Adherence to ASV Therapy in Heart Failure With Preserved Ejection Fraction Feasibility Study
Phase: NA
Conditions: Heart Failure With Normal Ejection Fraction, Sleep Apnea
Sponsor: ResMed

STUDY PROTOCOL 
 
Adherence to ASV Therapy in Heart Failure with Preserved Ejection Fraction 
Feasibility Study 
(CAT-PEF Feasibility) 
 
 
 
Study Number: MA-16-12-01 
NCT03195660 
 
Version: 1.0 
Date: 28Mar17 
 
 
Sponsor: 
ResMed Corp 
9001 Spectrum Center Blvd 
San Diego, CA  92123 
(800) 424-0737 
 
 
 
 
 
 
 
 
 
This protocol has been written in accordance with current applicable guidelines (IDE for USA) as well as all 
other relevant additional references, medical and legal. 

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The information herein is confidential and the property of ResMed Corp. It is to be used in confidence for 
the conduct of the clinical trial according to written agreement. 
 

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PROTOCOL REVISION HISTORY 
Version No. And Date 
Section 
Change 
Rationale 
Version 1.0 
28Mar17 
n/a 
n/a 
Original Release 
 
 
 

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Table of Contents 
1. 
Responsibilities and addresses ...................................................................................................... 6 
2. 
ABBREVIATIONS AND DEFINITIONS ............................................................................................... 7 
4. 
PROTOCOL SUMMARY ................................................................................................................... 8 
5. 
INTRODUCTION ............................................................................................................................ 10 
5.1. 
Background Information .............................................................................................................. 10 
5.2. 
Intended Use ................................................................................................................................ 11 
6. 
STUDY OBJECTIVES ....................................................................................................................... 11 
7. 
STUDY DESIGN.............................................................................................................................. 11 
7.1. 
Enrollment.................................................................................................................................... 11 
7.2. 
Selection of subjects .................................................................................................................... 12 
7.2.1. 
Informed Consent .................................................................................................................. 12 
7.2.2. 
Number of Subjects ................................................................................................................ 12 
7.2.3. 
Subject Inclusion Criteria ....................................................................................................... 12 
7.2.4. 
Subject Exclusion Criteria ....................................................................................................... 13 
8. 
STUDY DEVICES ............................................................................................................................ 13 
8.1. 
AirCurve™ 10 ASV ........................................................................................................................ 13 
8.2. 
ApneaLink Air ............................................................................................................................... 14 
8.3. 
Device Accountability................................................................................................................... 15 
8.4. 
Labeling ........................................................................................................................................ 15 
8.5. 
Packaging ..................................................................................................................................... 15 
8.6. 
Instruction for Use ....................................................................................................................... 15 
8.7. 
Required Training ......................................................................................................................... 15 
9. 
THERAPY ....................................................................................................................................... 15 
9.1. 
Treatment with Adaptive Servo-ventilation (AirCurve) ............................................................... 15 
9.2. 
Set up of AirCurve in ASVAuto Mode .......................................................................................... 15 
9.3. 
AirView ......................................................................................................................................... 16 
10. 
STUDY SCHEDULE ......................................................................................................................... 17 
10.1. 
Study Entry ............................................................................................................................. 17 
10.2. 
Study Flow .............................................................................................................................. 18 
10.3. 
Follow-Up ............................................................................................................................... 19 
10.4. 
Screening Procedures ............................................................................................................. 19 
10.5. 
Detailed Visit Schedule ........................................................................................................... 20 
10.5.1. 
Visit 1: Screening/Baseline ..................................................................................................... 20 
10.5.2. 
ASV Adherence Monitoring .................................................................................................... 20 
10.5.3. 
Visit 2: End of study Follow-up ............................................................................................... 20 
10.6. 
Overview of visits ................................................................................................................... 21 
10.7. 
Duration of the study ............................................................................................................. 21 
11. 
VISIT PROCEDURES ....................................................................................................................... 21 
11.1. 
Polygraphy .............................................................................................................................. 21 
11.2. 
KCCQ-12.................................................................................................................................. 21 
11.3. 
Mask and ASV Therapy Tolerance .......................................................................................... 21 
11.4. 
Treatment Adherence ............................................................................................................ 22 
11.5. 
Subject Discontinuation Criteria ............................................................................................ 22 
11.6. 
Device and Subject Disposition .............................................................................................. 22 
12. 
SAFETY .......................................................................................................................................... 22 
12.1. 
Hospitalization........................................................................................................................ 23 
12.2. 
Labeled Adverse Device Effects ............................................................................................. 23 

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13. 
STATISTICAL ANALYSIS ................................................................................................................. 23 
13.1. 
Justification of the Sample Size .............................................................................................. 23 
13.2. 
Primary endpoint analysis ...................................................................................................... 24 
13.3. 
Secondary endpoint analyses................................................................................................. 24 
14. 
DATA HANDLING AND RECORDKEEPING ..................................................................................... 24 
14.1. 
Data Collection ....................................................................................................................... 24 
14.2. 
Study Documentation ............................................................................................................ 24 
14.3. 
Query Generation and Resolution ......................................................................................... 24 
14.4. 
Data Storage ........................................................................................................................... 25 
14.5. 
Inspection of Records ............................................................................................................. 25 
14.6. 
Study Files and Record Retention .......................................................................................... 25 
14.7. 
Regulatory Documentation .................................................................................................... 25 
15. 
ETHICAL CONSIDERATIONS .......................................................................................................... 25 
15.1. 
Institutional Review Board (IRB)/Ethics Committee (EC)....................................................... 25 
15.2. 
Protocol Deviations ................................................................................................................ 26 
15.3. 
Risk Analysis and Confidentiality............................................................................................ 26 
15.3.1. 
Risk Determination of the Study ............................................................................................ 26 
15.3.2. 
Subject Data Confidentiality................................................................................................... 27 
16. 
QUALITY CONTROL AND QUALITY ASSURANCE ........................................................................... 27 
16.1. 
Site Selection .......................................................................................................................... 27 
16.2. 
Polygraphy Data ..................................................................................................................... 27 
16.3. 
Adherence to ASV Therapy .................................................................................................... 27 
16.4. 
Training ................................................................................................................................... 27 
16.5. 
Audits and Inspections ........................................................................................................... 28 
17. 
RESPONSIBILITIES ......................................................................................................................... 28 
17.1. 
Clinical Investigator Responsibilities ...................................................................................... 28 
17.2. 
Sponsor Responsibilities......................................................................................................... 28 
18. 
STUDY ORGANIZATION ................................................................................................................ 29 
18.1. 
Steering Committee ............................................................................................................... 29 
18.2. 
Adherence Core Lab ............................................................................................................... 29 
19. 
STUDY REPORTS AND PUBLICATIONS .......................................................................................... 29 
20. 
REFERENCES ................................................................................................................................. 30 
Appendix I. 
Site Sleep Therapist Guidance........................................................................................ 31 
Appendix II. 
Adherence Core Lab Guidance ....................................................................................... 33 
 
 

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1. Responsibilities and addresses 
Principal Investigator: Christopher M. O’Connor, M.D. 
Inova Heart & Vascular Institute  
Study Coordination: Amy Blase, CCRA 
ResMed Corp 
Medical Affairs Department  
Statistician: Leslee Willes 
Willes Consulting 
Steering Committee: Chair:  
Christopher M. O’Connor, MD, FACC, FESC, FHFSA 
Inova Heart & Vascular Institute 
Voting Members: 
JoAnn Lindenfeld, MD 
Vanderbilt University 
David Whellan, MD 
Thomas Jefferson University 
Olaf Oldenburg, MD 
Heart and Diabetes Center North Rhine-Westphalia 
Mona Fiuzat, PharmD 
Duke Clinical Research Institute 
Naresh Punjabi, MD, PhD 
Johns Hopkins Medical Institute 
Dalane Kitzman, MD 
Wake Forest Baptist Health 
Sponsor’s Representative (Non-Voting): 
Adam Benjafield, PhD 
ResMed Corp 
Leader, Site PIs: Lauren Cooper, MD 
Inova Heart & Vascular Institute 
Adherence Core Lab: Johns Hopkins University (Naresh Punjabi, MD) 
Thomas Jefferson University (David Whellan, MD) 
 

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2. ABBREVIATIONS AND DEFINITIONS  
ADE 
Adverse Device Effect 
AE 
Adverse Event 
AFib 
Atrial Fibrillation 
AHI 
Apnea-Hypopnea Index 
ASV 
Adaptive Servoventilation / Adaptive Servoventilator 
BNP 
B-type natriuretic peptide 
CPAP 
Continuous Positive Airway Pressure 
CSA 
Central Sleep Apnea 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
e/hr 
Events per hour 
EF 
Ejection Fraction 
EPAP 
Expiratory Positive Airway Pressure 
FDA 
Food and Drug Administration 
HF 
Heart Failure 
HFpEF 
Heart failure with preserved ejection fraction; LVEF≥50% 
HFrEF 
Heart failure with reduced ejection fraction 
IDE 
Investigational Device Exemption 
IRB 
Institutional Review Board 
KCCQ 
Kansas City Cardiomyopathy Questionnaire 
LV 
Left Ventricular 
LVEF 
Left ventricular ejection fraction 
MI 
Myocardial infarction 
NT pro-BNP 
N-terminal prohormone of b-type natriuretic protein 
ODI 
Oxygen Desaturation Index 
OSA 
Obstructive Sleep Apnea 
PAP 
Positive Airway Pressure 
SAE 
Serious Adverse Event 
SC 
Steering Committee 
SDB 
Sleep-Disordered Breathing, also referred to as sleep apnea 
SOP 
Standard Operation Procedures 
TIA 
Transient ischemic attack  
 
 
 

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4. PROTOCOL SUMMARY 
Objectives 
Demonstrate feasibility of study conduct and that acceptable adherence to ASV 
therapy can be achieved in recently hospitalized HFpEF patients with moderate to 
severe SDB. 
Study Design 
This study is a prospective, single-arm, unblinded, multi-center study. All subjects 
meeting criteria will receive adaptive servo-ventilation (ASV).  
Number of 
Subjects 
The study will aim to enroll 160 evaluable subjects. For the purposes of this study, 
an evaluable subject is one with ASV usage of at least 4hrs per night for 70% of the 
study nights, excluding nights hospitalized at 30 days after study entry. In order to 
achieve 160 evaluable subjects it is estimated that up to 300 subjects will be 
initially enrolled in the study. 
Selection 
criteria 
 
Inclusion criteria for the study are: 
1. Patients 18 years or older 
2. Patients with heart failure with preserved ejection fraction (HFpEF; LVEF 
≥50%)  
3. Hospital admission or equivalent (such as ER visit alone or clinic visit alone) 
and acute decompensated HF as determined by: 
a. Dyspnea at rest or with minimal exertion 
AND 
b. Treatment with at least one dose of IV diuretic or ultrafiltration 
AND 
c. At least two of the following signs and symptoms: 
i. Orthopnea 
ii. Pulmonary rales that do not clear with cough 
iii. Congestion on chest X-ray 
iv. Local BNP or NT pro-BNP level: 
A. No current atrial fibrillation (AFib): BNP≥100 pg/mL or NT pro-
BNP≥300 pg/mL  
OR 
B. Current AFib: BNP≥150 pg/mL or NT pro-BNP≥450 pg/mL  
4. Sleep disordered breathing (SDB) documented by screening polygraphy 
with an AHI≥15 events/hour (e/hr)  
5. Patient is able to fully understand study information and sign informed 
consent 
Exclusion criteria for the study are: 
1. Right-sided heart failure without left-sided failure 
2. Current chronic use (within 4 weeks of study entry) of any PAP therapy 
(eg, CPAP, APAP, or bi-level) or contraindicated for PAP therapy 

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3. Sustained systolic blood pressure <80 mmHg at baseline  
4. Complex congenital heart disease 
5. Constrictive pericarditis 
6. Chronic hypoxemia as evidenced by sustained oxygen saturation ≤ 85% at 
rest during the day or at start of nocturnal oximetry recording or regular 
use of oxygen therapy (day or night) 
7. Transient ischemic attack (TIA) or Stroke within 3 months prior to study 
entry  
8. Definite clinically evident acute myocardial infarction within 3 months of 
study entry 
9. Known amyloidosis, hypertrophic obstructive cardiomyopathy, or 
arteriovenous fistulas 
10. Moderate or greater valvular heart disease as the primary reason for 
heart failure 
11. Pregnant, or planning to become pregnant during the study period 
12. In the opinion of the investigator, the index acute decompensated HF 
event was due primarily to uncontrolled AFib with fast ventricular 
response rate 
13. Inability to comply with planned study procedures 
Primary 
Endpoints 
ASV Adherence rate (average hours used per day) at 3 months  
Secondary 
Endpoints 
• 
Feasibility of study conduct as measured by recruitment rate (subjects 
enrolled per month) by site, reasons for screen failures, and where in the 
hospital system patients are recruited (eg, HF clinic, general cardiology, 
etc) 
• 
Change in quality of life as measured by the Kansas City Cardiomyopathy 
Questionnaire (KCCQ-12) 
• 
Number of hospitalizations for any reason following study entry 
• 
Death for any reason during study participation 
Scheduled 
follow up 
For evaluation of the primary and secondary endpoints, subjects will be followed 
for a period of 3 months (12 weeks).  
• 
Visit 1 will occur at baseline for device set-up and KCCQ-12 
• 
Visit 2 will occur at 12 weeks for disposition of device, KCCQ-12, and 
determination of hospitalizations and death 
 
 

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5. INTRODUCTION 
5.1. 
Background Information 
Heart failure (HF) continues to present a social and economic burden, especially with regard to HF 
hospitalizations. The current HF treatment guidelines1,2 include a number of treatments focused 
on HF with reduced ejection fraction (HFrEF; left ventricular ejection fraction [LVEF] ≤45%), but no 
evidence-based therapies for HF with preserved ejection fraction (HFpEF; LVEF ≥50%). 
Sleep-disordered breathing (SDB) is very common in HF populations that have reduced as well as 
preserved ejection fraction, with reported prevalence rates of 50-75%3,4,5,. There are very few 
studies that have evaluated the impact of treating SDB in HFpEF, and the studies that do exist 
generally include a small number of patients6. 
The Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure Study (SERVE-HF) 
showed that ASV in patients with stable HFrEF and SDB with predominant central sleep apnea 
increased cardiovascular mortality7. The results of secondary multistate modeling analysis showed 
that the risk of direct sudden cardiovascular death and hospitalization for worsening HF were 
associated with poor left ventricular function that attenuated as the LVEF approached normal8. 
Cardiovascular Improvements with Minute Ventilation-targeted ASV Therapy in Heart Failure 
Study (CAT-HF) was a randomized controlled clinical trial in the United States and Germany. It was 
designed to evaluate the effect of ASV in hospitalized heart failure (HFrEF and HFpEF) patients on a 
global rank endpoint of survival free from CV hospitalization and improvement in functional 
capacity measured by 6-minute walk distance. Analysis of the 126 subjects that were randomized 
showed a neutral result for the primary endpoint; however, in the pre-specified analysis of the 
primary endpoint by LVEF strata, there was a favorable statistically significant difference in the 
HFpEF subgroup (p=0.036) (O’Connor in press). There was no safety signal for increased mortality 
risk in patients randomized to ASV. 
CAT-HF demonstrated that SDB can be effectively controlled by ASV in a HF population; however, 
adherence to ASV was very low, limiting the ability to determine the effect of ASV on HF 
outcomes. Despite this, analysis showed improved outcomes with ASV therapy in the HFpEF 
subgroup (O’Connor in press). Newer technologies include the web-based AirView system, which 
allows the patient’s care team to monitor adherence, and the myAir application, which provides 
patients with immediate feedback on their actual therapy use. These have been shown to improve 
adherence by addressing issues with therapy as they arise, thus increasing patient engagement 
and adherence to therapy9.  
Although the CAT-HF study showed a positive signal in the HFpEF subgroup, these patients 
represented a small percentage of the randomized subjects in the study. The current study aims to 
show that by applying newer technologies to support adherence, as well as focusing on the lessons 
learned in CAT-HF to identify and recruit HFpEF patients, acceptable adherence to ASV therapy can 
be achieved in HFpEF patients. Demonstrating feasibility of study conduct in this way will help 
support a future phase III randomized controlled trial with morbidity and mortality endpoints. 

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5.2. 
Intended Use 
The AirCurve 10 ASV device is indicated for the treatment of patients weighing more than 66 lb (30 
kg) with obstructive sleep apnea (OSA), central and/or mixed apneas, or periodic breathing. It is 
intended for home and hospital use. The humidifier is intended for single patient use in the home 
environment and re-use in a hospital/institutional environment. 
Contraindications 
ASV therapy is contraindicated in patients with chronic, symptomatic heart failure (NYHA II-IV) 
with reduced left ventricular ejection fraction (LVEF ≤ 45%) and moderate to severe predominant 
central sleep apnea. 
Positive airway pressure therapy may be contraindicated in some patients with the following pre-
existing conditions: 
• severe bullous lung disease 
• pneumothorax or pneumomediastinum 
• pathologically low blood pressure, particularly if associated with intravascular volume depletion 
• dehydration 
• cerebrospinal fluid leak, recent cranial surgery, or trauma. 
6. STUDY OBJECTIVES 
The objective of the study is to demonstrate feasibility of study conduct, and to evaluate adherence to 
ASV therapy at 3 months in HFpEF patients diagnosed with moderate to severe sleep apnea. Adherence 
will be monitored using cloud-based technology in which data from each ASV machine is automatically 
transmitted to a secure, HIPAA-compliant system (AirView). The system is accessible through the 
internet with a secure interface. This technology can be customized to “flag” patients who do not meet 
criteria for minimal use. Data will be reviewed by each site’s respiratory/sleep team, and in patients 
where the use of ASV is less than 3 hours per night, the respiratory/sleep team will contact the patient 
to troubleshoot the reasons for low usage, and provide appropriate solutions. In addition, a central 
Adherence Core Lab will oversee the ASV usage at all sites, providing guidance and support where 
necessary. 
7. STUDY DESIGN 
The CAT-PEF Feasibility Study is a prospective, single-arm, unblinded, multi-center, study of HFpEF 
subjects diagnosed with SDB using ASV therapy. 
This study will be conducted in up to 10 centers in the US and Germany.  
7.1. 
Enrollment 
Subjects will be recruited from in-patient clinical services or in the outpatient setting if within 14 
days of discharge. If a subject is willing to participate in the CAT-PEF Feasibility Study, a written 

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informed consent for the study must be obtained prior to any study related procedure. Before 
dispensing a device, all eligibility criteria must be confirmed.  
7.2. 
Selection of subjects 
7.2.1. 
Informed Consent 
The consent form is written in accordance with applicable data privacy acts and FDA 
Regulations and approved by the responsible Institutional Review board (IRB)/Ethics 
Committee (EC).  
The investigator or responsible staff will explain the nature, purpose and risks associated 
with the study. The patient will be given sufficient time to consider the study’s 
implications before deciding whether to participate. Information materials created by 
the investigators and Sponsor must be approved by the responsible IRB/EC prior to use.  
A signed, IRB/EC-approved consent form must be obtained from the patient prior to the 
performance of any protocol-related testing or procedures unless obtained as part of 
standard care. The consent process must be performed by a designated clinical study 
team member authorized by the IRB/EC to consent patients and listed on the Delegation 
of Authority Log as having privileges to consent patients. A signed copy of the consent 
form must be maintained in the study files and a copy provided to the patient. The 
patient’s permanent medical records should indicate study participation.  
7.2.2. 
Number of Subjects 
Up to 300 subjects will be initially enrolled in this study. For endpoint evaluation, 160 
evaluable subjects are required. For the purposes of this study, an evaluable subject is 
one with ASV usage of at least 4hrs per night for 70% of the study nights, excluding 
nights hospitalized after 30 days (1 month) of ASV usage.  
7.2.3. 
Subject Inclusion Criteria 
1. Patients 18 years or older 
2. Patients with heart failure with preserved ejection fraction (HFpEF; LVEF ≥50%)  
3. Hospital admission or equivalent (such as ER visit alone or clinic visit alone) and 
acute decompensated HF as determined by: 
a. Dyspnea at rest or with minimal exertion 
AND 
b. Treatment with at least one dose of IV diuretic or ultrafiltration 
AND 
c. At least two of the following signs and symptoms: 
i. Orthopnea 
ii. Pulmonary rales that do not clear with cough 
iii. Congestion on chest X-ray 

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iv. Local BNP or NT pro-BNP level: 
A. No current atrial fibrillation (AFib): BNP≥100 pg/mL or NT pro-
BNP≥300 pg/mL  
OR 
B. Current AFib: BNP≥150 pg/mL or NT pro-BNP≥450 pg/mL  
4. Sleep disordered breathing (SDB) documented by screening polygraphy with an 
AHI≥15 events/hour (e/hr)  
5. Patient is able to fully understand study information and sign informed consent 
7.2.4. 
Subject Exclusion Criteria 
1. Right-sided heart failure without left-sided failure 
2. Current chronic use (within 4 weeks of study entry) of any PAP therapy (eg, CPAP, 
APAP, or bi-level) or contraindicated for PAP therapy 
3. Sustained systolic blood pressure <80 mmHg at baseline  
4. Complex congenital heart disease 
5. Constrictive pericarditis 
6. Chronic hypoxemia as evidenced by sustained oxygen saturation ≤ 85% at rest during 
the day or at start of nocturnal oximetry recording or regular use of oxygen therapy 
(day or night) 
7. Transient ischemic attack (TIA) or Stroke within 3 months prior to study entry  
8. Definite clinically evident acute myocardial infarction within 3 months of study entry 
9. Known amyloidosis, hypertrophic obstructive cardiomyopathy, or arteriovenous 
fistulas 
10. Moderate or greater valvular heart disease as the primary reason for heart failure 
11. Pregnant, or planning to become pregnant during the study period 
12. In the opinion of the investigator, the index acute decompensated HF event was due 
primarily to uncontrolled AFib with fast ventricular response rate 
13. Inability to comply with planned study procedures  
8. STUDY DEVICES 
8.1. 
AirCurve™ 10 ASV 
The AirCurve 10 ASV (“AirCurve”) is a market-released device that has been FDA-cleared in the US 
(K160822) and CE-marked in Germany to provide non-invasive ventilatory support to treat patients 
weighing more than 66 lbs (30 kg) with OSA, central and/or mixed apnea or periodic breathing. The 
device is intended for home and hospital use. 
AirCurve is a non-invasive device, providing minute ventilation-targeted ASV algorithms to deliver 
ventilatory support for OSA, CSA and/or mixed apnea, and periodic breathing by automatically 
adjusting the pressure support (PS) in a defined pressure range to maintain a target minute 
ventilation. The AirCurve 10 ASV device offers three different therapy modes, CPAP mode, ASV 

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mode and ASVAuto mode. The CAT-PEF Feasibility Study will only use the ASVAuto mode. Ancillary 
equipment includes the humidifier, air delivery hose, mask, and headgear.  
In ASVAuto mode, the device automatically adjusts the expiratory pressure in order to provide 
only the amount of pressure (EPAP) required to maintain upper airway patency. The device 
analyzes the state of the patient’s upper airway on a breath-by-breath basis and delivers 
expiratory pressure within the allowed range (Min EPAP and Max EPAP) according to the degree of 
obstruction. EPAP is automatically adjusted depending on three parameters: inspiratory flow 
limitation, snore, and obstructive apnea. 
Pressure Support (PS) is defined as the difference between the peak pressure at the end of 
inspiration, and the minimum pressure at the end of expiration (ie, the amplitude of the pressure 
waveform delivered). The AirCurve pressure support (Inspiration:Expiration and 
Expiration:Inspiration) trigger points are set automatically based on measurement of the patient 
respiratory flow. The AirCurve algorithm will automatically adjust pressure delivery to keep the 
patient’s respiratory flow even. 
See AirCurve Clinician's Manual for details. 
8.2. 
ApneaLink Air 
The ApneaLink Air (“ApneaLink”) is a market-released polygraphy (“home sleep testing [HST]”) 
device that has been FDA-cleared (K143272) for use by Health Care Professionals, where it may aid 
in the diagnosis of sleep disordered breathing for adult patients. ApneaLink records the following 
data: patient respiratory nasal airflow, snoring, blood oxygen saturation, pulse, and respiratory 
effort during sleep. ApneaLink uses these recordings to produce a report that may aid in the 
diagnosis of sleep disordered breathing or for further clinical investigation. The ApneaLink may be 
used with an optional dual-lumen cannula in cases where the patient cannot be taken off low flow 
oxygen therapy for the duration of the test. 
The ApneaLink Air recorder is a 4-channel battery-powered respiratory pressure sensor and 
oximetry system. The ApneaLink Air recorder and the respiratory effort sensor must be fastened 
with the re-usable belt on the patient's chest. All relevant respiratory information during sleep will 
be collected via nasal cannula, pulse oximetry adapter and respiratory effort sensor. The 
disposable plastic nasal cannula is connected to the ApneaLink Air recorder and fixed at the 
patient's nose. The oximetry sensor is connected to the patient's finger. The respiratory effort 
sensor is connected to the ApneaLink recorder and held in place by the belt. The physician can 
generate a report with the recorded and analyzed data through the web-based AirView. The 
default settings for the ApneaLink Air includes a flow reduction of 80% for at least 10 seconds to 
automatically score an apnea, a flow reduction of 30% combined with a desaturation of 3% to 
automatically score a hypopnea, and a respiratory effort sensor to differentiate between central, 
obstructive and mixed apneas. 
See ApneaLink Air Clinician's Manual for details. 

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8.3. 
Device Accountability 
An accurate and current accounting of the dispensing of ResMed devices (AirCurve, ApneaLink) will 
be maintained on an on-going basis by a qualified member of the study site using the Sponsor-
provided “Device Disposition Log”. Devices will be made available to the investigator by ResMed. If 
a replacement device is dispensed, it will be documented per device accountability procedure. All 
non-disposable ResMed devices must be returned to ResMed at the end of the study. 
8.4. 
Labeling 
The label contains the information as required by relevant regulatory requirements: 
a) Sponsor name and address 
b) Serial number to identify the individual device 
c) Instruction For Use 
8.5. 
Packaging 
The AirCurve 10 ASV and ApneaLink Air study devices are FDA 510(k) cleared and will be used with 
the standard packaging. The devices are CE marked according to the European Declaration of 
Conformity. 
8.6. 
Instruction for Use 
The devices will be used as specified in the relevant Instructions for Use. 
8.7. 
Required Training 
Subjects will be instructed on usage of the devices by the local Investigators or designee. ResMed 
will provide the investigators' training.  
9. THERAPY 
9.1. 
Treatment with Adaptive Servo-ventilation (AirCurve) 
The AirCurve device will be used at home; however the therapy can be initiated in the hospital or 
as an outpatient within 14 days of hospital discharge. Although the AirCurve has three therapy 
modes, CPAP, ASV, and ASVAuto, only the ASVAuto mode will be used for this study. Subjects are 
advised to use the AirCurve device during any significant sleeping period, including naps. Ideally, 
AHI should be at or below 5 e/hr. However, if the AHI cannot be maintained below 10 e/hr, the 
subject’s therapy should be adjusted (mask and/or pressure settings). 
9.2. 
Set up of AirCurve in ASVAuto Mode 
For initiation of therapy, AirCurve will be set to a minimum expiratory PAP (EPAP) of 4 cmH20, a 
maximum EPAP of 15 cmH2O, a minimum pressure support of 3 cmH2O, and a maximum pressure 
support of 15 cmH2O. All subjects will be provided humidifiers and ClimateLine tubing to address 

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any instance of upper airway dryness or other forms of discomfort with the airflow of the device 
during the initiation or during therapy with the device. For the initiation of therapy, a ResMed full 
face mask is recommended, but if this mask is unsuitable for the subject another type of mask 
such as a nasal mask or nasal pillows mask will be tried. Adherence to therapy will be evaluated 
centrally through AirView. The recommended target for AHI within 7 days of therapy initiation is 
lower than 10 e/hr, and major mask leaks should be avoided. If these targets are not able to be 
achieved, the subject will be contacted to implement corrective actions.  
The subject’s AirCurve device will be added to the Trial AirView account for ongoing monitoring 
during the study. 
9.3. 
AirView 
AirView is the HIPAA compliant web based system that is routinely used for telemonitoring. The 
AirCurve device contains built in wireless connectivity which transmits data via a mobile network 
to a secure data center. Data is transmitted at the completion of each period of use (e.g. after each 
night of use). Data can then be accessed, via a login code, by the respiratory/sleep team to assess 
items such as device efficacy (AHI), mask leak, and usage hours.  
The Adherence Core Lab will review data at least once per week for each site. Enrolling sites 
consistently not achieving an average of 3 hours of use per night with their subjects will be 
identified and contacted. The Adherence Core Lab will provide an analysis of adherence to better 
target potential interventions. For example, if the participant did not initiate use, the 
recommended intervention may be focused on remembering to put the mask on at night and 
promoting adherence. If the data shows that ASV was initiated but was discontinued within 1 
hour, the intervention by the site may be focused on mask comfort. The study team will intervene 
if the subject is having issues with therapy or is struggling with compliance. See Appendix I. 
AirView is compliant with HIPAA, EU 95/46/EC, and national privacy laws. Data are encrypted and 
all database accesses are logged and can be re-traced. 
In addition to AirView, a patient-focused version of the data is available through the myAir 
application. The myAir application can be accessed via the subject’s smartphone and allows the 
subject to monitor their own treatment data. The myAir application also provides tips to the 
subject on things like coping with therapy, managing mask leaks, and adjusting comfort settings. 
These tips are personalized based on each individual’s data. Although the myAir App is not 
mandatory in this trial, subjects will be strongly recommended to use it to assist their usage of 
ASV. If subjects are unable to use the App they will be shown how to access equivalent 
information (myAir website). 

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10. STUDY SCHEDULE 
10.1. Study Entry 
A patient meets eligibility criteria of the study if all of the inclusion criteria and none of the 
exclusion criteria are met. Subjects will stay enrolled for the duration of the study even if they are 
re-hospitalized during their enrollment. 

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10.2. Study Flow 
Identify potential subject (CV1) 
(Most recent EF≥50%, dyspnea, S&Sx of ADHF, no right HF w/o left HF) 
Obtain informed consent (CV) and 
Perform ApneaLink test (RT2) 
AHI≥15 e/hr on 
ApneaLink  
Subject can 
tolerate mask & 
ASV therapy (RT) 
Subject participation confirmed  
Document baseline data (CV) 
AirCurve setup and training (RT) 
12 Week Follow-up  
Collect follow-up data (CV), disposition device, and 
refer to sleep therapist (RT) 
Document screen failure; 
refer to sleep therapist  
Yes 
Yes
No 
No 
Follow-up phone call: 2-3 days post-
therapy start (RT)  
Document screen 
failure  
Week 5 – 12: Monitor 
adherence and intervene as 
needed (RT) 
1CV = Cardiology Study Coordinator 
2RT = Respiratory/Sleep Team 
Week 1 – 4: Monitor adherence, 
intervene as needed, and confirm 
adherence (RT) 
Adherent 
Document discontinuation; 
refer to sleep therapist  
Non- 
Adherent 

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10.3. Follow-Up 
The clinical study plan for the CAT-PEF Feasibility Study includes 1 follow up visit, which may be 
conducted by phone, at 3 months. 
See Section 11 for description of specific study procedures. 
10.4. Screening Procedures 
Patients who have been admitted to the hospital, or in the outpatient setting, if within 14 days of 
discharge, and have symptoms of acute decompensated heart failure will first be evaluated for 
eligibility for the study based on chart review.  
Review the patient's records to ensure the following: 
1. Evidence of HFpEF (EF≥50%) that is not solely right-sided. HFpEF is based on most recent 
echocardiogram results, but must be within last 12 months. 
2. This (or the most recent) hospitalization includes acute decompensated HF as determined by 
dyspnea and other signs and symptoms as listed in inclusion criteria. 
3. The first healthcare encounter related to this hospitalization (e.g., ER, cath lab) was at least 
24 hours and no more than 14 days prior to consent. 
If the patient appears to be eligible based on the cardiology-related entry criteria, they may be 
approached about study participation. A brief interview may be conducted to further address 
potential eligibility criteria.  
If the patient continues to appear to be eligible for participation in the study then consent will be 
obtained. A log of patients screened but not eligible for the study will be maintained. 
NOTE: All subjects who sign a consent form must be entered in the data management system, 
whether or not they are entered into the study. 
1. Document demographics and eligibility criteria data  
2. Arrange for AHI measurement using the ApneaLink overnight. Subject is not eligible for study 
entry if AHI<15 e/hr from ApneaLink. 
3. If AHI≥15 e/hr with ApneaLink Air and other entry criteria are met, confirm tolerability of the 
mask and ASV therapy by having the subject use the system for a short time (awake or 
asleep). 
4. If they are not eligible for study entry, document the reason for screen failure in the data 
management system.   
 
 

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10.5. Detailed Visit Schedule 
The following visit schedule applies to subjects who met all eligibility criteria, and are enrolled in 
the CAT-PEF Feasibility Study.  
10.5.1. Visit 1: Screening/Baseline 
Primary 
Responsibility 
 
Cardiology 
Sleep 
Determination of eligibility 
X 
 
ApneaLink Test 
 
X 
Mask fitting, ASV set-up and training, myAir set-up 
 
X 
Document demographics and baseline data 
X 
 
KCCQ-12 
X 
 
 
10.5.2. ASV Adherence Monitoring 
Primary 
Responsibility 
 
Cardiology 
Sleep 
Follow-up with subject 2-3 days after start of therapy 
 
X 
Review AirView for adherence flags weekly 
 
X 
Contact subjects with sub-optimal adherence as needed 
 
X 
Review overall adherence at 30 days post-therapy start. Subjects not 
meeting adherence criteria will be discontinued from the study  
 
X 
Document contact in EDC  
 
X 
 
10.5.3. Visit 2: End of study Follow-up 
Primary 
Responsibility 
 
Cardiology 
Sleep 
Collect follow up data on death and hospitalizations 
X 
 
Disposition AirCurve device and refer to sleep therapist 
 
X 
KCCQ-12  
X 
 
 
 
 

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10.6. Overview of visits 
 
Screening 
Baseline 
"Day 0" 
(≤3 days from 
AL report) 
2-3 days 
Post-device 
start 
30 days 
(±2 days) 
"1 mo" 
Weekly 
during study 
12 weeks 
(±2 weeks) 
"3 mo" 
Visit Location:  
Hospital or 
Clinic 
Hospital or 
Clinic 
Phone call 
 
 
Clinic or 
Phone Call 
 Review of HF history, 
signs & symptoms 
X 
 
 
 
 
 
 ApneaLink Air test 
X 
 
 
 
 
 
ASV therapy and mask 
tolerance 
X 
 
 
 
 
 
KCCQ-12 
X 
 
 
 
 
X 
Initiation of ASV 
Therapy  
 
X 
 
 
 
 
ASV Device use 
monitoring 
 
 
X 
X* 
X 
X 
 
 
*Check to confirm adequate device use 
10.7. Duration of the study 
An individual subject’s participation is expected to be 3 months.  
With an expected enrollment period of up to 24 months for 160 evaluable subjects, and a follow-
up period of 3 months, the overall study duration is calculated to be approximately 27 to 30 
months. 
11. VISIT PROCEDURES 
11.1. Polygraphy 
Every subject in the study will undergo polygraphy (including pulse oximetry) using ApneaLink at 
screening. Data acquisition and analysis is described in the ApneaLink Systems Clinical Guide and 
data collection and the settings required for automatic scoring will be described in the Manual of 
Procedures. Completion of the test is defined as the time the report is generated. 
11.2. KCCQ-12 
The short form of the Kansas City Cardiomyopathy Questionnaire is a 12-item instrument that 
quantifies physical function, symptoms (frequency, severity and recent change), social function, 
self-efficacy and knowledge, and quality of life. 
11.3. Mask and ASV Therapy Tolerance 
All subjects meeting eligibility criteria (AHI≥15 e/hr per ApneaLink) will be fitted with a mask and 
set up on the AirCurve. Subjects will also be entered into the AirView system, and be encouraged 
to use the myAir application. Preferably, subjects will use the AirCurve device and mask overnight 
to determine tolerance; however, if that is not possible (due to planned discharge, outpatient 
clinic, eg), the device and mask should be used long enough to demonstrate tolerance (awake or 

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asleep). Subjects who are unable to tolerate the mask or the delivered pressure will not continue 
with the study.  
If the subject can tolerate the mask and delivered pressure, they will complete the baseline 
assessments and be issued an AirCurve device.  
11.4. Treatment Adherence 
Adherence to therapy with ASV is determined by evaluating the usage data from the AirCurve 
device in AirView. Additionally, discussion with the subject will indicate issues with the mask or 
other barriers to use. See Appendix I. 
11.5. Subject Discontinuation Criteria 
If, after 30 days after initiation of therapy, a subject has not met the adherence criteria of at least 
4hrs ASV usage per day (24hr period) for 70% of the days enrolled (excluding days spent in the 
hospital), they will be discontinued from the study. Follow procedures for Device and Subject 
Disposition in Section 11.6. Record the number of hospitalizations and date of discontinuation on 
the end of study eCRF. 
11.6. Device and Subject Disposition 
When the subject completes their participation in the CAT-PEF Feasibility Study, the AirCurve 
device must be dispositioned and the subject must be referred for further management. 
• 
If the subject wishes to keep their device and continue ASV therapy, they may do so and 
should be referred to the appropriate sleep care team for continued management 
• 
If the subject does not wish to continue therapy, they should be referred to the 
appropriate sleep care team for discussion of options for treating their SDB 
Document the device disposition in the eCRF. If the subject does not continue therapy (or has left 
the study for other reasons, such as death), the device must be returned to the clinical site either 
at a clinic visit or by mail. Return labels will be provided by the sponsor. 
12. SAFETY 
The investigator is responsible for monitoring the safety of subjects enrolled into the study at the 
study site. The investigator or qualified designee will enter the required initial and follow-up 
information regarding events on the appropriate eCRF within the EDC system. Investigators are 
responsible for following all serious adverse events (SAEs) until resolution, stabilization, or the 
event is otherwise explained, and to report serious adverse events as well as serious injury or 
death that were related to (caused by or contributed to) the AirCurve devices in accordance with 
their local IRB/EC requirements. Investigators should follow usual clinical practice at their 
institutions for reporting serious events to the regulatory authorities. 

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12.1. Hospitalization 
For this protocol, the definition of hospitalization is in-patient care of more than one calendar day 
(overnight admission). The number of hospitalizations the occurred during a subject’s participation 
in the study will be recorded at the final visit. 
12.2. Labeled Adverse Device Effects 
Expected adverse device events are determined to be mild and are related to the interface (mask) 
between the device (AirCurve) and the subject. In this study any skin or eye irritation that is 
transient (ie, resolves within 24 hours following device use and requires no medical intervention), 
will not be classified as an adverse device effect. 
Mask  
• 
Mild skin irritation around the nose and forehead from the mask 
• 
Mild facial abrasions from ill-fitting mask interface  
• 
Eye irritation, caused by leakage of air from the sides of the mask  
Flow Generator 
• 
Drying of the nose, mouth, or throat 
• 
Nosebleed 
• 
Bloating 
• 
Ear or sinus discomfort 
• 
Eye irritation 
• 
Skin rashes 
13. STATISTICAL ANALYSIS 
This study aims to evaluate the adherence to ASV therapy in HFpEF patients with moderate to 
severe SDB. Descriptive summaries, including means, standard deviations, medians, 25th, and 75th 
percentiles will be presented for continuous variables; the number and frequency of subjects in 
each category will be presented for nominal variables. Analyses will be performed using SAS 
Version 9.3 or later.  
13.1. Justification of the Sample Size 
The sample size has been determined to estimate the primary objective (the mean usage in hours 
per night) with sufficient precision. A sample size of 160 evaluable subjects yields a margin of error 
equal to 0.25 hours per night or less, when the confidence level is 95% and the standard deviation 
of usage is 1.6 hours per night or less (as observed in a similar study of myAir9). Subjects not 
meeting the evaluability criteria of at least 4hrs ASV usage per day (24hr period) for 70% of the 
days enrolled (excluding days spent in the hospital) within the first 30 days of therapy initiation, 
will be discontinued from the study. Assuming that 60% of the study subjects will be evaluable, 
266 (which can be rounded up to 300) subjects are expected to be initially enrolled in the study.  

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13.2. Primary endpoint analysis 
The mean usage and its 95% confidence interval will be estimated. 
13.3. Secondary endpoint analyses 
The mean change in KCCQ-12 scores and its 95% confidence interval will be estimated.  The 
morbidity rate (the average number of hospitalizations per subject) and its 95% confidence 
interval will be estimated. 
14. DATA HANDLING AND RECORDKEEPING 
14.1. Data Collection 
The investigator, sub-investigator(s), or study coordinator participating in the study will record 
progress notes to document all data required by the protocol. 
In addition, any contact with the subject via telephone or other means that provide significant 
clinical information must be documented in the progress notes as described above. 
Any changes to information in the study progress notes, or other source documents, must be 
initialed and dated on the date the change is made by a clinician authorized to make the change. 
14.2. Study Documentation 
Throughout the conduct of the study, all required data will be entered into the eCRF for each 
subject. The investigator should ensure the accuracy, completeness, and timeliness of the data 
reported to the Sponsor in the eCRFs and in all required reports. Data entered into the eCRF must 
be consistent with source documents. Any change or correction to an eCRF will be captured in the 
EDC system audit trail.  
The clinical site will provide study data to the Sponsor by recording data in the EDC System (21 CFR 
Part 11 compliant).  
In cases of subject-reported data, the eCRF will be the source record. 
 
The information entered into the eCRF will be accessible to the appropriate ResMed Medical 
Affairs personnel. 
14.3. Query Generation and Resolution 
Queries will be generated based upon anomalous or missing data and will be tracked via the EDC 
System. 
Once all queries are resolved, the database will be verified by ensuring all electronic files were 
completely and correctly loaded.  

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14.4. Data Storage 
Access to data maintained in the EDC System and AirView is strictly limited to authorized 
personnel. 
14.5. Inspection of Records 
Periodically the Sponsor or representative may review the Investigator study file and the study 
data to verify compliance with applicable regulations and the protocol, and to verify accuracy of 
the data. 
14.6. Study Files and Record Retention 
The investigator must maintain adequate and accurate records as specified in Essential Documents 
for the Conduct of a Clinical Trial (E6, Section 8 of the ICH Guideline for GCP) to enable the conduct 
of the study to be fully documented and the study data to subsequently be verified. These 
documents should be classified into two separate categories: (1) investigator’s study file and (2) 
subject clinical source documents. 
Essential documents must be retained until at least 2 years after notification by the Sponsor that 
the investigations have been discontinued OR 2 years after the last approval of a marketing 
application. The investigator must notify the Sponsor prior to destroying any clinical study records. 
14.7. Regulatory Documentation 
Documents that must be provided to the Sponsor prior to study initiation are: 
• 
Signed, dated current (within 2 years) curriculum vitae of Investigator and Sub-Investigator(s) 
• 
Financial disclosure for physicians and nurses 
• 
Signed (original), dated Investigator Agreement 
• 
Assurance that the IRB/EC complies with requirements set forth in Title 21 Part 56 of the Code 
of Federal Regulations. The required documentation consists of name and address of the 
IRB/EC, a current list of members including title, gender, occupation and any institutional 
affiliation of each member. A general assurance number from the Department of Health and 
Human Services may be substituted for this list. 
• 
Written notification (copy) to the Investigator from the IRB/EC approving the protocol 
• 
IRB/EC approved informed consent (copy) and any other adjunctive materials to be used in the 
study as required. 
15. ETHICAL CONSIDERATIONS 
15.1. Institutional Review Board (IRB)/Ethics Committee (EC) 
The investigator must have written and dated approval from the IRB/EC for the protocol, consent 
form, subject recruitment materials/process (advertisements), and any other written information 
to be provided to subjects. The investigator should also provide the IRB/EC with a copy of the 
product labeling information and any updates. The investigator will provide the IRB/EC with 

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reports, updates, and other information (e.g., safety updates and protocol amendments) as 
required by regulations. 
15.2. Protocol Deviations 
An investigator is required to conduct this study in accordance with the signed Investigator's 
Agreement, this Investigational Plan, applicable laws and FDA regulations, and any conditions of 
approval imposed by the reviewing IRB/EC and FDA. According to FDA regulation 21 CFR § 
812.150(a)(4), an investigator shall notify the sponsor and the reviewing IRB/EC of any deviation 
from the investigational plan to protect the life or physical well-being of a subject in an 
emergency. Such notice shall be given as soon as possible, but no later than five working days after 
the emergency occurred. Except in such an emergency, prior approval by the sponsor is required 
for a change in or deviations from a plan and, if these changes or deviations could affect the 
scientific soundness of the plan or the rights, safety or welfare of human subjects, FDA and IRB/EC 
approval may also be required in accordance with 21 CFR § 812.35(a). 
A list of subjects with protocol deviations will be compiled based on entry criteria deviations as 
well as deviations from study conduct and assessments. Prior to data base lock, an evaluation of 
subjects with significant protocol deviations will be performed to assess the appropriateness of 
their inclusion in the analysis. 
15.3. Risk Analysis and Confidentiality 
15.3.1. 
Risk Determination of the Study 
The AirCurve device has been cleared by FDA to provide non-invasive ventilatory support to treat 
patients weighing more than 66 lbs (30 kg) with OSA, central and/or mixed apnea or periodic 
breathing. The device is intended for home and hospital use. The purpose of this study is to 
evaluate the effect of an adjunctive therapy for adult patients with acute decompensated heart 
failure and moderate to severe sleep apnea.  
Clinical personnel will observe the subject on the fitting and use of all AirCurve devices. They will 
monitor the subject’s clinical parameters, which include hemodynamics and will intervene, if 
required. 
This study is considered to be of moderate risk to the patients receiving ASV therapy. PAP therapy 
is the most widely accepted and effective form of treatment for SDB, and the risks associated with 
its use in this study are reasonable in terms of knowledge gained and potential benefits to 
patients. By its nature, use of PAP therapy may be associated with minor side effects. Side effects 
may cause minor discomfort, especially in a patient who has not previously used PAP therapy. In 
this study, these side effects will not be classified as adverse events unless they do not resolve 
within a reasonable period of time when PAP therapy is discontinued. 
Subjects should be encouraged to discuss any issues they are having with PAP therapy during the 
study. The investigator should assess for changes in the health or well-being of the subject in 

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response to general, non-directed questioning (e.g., “How has your health been since the last 
visit?”).  Side effects should be documented on the site’s source documents. Any transient side 
effects, at a minimum, should be documented in the clinic record.  
15.3.2. 
Subject Data Confidentiality 
All information and data collected for the CAT-PEF Feasibility Study concerning subjects or their 
participation in this investigation will be considered confidential. Only authorized Sponsor 
personnel or a Sponsor representative will have access to these confidential files. All data will be 
handled in accordance with applicable local laws. Authorized FDA personnel or Regulatory 
Authorities have the right to inspect and copy all records pertinent to this investigation. All data 
used in the analysis and reporting of this investigation will be without identifiable reference to 
specific subject name. 
16. QUALITY CONTROL AND QUALITY ASSURANCE 
Quality Control is defined as the operational techniques and activities, such as monitoring, 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. 
16.1. Site Selection 
The sites should have previously participated in clinical studies and must have adequate 
experience, time, staff, and facilities to perform all required duties. In addition, sites must include 
both cardiology and sleep expertise involvement. Sites must permit clinical trial related 
monitoring, audits, IRB/EC review, and regulatory inspections, providing direct access to source 
data/documents, as appropriate. 
16.2. Polygraphy Data 
Each participating site will be trained and follow the clinical guide for use of the ApneaLink device 
and interpretation of data produced in the report. 
16.3. Adherence to ASV Therapy 
Leak, residual AHI, and therapy adherence will be monitored by a trial sleep therapist using data 
from AirView. Suggestions provided to the subjects and personnel at each clinical site on ways to 
optimize AirCurve/mask use and subject adherence. See Appendix I. 
16.4. Training 
The Sponsor will conduct an initiation visit at each site to review relevant documentation such as 
the clinical protocol, ApneaLink and AirCurve Instructions for Use, and investigator’s obligations 
with site study personnel. In addition, training on the Data Management System will be conducted. 

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If new study staff members are employed at the site after the initiation meeting, experienced site 
personnel must train new employees as noted above and document the training (contact the 
Sponsor for instructions on how to document the training). 
16.5. Audits and Inspections 
The Sponsor (or designee), FDA, NIH and any other regulatory agencies may request access to all 
study records, including source documents, for inspection and copying, in keeping with Federal 
regulations. The investigator must immediately notify the Sponsor of an upcoming FDA or other 
regulatory agency inspection. Audits may also be conducted by representatives of the study 
Sponsor. 
17. RESPONSIBILITIES 
17.1. Clinical Investigator Responsibilities 
With the approval of their institution‘s IRB/EC, qualified investigators will conduct the CAT-PEF 
Feasibility Study in accordance with the Declaration of Helsinki: “Recommendations Guiding 
Medical Doctors in Biomedical Research Involving Human Subjects”. Each site principal investigator 
and their co-investigators are responsible for the following: 
• 
Completion of all required agreements  
• 
Screening and evaluation of subjects 
• 
Strict adherence to the Clinical Protocol, Study Manual of Procedures and all Federal 
Regulations 
• 
Supervising investigational device use and return 
• 
Obtaining informed consent prior to study related procedures and the collection of data 
during study and follow-up examinations in a timely manner 
• 
Timely reporting of all SAEs and UADEs 
• 
Providing death notes, when applicable 
It is acceptable for the site principal investigator to delegate one or more of the above functions to 
an associate or co-investigator, however, the site principal investigator remains responsible for 
proper conduct of the clinical investigation and signing an investigator agreement. The 
investigation is non-transferable to other centers attended by the investigator unless prior 
approval is obtained from the appropriate IRB/EC and the Sponsor. 
17.2. Sponsor Responsibilities 
The Sponsor will provide each site with study materials. The Sponsor will train study personnel on 
the clinical study protocol and procedures. Sponsor representatives will ensure that the study is 
progressing as expected, study data are accurate and up to date, data recording is complete, and 
protocol deviations are recorded and reviewed with the PI. Throughout the study period, the 
sponsor representative will be available to address any issues that may arise. This availability 
includes access by phone and/or e-mail.  

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18. STUDY ORGANIZATION 
18.1. Steering Committee 
The steering committee for the study will include at least three cardiologists, a sleep expert, and a 
representative (non-voting) from ResMed Medical Affairs.  
Any required modifications to the protocol will be reviewed and approved by the committee prior 
to implementation. 
18.2. Adherence Core Lab 
An Adherence Core Lab comprised of at least one sleep expert and one cardiologist will 
periodically review ASV adherence data in AirView for all sites over the course of the study. The 
Adherence Core Lab may contact sites when adherence is low to help troubleshoot issues (See 
Appendix II), and will provide reports to the Steering Committee as needed.  
19. STUDY REPORTS AND PUBLICATIONS 
Sponsor is responsible for preparing and providing the appropriate regulatory authorities with 
clinical study reports according to the applicable regulatory requirements. Publication policy is 
discussed in the Investigator’s Clinical Trial Agreement. 

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20. REFERENCES  
 
1 Yancy CW, Jessup M, Bozkurt B, et al. 2016 ACC/AHA/HFSA Focused Update on New Pharmacological 
Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart 
Failure. J Card Fail 2016;22:9, 659-669 
2 Ponikowski P, Voors AA, Anker SD, et al. ESC Guidelines for the diagnosis and treatment of acute and 
chronic heart failure 2016. European Heart Journal (2016) 37, 2129–2200 
3 Kapur VK, Baldwin CM, Resnick HE, et al. Sleepiness in patients with moderate to severe sleep-disordered   
breathing. SLEEP 2005;28(4):472-77. 
4 Arzt M, Young T, Finn L, et al. Sleepiness and sleep in patients with both systolic heart failure and 
obstructive sleep apnea. Arch Intern Med. 2006 Sep 18;166(16):1716-22. 
5 Levy P, Pepin J-L, Arnaud C, et al. Intermittent hypoxia and sleep-disordered breathing: current concepts 
and perspectives. Eur Respir J 2008; 32: 1082–1095. 
6 Mentz RJ, Kelly JP, von Lueder TG. Noncardiac Comorbidities in Heart Failure With Reduced Versus 
Preserved Ejection Fraction. J Am Coll Cardiol. 2014 December 2; 64(21): 2281–2293 
7 Cowie MR, Woehrle H, Wegscheider K. Adaptive Servo-Ventilation for Central Sleep 
Apnea in Systolic Heart Failure. N Engl J Med 2015; 373:1095-1105 
8 Eulenburg C, Wegscheider K, Woehrle H, et al. Mechanisms underlying increased mortality risk in patients 
with heart failure and reduced ejection fraction randomly assigned to adaptive servoventilation in the 
SERVE-HF study: results of a secondary multistate modelling analysis. The Lancet Respiratory Medicine , 
Volume 4 , Issue 11 , 873 - 881 
9 Crocker M, Lynch S, Willes L, et al. A Propensity-Adjusted Comparative Analysis of PAP Adherence 
Associated With Use of MyAir. Chest. 2016;150(4_S):1269A 

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Appendix I. Site Sleep Therapist Guidance 
This guidance is to inform the Site Sleep Therapist of steps to be taken when contacting the study 
subjects for the post-therapy initiation phone call, and for on-going monitoring of ASV adherence. The 
purpose of this guidance is to keep the contact and information given to the subjects consistent among 
all subjects and sites. 
Post-Therapy Initiation Follow-up Call (2-3 days following start of therapy) 
STEP 
ACTIVITY 
COMMENTS 
1 
When a new subject has been enrolled 
in the study, ensure the subject and 
their device have been entered into the 
Study AirView Account 
Remember to keep the subject details in your 
restricted, password protected file 
2 
Phone the subject after they have been 
enrolled in the study for 3 nights. 
Introduce yourself to the subject. 
 
 
 
 
If the 3 day phone call falls on a weekend, the Site 
Sleep Therapist may delay the call until the following 
Monday. 
 
If you are unable to contact the subject, you may try 
again after 4 nights and 5 nights. If you are still unable 
to contact the subject you should contact the cardio 
study coordinator and ask for assistance. Document 
any activities in the Adherence Follow Up Call CRF 
3 
Remind the subject of the basics of 
good sleep hygiene 
 
 Refrain from drinking alcoholic beverages within 2 
hours of bedtime 
 Refrain from drinking caffeinated beverages  within 
6 hours of bedtime  
 Exercise regularly, but try not to do strenuous 
exercise within 4 hours of bedtime 
 Avoid smoking as bedtime approaches, or quit 
altogether! 
 Use your bedroom only for sleep and intimate 
activities;  for example, do not watch TV in bed 
 Go to bed and wake up at approximately the same 
time each day 
 Try to avoid taking a nap past 3pm. 
 Manage stress by relieving your worries through 
relaxation techniques such as Yoga or Meditation, or 
talking to a trusted companion 
 Select a relaxing bedtime ritual, like a hot bath, 
listening to calming music or 10 minutes of reading 
4 
Review the subject’s usage so far. 
- 
Ask the subject how they have 
found using ASV 
- 
Provide reassurance and 
troubleshoot any issues 
[refer to On-going Monitoring below for ASV hints and 
tips] 
If the subject is having extreme difficulties with their 
ASV you may suggest a clinic visit.  
5 
Remind subjects of your contact details 
and let them know they can contact you 
if any additional queries come up. 
Remind the subjects that you will be 
monitoring their data on an on-going 
basis. 
 
6 
Complete the Adherence Follow Up 
Call CRF  
 
 

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On-going Adherence Monitoring 
STEP 
ACTIVITY 
COMMENTS 
1 
Monitor the Study AirView database 
regularly (at least once a week) 
 
If, for ≥3 nights you see any issues 
such as the following: 
- 
Compliance is low (<3 hours per 
night); 
- 
leak is high (>24L/min); 
- 
treatment is not optimal (AHI≥10) 
 
Contact the subject. Troubleshoot the 
issue. If the issue doesn’t improve over 
the next few nights, consider arranging 
a clinic visit with the subject. 
Contact is at your discretion. If the leak is high but 
compliance is excellent and the SDB is well controlled, 
you may choose not to intervene.  
 
 
2 
Complete the Adherence Follow Up 
Call CRF to document any contact 
which was made and any additional 
steps taken 
 
Non-Compliant Patients 
STEP 
ACTIVITY 
COMMENTS 
1 
There is no maximum number of 
interventions that may be made by the 
Site Sleep Therapist.  
However if despite repeated attempts 
(≥5 discussions with the subject or 
attempted contacts with the subject) the 
subject doesn’t appear to be making 
any efforts to improve ASV compliance, 
the subject may be considered non-
compliant. 
The Site Sleep therapist cannot exclude subjects from 
the trial. 
 
 
 
 
 

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Appendix II. Adherence Core Lab Guidance 
This guidance is to inform the Adherence Core Lab of steps to be taken for on-going monitoring of ASV 
adherence for all sites in the study. The purpose of this guidance is to keep the contact and information 
given to the sites consistent. 
On-going Adherence Monitoring 
STEP 
ACTIVITY 
COMMENTS 
1 
Monitor the Study AirView database 
regularly (at least once a week) for 
adherence triggers. 
 
If a site has multiple subjects with 
adherence issues such as the following: 
- 
Compliance is low (<3 hours per 
night); 
- 
leak is high (>24L/min); 
- 
treatment is not optimal (AHI≥10) 
 
Contact the Site Sleep Therapist to help 
troubleshoot the issue.  
Contact is at your discretion. If a site’s subjects 
generally have good adherence, you may choose not 
to intervene.  
 
 
2 
Overall adherence status for the study 
should be compiled for each site on a 
monthly basis for review with the CAT-
PEF Study Steering Committee.