaning global end of study will be 
declared. 
The mean duration of patient’s participation will be about 16 months. Every patient stays in follow-up until the 
global end of the study or death or withdrawal of consent. 
9.2.4 
Withdrawal from consent of use of medical data 
Patients are free to withdraw from their consent of use of medical and telemetric data at any time. In this event the 
date of withdrawal will be documented in the electronic case report form (e-CRF). According to ISO 14155 section 
6.10, the reason(s) for withdrawal shall also be recorded in the e-CRF. In addition, all reasonable efforts should 
be made by the responsible investigator to complete assessments and retrieve any outstanding data. Those 
patients will not have drawbacks in treatment, healthcare supply or in the relationship to the sites or the sponsor. 
Data collected and documented until withdrawal will be included in the analysis. 
Patients cannot be withdrawn from this observational study by investigators for medical or any other reasons. 
9.3 
Study Visits 
9.3.1 
Pre-Screening and check of eligibility 
Routine clinical care patients are diagnosed and checked for potential eligibility of study participation based on 
existing data generated in routine clinical care which is not part of this observational study. 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 19 of 34 
9.3.2 
Prescription of treatment 
The decision of prescription of NIV therapy to the individual patient lies with the treating physician during the 
course of routine clinical care and is not part of this observational study. Diagnosis of COPD and indication of NIV 
therapy as well as initiation of treatment should follow applicable medical guidelines and local clinical care policy. 
Prescription and use of adequate ResMed NIV devices with tele-monitoring option according to Annex 1, 3. have 
to follow the current instructions for use (IFU) of each device. 
9.3.3 
Screening and enrolment visit 
Patients will be screened and enrolled by contracted study sites only, i.e. NIV expert centres.  
Screening of potentially eligible patients will be performed within routine clinical care using data created within 
routine clinical care. Adequate staff members of the study site will inform potentially eligible patients about the 
potential use of their medical and telemetric data within this observational study by information documents which 
have been approved by the responsible Ethics Committee. Within this study medical care of the patient is not in 
any way touched by protocol definitions but an individual decision by the treating physician in routine clinical care. 
Only use and handling of medical and telemetric data for scientific purposes defined in this protocol are elements 
of informed consent. The patient will be given sufficient time to consider informed consent to data handling and to 
get answers to his questions. If the patient agrees, the informed consent form for data use will be provided for 
signature. 
After patients’ signing, patients are screened and checked for eligibility according to in- and exclusion criteria by 
the participating sites, either on every day consecutively or at pre-defined schedules (e.g. on defined days of the 
week, only) to minimise selection bias. Medical screening includes check of COPD according to medical 
guidelines.  
Study relevant data will be reported in the e-CRF. The system will automatically display the patient ID as 
consecutive number across all participating study sites, i.e. without reference to the recruiting site. 
The following data items will be documented of each participating patient: 
 
Demographic data 
 
Patient’s physical status 
 
Patient’s social status 
 
Medical history 
 
Concomitant medication and diseases 
 
Data regarding COPD diagnosis 
 
Spirometry results (no older than 1 month) 
 
Blood gas analyses (carbon dioxide and bicarbonate concentration) during spontaneous breathing (pH>7.35) 
at date of decision making on initiation of NIV therapy 
 
Date of NIV therapy prescription 
 
Telemetric data of NIV device settings will be recorded as soon as the device has been delivered to the 
patient and was used for the first time 
 
Amount of supplemental oxygen during NIV (if needed) 
The patients will further be asked to answer the SRI questionnaire (refer to Annex 2), and the CAT questionnaire 
(refer to Annex 3). 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 20 of 34 
9.3.4 
Initiation of treatment 
Initiation of NIV therapy (the device has been delivered to the patient and was used for the first time) after 
prescription should start according to local routine clinical care before or as soon as possible after enrolment into 
the study (with a maximum of 7 days before enrolment). Current medical guidelines and recommendations apply, 
however, they might differ in participating countries, and thus, prescription and initiation of NIV therapy is the 
decision of the treating physician and will follow local policies. Data on initiation of NIV therapy will be recorded by 
telemetric data as soon as the device has been delivered to the patient and was used for the first time. 
9.3.5 
Follow-up visits 
In routine clinical care, a first control visit of the patient at the site after NIV therapy initiation should take place 
within the first 6 months together with nocturnal assessment of ventilator therapy [12]. It is recommended that 
subsequent control visits at the site should be performed at least 1–2 times a year [12]. To ensure comparability 
of FU data, at least one follow-up visit at the site within 12 months of follow-up should be performed (if in line with 
routine clinical care). 
At the FU visit at the site the following data from routine clinical care data should be documented in the e-CRF: 
 
Patient status 
 
Concomitant medication and diseases 
 
Spirometry results (no older than 3 months) 
 
Body plethysmography (if available) 
 
Blood gas analyses (carbon dioxide, pH and bicarbonate concentration) during spontaneous breathing 
 
Serious adverse events since last site visit. 
 
History of exacerbations not leading to a hospitalisation 
The patient will again be asked to answer to the SRI and CAT questionnaires. 
NIV device settings and other device data will continuously be transferred in FU as tele-monitoring data. 
9.3.6 
Follow-up questionnaires 
Every six months of follow-up short questionnaires asking for hospitalisations and other potential SAEs since last 
contact will be sent by mail to all patients. Closed envelopes with PID outside including the questionnaire and a 
free return envelope will be prepared and sent to site by the CRO. Site staff will forward the envelope to the 
corresponding patient who is asked to return the completed questionnaire (which contains pseudonymous data 
only) directly to CRI using the free reply envelope. In case of missing answer after one written reminder the study 
site should contact the patient by phone in order to obtain the required information. 
Data regarding hospitalisations or SAEs reported by the patient will be documented in the e-CRF primarily by the 
CRO on the basis of available medical data. In case a patient reports a hospitalisation or other SAE, the 
responsible study site will be informed by the CRO and will subsequently contact the patient's family doctor 
respectively the hospital where the patient was treated and ask for supportive documents (i.e. hospital discharge 
letter, diagnostic reports) as applicable. The study site is subsequently responsible for completion of event data. 
These procedures will not be performed in study patients enrolled in the ANTADIR registry in France and used for 
joined analysis in this study. Thus, analysis of hospitalisations will therefore be performed for patients enroled in 
Germany, Spain, UK and other potentially participating countries but not for patients from France. 
 
 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 21 of 34 
9.3.7 
Visit table 
Assessments 
Screening and 
enrolment visit 
FU visits 
FU questionnaire Tele-monitoring 
data 
Data privacy consent 
X 
 
 
Demographic data 
X 
 
 
Medical history 
X 
 
 
Patient’s status 
X 
X 
 
 
Spirometry* 
X 
X 
 
 
Blood gas examination* 
X 
X 
 
 
Medication 
X 
X 
 
 
Quality of life questionnaires 
X 
X 
 
 
Serious Adverse Events 
X 
X 
 
NIV settings & other device 
data 
 
 
 
X 
* If data are available in routine clinical care. 
9.4 
Variables 
All clinical variables are documented in a web-based e-CRF. Study relevant data available in routine clinical care 
will be entered into the e-CRF by adequate site staff members: demographic data, medical and treatment history 
and co-morbidities, physical status, and current medication as well as data on the aetiology of COPD, diagnosis 
parameters to determine the reasons for NIV therapy prescription. The patient will be asked to fill out SRI and 
CAT questionnaires. 
9.5 
Data sources 
9.5.1 
Data documented by study sites 
Data will be derived from routine clinical care records and findings, observations or other sources (e.g. hospital 
records, clinical and office charts, electronic patient records, laboratory notes, recorded data from automated 
devices, patient files, laboratories and medico technical departments). In cases where data are collected while 
speaking to the patient, the e-CRF is the source document (if the patient’s answer is documented there without 
prior documentation in other media). 
Serious Adverse Events during FU will be assessed by the treating investigator. 
9.5.2 
Data obtained from patients 
Baseline and follow-up data derived from quality of life questionnaires SRI and CAT. 
Every six months of follow-up short questionnaires asking for hospitalisations and other potential SAEs since last 
contact will be sent by mail to all patients and replied to the CRO for documentation in the e-CRF. 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 22 of 34 
9.5.3 
Data transferred from NIV devices 
All ResMed devices to be used for NIV therapy within this study (refer to Annex 1, 3.) are CE-certified, marketed 
devices. All are used for NIV treatment in line with the corresponding instruction for use. Tele-monitoring data of 
the devices will be sent remotely to a central tele-monitoring server managed by an independent certified health 
data hosting service provider, located in France. Pre-defined technical and usage monitoring data will 
subsequently be transferred to the CRO as coded (pseudonymised) data for scientific analysis together with data 
derived from the e-CRF. 
Tele-monitoring data of study patients are recorded and transferred to a central server located in France as part of 
routine clinical care settings. Treating physicians have in routine clinical care secured access to a web platform 
provided by the manufacturer of the NIV devices which reports in dashboards and other report formats usage and 
technical data of the corresponding patients on NIV therapy to be used for monitoring and individual management 
of the out-hospital patients. 
9.6 
Study size 
A total of about 550 patients will be enrolled across Europe, out of which 231 patients have already been enrolled 
in the phase 1 of the study. 
About 25 NIV expert centres in several European countries, e.g. Germany, Spain, UK are expected to participate 
in the study. In addition, data of comparable patients included by NIV expert centres in France in the “Cohorte de 
l'ANTADIR” (ANTADIR registry) will be used for joined analysis. 
9.7 
Data management 
Study and site management as well as data cleaning, data management and statistical analysis was delegated by 
the sponsor to CRI – The Clinical Research Institute, Munich, Germany, as responsible CRO. 
Applicable national and international legal requirements for data handling and data archiving will be met. All data 
will be collected using the web-based MARVIN system, a GCP and 21 CFR 11 compliant EDC and CTMS 
software based on CDISC data standards. Medical data within this study will be recorded directly in the e-CRF at 
the site without use of paper documents. The e-CRF system is available for all participants in the study 24 hours/7 
days during the course of the study. After closure of the study, all participating sites will be provided media with 
PDFs of all e-CRF data ever entered in the corresponding site together with all related metadata (e. g. audit trail, 
data queries). 
9.7.1 
Electronic case reporting form 
The e-CRF has been approved by the Steering Committee. It is identical for each country and is provided in local 
language. Data will also be collected about the site itself (e.g. type of institution and other administrative data), 
and basic, pooled details about their patients to allow for control of selection bias. 
9.7.2 
Personal Data and Data Protection 
All data obtained in the context of this clinical study are subject to data protection. The storage of data for 
statistical assessment shall likewise be performed only under the patient’s study number. Only adequate staff 
members in each site can assign identifiers to personal data. If personal data are stored and processed, 
requirements for data protection will be followed. The study database is centrally stored on redundant servers in 
Germany provided by the e-CRF system vendor. 
All recorded data will be pseudonymised for storage in the central database during the course of the study. As the 
decoding information is held only by the treating study sites, nobody else will know the identity of the participating 
subjects. After the end of the project, the data will be anonymised, deleted from the vendor’s servers and 
transferred to the sponsor where it will be stored for ten years. 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 23 of 34 
Data will only be collected and processed to reach the goals of the study. Personal data of the patient are 
demographic data (e.g. height, weight, data on comorbidities, data on current medication intake), data on quality 
of life (section 9.5.2), serious adverse events (section 11) and therapy data (section 9.5.3). Data will be 
transferred to the CRO (database management, questionnaire data entry, data analysis), to ResMed subsidiaries 
within the EU and to the scientific Steering Committee. 
The patient will be informed about the study and her/his rights in terms of data usage, data storage, correction of 
data and deletion of stored data. 
9.7.3 
Completion of Case Report Forms 
All medical data in this study will be recorded directly in the e-CRFs without the use of paper documents. The 
investigator must ensure the accuracy, completeness, legibility and timeliness of data reported in the e-CRF and 
of all required clinical reports (e. g. in case of SAEs). Any change or correction to a data in the e-CRF must be 
explained as a prerequisite of the e-CRF system. Any change or correction to an e-CRF item will automatically be 
tracked (audit trail), recording the person logged-in as well as the time stamp of the change and the reason for 
change. The e-CRF system will not accept changes without given reason. The history of changes to a single item 
including original entries is always visible to the responsible local research team and to the CRO. Data reported in 
the e-CRF that are derived from source documents should be consistent with the source documents or existing 
discrepancies should be explained. After completion of a patient visit, the investigator should agree to have 
correctly completed by electronically signing the corresponding parts of the e-CRF. Upon entry into the e-CRF the 
data will be automatically stored in the central study database in pseudonymised form. 
9.8 
Data analysis 
Data from all sites will be pooled for analysis. Standard statistical methods will be used to analyse all data. 
Continuous variables will be summarised using the number of observations, mean, median, standard deviation, 
minimum and maximum values. Categorical variables will be summarised using the number of observations and 
percentages. Two-sided, 95% confidence intervals will be used to characterise the major parameters. 
Demographic variables will be tabulated and summarised using descriptive statistics. 
A separate Statistical Analysis Plan (SAP) will be prepared by the CRO and approved by the sponsor prior to the 
start of data analysis, detailing the statistical analysis methods that will be used. 
9.9 
Quality control 
Quality control is defined as the operational techniques and activities undertaken within the quality assurance 
system to verify that the requirements for quality of the study-related activities have been fulfilled. Quality control 
should be applied to each stage of data handling to ensure that all data are reliable and have been processed 
correctly. 
A site initiation visit will be performed by the sponsor when a new site joins the study. 
Quality assurance is defined as the planned and systematic actions that are established to ensure that the study 
is performed, and the data generated, documented (recorded) and reported, in compliance with Good Clinical 
Practice (GCP) and the applicable regulatory requirements. 
9.9.1 
Source Data 
Source data are defined as all information obtained in clinical routine care and stored in original records and 
certified copies of original records of clinical findings, observations or other activities in a clinical study necessary 
for the reconstruction and evaluation of the study. Source data are contained in source documents (original 
records or certified copies). 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 24 of 34 
9.9.2 
Source Documents 
Source documents are defined as original documents, data and records in clinical routine care (e.g. hospital 
records, clinical and office charts, laboratory notes, memoranda or evaluation check lists, pharmacy dispensing 
records, recorded data from automated instruments, copies or manuscripts certified after verification as being 
accurate copies, microfiches, photographic negatives, microfilm or magnetic media, x- rays, patient files, records 
kept at pharmacy, at the laboratories and at medico technical departments). 
9.9.3 
Access to Source Data/Document 
The investigator will permit, and participating subjects will consent for, potential study-related monitoring, audits, 
Ethics Committee review and regulatory inspections, providing direct access to primary patient data (i.e. source 
data) that support data in the e-CRFs, i.e. general practice charts, hospital notes, appointment books, original 
laboratory records, etc. Because this is a patient confidentiality issue, access to such data must form part of the 
Informed Consent Form to be signed by the patient. 
9.9.4 
Direct Access 
Direct access is defined as the permission to examine, analyse, verify and reproduce any records and reports that 
are important to the evaluation of a clinical study. No identifiable subject data can be released from a site. Any 
party (e.g. regulatory authorities, the sponsor and/or authorised representatives of the sponsor such as monitors 
and auditors) with direct access should take all reasonable precautions within the constraints of the applicable 
regulatory requirements to maintain the confidentiality of patient identities and sponsor proprietary information. 
9.9.5 
Audits 
An audit is a systematic and independent review of study-related activities and documents to determine whether 
the validated study-related activities were conducted and the data were recorded, analysed and accurately 
reported according to the protocol, designated Standard Operating Procedures (SOP), GCP and the applicable 
regulatory requirements. An independent audit at the site may take place at any time during or after the study. 
9.10 Limitations of the research methods 
This clinical study is purely observational. All procedures and therapies used within the study are routine clinical 
care based on individual decisions of the treating physician and are not defined in the study protocol. It is 
expected that observed variations in diagnosis and treatment of COPD will be larger compared to controlled 
clinical trials with given standards. 
The data of this study represent clinical routine care of COPD patients without limitations normally given by 
protocol definitions of controlled clinical trials. Thus, the generalisability of results is deemed to be higher 
compared to those of controlled clinical trials. However, due to the expected larger range of variations in 
procedures and therapies the level of statistical significance is expected to be smaller but allowing for generation 
of hypotheses which might be investigated in subsequent clinical research projects. 
9.11 Other aspects 
This clinical study is industry funded and solely financed by the sponsor. The costs necessary to perform the 
study, i.e. to reimburse the time spent by site staff for documentation work, will be agreed upon with each study 
site and will be documented in a separate financial agreement which will be signed by the investigator and the 
CRO on behalf of the sponsor, prior to the study commencing. 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 25 of 34 
10. Protection of human subjects 
This clinical study is purely observational. No risks or benefits compared to routine clinical care will be added 
because all therapeutic decisions and procedures are performed in routine clinical care following all applicable 
medical guidelines, local policies, and ethical and regulatory standards. The study will be conducted in 
accordance with the principles laid down in the Declaration of Helsinki in its version of October 2013 (Fortaleza) 
and in accordance with ISO 14155:2011. 
Before initiating the study at a site, approval of the corresponding Ethics Committees will be obtained. 
11. Management and reporting of Adverse Events/Adverse Reactions 
All Serious Adverse Events (SAEs) will be documented according to ISO 14155 and reported in accordance with 
applicable national standards. Since the study design is observational, all therapies and procedures are routine 
clinical care and in line with applicable medical guidelines, market authorisations and corresponding Instructions 
For Use (IFUs). Since no risks or benefits compared to routine clinical care will be added, the rate of non-serious 
adverse events (AEs) will be identical to routine clinical care, thus, AEs will not be documented within this study. 
Definitions 
Adverse Event (AE): 
Any untoward medical occurrence in a subject. This includes any undesired symptom, sign, illness, or experience, 
which develops or worsens in severity and/or frequency during the course of the study (i.e. any undesired change 
from baseline). 
Serious Adverse Event (SAE): 
According to ISO 14155, SAE is an adverse event that has resulted in any of the following consequences or could 
result in the following consequences: 
 
Death 
 
A serious deterioration in the health of the subject that 
 resulted in a life-threatening illness or injury, 
 resulted in a permanent impairment of a body structure or a body function, 
 required in-patient hospitalisation or prolongation of existing hospitalisation, 
 resulted in medical or surgical intervention to prevent permanent impairment to a body structure or a body 
function 
 
Fetal distress, fetal death or a congenital abnormality or birth defect 
 
Any other medically important event 
Medically important event 
Medical and scientific judgement should be exercised in deciding whether other situations should be considered 
as serious reactions. Some medical events may jeopardise the subject or may require an intervention to prevent 
one of the above characteristics/consequences. Such important medical events should be considered as serious.  
 
 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 26 of 34 
Life-threatening 
The definition of an SAE refers to an event in which the patient was at risk of death at the time of the event. It 
does not refer to an event which hypothetically might have caused death if it was more severe. 
Hospitalisation 
 
Hospitalisation is within this protocol defined as inpatient care of more than one calendar day (overnight 
stay) for any cause. Overnight survey visits (e.g. sleep lab) are not considered “hospitalisation”. 
 
Unplanned hospitalisation is within this protocol defined as ill-defined hospital admissions in acute inpatient 
medical settings for any cause for more than one calendar day (overnight stay) where managing demand for 
unplanned admissions is a priority [13]. 
 
COPD-caused hospitalisation is within this protocol defined as COPD exacerbation leading to 
hospitalisation as defined above. 
 
COPD exacerbation is defined as an acute worsening of respiratory symptoms that results in additional 
therapy with systemic steroids and / or antibiotics [14]. 
The investigator will document in the e-CRF each hospitalisation of study patients including a statement if he 
classifies it as “unplanned” and as “COPD-caused”. As second source of information, patients will be asked to 
report hospitalisations and other potential SAEs every six months of follow-up using a short questionnaire (refer to 
9.3.6). 
Because hospitalisation decisions might be subject to local practices, social considerations, bed availability, and 
so on, all hospitalisations will be reviewed by an independent Endpoint Review Committee (ERC) based on coded 
(pseudonomysed) copies of corresponding medical files to assess the reason and appropriateness of each 
hospitalisation, i.e. whether it is “unplanned” and “COPD-caused”. 
Adverse Device Effect (ADE) 
Any untoward and unintended response to a medical device. This includes any event resulting from insufficiencies 
or inadequacies in the instructions for use or the deployment of the device. 
Serious Adverse Device Effect (SADE) 
Adverse Device Effect that has resulted in any of the consequences characteristic of a Serious Adverse Event or 
that might have led to any of these consequences if suitable action had not been taken or intervention had not 
been made or if circumstances had been less opportune. 
Unexpected Serious Adverse Device Effects (USADEs) 
Are defined as any Serious Adverse Effect on health or safety or any life-threatening problem or death caused by, 
or associated with, a device, if that effect, problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan or application (including a supplementary plan or application), or 
any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of 
subjects.  
Medical judgment should be exercised in deciding whether an AE/ADE is serious in other situations. Important 
AE/ADE that are not immediately life-threatening or do not result in death or unplanned hospitalisation of a 
planned hospitalisation but may jeopardise the patient or may require intervention to prevent one of the other 
outcomes listed in the definition above, should also be considered serious. 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 27 of 34 
11.1 Recording and reporting Adverse Events/Adverse Device Effects 
The investigator shall report in detail all serious adverse events (SAEs) and device deficiencies that could have 
led to serious adverse device effect. The investigator shall document any SAE in the e-CRF in the “SAE visit”. All 
items of the form should be filled in adequately and promptly. 
The investigator should not wait to receive further information before reporting such an event. The initial report 
should carefully be followed until the event is resolved. 
The sponsor of the study is responsible for reporting of Adverse Events/Adverse Device Effects to regulatory 
bodies according to his duties in routine clinical care. 
12. Plans for disseminating and communicating study results 
12.1 Publication policy 
Study results will be pooled across all participating sites for the purpose of publication that will be coordinated by 
the sponsor. Preparation of the comprehensive publication will occur at the completion of the study, but the 
sponsor may, at its discretion, coordinate an additional, interim publication. The order of authorship will be 
determined by the sponsor and will be based in part on the number of qualified and completing subjects at each 
site. 
An investigator intending to publish results of the study must provide the sponsor with a copy of any proposed 
publication, abstract, or presentation at least 60 days prior to submission for publication or presentation. The 
sponsor will have the right to object to the publication, abstract, or presentation if, in the sponsor’s reasonable 
opinion, such publication (i) contains confidential information; or (ii) will adversely affect any intellectual property 
or proprietary right of the sponsor. In the event of an objection by the sponsor, the investigator must either modify 
or delay the publication, abstract, or presentation for a period requested by sponsor not to exceed ninety (90) 
days to permit the sponsor to re-dress or mitigate risks. 
Investigators and sites must acknowledge the sponsor in all publications or presentations resulting from this study 
and provide any required disclosures. 
All relevant measures for transparency of clinical studies, and especially the recommendations of the editors of 
the major medical journals, will be met. 
 
 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 28 of 34 
13. References 
1. 
Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis Management and 
Prevention of COPD 2015. Available from: 
http://www.goldcopd.org/uploads/users/files/GOLD_Report_2015_Feb18.pdf. 
2. 
World Health Organisation. Chronic obstructive pulmonary disease (COPD)/Burden of COPD. 2018. 
Available from: http://www.who.int/respiratory/copd/burden/en/. 
3. 
Chandra, D., et al., Outcomes of noninvasive ventilation for acute exacerbations of chronic obstructive 
pulmonary disease in the United States, 1998-2008. Am J Respir Crit Care Med, 2012. 185(2): p. 152-9. 
4. 
Kohnlein, T., et al., Non-invasive positive pressure ventilation for the treatment of severe stable chronic 
obstructive pulmonary disease: a prospective, multicentre, randomised, controlled clinical trial. Lancet Respir 
Med, 2014. 2(9): p. 698-705. 
5. 
Demoule, A., et al., Benefits and risks of success or failure of noninvasive ventilation. Intensive Care Med, 
2006. 32(11): p. 1756-65. 
6. 
Cheng, L., Chan, V.,  and Chu, C.-M., A pilot study of treatment compliance in home non-invasive ventilation. 
European Respiratory Journal, 2011. 38(Suppl 55). 
7. 
Sullivan, S.D., Ramsey, S.D. and Lee, T.A. The economic burden of COPD. Chest, 2000. 117(2 Suppl): p. 
5s-9s. 
8. 
Mannino, D.M. and Buist, A.S., Global burden of COPD: risk factors, prevalence, and future trends. Lancet, 
2007. 370(9589): p. 765-73. 
9. 
Joshi, M., Joshi, A., and Bartter, T., Symptom burden in chronic obstructive pulmonary disease and cancer. 
Curr Opin Pulm Med, 2012. 18(2): p. 97-103. 
10. Janson, C., et al., The impact of COPD on health status: findings from the BOLD study. Eur Respir J, 2013. 
42(6): p. 1472-83. 
11. Murphy, P.B., Rehal, S., Arbane, G., et al. Effect of Home Noninvasive Ventilation With Oxygen Therapy vs 
Oxygen Therapy Alone on Hospital Readmission or Death After an Acute COPD Exacerbation: A 
Randomized Clinical Trial. JAMA. 2017. 317(21): p. 2177–2186.  
12. Windisch, W., et al., Guidelines for non-invasive and invasive mechanical ventilation for treatment of chronic 
respiratory failure. Published by the German Society for Pneumology (DGP). Pneumologie, 2010. 64(10): p. 
640-52. 
13. Walsh B. et al., Features and outcomes of unplanned hospital admissions of older people due to ill-defined 
(R-coded) conditions: Retrospective analysis of hospital admissions data in England. BMC Geriatr. 2011; 11: 
62. doi: 10.1186/1471-2318-11-62 
14. Global Initiative For Chronic Obstructive Disease. Global strategy for the diagnosis, management, and 
prevention of chronic obstructive pulmonary disease (2019 report); https://goldcopd.org › GOLD-2019-v1.7-
FINAL-14Nov2018-WMS.pdf 
 
 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 29 of 34 
 List of stand-alone documents 
Annex 1.
Number 
Title 
1 
Item list of e-CRF 
2 
List of participating investigators 
3 
List of adequate ResMed NIV therapy devices 
4 
Follow-up questionnaire (patient questionnaire on events and hospitalisations) 
 
 
 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 30 of 34 
 SRI questionnaire 
Annex 2.
Only sample – the form to be used throughout the study will be made available as a separate document. 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 31 of 34 
  

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 32 of 34 
 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 33 of 34 
 

HOmeVent Connect 
Confidential 
Version no. 2.0 dated 2020-01-10 
HomeVent Connect Protocol_v 2.0_200110.docx 
 
Page 34 of 34 
 CAT questionnaire 
Annex 3.
Only sample – the form to be used throughout the study will be made available as a separate document.