CardioMEMS HF System OUS Post Market Study
Conditions: Heart Failure, Left-Sided Heart Failure, Congestive Heart Failure
Sponsor: Abbott Medical Devices

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used 
without the express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 1 of 44 
 
SJM-CIP-10147 
CardioMEMSTM HF System OUS Post Market Study 
Version Number 
C 
Date 
April 18, 2018 
Coordinating Investigator 
Martin Cowie, MD 
Planned Number of Sites and 
Region(s) 
85 clinical sites Outside the United States 
Clinical Investigation Type 
Prospective, multi-center, open-label clinical trial 
Sponsor Medical Expert 
Philip B. Adamson, MD, MSc, FACC  
Divisional Vice President and Medical Director  
6300 Bee Cave Rd, Bldg 2. #100 
Austin, TX  78746 USA 
Tel: +1 512 286 4526 
Email: philip.adamson@abbott.com 
 
Sponsor 
 
St. Jude Medical 
23 Fourth Avenue 
Burlington, MA 01803 
United States of America 
Electronic Data Capture Software Oracle Clinical 
CIP Author of Current Version  
Marie-Elena Brett 
 
 
 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 2 of 44 
TABLE OF CONTENTS 
1. 
LIST OF ABBREVIATIONS .............................................................................................. 5 
2. 
PROTOCOL SYNOPSIS ................................................................................................... 6 
3. 
BACKGROUND AND RATIONALE .................................................................................. 9 
3.1. 
Introduction .......................................................................................................... 9 
3.2. 
CHAMPION Trial Results ..................................................................................... 9 
3.3. 
Indication for Use ................................................................................................. 9 
3.4. 
CardioMEMS HF System ..................................................................................... 9 
4. 
STUDY OBJECTIVE ....................................................................................................... 12 
5. 
STUDY DESIGN .............................................................................................................. 12 
6. 
STUDY POPULATION .................................................................................................... 13 
6.1. 
Inclusion Criteria ................................................................................................ 13 
6.2. 
Exclusion Criteria ............................................................................................... 13 
7. 
STUDY OR SITE TERMINATION .................................................................................... 14 
8. 
STUDY PROCEDURES .................................................................................................. 15 
8.1. 
Screening Visit ................................................................................................... 15 
8.2. 
Right Heart Catheterization and Implant Procedure (Baseline Visit) ................... 16 
8.3. 
Study Follow-Up Visits 1, 2, 3, 4, and 5 (Months 1, 6, 12, 18, and 24) ............... 16 
8.4. 
Subject contact throughout the study ................................................................. 17 
8.5. 
Subject Home PA Pressure Readings................................................................ 17 
8.6. 
PA Pressure Readings in the hospital ................................................................ 18 
8.7. 
Criteria for Withdrawal ....................................................................................... 18 
8.8. 
Deviations from CIP ........................................................................................... 19 
9. 
SAFETY ANALYSES ...................................................................................................... 20 
9.1. 
Primary Safety Endpoints................................................................................... 20 
9.1.1. 
Device / System-related Complication Criteria ..................................... 20 
9.1.2. 
Sensor Failure Criteria ......................................................................... 20 
10. 
EFFECTIVENESS ANALYSES ....................................................................................... 21 
10.1. 
Primary Effectiveness Endpoint ......................................................................... 21 
10.2. 
Supplemental Analyses ..................................................................................... 21 
10.2.1. 
Mortality ............................................................................................... 21 
10.2.2. 
HF Hospitalization or Death ................................................................. 21 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 3 of 44 
10.2.3. 
Patient Compliance .............................................................................. 21 
10.2.4. 
Quality of Life Evaluation...................................................................... 21 
10.2.5. 
Subgroup Analyses .............................................................................. 21 
10.2.6. 
Subject Contact .................................................................................... 21 
11. 
ADVERSE EVENTS ........................................................................................................ 22 
11.1. 
Adverse Event (AE) ........................................................................................... 22 
11.2. 
Serious Adverse Event (SAE) ............................................................................ 22 
11.3. 
Device-Relatedness ........................................................................................... 22 
11.4. 
Device Deficiency/Malfunction Reporting ........................................................... 22 
11.5. 
Procedures for Reporting Adverse Events ......................................................... 23 
11.6. 
Adverse Event Reporting to Country Regulatory Authorities by the Sponsor ..... 23 
11.7. 
Anticipated Adverse Events ............................................................................... 23 
12. 
STATISTICAL ANALYSIS .............................................................................................. 24 
12.1. 
Populations for Analysis ..................................................................................... 24 
12.2. 
Sample Size Considerations .............................................................................. 24 
12.3. 
Safety Sample Size Determinations ................................................................... 25 
12.4. 
Missing Data ...................................................................................................... 27 
12.5. 
Subject Accountability and Baseline Information ................................................ 27 
12.6. 
Demographic and Baseline Information ............................................................. 27 
12.7. 
Safety Analyses ................................................................................................. 27 
12.7.1. 
Primary Safety Endpoints ..................................................................... 27 
12.8. 
Effectiveness Analyses ...................................................................................... 28 
12.8.1. 
Primary Effectiveness Endpoint............................................................ 28 
12.8.2. 
Supplemental Analyses ........................................................................ 28 
12.8.2.1. Mortality ................................................................................. 28 
12.8.2.2. HF Hospitalization or Death ................................................... 28 
12.8.2.3. Patient Compliance ................................................................ 29 
12.8.2.4. Quality of Life (QoL) ............................................................... 29 
12.8.2.5. Subgroup Analyses ................................................................ 29 
12.8.2.6. Subject Contact ...................................................................... 29 
13. 
DATA COLLECTION, STUDY MONITORING, AND DATA DISCLOSURE .................... 30 
13.1. 
Data Collection and Reporting ........................................................................... 30 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 4 of 44 
13.2. 
Site Qualification ................................................................................................ 30 
13.3. 
Training .............................................................................................................. 30 
 
 
13.3.1 Site Training…………………………………………………………………….30 
13.4. 
Study Monitoring ................................................................................................ 30 
13.5. 
Source Data Verification .................................................................................... 31 
13.6. 
Definition of Source Data ................................................................................... 31 
13.7. 
Data Disclosure and Subject Confidentiality ....................................................... 31 
14. 
ETHICAL CONSIDERATIONS AND STUDY ADMINISTRATION ................................... 32 
14.1. 
Human Subjects Protection ................................................................................ 32 
14.2. 
Protocol Amendments ........................................................................................ 32 
14.3. 
Retention of Records ......................................................................................... 32 
14.4. 
Finance, Insurance, and Publication .................................................................. 32 
15. 
REFERENCES ................................................................................................................ 33 
16. 
APPENDIX A:  SCHEDULE OF EVENTS ....................................................................... 34 
17. 
APPENDIX B:  NYHA FUNCTIONAL CLASSIFICATION FOR HEART FAILURE ......... 35 
18. 
APPENDIX C:  MANAGEMENT OF HEMODYNAMIC PARAMETERS .......................... 36 
19. 
APPENDIX D:  BMI CALCULATOR................................................................................ 39 
20. 
APPENDIX E:  GLOMERULAR FILTRATION RATE ...................................................... 39 
21. 
APPENDIX F:  PROTOCOL DEFINITIONS..................................................................... 40 
22. 
APPENDIX G: CIP REVISION HISTORY ........................................................................ 41 
 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 5 of 44 
1.  LIST OF ABBREVIATIONS 
AE 
Adverse Event 
ADE 
Adverse Device Effect 
CEC 
Clinical Events Committee 
CRF 
Case Report Form 
CRT-D 
Cardiac Resynchronization Therapy Defibrillator 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GFR 
Glomerular Filtration Rate 
HF 
Heart Failure 
HFH 
Heart Failure Hospitalization 
ICH 
International Committee on Harmonization 
IEC 
Independent Ethics Committee 
INR 
International Normalized Ratio 
IEC  
Independent Ethics Committee  
IV 
Intravenous 
LVEF 
Left Ventricular Ejection Fraction 
MedDRA 
Medical Dictionary for Regulatory Activities  
MI  
Myocardial Infarction 
NYHA 
New York Heart Association 
OPC 
Objective Performance Criterion 
PA 
Pulmonary Artery 
PMS 
Post Market Study 
PT 
Prothrombin Time 
PTT 
Partial Thromboplastin Time 
RHC 
Right Heart Catheterization 
RF 
Radio Frequency 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SOP 
Standard Operating Procedure 
 
 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 6 of 44 
2. PROTOCOL SYNOPSIS 
Sponsor: 
St. Jude Medical, Atlanta, GA 
Protocol Title: 
CardioMEMS HF System OUS Post Market Study 
Document Control 
Number: 
SJM-CIP-10147 
Device: 
The CardioMEMSTM HF System consists of a wireless, battery-less 
pressure sensor implanted into the pulmonary artery and an external 
electronics that powers and communicates with the sensor and 
transmits pulmonary artery pressure waveforms and measurements 
to a secure website for Investigator review and patient management. 
Purpose: 
The purpose of this Post Market Study (PMS) is to evaluate the use 
of the CardioMEMSTM HF System in patients with Class III Heart 
Failure in a real-world setting.   
Objective: 
The objective of this PMS is to confirm safety and effectiveness in a 
real-world setting.   
Study Population: 
Adults with New York Heart Association (NYHA) Class III Heart 
Failure (HF) who have experienced a heart failure hospitalization 
within the past 12 months.   
The patients will serve as their own historical controls for 
effectiveness (1 year prior to implantation). 
All subjects who sign the informed consent form and satisfy the 
inclusion/exclusion criteria. 
Ejection fraction data must be taken within the last 6 months or prior 
to implantation. 
Study Design: 
This is a prospective, multi-center, open-label trial conducted in 
centers located outside of the United States (US).   
All subjects who sign the informed consent form and satisfy the 
inclusion/exclusion criteria will be enrolled into the CardioMEMSTM 
HF System PMS and will be scheduled for follow-up visits at 1 month 
and every 6 months for 2 years. 
Following sensor implant and hospital discharge, subjects will take 
PA pressure measurements on a daily basis, or as directed by the 
investigator.  These measurements will be automatically transmitted 
to the secure patient database (Merlin.net website).   
Timeline: 
Study visits will be scheduled at Month 1, Month 6, and every 6 months 
thereafter for 2 years or until study termination. 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 7 of 44 
Number of Subjects 
Up to 800 subjects will be enrolled. Enrollment will be limited to 15% 
of the total study population at any one site.  
Number of Sites: 
This is a prospective, multi-center, open-label clinical trial to be 
conducted at up to 85 sites. 
Safety Measures: 
Primary safety endpoints will be evaluated at 2 years: 1) freedom 
from device/system related complications and 2) freedom from 
pressure sensor failure.  
Safety will also be assessed throughout the study by the frequency 
of Adverse Device Effects (ADEs), Serious Adverse Events (SAEs), 
and Serious Adverse Device Effects (SADEs). 
Effectiveness 
Measures: 
The primary effectiveness endpoint is the annualized HF 
hospitalization rate at 1 year.   
Supplemental analyses include mortality at 1 year, HF hospitalization 
or death at 1 year, patient compliance over the trial, training 
evaluation, and subgroup analyses.   
Information regarding all hospitalization and deaths will be collected 
throughout the study.   
Statistical 
Considerations: 
Primary Safety Endpoints 
The primary safety hypotheses are that the device / system-related 
complication-free proportion of subjects will be at least 80% at 24 
months (OPC used in the CHAMPION trial) and that the pressure 
sensor failure-free proportion of subjects will be at least 90% at 24 
months (OPC used in the CHAMPION trial).  Plotting and analysis of 
safety endpoints will also be displayed using Kaplan-Meier methods. 
All safety analyses will be performed on the safety population. 
 
Primary Effectiveness Endpoint  
The primary effectiveness evaluation will compare the annualized HF 
hospitalization rate at 1 year compared to the HF hospitalization rate 
in the year prior to enrollment.   
The effectiveness population consists of all subjects who received a 
sensor implant regardless of study completion status. 
Supplemental Analyses  
Mortality at 1 year will be analyzed.  Plotting and analysis of mortality 
will be displayed using Kaplan-Meier methods. 
The annualized HF hospitalization or death rate at 1 year in study will 
be compared to the HF hospitalization rate in the year prior to 
enrollment. 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 8 of 44 
Patient compliance over the trial will be examined.  The total number 
of PA pressure readings taken will be reported as a percentage of 
patient days at home. 
Effectiveness analyses will be performed by the following subgroups:  
Women, Men, Reduced Ejection Fraction (< 40%), Preserved 
Ejection Fraction (≥ 40%), Ischemic Etiology, Non-ischemic Etiology, 
With ICD/CRT-D, and Without ICD/CRT-D. 
Frequency, purpose and outcome of all contacts made between site 
staff and implanted subjects post the implant visit will be examined. 
Version: 
C 
Date: 
 18Apr2018 
 
 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 9 of 44 
3. BACKGROUND AND RATIONALE 
3.1. 
Introduction 
Heart failure (HF) is a clinical syndrome characterized by frequent hospitalization, poor quality of life, 
multiple comorbidities, high mortality and a complex therapeutic regimen.  Affected individuals have a 
variety of symptoms such as dyspnea, fatigue, limited exercise tolerance, fluid retention, pulmonary 
congestion and peripheral edema.  Patients suffer impairment in functional capacity and quality of life.   
The incidence of HF is on the rise, affecting more than 5 million people in the US alone. Despite current 
guideline recommended therapies, rates of heart failure hospitalization remain high. Heart failure is the 
primary diagnosis in >1 million hospitalizations annually. Patients hospitalized for HF are at high risk for 
all-cause re-hospitalization, with a 1-month readmission rate of 25% (Go, et al., 2013). 
3.2. 
CHAMPION Trial Results 
The CHAMPION trial demonstrated that management of heart failure using pulmonary artery pressure 
information obtained with the CardioMEMS HF System, in addition to traditional signs and symptoms, 
reduced HF hospitalizations.   
The CHAMPION trial was conducted at 64 U.S. centers and enrolled 550 patients with NYHA Class III 
heart failure who had been hospitalized for heart failure in the previous year.  All patients were implanted 
with a sensor and then randomized to Treatment (heart failure management on the basis of pulmonary 
artery pressure and standard of care) or Control (heart failure management on the basis of standard of 
care). CHAMPION met its primary endpoint of reduction in the rate of heart failure hospitalizations at 6 
months with Treatment patients having 28% fewer heart failure hospitalizations compared to Control 
patients; benefit was sustained with a 37% reduction in heart failure hospitalizations over the full 
randomized study duration (Abraham, et al., 2011).  All secondary endpoints were met with reduction in 
pulmonary artery pressures, reduction in proportion of patients hospitalized for heart failure, increase in 
days alive outside the hospital and improved quality of life.  
The CardioMEMSTM HF System received CE Mark in 2011 and the current certificate was issued by BSI 
on May 1st 2014.  The system received Food and Drug Administration (FDA) approval on May 28th 2014 
for use in the United States. 
3.3. 
Indication for Use 
The CardioMEMSTM HF System is indicated for wirelessly measuring and monitoring pulmonary artery 
(PA) pressure and heart rate in New York Heart Association (NYHA) Class III heart failure patients who 
have been hospitalized for heart failure in the previous year.  The hemodynamic data are used by 
physicians for heart failure management and with the goal of reducing heart failure hospitalizations. 
3.4. 
CardioMEMSTM HF System  
The CardioMEMS™ HF System provides pulmonary artery (PA) hemodynamic data used for the 
monitoring and management of heart failure (HF) patients. The system measures changes in PA 
pressure which physicians use to initiate or modify heart failure treatment. 
The system includes the following components: 
• 
Implantable wireless sensor with delivery catheter 
• 
Patient or hospital electronics system 
• 
Patient database (Merlin.net Website) 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 10 of 44 
 
Figure 1.  CardioMEMS HF System 
 
 
 
 
 
The system provides the physician with the patient’s PA pressure waveform including systolic, diastolic, 
and mean pressures as well as heart rate.  The Sensor is permanently implanted into the distal PA using 
transcatheter techniques in the catheterization laboratory; the sensor baseline is set to the mean PA 
pressure using a pulmonary artery catheter.  Daily PA hemodynamic measurements are taken by the 
patient in a supine position at home.  The patient measurement system consists of an antenna and 
electronics unit that guides the patient through the short reading process.  The data can be recorded 
from the home, hospital, physician’s office, or clinic.  The hemodynamic data is transmitted to the website 
which is accessible via a secure website to the patient’s physician or nurse. 
Implantable Sensor  
The sensor measures pulmonary artery pressure using MEMS (micro-electromechanical systems) 
technology and requires neither batteries nor leads. It is silicon wafer fabricated and measures 15 mm in 
length, 3.4 mm in width and 2 mm in thickness.  The sensor is permanently implanted in a branch of the 
left or right pulmonary artery via a catheter. The Patient Electronics Unit provides both wireless 
communication and power to the sensor. 
Implantable Sensor Delivery System 
PA Pressure Sensor on Catheter Delivery System
120cm
4.5cm
Hospital Electronics System 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 11 of 44 
The sensor is tethered to an over-the-wire delivery catheter. A right heart catheterization is performed, 
and a hand injected selective pulmonary angiogram is performed via the pulmonary artery catheter to 
define the distal pulmonary artery branch anatomy.  A 0.018” guidewire is then advanced through the 
pulmonary artery catheter into the distal pulmonary artery.  The pulmonary artery catheter is removed, 
and the delivery system is advanced over the guidewire.  Once it is optimally positioned, the sensor is 
separated from the delivery system by releasing the tether wires and delivery system is then removed.   
Patient Electronics System 
The electronics unit uses an antenna to transmit low power pulses of radiofrequency energy to power 
and communicate with the sensor. The electronics unit transmits the PA pressure information to the 
Merlin.net website. 
Merlin.net website 
The Merlin.net website provides a secure user interface through a website for the clinician to review the 
PA pressure data from the CardioMEMS HF System.  

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 12 of 44 
4. STUDY OBJECTIVE 
The objective of this Post Market Study is to provide safety and effectiveness data regarding the use of 
the CardioMEMSTM HF System in a commercial setting 
5. STUDY DESIGN 
This is a prospective, multi-center, open-label clinical trial to be conducted up to 85 sites in centers 
located outside of the US.        
Subjects who sign the informed consent form and meet the eligibility criteria at the Baseline visit will be 
eligible for the trial.  Subjects will undergo the study-related procedures, including clinical laboratory 
measurements and body mass index (BMI) calculation.  Note that for study related procedures/visits 
Investigator refers to the Principal Investigator or designee. 
Eligible subjects will be scheduled for the Implant procedure (PA sensor implant in conjunction with a 
RHC procedure).  
Subjects must also have an appropriately sized (≥7mm diameter) pulmonary artery branch identified by a 
selective pulmonary angiogram prior to Sensor implant.  Subjects who do not meet this inclusion criteria 
will be documented as consented not implanted and will be followed for 30 days for safety.   
Prior to hospital discharge, subjects will be trained on the home monitoring system and instructed to take 
pulmonary artery pressure measurements daily or as directed by their physician.  Subjects will be 
supplied with a patient implant identification card, a Patient System Manual, and a Helpline phone 
number. 
After discharge, the subject will take PA pressure measurements at home, as directed by the 
investigator, utilizing the CardioMEMS HF System.  These measurements will be transmitted via modem 
to a secure data base. Patient compliance will be monitored by the sponsor and reported to the 
Investigator.   
The Investigator or designee will review the PA pressure measurements transmitted from the home 
monitoring unit.  Pressure thresholds are automatically set as described in Appendix C.  These threshold 
notifications are intended to guide the Investigator to review the Merlin.net website.  If the PA pressures 
are elevated or low, the Investigator or designee should make medication changes according to the 
guidelines in Appendix C.  The Investigator or designee will review the PA pressure measurements on a 
weekly basis at a minimum and appropriately utilize the information obtained to assist in the clinical 
management of subjects.  Weekly logins to the database will be monitored by the sponsor.  Reminders 
will be sent to the clinical sites if there are no logins noted during the course of a 7 day window. Clinical 
and technical support will be available to the Investigator as needed.   
• 
Follow-up study visits will be scheduled at Month 1, Month 6, and every 6 months thereafter 
for 2 years.  Follow-up visits will include a physical exam, evaluation of NYHA Class 
(Appendix B), AE assessment, heart failure medications review, quality of life assessment, 
and assessment of any hospitalizations (including HF hospitalizations), that may have 
occurred between visits.   
In addition, all contacts between site staff and study subjects post implant will be recorded on a log to 
capture frequency, purpose and outcome of each contact. 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 13 of 44 
6. STUDY POPULATION 
Study subjects must meet the following inclusion and none of the exclusion criteria to be eligible for the 
study.  
6.1. 
Inclusion Criteria 
1. Written informed consent obtained from subject  
2. > 18 years of age 
3. Diagnosis of NYHA Class III Heart Failure 
4. At least 1 HF hospitalization within 12 months of Baseline visit 
5. Subjects with reduced LVEF heart failure should be receiving a beta blocker for 3 months and 
an ACE-I or ARB for one month unless in the investigator’s opinion, the subject is intolerant to 
beta blockers, ACE-I or ARB.   
6. Subjects with a BMI ≤ 35.  Subjects with BMI >35 will require their chest circumference to be 
measured at the axillary level, if > 65 inches the patient will not be eligible for the study.    
7. Subjects with pulmonary artery branch diameter ≥ 7mm - (implant target artery - assessed 
during the RHC) 
8. Subjects willing and able to comply with the follow-up requirements of the study 
6.2. 
Exclusion Criteria 
1. Subjects with an active infection 
2. Subjects with history of recurrent (> 1) pulmonary embolism or deep vein thrombosis 
3. Subjects who, in the Investigator’s opinion, are unable to tolerate a right heart catheterization 
4. Subjects who have had a major cardiovascular event (e.g., myocardial infarction, open heart 
surgery, stroke, etc.) within 2 months of Baseline Visit 
5. Subjects with Cardiac Resynchronization Device (CRT) implanted < 3 months prior to 
enrollment 
6. Subjects with a Glomerular Filtration Rate (GFR) < 25 ml/min (obtained within 2 weeks of the 
baseline visit) who are non-responsive to diuretic therapy or who are on chronic renal dialysis 
7. Subjects with congenital heart disease or mechanical right heart valve(s) 
8. Subjects likely to undergo heart transplantation or VAD within 6 months of baseline visit 
9. Subjects with known coagulation disorders 
10. Subjects with a hypersensitivity or allergy to aspirin, and/or clopidogrel (not applicable for 
subjects taking anti-coagulation therapy or other approved anti-platelets therapy). 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 14 of 44 
7. STUDY OR SITE TERMINATION 
The Sponsor or the Investigator has the right to discontinue the study at any time.  As much as possible, 
this should occur after mutual consultation.  The Investigator (or sponsor, where appropriate) is 
responsible for informing the Independent Ethics Committee (IEC) of trial closure. 
Conditions may arise during the study that could prompt termination of the study or the study sites.  
Conditions that may prompt such considerations include, but are not limited to, the following: 
• 
The discovery of unexpected, serious, or unacceptable risk to the subjects enrolled in the 
study 
• 
A decision on the part of Sponsor to suspend, discontinue, or shorten the study 
• 
Study conduct at the study site may warrant termination under conditions that include the 
following: 
• 
Failure of Investigator(s) to enroll eligible subjects into the study 
• 
Failure of Investigator(s) to comply with regulations 
• 
Submission of false information from the research facility to Sponsor, the Clinical 
Monitor, or a regulatory authority 
• 
Insufficient adherence to protocol requirements 
• 
A conflict of interest of the Investigator, his/her institution, or site personnel that would 
negatively impact the integrity of the clinical trial 
• 
Institution or IEC under investigation  
 
 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 15 of 44 
8. STUDY PROCEDURES 
All subjects will be followed for 2 years.  A subject is considered to have successfully completed the 
study upon completion of the 2 year visit (see Appendix A for the Schedule of Events). 
8.1. 
Screening Visit  
During the screening visit, the following procedures/assessments will be performed to determine subject 
eligibility: 
• 
Informed Consent prior to the conduct of any study-related procedures 
• 
Physical examination including vital signs (temperature, heart rate, blood pressure), weight, 
height, BMI calculation (refer to Appendix D)  
• 
Medical and surgical history including ejection fraction data must be taken within the last 3 
months to enroll in the study. If ejection fraction data is older than six months, ejection fraction 
data is required to be obtained at screening visit or prior to implantation. 
• 
Patient history of all heart failure hospitalizations in the 12 months previous to the baseline visit 
as documented with information provided by the patient’s cardiologist, internist, or referring 
physicians and review of all source documents of any heart failure hospitalizations reported in the 
previous year.   
• 
Demographics 
• 
NYHA Functional Classification  
• 
Calculation of GFR (requires creatinine - refer to Appendix E) 
• 
Assessment of medications 
• 
Assessment of enrollment eligibility (inclusion/exclusion criteria) 
• 
Completion of Quality of Life Questionnaire EQ-5D-5L 
Eligible subjects will be scheduled for the Implant procedure.  Subjects on anticoagulation therapy (e.g. 
warfarin) may be instructed by the Investigator to discontinue use 1-2 days prior to pressure sensor 
placement.  The investigator should consider utilizing enoxaparin (Lovenox) per the site’s standard of 
care as bridge therapy to Sensor placement in subjects who were on anticoagulation therapy. 
For subjects at risk for gastro-intestinal bleeding during the period in which dual antiplatelet therapy is 
given, the investigator should consider a proton pump inhibitor such as omeprazole (Prilosec).  Subjects 
at risk include the elderly, those with a history of gastroduodenal ulcers, GERD, esophagitis, intestinal 
polyps or cancer.  Subjects who smoke or who are using steroids or non-steroidal anti-inflammatory 
drugs may also be at risk.  

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 16 of 44 
8.2. 
Right Heart Catheterization and Implant Procedure (Baseline Visit)  
Before the RHC, the following procedures/assessments will be performed: 
• 
Abbreviated physical examination (i.e., vital sign assessments and significant changes since 
Screening Visit) and weight 
• 
Confirmation of enrollment eligibility (other than angiographic criteria) 
• 
PT/PTT with International Normalized Ratio (INR) per institution standards for subjects previously 
on warfarin 
• 
Assessment of heart failure medications 
• 
Record any changes in medical history that occurred since screening visit.  
The patient will then undergo a standard RHC. A selective, hand injected pulmonary angiogram will be 
performed via the pulmonary artery catheter to identify a suitable pulmonary artery branch for sensor 
implantation. Subjects must have an appropriately sized (≥ 7mm diameter) pulmonary artery branch.  
These procedures are considered standard of care for the sensor implant and are described in the User 
Manual.  Subjects who do not meet this inclusion criterion will not receive the PA Sensor implant and will 
be considered ineligible for the study.  These subjects will be documented as consented not implanted 
and will be followed for 30 days for safety.  Patients with a suitable target pulmonary artery branch will 
undergo: 
• 
Wireless implantable hemodynamic sensor implant  
• 
Pulmonary artery catheter measurements (pulmonary systolic, pulmonary diastolic, heart rate, 
pulmonary mean, cardiac output) done 3 times consecutively with sensor measurements for 
setting of sensor baseline. 
• 
Provide post-procedure vascular access site care per standard procedure 
• 
At the Investigator’s discretion, subjects should be discharged once stable with respect to the 
procedure and their heart failure. 
• 
Please see User’s Manual for implant details 
Subjects who are currently on anticoagulant therapy (warfarin or other approved anticoagulants) will 
restart treatment.  The subject’s INR should be checked per the institutions standards.  Those subjects 
not on chronic warfarin will be placed on aspirin and clopidogrel or other approved anti-platelet daily for 1 
month starting on the day of Sensor placement.  Any approved anticoagulant or anti-platelet therapy may 
be used as well.  After 1 month, the subject will continue with aspirin therapy and clopidogrel (or other 
approved anti-platelet therapy) will be discontinued.   
8.3. 
Study Follow-Up Visits 1, 2, 3, 4, and 5 (Months 1, 6, 12, 18, and 24)  

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 17 of 44 
Implanted subjects will be evaluated at Month 1 (± 7 days) and at Months 6, 12, 18, and 24 (± 30 days) 
and the following procedures/assessments will be performed: 
• 
Updated medical and surgical history 
• 
Assessment of SAEs, ADEs, and SADEs that occurred since the last visit 
• 
Reporting of any HF hospitalizations that have occurred since the last visit 
• 
Abbreviated physical examination (significant changes since previous visit) including vital signs 
(heart rate, blood pressure), and weight  
• 
Assessment of NYHA functional class 
• 
Completion of Quality of Life Questionnaire EQ-5D-5L (6, 12, 18, and 24 month visits) 
• 
Heart failure medication review 
• 
PA pressure measurements may be obtained at the Investigator’s discretion 
Subjects will be reminded to obtain pulmonary artery pressure measurements utilizing the CardioMEMS 
HF System as directed.  Subjects will be reminded of the current ACC/AHA guidelines or of the ESC 
guidelines regarding sodium and fluid restrictions.   
8.4. 
Subject contact throughout the study 
All contacts between site staff and study subjects post implant will be documented on a Subject Contact 
Log and the following information will be captured: 
• 
Date of contact 
• 
Reason for contact 
• 
Ability to reach the subject (Call success) 
• 
Name and role of person contacting the patient 
• 
Call outcome (Instructions given) 
• 
Other action required  
8.5. 
Subject Home PA Pressure Readings 
Following the sensor implant procedure, subjects will be instructed on how to take their own pulmonary 
artery pressure measurements, utilizing the CardioMEMSTM HF System.  Subjects will provide returned 
demonstration on: setting up the unit, connecting the system to a phone line, proper positioning for 
obtaining the optimum sensor signal, taking and transmitting the daily pressure measurements.  The unit 
will transmit the data to a database using the system’s modem.  
The home measurements will be taken while the subject is lying down (supine) in bed positioned on a 
padded, flat antenna. It is recommended that subjects obtain home measurements in a supine position 
however, if the subject is unable to lie flat, measurements can be obtained in a sitting or reclined 
position.  It is important the anatomical position is consistent for every measurement.   

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 18 of 44 
The home electronics system is small enough for placement on a bedside table.  The unit will provide 
audio and visual prompts for the subject to guide them through signal acquisition.  Once the subject is 
positioned and a signal is acquired, the subject will be notified of the successful reading and the data is 
automatically transmitted to a remote database.  St. Jude Medical will provide instructions for use and a 
help line will be available.  Please refer to subject’s Patient System Guide for more detailed information. 
8.6. 
PA Pressure Readings in the hospital  
If a subject is hospitalized, seen in the emergency room (ER) or has a clinic visit, the CardioMEMSTM HF 
System may be used to obtain pulmonary artery pressure measurements at the investigators discretion.   
Following sensor implant, subsequent RHC procedures or pulmonary artery catheter insertions must be 
performed under fluoroscopic guidance.   
Resetting of the sensor baseline will be performed as deemed necessary by Sponsor.  Baseline resetting 
may require an echocardiogram or a RHC procedure. 
Following the sensor implant, should a RHC procedure or PA catheter evaluation be clinically warranted, 
comparative pulmonary artery pressures utilizing the CardioMEMSTM HF System should also be obtained 
utilizing the hospital electronics unit. 
8.7. 
Criteria for Withdrawal 
Subjects may be withdrawn from the study for any of the following reasons: 
1. Subject withdraws his/her consent 
2. Investigator determines that other treatment is warranted to protect the health and safety of the 
subject  
3. Investigator determines that the subject is noncompliant with study related procedures 
4. Subject is lost to follow-up:  site must document attempts made to contact the subject for an early 
discontinuation visit (e.g., 2 – 3 phone calls, followed by 1 certified letter, documentation of repetitive 
missed study visits, etc.) 
The Investigator will notify the Sponsor and document on the appropriate CRF the reason/circumstances 
for early discontinuation. All subjects who withdraw from the study should have the following study exit 
procedures performed if possible: 
• 
Assessment of SAEs, ADEs, and SADEs, that occurred since the last visit 
• 
Reporting of any HF hospitalizations that have occurred since the last visit  
• 
Abbreviated physical examination (only significant changes since Enrollment) including vital signs 
(temperature, heart rate, blood pressure), and weight  
• 
Assessment of NYHA functional class 
• 
Heart failure Medication Review 
• 
PA pressures may be obtained at the Investigator’s discretion  

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 19 of 44 
All reasonable efforts should be made to retain subjects in the clinical trial until its completion.  If a 
patient moves from the geographic area of their investigator, St. Jude Medical will attempt to place the 
patient with another investigator.  
8.8. 
Deviations from CIP 
A deviation is defined as an instance(s) of failure to follow, intentionally or unintentionally, the 
requirements of the CIP. The investigator should not deviate from the CIP. 
In some cases, failure to comply with the CIP may be considered failure to protect the rights, safety and 
well-being of subjects; such non-compliance exposes subjects to unreasonable risks. Examples: failure 
to adhere to the inclusion/exclusion criteria, failure to report SAEs within given timeframe as per CIP, etc. 
Investigators should seek to minimize such risks by adhering to the CIP. 
The PI must maintain accurate, complete, and current records, including documents showing the date of 
and reason for each deviation from the CIP. Relevant information for each deviation will be documented 
as soon as possible on the applicable CRF. The site will submit the CRF to the Sponsor. 
The PI is required to adhere to local regulatory requirements for reporting deviations to the site IEC. 
 
 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 20 of 44 
9. SAFETY ANALYSES 
9.1. 
Primary Safety Endpoints 
Primary safety endpoints will be evaluated at 2 years: 
1) Freedom from device/system related complications 
2) Freedom from pressure sensor failure 
9.1.1. Device / System-related Complication Criteria 
A device / system-related complication is an adverse event that is, or is possibly, related to the system 
(wireless pressure sensor or external electronics) and has at least one of the following characteristics:  
• 
is treated with invasive means (other than intramuscular medication or a right heart catheterization 
which is used for diagnostic purposes) 
• 
results in the death of the subject 
• 
results in the explant of the device 
9.1.2. Sensor Failure Criteria 
A Sensor failure occurs when no readings can be obtained from it after troubleshooting the system to 
rule out any problems with the external electronics. 
 
 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 21 of 44 
10. EFFECTIVENESS ANALYSES 
10.1. Primary Effectiveness Endpoint  
The primary effectiveness endpoint will compare the annualized HF hospitalization rate at 1 year in the 
study to the HF hospitalization rate in the year prior to enrollment. 
10.2. Supplemental Analyses  
10.2.1. Mortality 
The mortality rate at 1 year in study will be analyzed. 
10.2.2. HF Hospitalization or Death 
The annualized HF hospitalization or death rate at 1 year in the study will be compared to the HF 
hospitalization rate in the year prior to enrollment.   
10.2.3. Patient Compliance  
Patient device usage over the course of the trial will be examined.  
10.2.4. Quality of Life Evaluation 
Quality of Life will be measured using the EuroQOL Five Dimensions Questionnaire (EQ-5D-5L). 
10.2.5. Subgroup Analyses 
The effectiveness analyses will be evaluated in each of the following subgroups: Women, Men, Reduced 
Ejection Fraction (< 40%), Preserved Ejection Fraction (≥ 40%), Ischemic Etiology, Non-ischemic 
Etiology, With ICD/CRT-D, and Without ICD/CRT-D.   
10.2.6. Subject Contact 
Frequency, purpose and outcome of all contacts between site staff and study subjects post implant will 
be examined. 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 22 of 44 
11. ADVERSE EVENTS 
11.1. Adverse Event (AE) 
An adverse event (AE) is any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in subjects, users or other persons, whether or not 
related to the medical device under investigation. 
Note 1: This definition includes events related to the medical device under investigation or the 
comparator. 
Note 2: This definition includes events related to the procedures involved. 
Note 3: For users or other persons, this definition is restricted to events related to medical devices under 
investigation. 
11.2. Serious Adverse Event (SAE) 
If the AE meets any of the criteria below, it is regarded as a serious adverse event (SAE).  
a) Led to a death, 
b) Led to a serious deterioration in health of the subject, that either resulted in  
1. a life-threatening illness or injury, or 
2. a permanent impairment of a body structure or a body function, or 
3. in-patient hospitalization or prolongation of existing hospitalization, or 
4. medical or surgical intervention to prevent life threatening illness or injury or permanent impairment 
to a body structure or a body function. 
5. chronic disease  
c) Led to fetal distress, fetal death or a congenital abnormality or birth defect. 
Note: A planned hospitalization for pre-existing condition, or a procedure required by the CIP, without a 
serious deterioration in health, is not considered to be an SAE. 
11.3. Device-Relatedness 
An AE or SAE that is definitely or possibly related to the device or the insertion procedure should be 
considered device-related. A serious adverse device effect (SADE) is an event that meets any of the 
above SAE criteria and is considered definitely or possibly related to the device or the insertion 
procedure by the Investigator. All other events considered definitely or possibly related to the device or 
insertion procedure are non-serious adverse device effects (ADEs). 
If it is not certain that an event meets the above definitions, contact the Study Manager.  
11.4. Device Deficiency 
Device deficiency is defined as inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety or performance. 
Device deficiencies will not be collected on the case report forms for this study. 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 23 of 44 
All device deficiencies should be reported to Sponsor via email: CardioMEMS_Complaints@sjm.com or 
contacting your local representative (Australia, Canada, and New Zealand can report deficiencies by 
calling 1- 877-696-3754, European Countries can call +46 847 44147. 
11.5.  Procedures for Reporting Adverse Events 
Safety surveillance and reporting starts as soon as the patient is enrolled in the clinical investigation. 
Safety surveillance and reporting will continue until the last follow-up visit has been performed, the 
subject is deceased, the subject concludes participation in the clinical study or the subject withdraws 
from the clinical study. All ADEs, SAEs, and SADEs, including deaths, will be collected throughout the 
time period defined above and will be reported to the Sponsor on a CRF.  
The investigator should report all SAEs to the Sponsor as soon as possible but no later than outlined 
below.  
Clinical Site 
Reporting timelines 
All Sites 
SAEs must be reported to the Sponsor no later than 3 calendar days from the 
day the site personnel became aware of the event or as per the investigative 
site’s local requirements, if the requirement is more stringent than those outlined. 
The date the site staff became aware the event met the criteria of an SAE must be recorded in the 
source document.  The Investigator will further report the SAE to the local EC according to the 
institution’s EC reporting requirements. 
11.6. Adverse Event Reporting to Country Regulatory Authorities by the Sponsor  
The Sponsor will report SAEs, SADEs and ADEs to the country regulatory authority, per local 
requirements.  
11.7. Anticipated Adverse Events  
Risks associated with the CardioMEMS™ PA Sensor or the implant procedure (in conjunction with RHC) 
or post-implantation complications, together with their likely incidence, are described in the User’s 
Manual.   
 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 24 of 44 
12. STATISTICAL ANALYSIS 
The data will be summarized using univariate statistics (e.g., N, mean, standard deviation, median, 
minimum and maximum) or frequency (e.g., N, %) as appropriate for continuous or categorical variables, 
respectively. 
 
The primary time point for safety analyses is 24 months post enrollment.  Enrollment is defined as having 
a successful Sensor implant.  The primary time point for effectiveness analyses is 12 months post 
enrollment.  
  
Unless otherwise specified, all statistical tests will be 2-sided with a significance level of 0.05. 
 
12.1. Populations for Analysis 
Safety Population:  The Safety Population consists of all subjects who received a Sensor implant or 
underwent the implant procedure but were never implanted, regardless of study completion status.  All 
safety analyses will be performed on the Safety population. 
Subjects who are found not to have an appropriately sized pulmonary artery branch and did not receive 
the Sensor implant will be considered ineligible for the study.  However, these subjects will be followed 
for 30 days for safety and all safety related data for these subjects will be provided.   
Effectiveness Population:  The effectiveness population consists of all subjects who received a Sensor 
implant regardless of study completion status.  All effectiveness analyses will be performed on the 
effectiveness population. 
Pooled Safety Population: The Pooled Safety Population will consist of the Safety Population from this 
study and the Safety Population from other similar study(ies) (demonstrated to be poolable with this 
study) that have been combined to form a larger safety analysis population to permit more robust 
analyses.  
Pooled Effectiveness Population: The Pooled Effectiveness Population will consist of the Effectiveness 
Population from this study and the Effectiveness Population from other similar study(ies) (demonstrated 
to be poolable with this study) that have been combined to form a larger effectiveness analysis 
population to permit more robust analyses. 
 
12.2. Sample Size Considerations 
Effectiveness Sample Size Determination 
For the primary effectiveness endpoint of HF hospitalization rate during 1 year, 250 subjects will provide 
greater than 90% power to meet the efficacy goal, using a one-sample, one-sided Poisson rate test with 
alpha of 0.025.   
The HF hospitalization (HFH) rate for Control and Treatment groups at 1 year in Part 1 of the 
CHAMPION trial were 0.75 and 0.52 (HFH/patient-year), respectively.  For this trial, HF hospitalization 
rates at 1 year will be compared to the rate observed in the trial subjects 1 year prior to enrollment (i.e., 
1.0 or greater).  Using a one-sample, 1-sided Poisson rate test with alpha of 0.025 (equivalent to 2-sided 
test at alpha of 0.05) (see table below), at least 149 subjects will provide >90% power to show a 
difference between a Treatment rate as high as 0.75 (conservative estimate) and the subject’s own 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 25 of 44 
historical rate from the year prior estimated at a minimum of 1.0.  To account for early withdrawal, and to 
allow additional countries to enroll sufficient number of subjects each, 800 subjects will be enrolled. 
Numeric Results for a One-Sample Poisson Rate Test 
Null Hypothesis: λ1 ≥ λ0     Alternative Hypothesis: λ1 < λ0 
 
 
 
Target 
Actual 
 
 
Diff 
Effect 
Power 
n 
Alpha 
Alpha 
λ0 
λ1 
(λ1-λ0) 
Size 
Beta 
0.9052 
36 
0.0250 
0.0224 
1.00 
0.52 
-0.48 
0.6656 
0.0948 
0.9048 
42 
0.0250 
0.0221 
1.00 
0.55 
-0.45 
0.6068 
0.0952 
0.9012 
55 
0.0250 
0.0213 
1.00 
0.60 
-0.40 
0.5164 
0.0988 
0.9030 
73 
0.0250 
0.0232 
1.00 
0.65 
-0.35 
0.4341 
0.0970 
0.9034 
102 
0.0250 
0.0238 
1.00 
0.70 
-0.30 
0.3586 
0.0966 
0.9016 
149 
0.0250 
0.0247 
1.00 
0.75 
-0.25 
0.2887 
0.0984 
 
Report Definitions 
Power is the probability of rejecting a false null hypothesis. It should be close to one. 
n is the size of the sample drawn from the population. To conserve resources, it should be small. 
Alpha is the probability of rejecting a true null hypothesis. It should be small. 
λ0 is the value of the population mean rate under the null hypothesis. 
λ1 is the value of the population mean rate under the alternative hypothesis. 
Diff is the value of λ1 - λ0, the difference being tested. 
Effect Size is the value of (λ1 - λ0) / √(λ1). 
Beta is the probability of accepting a false null hypothesis. It should be small. 
12.3. Safety Sample Size Determinations 
The freedom from device-related complications observed in CHAMPION over 2 years was 98.6%. For 
the two-year primary safety endpoint of freedom from device-related complications, using an exact one-
sided test for one-sample binomial proportions with alpha of 0.025 (equivalent to 2-sided test at alpha of 
0.05) (see table below), a sample size of 137 subjects will provide greater than 90% power to detect a 
difference as small as 10% from the null proportion rate of 0.80 (i.e., objective performance criterion of 
80%).  For sensor failures at 2 years, a sample size of 292 subjects provides greater than 90% power to 
detect a difference as small as 5.0%  from the null proportion rate of 0.90 (i.e., objective performance 
criterion of 90%)(see table below).  
To account for early withdrawal, and to allow additional countries to enroll sufficient number of subjects 
each, 800 subjects will be enrolled. 
 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 26 of 44 
Tests for One Proportion - Freedom from Device-related Complications 
Numeric Results for Testing One Proportion using the Exact Test 
Alternative Hypothesis: One-Sided   (H0: P ≤ P0 vs. H1: P > P0) 
 
 
 Proportion Proportion 
 
 
 
 
 
 
Given H0 
Given H1 
Difference 
Target 
Actual 
Reject H0 
Power* 
n 
P0 
P1 
P1-P0 
Alpha 
Alpha* 
If R ≥ 
0.91001 
137 
0.8000 
0.9000 
0.1000 
0.0250 
0.0245 
119 
0.90023 
107 
0.8000 
0.9100 
0.1100 
0.0250 
0.0233 
94 
0.90756 
88 
0.8000 
0.9200 
0.1200 
0.0250 
0.0238 
78 
0.92186 
75 
0.8000 
0.9300 
0.1300 
0.0250 
0.0243 
67 
0.92273 
62 
0.8000 
0.9400 
0.1400 
0.0250 
0.0238 
56 
0.90933 
48 
0.8000 
0.9500 
0.1500 
0.0250 
0.0248 
44 
0.91958 
41 
0.8000 
0.9600 
0.1600 
0.0250 
0.0244 
38 
0.91882 
34 
0.8000 
0.9700 
0.1700 
0.0250 
0.0226 
32 
0.90520 
26 
0.8000 
0.9800 
0.1800 
0.0250 
0.0227 
25 
* Power and actual alpha were computed using binomial enumeration of all possible outcomes. 
 
Tests for One Proportion – Freedom from Sensor Failures 
Numeric Results for Testing One Proportion using the Exact Test 
Alternative Hypothesis: One-Sided   (H0: P ≤ P0 vs. H1: P > P0) 
 
 
 Proportion Proportion 
 
 
 
 
 
 
Given H0 
Given H1 
Difference 
Target 
Actual 
Reject H0 
Power* 
n 
P0 
P1 
P1-P0 
Alpha 
Alpha* 
If R ≥ 
0.90193 
292 
0.9000 
0.9500 
0.0500 
0.0250 
0.0242 
273 
0.91154 
193 
0.9000 
0.9600 
0.0600 
0.0250 
0.0242 
182 
0.91132 
127 
0.9000 
0.9700 
0.0700 
0.0250 
0.0250 
121 
0.90879 
85 
0.9000 
0.9800 
0.0800 
0.0250 
0.0245 
82 
0.96665 
70 
0.9000 
0.9900 
0.0900 
0.0250 
0.0242 
68 
* Power and actual alpha were computed using binomial enumeration of all possible outcomes. 
 
Report Definitions 
Power is the probability of rejecting the null hypothesis when it is false. It should be close to one. 
n is the size of the sample drawn from the population. To conserve resources, it should be as small as possible. 
P0 is the value of the population proportion under the null hypothesis. 
P1 is the value of the population proportion under the alternative hypothesis. 
P1-P0 is the difference to be detected by the study. 
Alpha (significance level) is the probability of rejecting the null hypothesis when it is true. It should be small. 
Target Alpha is the significance level that the study design is meant to achieve. 
Actual Alpha is the significance level that is actually achieved by the design. 
Reject H0 If... gives the critical value(s) for the test. 
References for Sample Size Calculations 
Chow, S. C., Shao, J., and Wang, H. 2008. Sample Size Calculations in Clinical Research, Second 
Edition.     Chapman & Hall/CRC. Boca Raton, Florida. 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 27 of 44 
Fleiss, J. L., Levin, B., and Paik, M.C. 2003. Statistical Methods for Rates and Proportions. Third Edition.    
John Wiley & Sons. New York. 
Lachin, John M. 2000. Biostatistical Methods. John Wiley & Sons. New York. 
Machin, D., Campbell, M., Fayers, P., and Pinol, A. 1997. Sample Size Tables for Clinical Studies, 2nd 
Edition. Blackwell Science. Malden, Mass. 
Ryan, Thomas P. 2013. Sample Size Determination and Power. John Wiley & Sons. Hoboken, New 
Jersey. 
Zar, Jerrold H. 2010. Biostatistical Analysis (Fifth Edition). Prentice-Hall. Englewood Cliffs, New Jersey. 
 
12.4. Missing Data 
Missing data will be tracked in the Electronic Data Capture system; queries will be generated and 
provided to the site.  In addition, St. Jude Medical representative, or designee will routinely perform 
remote data check and on site monitoring per monitoring plan. Data queries will be addressed until 
resolution.  Missing data that are not resolved will not be imputed unless specified below.  
12.5. Subject Accountability and Baseline Information 
Descriptive summaries will be generated to describe the disposition of all enrolled subjects.  
12.6. Demographic and Baseline Information 
Descriptive summaries will be generated for all relevant baseline variables.  These variables include, but 
are not limited to, demographic data and conditions at the time of enrollment.  
12.7. Safety Analyses 
The safety analyses will be performed using the Safety Population.  The data will be summarized using 
univariate statistics (e.g., N, mean, standard deviation, median, minimum and maximum) or frequency 
(e.g., N, %) as appropriate. 
12.7.1. Primary Safety Endpoints 
The primary safety analysis will be based on the following objective performance criteria:  the lower limit 
of the one-sided 97.5% confidence interval on the freedom from device / system-related complication 
rate at 24 months is greater than 80% and b) the lower limit of the one-sided 97.5% confidence interval 
on the freedom from pressure sensor failure rate at 24 months is greater than 90%.  The study will be 
judged to have provided positive safety results if both tests of the primary safety analysis endpoints are 
statistically significant (i.e., p<0.025).   
Mathematically stated, the primary safety hypotheses are: 
H0: P (Freedom from device / system-related complications at 24 months) ≤ 80% 
Ha: P (Freedom from device / system-related complications at 24 months) > 80% 
 
a) H0: P (Freedom from pressure sensor failure at 24 months) ≤ 90% 
Ha: P (Freedom from pressure sensor failure at 24 months) > 90% 
Plotting and analysis of safety endpoints will also be displayed using Kaplan-Meier methods. 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 28 of 44 
 
Safety will also be assessed throughout the study by the frequency of Adverse Events (AEs), Adverse 
Device Events (ADEs), Serious AEs (SAEs), Serious Adverse Device Event (SADEs), unanticipated 
serious adverse device effects (USADEs), and device / system-related complications by relationship to 
the device via Medical Dictionary for Regulatory Activities (MedDRA) preferred term.  Physical 
examination, and subject survival data through 24 months will be tabulated across study period 
assessments.    
12.8. Effectiveness Analyses 
Effectiveness analyses will be conducted in the effectiveness population. The data will be summarized 
using univariate statistics (e.g., N, mean, standard deviation, median, minimum and maximum) or 
frequency (e.g., N, %) as appropriate. 
12.8.1. Primary Effectiveness Endpoint 
The primary time point for analyses is 12 months post-enrollment.  The primary effectiveness endpoint 
will compare the annualized HF hospitalization rate parameter, γ, at 1 year versus the HF hospitalization 
rate in the year prior to enrollment using a one-sample, one-sided Poisson rate test.  If the one-sided, 
upper 97.5% confidence interval for the PMS rate parameter is less than the rate in the year prior to 
enrollment, then the primary effectiveness endpoint will be met.   
Mathematically stated, the primary effectiveness hypothesis is: 
H0: γ (12 month HF Hospitalization Rate) ≥ γ (HF hospitalization rate in year prior to enrollment) 
Ha: γ (12 month HF Hospitalization Rate) < γ (HF hospitalization rate in year prior to enrollment) 
where γ (12 month HF Hospitalization Rate) = the HF hospitalization rate parameter at 1 year in the PMS and γ (HF 
hospitalization rate in year prior to enrollment) = the HF hospitalization rate in the year prior to enrollment. 
12.8.2. Supplemental Analyses 
12.8.2.1. Mortality 
The mortality rate over 1 year in study will be reported. Plotting and analysis of survival data will be 
displayed using Kaplan-Meier methods. 
12.8.2.2. HF Hospitalization or Death 
The annualized HF hospitalization or death rate parameter, λ, at 1 year will be compared to the HF 
hospitalization rate in the year prior to enrollment using a one-sample, one-sided Poisson confidence 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 29 of 44 
interval.  If the one-sided, upper 97.5% confidence interval for the PMS rate parameter is less than that in 
the year prior to enrollment, then the hypothesis will be met.   
Mathematically stated, the hypothesis is: 
H0: λ (12 month HF Hospitalization or Death Rate) ≥ λ (HF hospitalization rate in year prior to enrollment) 
Ha: λ (12 month HF Hospitalization or Death Rate) < λ (HF hospitalization rate in year prior to enrollment) 
where λ (12 month HF Hospitalization or Death Rate) = the HF hospitalization or death rate parameter at 1 year in the 
PMS and λ (HF hospitalization rate in year prior to enrollment) = the HF hospitalization rate in the year prior to enrollment. 
12.8.2.3. Patient Compliance 
Patient device usage over the course of the trial will be examined.  The total number of PA pressure 
readings taken will be reported as a percentage of patient days at home.  
12.8.2.4. Quality of Life (QoL) 
Patient improvement in Quality of Life will be reported.  The difference between the Quality of Life scores 
at 6 months, 12 months, 18 months, and 24 months will be compared to the baseline values.  Quality of 
Life will be measured using the EuroQOL Five Dimensions Questionnaire (EQ-5D-5L) 
12.8.2.5. Subgroup Analyses  
The effectiveness analyses will be evaluated in each of the following subgroups:   
1) Women 
2) Men 
3) Reduced Ejection Fraction (< 40%) 
4) Preserved Ejection Fraction (≥ 40%) 
5) Ischemic Etiology 
6) Non-ischemic Etiology 
7) With ICD/CRT-D 
8) Without ICD/CRT-D 
12.8.2.6. Subject Contact  
All contact between site staff and study subjects post implant will be documented and the frequency, 
purpose and outcome of all contacts will be examined to estimate resource utilization. 
 
 
 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 30 of 44 
13. DATA COLLECTION, STUDY MONITORING, AND DATA DISCLOSURE  
13.1. Data Collection and Reporting 
Electronic CRFs (eCRFs) will be utilized.  Site staff will enter the information required by the protocol 
onto eCRFs using a validated sponsor system that conforms to IEC requirements for electronic data 
capture.  All data fields will be completed where appropriate.  However, if data are not available (i.e., 
missed visit, etc.), the site will receive instruction regarding electronic documentation.  As data are 
entered, automated cross-check programs will search for any data discrepancies in the eCRFs.  
Appropriate error messages will be generated, allowing for the modification or verification of the entered 
data.  Queries will generally be sent to the study site using an electronic data query system that includes 
an automated audit trail of the corrections.   
Monitoring personnel of St. Jude Medical, or its designee, will review the eCRFs for completeness and 
accuracy and will instruct site personnel to make any corrections or additions.  The Investigator, or 
designee, will certify that the data are complete and accurate by applying an electronic signature to the 
eCRF.  Any subsequent alterations, corrections, or additions will be reviewed and electronically signed 
by the Investigator prior to database lock. 
13.2. Site Qualification 
 A site visit will be performed by St. Jude Medical or designee prior to the start of the study to review the 
protocol in detail, to ensure the availability of appropriate trial personnel, adequate resources and to 
assess their ability to properly conduct the study according to ICH-GCP guidelines and local 
requirements. 
13.3. Training  
Detailed training to cover aspects of the hemodynamic management of heart failure (HF), identification of 
prospective patients, HF sensor implant procedures, the use of the heart failure electronic units, and the 
use of the Merlin.net website to view the patient’s hemodynamic parameters will occur for all sites prior to 
enrollment of patients. 
13.3.1. Site Training 
All Investigators and clinical investigation personnel are required to attend Sponsor training sessions, 
which may be conducted at an Investigator's meeting, a site initiation visit or other appropriate training 
sessions. Over-the-phone or self-training may take place as required. Training of Investigators and 
clinical investigation personnel will include, but is not limited to, the CIP requirements, investigational 
device usage, electronic case report form completion, and clinical investigation personnel 
responsibilities. All Investigators and clinical investigation personnel that are trained must sign a training 
log (or an equivalent) upon completion of the training. Prior to signing the training log, Investigators and 
clinical investigation personnel must not perform any CIP-related activities that are not considered 
standard of care at the site. The CardioMEMSTM HF System physician training plan (document 
CL1002501) is designed to provide essential didactic and field training.    
13.4. Study Monitoring 
St. Jude Medical or designee will monitor the study to meet the sponsor’s monitoring Standard Operating 
Procedures (SOPs), ICH-GCP guidelines, and applicable regulatory requirements and to ensure that 
study initiation, conduct, and closure are adequate. 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 31 of 44 
Clinical Monitors will periodically audit CRFs/eCRFs and corresponding source medical records for each 
subject.  The monitoring visits provide the Sponsor with the opportunity to evaluate the progress of the 
study, to verify the accuracy and completeness of CRFs/eCRFs, to resolve any inconsistencies in the 
study records, and to assure that all protocol requirements, applicable regulatory or country-specific 
regulations, other requirements, and Investigator’s obligations are being fulfilled. 
The Investigator and his/her staff will be expected to cooperate with St. Jude Medical personnel or 
agents of St. Jude Medical and to be available during the monitoring visits to answer questions 
sufficiently and to provide any missing information. 
The Investigator(s)/institution(s) will permit direct access to source data/documents for trial-related 
monitoring, audits, IRB/IEC and regulatory inspection(s). 
13.5. Source Data Verification 
Source data verification ensures accuracy and credibility of the data obtained.  During monitoring visits 
reported data are reviewed with regard to being accurate, complete, and verifiable from source 
documents (e.g., subject files, physician notes, discharge summaries, operative records, etc.).   
13.6. Definition of Source Data 
Source data includes all information in source documents (original records, certified copies of original 
records, and original data recorded on customized worksheets) and includes all original recordings or 
certified copies of clinical findings, observations, or other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial.  
13.7. Data Disclosure and Subject Confidentiality 
Subject medical information obtained as a result of this study is considered confidential and disclosure to 
third parties other than those noted below is prohibited.  All reports and communications relating to 
subjects in this study will identify each subject only by their number.  Medical information resulting from a 
subject’s participation in this study may be given to the subject’s personal physician or to the appropriate 
medical personnel responsible for the subject’s welfare.  Data generated as a result of this study are to 
be available for inspection upon request by government regulatory agency auditors, the Sponsor and the 
IEC. 
The information developed in this clinical study will be used by the Sponsor in the clinical development of 
the study device and therefore may be disclosed by the Sponsor as required for disclosure as to other 
clinical Investigators, to other companies, and to other government agencies. 
 
 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 32 of 44 
14. ETHICAL CONSIDERATIONS AND STUDY ADMINISTRATION  
14.1. Human Subjects Protection 
Subject’s informed consent has to be obtained and documented in accordance with local regulations, 
ICH-GCP requirements, and the ethical principles that have their origin in the principles of the 
Declaration of Helsinki. 
Before initiation of this study, the Investigator or designee and the Sponsor will jointly develop the 
consent form.  Written IEC approval of the protocol and the consent form must be provided to the 
Sponsor prior to enrollment of subjects. This approval must refer to the consent form and to the study 
title and protocol number as given by the Sponsor on the cover page of the protocol. 
Prior to participation in the study, the written informed consent form must be signed and personally dated 
by the subject, and by the person who conducted the informed consent discussion (Investigator or 
designee). The subject must receive a copy of the signed and dated informed consent form. As part of 
the consent process, each subject must consent to direct access to his/her medical records for trial-
related monitoring, auditing, IEC review, and regulatory inspection. 
The informed consent form should be updated or amended whenever new information becomes 
available that may be relevant to the subject. The subject should then sign the revised informed consent 
form as directed by the IEC. 
A list of IEC voting members, their titles or occupations, and their institutional affiliations should be 
provided to the Sponsor before study initiation.   
The IEC must be notified of completion of the study and a final report must be provided to the IEC.  A 
copy of these reports must be forwarded to the sponsor.  The Investigator must maintain an accurate and 
complete record of all submissions made to the IEC, including a list of all reports and documents 
submitted.  Adverse experiences which are reported to the regulatory agencies, as Expedited Safety 
Reports, must be submitted promptly to the IEC. 
This trial will be conducted in accordance with ICH-GCP regulations.  
14.2. Protocol Amendments 
The Investigator will not modify the protocol without first obtaining concurrence in writing from the 
Sponsor.  If an amendment is required, this must be made in written form and receive approval according 
to the appropriate SOP.  All changes to the protocol must be submitted to the IEC.  Protocol 
modifications that impact subject safety or the validity of the study must be approved by the IEC and 
submitted to the appropriate regulatory agencies before initiation. 
14.3. Retention of Records 
The Sponsor and Investigator/Site will archive and retain all documents pertaining to the clinical 
investigation as per the applicable regulatory record retention requirements. The Investigator must obtain 
permission from Sponsor in writing before destroying or transferring control of any clinical investigation 
records. 
 
14.4. Finance, Insurance, and Publication 
Insurance coverage will be handled according to local requirements. 
Finance, insurance, and publication rights are addressed in separate agreements as appropriate. 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. D 
 
 
 
 
 
 
 
 
Page 33 of 44 
15. REFERENCES 
Adamson, P. B., Magalski, A., Branschweig, F., Bohm, M., Reynolds, D., Steinhaus, D., et al. (2003). 
Ongoing right ventricular hemodynamics in heart failure: clinical value of measurements derived from an 
implantable monitoring system. Journal of the American College of Cardiology , 41, 565-71. 
Abraham, W. T., Adamson, P. B., Bourge, R. C., Aaron, M. F., Costanzo, M. R., Stevenson, L. W., Yadav, 
J. (2011). Wireless pulmonary artery haemodynamic monnitoring in chronic heart failure: a randomised 
controlled trial. Lancet, 377, 658-66. 
Bourge, R. C., Abraham, W. T., Adamson, P. B., Aaron, M. F., Aranda, J. M., Magalski, A., . . . Group, C.-
H. S. (2008). Randomized Controlled Trial of an Implantable Continuous Hemodynamic Monitor in Patients 
with Advanced Heart Failure: The COMPASS-HF Study. Journal of the American College of Cardiology, 
51, 1073-79. 
Cui L, Hung HMJ, Wang, SJ.  Modification of Sample Size in Group Sequential Clinical Trials. Biometrics 
1999;55:853-857. 
Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics–2013 update: a report from the 
American Heart Association. Circulation 2013;127:e6–245. 
HFSA, Lindenfeld, J., Albert, N. M., Boehmer, J. P., Collins, S. P., Ezekowitz, J. A., et al. (2010). Executive 
Summary: HFSA 2010 Comprehensive Heart Failure Practice Guidelines. Journal of Cardiac Failure , 16, 
475e-539e. 
Setoguchi, S. N. (2009). Maximum potential benefit of implantable defibrillators in preventing sudden 
cardiac death after hospital admission because of heart failure. Canadian Medical Association Journal , 
180 (6), 611-16. 
Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline for the Management of 
Heart Failure: A Report of the American College of Cardiology Foundation/American Heart 
Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62(16):e147-e239. 
doi:10.1016/j.jacc.2013.05.019. 
  
 
 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express written consent of Abbott 
Template: 86357 Rev. E 
 
 
 
 
 
 
 
 
Page 34 of 44 
16. APPENDIX A:  Schedule of Events 
 
Screening 
Baseline 
(Implant) 
Month 1 
Months 6 and every 6 Months 
thereafter until Study Termination 
Procedures 
Prior to 
Implant 
(within 30 days of 
Screening) 
Visit 1 
(30 ± 7 days) 
Visits 2-5 or Study Termination 
(± 30 day window) 
Informed Consent 
X 
 
 
 
Demographics 
X 
 
 
 
Past Medical & Surgical History.  Ejection 
Fraction is part of this assessment and must be 
obtained within 3 months of the baseline visit or 
prior to implantation.   
X 
 
 
 
Inclusion/Exclusion Criteria Review 
X 
X 
 
 
GFR (within 2 weeks of the implant procedure) 
X 
 
 
 
INR (if indicated) 
 
X 
 
 
Pulmonary artery measurement 
 
X 
 
 
Physical Examination (including weight) 
X1 
X2 
X2 
X2 
NYHA HF Classification 
X 
 
X 
X 
Pulmonary Artery Angiography 
 
X 
 
 
Sensor Implant 
 
X 
 
 
Sensor Measurements  
 
X 
X (Investigator discretion) 
X (Investigator discretion) 
Adverse Events Assessment 
 
X 
X 
X 
HF Hospitalizations  
X 
 
X 
X 
Quality of Life Assessment (EQ-5D-5L) 
X 
 
 
X  (6, 12, 18, 24 months) 
Medication Assessment (heart failure) 
X 
X 
X 
X 
Subject Contact Log3 
 
 
X 
X 
1 Includes weight, height and vital signs (temperature, blood pressure, pulse, respirations).  
2 Includes weight, vital signs and significant changes from previous physical examination 
3 To be completed each time contact is made between the site staff and  a study subject  
 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used 
without the express written consent of Abbott 
Template: 86357 Rev. E 
 
 
 
 
 
 
 
 
Page 35 of 44 
17. APPENDIX B:  NYHA Functional Classification for Heart Failure 
The New York Heart Association (NYHA) Functional Classification provides a simple way of 
classifying heart disease (originally cardiac failure), useful for pre-operative and post-operative 
assessment.  It places subjects in one of four categories, based on how much they are limited 
during physical activity: 
Class I (Mild): Subjects with no limitation of activities; they suffer no symptoms.  
Class II (Mild): Subjects with slight, mild limitation of activities and suffer mild symptoms (slight 
swelling of extremities).  
Class III (Moderate): Subjects with marked limitation of activity; they are comfortable only at 
rest.  
Class IV (Severe): Subjects who are unable to do any physical activity without discomfort; they 
suffer with HF symptoms at rest and are confined to bed or chair.  
 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used 
without the express written consent of Abbott 
Template: 86357 Rev. E 
 
 
 
 
 
 
 
 
Page 36 of 44 
18. APPENDIX C:  Management of Hemodynamic Parameters 
The CardioMEMS HF System allows intermittent assessment of pulmonary artery systolic, 
diastolic and mean pulmonary artery pressures.  Hemodynamic information obtained by the 
system should be used for clinical decision making in addition to symptoms, weights or physical 
examination (traditional markers of volume). 
Pulmonary Artery Pressure Ranges: 
PA Systolic  
15 - 35 mmHg 
PA Diastolic  
8 - 20 mmHg 
PA Mean  
10 - 25 mmHg 
 
Initially, thresholds will be set automatically at the acceptable range.  The physician can adjust 
the thresholds specifically for each patient.  These threshold notifications are intended to guide 
the physician to review the Merlin.net website.  Every attempt should be made to keep the 
pulmonary artery pressures within the specified pulmonary artery pressure ranges utilizing the 
guidelines.  In order to clinically manage patient’s PA pressures, the physician must review the 
PA pressure measurements on a frequent basis, for example, some patients may require a daily 
review of their PA pressure measurements, while some patients may need a weekly review.  
The physician or designee has unlimited access to the Merlin.net website.   
An elevation of pressures beyond the patient’s pressure ranges should be considered a volume 
overloaded status and should be managed according to the hyper-volemic guidelines (see 
below). Diuretics and vasodilators should be adjusted based on the patient’s baseline diuretic 
requirement, knowledge of the patient’s prior response to these agents, and clinician judgment 
to accomplish the pressure goals set forth in this guideline.   
A decrease in the pulmonary pressures below the patient’s pressure ranges should be 
considered a volume depletion event and managed according to the hypo-volemia guidelines 
(see below) (see below).  Diuretic therapy should be held and the chronic dose should be 
lowered. 
In addition to these specific guidelines, the physician should also incorporate the 
recommendations set forth in the ACC/AHA 2013 Guidelines for the Diagnosis and 
Management of Heart Failure in the Adult or in the ESC Guidelines on Acute and Chronic Heart 
Failure 2016.  
The PA pressure readings should be used in addition to weights, signs and symptoms, 
laboratory values and other traditional markers of volume in the management of heart failure. It 
is important to review the trend of PA pressures. As with all other diagnostic information, 
physicians should consider the entire medical history of each patient when initiating or modifying 
therapies. 
Elevated PA Pressures (Hyper-volemic) 
Hyper-volemic Definitions 
• 
Subject symptoms:  Congestive symptoms (wet) 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used 
without the express written consent of Abbott 
Template: 86357 Rev. E 
 
 
 
 
 
 
 
 
Page 37 of 44 
• 
CardioMEMS HF System Parameters:  above  the acceptable range 
• 
Daily trends:  elevated trend data outside the acceptable range 
• 
Weekly trends:  elevation in trend data 
Treatment Recommendations 
• 
Add or increase diuretic (and appropriate electrolyte replacement) 
a. Increase or add loop diuretic 
b. Change to another loop diuretic 
c. Add thiazide diuretic (with caution) 
d. IV doses of loop diuretic  
e. Serum electrolyte evaluation with change in baseline medication 
f. Re-assess pulmonary artery pressure utilizing the CardioMEMS HF System at least 2 
– 3 days per week until optivolemic 
• 
Add or increase vasodilators including long-acting nitrates  
• 
Re-educate in salt intake and fluid restriction 
• 
If subject has signs and symptoms of poor perfusion (cold) in addition to being hyper-volemic: 
a. Consider admission if clinical evidence suggests need for IV diuretics, telemetry 
monitoring or the IV therapeutic agents 
b. Consider invasive hemodynamic monitoring for determination of Cardiac Output, if 
indicated 
 
Low PA Pressures (Hypo-volemic) 
Hypo-volemic Definitions 
• 
Subject symptoms:  poor perfusion in absence of signs and symptoms of congestion 
• 
CardioMEMS HF System Parameters:  below the acceptable range 
• 
Daily trends:  decrease in trend data outside the acceptable range 
• 
Weekly trends:  decrease in trend data 
Treatment Recommendations 
• 
Lower or discontinue diuretic 
a. If on a thiazide diuretic with loop diuretic, lower or discontinue the dose of thiazide 
(and adjust electrolyte replacement) 
b. If on only loop diuretic, lower the dose or discontinue  
c. Consider liberalization of oral fluid restriction and salt restriction 
• 
If postural hypotension, hold or lower vasodilators and/or oral nitrates, especially if 
hypotensive when sitting or supine 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used 
without the express written consent of Abbott 
Template: 86357 Rev. E 
 
 
 
 
 
 
 
 
Page 38 of 44 
• 
If worsening renal function, hold or lower ACE/ARB dose, especially if hypotensive 
• 
If subject had signs and symptoms of poor perfusion (cold) in addition to being hypo-
volemic: 
a. Consider admission if clinical evidence suggests need for IV fluid repletion, telemetry 
monitoring or the use of IV therapeutic agents 
b. Consider invasive hemodynamic monitoring for determination of Cardiac Output, if 
indicated  
 
Recommended Frequency of CardioMEMS HF System Review 
Subject Status 
Weekly 
At least  2– 3 times 
per week until 
optivolemic 
At least 2 – 3 times 
per week until 
pressure stabilizes 
Acceptable PA 
Pressure  
(Opti-volemic) 
X 
 
 
Elevated PA Pressure 
(Hyper-volemic) 
 
X 
 
Low PA Pressure 
(Hypo-volemic) 
 
X 
 
Medication 
modifications 
 
 
X 
Significant deviations in 
trend data 
 
 
X 
 
 
 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used 
without the express written consent of Abbott 
Template: 86357 Rev. E 
 
 
 
 
 
 
 
 
Page 39 of 44 
19. APPENDIX D:  BMI Calculator 
 
To calculate subjects Body Mass Index using the website below:  
 
http://www.nhlbisupport.com/bmi/bmi-m.htm  
 
Enter the subjects Weight and Height and then calculate BMI (print screen for source 
documentation) 
 
Formulas used to calculate Body Mass Index: 
 
English BMI Formula 
BMI = Weight in pounds/ (height in inches x height in inches) x 703 
 
Metric BMI Formula 
BMI = Weight in kilograms/ (height in meters x height in meters)  
 
Note that BMI may also be calculated within the eCRF. 
20. APPENDIX E:  Glomerular Filtration Rate 
 
To calculate subjects Glomerular Filtration Rate use the website below: 
 
http://www.nephron.com/cgi-bin/CGSI.cgi 
 
Enter the subjects Creatinine level, Age, Race, Gender then calculate (print screen for source 
documentation) 
 
GFR (mL/min/1.73 m2) =  186 x(Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if African 
American) 
 
 
Note that GFR may also be calculated within the eCRF. 
 
 
 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used 
without the express written consent of Abbott 
Template: 86357 Rev. E 
 
 
 
 
 
 
 
 
Page 40 of 44 
21. APPENDIX F:  Protocol Definitions 
Enrollment – After signing the Informed consent,  meeting study inclusion criteria and following 
successful Sensor implant, subjects are considered enrolled. 
HF Hospitalization – A HF hospitalization of greater than or equal to 24 hours in a hospital 
Active Infection- Febrile, elevated WBC, left shift, on antibiotics, positive cultures (blood, 
sputum or urine). 
PI – Appropriate clinician designated as the Principal Investigator on the “Investigator 
Agreement” received and approved by St. Jude Medical.  For study related procedures/visits PI 
refers to the PI or his/her designee. 
Source documents – Primary study documentation including electronic, paper, phone 
messages, etc. containing study-pertinent information such as visit information, clinical history, 
medications, (S)AE reporting, etc. These documents are originals and should be treated as 
such. Information from these documents will be transferred from and compared against 
information reported in study CRFs. 
Sub-investigator – Clinical personnel designated as a sub-investigator on the “Investigator 
Agreement” received and approved by St. Jude Medical. 
Worksheets –Source documents used for calculation of clinical values such as BMI or EGFR 
from screening to end of study.  Worksheets may also be used during the sensor implant or 
follow-up visits to capture information not captured in the medical record.  In order for these 
worksheets to be considered valid, the Investigator must sign and date the worksheet.   
 
 
 
 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used 
without the express written consent of Abbott 
Template: 86357 Rev. E 
 
 
 
 
 
 
 
 
Page 41 of 44 
 
 
 
22.  APPENDIX G: CIP Revision History 
 
Revision History 
Amendment 
Number 
Version 
Date 
Rationale 
Details 
Not 
Applicable 
A 
06 June 2016 
First release of CIP 
NA 
1 
B 
18 July 2016 
Additional data collection 
is added for 
documentation of contact 
between site and study 
subjects.  This data will 
be used to analyze 
resource utilization post 
implant. 
 
 
As all data is submitted 
via electronic Case 
Report Forms (eCRFs) 
there is no need for the 
site to fax the 
SAE/ADE/SADE forms to 
SJM.   
 
There will be no Clinical 
Events Committee (CEC) 
for this study. 
 
This study will completed 
using only centers 
outside of the United 
States.   
 
 
 
A Subject Contact log 
will be completed by 
the site to document 
the frequency, 
purpose and outcome 
of all contacts 
between site staff and 
study subjects. 
 
Removed the fax, 
email and telephone 
numbers for the 
reporting of adverse 
events. 
 
 
 
Removed references 
to CECs that were 
included in error. 
 
References to the 
FDA were removed 
where appropriate. 
References to the 
ESC guidelines were 
added  
Removed legal 
representative  

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used 
without the express written consent of Abbott 
Template: 86357 Rev. E 
 
 
 
 
 
 
 
 
Page 42 of 44 
Informed consent 
process  
Ethics approval  
 
 
Adverse event definition 
revised  
 
For unexpected serious 
adverse device effect, the 
term UADE is used for 
studies following FDA 
regulations and USADE 
for studies following ISO 
14155 regulations   
 
Reporting SAE, ADE, 
SADE timelines revised  
 
Revise the anticipated 
adverse events list to 
ensure consistency 
between study 
documentation (CIP, 
Informed Consent 
Template and the device 
User’s Manual) 
 
No annual approval 
renewal needed for 
countries OUS 
 
Adverse event 
definition clarified 
 
UADEs replaced by 
USADEs  
 
 
 
 
Reporting SAE, ADE, 
SADE timelines 
revised  
 
Added Allergic 
reaction, bruising, 
chest pain, nausea 
and sepsis to the CIP; 
added hemoptysis and 
sepsis to the PIS 
2 
C 
18Apr2018 
Study Population 
 
 
 
 
 
Number of subjects/sites 
 
 
 
 
 
International Normalized 
Ratio (INR)  
 
Removed requirement 
for 35% women; this 
was only required by 
FDA for US PAS 
 
Increased to 800 
subjects/85 sites in 
order to expand to 
other countries in EU, 
AUS  
 
The INR has been 
revised to reflect 
institution standards. 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used 
without the express written consent of Abbott 
Template: 86357 Rev. E 
 
 
 
 
 
 
 
 
Page 43 of 44 
 
Aspirin dose 
 
 
 
Adverse Events 
 
 
 
 
 
 
 
 
 
 
 
Deviations from CIP 
 
 
 
 
 
Retention of Records 
 
 
 
Appendix G 
 
 
Cover Page/Document 
Template 
 
 
Document Title Change 
 
 
 
 
 
 
Ejection Fraction 
 
 
 
 
 
 
 
Specific dosages have 
been removed from 
this section. 
 
Updated definitions 
and reporting 
requirements 
language to align with 
harmonized CIP 
template (Rev. E); 
added 3 day reporting 
requirement for SAEs; 
Removed USADEs as 
not applicable to post-
market study 
 
New section to 
describe in detail 
expectations for 
protocol deviations 
 
 
Language updated to 
reflect harmonized 
CIP template (Rev. E) 
 
Removed ICF; will 
now route separately  
 
Revised formatting 
 
 
 
The title has been 
changed from Post 
Approval Study to 
Post Market Study in 
order to accurately 
reflect study type. 
 
The time window of 
ejection fraction 
measurement has 
been increased from 3 
months to 6 months as 
decompensation of 
ejection fraction is not 

SJM-CIP-10147 Ver. C 
CardioMEMSTM HF System OUS Post Market Study 
Clinical Investigation Plan 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used 
without the express written consent of Abbott 
Template: 86357 Rev. E 
 
 
 
 
 
 
 
 
Page 44 of 44 
 
 
 
 
 
 
 
 
 
Device Tracking 
that volatile. 
Additionally, if ejection 
fraction has not been 
measured prior to 
screening, it can be 
measured at the 
screening visit or prior 
to implantation. 
 
Device tracking is not 
a requirement of a 
Post Market Study, 
therefore this section 
has been removed.