MultiPoint Pacing™ Post Market Study
Conditions: Heart Failure
Sponsor: Abbott Medical Devices

Reference:  
SJM-CIP-10149 
 
 “MultiPoint Pacing™ Post Market Study (MPP PMS)” 
Clinical Investigation Plan (CIP) 
 
 
 
 
Version Number 
A 
 
Date 
 
May 24, 2016 
 
Planned Number of Sites and Region(s) 
 
Up to 140 sites worldwide 
 
 
Clinical Trial Type 
The MPP Post-Market Trial is a prospective, multi-center, non-randomized 
registry/observational study 
 
Sponsor 
 
 
St. Jude Medical. Inc. 
 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
Reference:  
SJM-CIP-10149 
 
 
 “MultiPoint Pacing™ Post Market Study (MPP PMS)” 
Clinical Investigation Plan (CIP) 
 
Sponsor  
 
 
 
St. Jude Medical, Inc. 
 
 
 
 
 
 
 
                                                                                                                       Page 1 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 
Table of Contents 
Page 
1.0 
Synopsis .................................................................................................................................................... 4 
1.1 Study Flow Chart ................................................................................................................................................. 6 
1.2 Study Contacts ..................................................................................................................................................... 7 
2.0 
Background and Justification for Clinical Study ...................................................................................... 8 
3.0 
Study Design ........................................................................................................................................... 10 
3.1 Purpose ............................................................................................................................................................... 10 
3.2 Study Design and Scope ..................................................................................................................................... 10 
3.3 Objectives ........................................................................................................................................................... 10 
3.4 Inclusion and Exclusion Criteria ........................................................................................................................ 11 
3.5 Subject Population ............................................................................................................................................. 11 
3.6 Informed Consent Process .................................................................................................................................. 12 
4.0 
Device ..................................................................................................................................................... 12 
4.1 Device Description ............................................................................................................................................. 12 
4.2 Device Handling & Storage ............................................................................................................................... 14 
5.0 
Procedures .............................................................................................................................................. 15 
5.1 Study Flow Chart ............................................................................................................................................... 15 
5.2 Evaluation of responder status ........................................................................................................................... 16 
5.3 Procedures .......................................................................................................................................................... 17 
5.4 Enrollment .......................................................................................................................................................... 18 
5.5 Scheduled Follow-ups ........................................................................................................................................ 20 
5.6 Unscheduled Visits ............................................................................................................................................. 22 
6.0 
Clinical Events/ Hospitalizations ............................................................................................................ 22 
6.1 Health Care Economic Data ............................................................................................................................... 23 
6.2 Subject Study Completion .................................................................................................................................. 23 
6.3 Criteria And Procedures For Subject Withdrawal Or Discontinuation .............................................................. 23 
7.0 
Compliance to CIP .................................................................................................................................. 24 
7.1 Statements of Compliance .................................................................................................................................. 24 
7.2 Adherance to the Clinical Investigational Plan .................................................................................................. 24 
7.3 Repeated and Serious Non-Compliance ............................................................................................................. 25 
8.0 
Risks and Benefits of the Clinical Study ................................................................................................ 26 
9.0 
Adverse Event, Adverse Device Effect, Device complaints ................................................................... 26 
9.1 Definitions .......................................................................................................................................................... 26 
9.2 Procedure For ASessing, Recording And Reporting Adverse Events, Device Complaints, Adverse Device 
Effects, Serious Adverse Events, And Serious Adverse Device Effects:.................................................................... 27 
9.3 Subject Death ..................................................................................................................................................... 30 
9.4 Device Complaints ............................................................................................................................................. 30 
10.0 Data Management ................................................................................................................................... 31 
10.1 Data Management Plan ...................................................................................................................................... 31 
10.2 Document And Data Control .............................................................................................................................. 31 
11.0 Monitoring .............................................................................................................................................. 32 
12.0 Statistical considerations ........................................................................................................................ 32 
12.1 Statistical Design, Hypotheses, Method And Analytical Procedures ................................................................. 32 
12.2 Sample Size ........................................................................................................................................................ 32 
12.3 Maximum Number Of Subjects To Be Included For Each Center ..................................................................... 33 
                                                                                                                       Page 2 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
13.0 Document Retention ............................................................................................................................... 33 
14.0 Amendments to Clinical Investigational Plan ........................................................................................ 33 
15.0 Study Committees ................................................................................................................................... 33 
15.1 Steering Committee (SC) ................................................................................................................................... 33 
16.0 Investigation Suspension or Termination ............................................................................................... 33 
16.1 Premature Termination Of The Whole Clinical Study Or Of The Clinical Study In One Or Nore Investigational 
Sites  ............................................................................................................................................................................ 33 
16.2 Resuming The Study After Temporary Suspension ........................................................................................... 35 
16.3 Study Conclusion ............................................................................................................................................... 35 
17.0 Publication Policy ................................................................................................................................... 35 
18.0 Bibliography ........................................................................................................................................... 37 
Appendix A: Abbreviations .............................................................................................................................. 39 
Appendix B: CIP Revision History .................................................................................................................. 40 
Appendix C: Declaration of Helsinki ............................................................................................................... 41 
Appendix D: List of Clinical Investigation Sites and IRB/EC ......................................................................... 42 
Appendix E: Sample Informed Consent ........................................................................................................... 43 
Appendix F: Case Report Forms ...................................................................................................................... 51 
Appendix G: Minnesota Living With Heart Failure Questionnaire ................................................................. 52 
Appendix H: EQ-5D Quality of life Questionnaire .......................................................................................... 54 
Appendix I: MultiPoint Pacing programming guidance ................................................................................... 56 
 
 
 
                                                                                                                       Page 3 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 SYNOPSIS  
1.0
Title: 
MultiPoint™ Pacing (MPP) Post Market Study 
Acronym: 
MPP PMS 
Purpose: 
The purpose of this post market study is to characterize real-world use of 
MPP technology in patients  indicated for a cardiac resynchronization 
therapy (CRT) device. 
Objectives: 
The primary objective of this post market study is to understand the use of 
the MPP technology in real-world clinical practice. The study should 
provide an understanding of the impact of MPP technology on: 
• Overall CRT response rate measured by Clinical Composite Score 
(CCS). (A responder is defined as improved or unchanged from 
baseline and non-responder is defined as worsened from baseline.) 
• Quality of Life (QOL), left ventricular ejection fraction (LVEF, if 
available) and left ventricular end systolic volume (LVESV, if 
available) 
• Programming timing and workflow 
• Rates of heart failure (HF) hospitalization events, cardiovascular 
hospitalizations, and HF 30-day hospitalization rates 
• Costs associated with HF-related health care utilizations 
• All-cause mortality 
Design: 
This is a prospective, multicenter, non-randomized registry/observational 
study. The study will enroll up to 2,000 patients with successful SJM CRT 
MP device implant from up to 140 centers undergoing CRT implantation. 
Any patient who received a market approved SJM Quadra Allure MP, 
Quadra Assura MP, or newer SJM CRT MP device is eligible for enrollment 
in the study. MPP programming guidance will be specified in the protocol.  
Patients will be followed for 12 months after implant. Data will be collected 
at Baseline (within 30 days prior to implant), Post-Implant (within 30 days 
following successful CRT device implant), 3, 6, 12 months and during any 
unscheduled follow-up visit.  
 
 
 
 
Devices used: 
Market-approved SJM Quadra Allure MP, Quadra Assura MP device, or 
newer SJM CRT MP device and market-approved SJM Quadripolar LV 
lead 
Study Population 
All subjects who meet inclusion criteria, do not meet exclusion criteria, sign 
an IRB/EC approved informed consent, complete a Baseline visit prior to 
device implant and have an attempted implant of the SJM Quadra Allure 
MP, Quadra Assura MP, or newer SJM CRT MP device will be considered 
 A                                                                                                                       Page 4 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
enrolled in the study.  
Inclusion/Exclusion 
Criteria  
Inclusion Criteria 
Eligible patients will meet all of the following: 
• Are scheduled to receive a new CRT implant or an upgrade from an 
existing ICD/Pacemaker implant (SJM CRT MP device and SJM 
QUAD Lead) with no prior LV lead placement 
• Have the ability to provide informed consent for study participation 
and are willing and able to comply with the prescribed follow-up 
tests and schedule of evaluations  
 
Exclusion Criteria 
Patients will be excluded if they meet any of the following: 
• Are expected to receive a heart transplant during the duration of the 
study 
• Have an epicardial ventricular lead system (active or inactive) 
• Are less than 18 years of age 
• Are currently participating in a clinical investigation including an 
active treatment arm and belong to  the active arm 
• Are not expected to complete the study follow-up schedule or 
duration due to any health condition other than heart failure, such as 
malignancy, indication for heart transplant or hospice care. 
Data Collection 
All patients will complete a Baseline visit within 30 days prior to implant. 
During this visit, inclusion/exclusion criteria evaluation, informed consent, 
NYHA class, QOL questionnaires (Minnesota Living with Heart Failure – 
MLWHF and EQ-5D) will be completed. All subjects will undergo SJM 
CRT MP device implant per standard of care. Device measurements will be 
collected within 30 days of successful SJM CRT MP device implant during 
the Post-implant visit. Patients will be followed for 12 months after 
successful CRT implant. Follow-up data will be collected at 3, 6 and 12 
months post implant and during any unscheduled follow-up visits. During 
the study mandated follow-up visits, arrhythmic episode diagnoses, device 
data, stored electrograms, LVEF (if available), LVESV (if available), 
NYHA class, Patient Global Assessment (PGA), and QOL questionnaires 
(Minnesota Living with Heart Failure – MLWHF and EQ-5D) will be 
collected. All clinical events for cardiovascular reasons, such as 
hospitalizations and emergency room visits, will also be collected. All study 
data, including device data and stored electrograms, will be sent to SJM via 
the electronic data capture (EDC) system. 
 
 
 
                                                                                                                       Page 5 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
1.1 STUDY FLOW CHART 
 
6 Month Visit (+ 30 days)
12 Month Visit (+ 45 days)
Post Implant Visit
≤ 30 days POST successful SJM 
CRT MP implant)
3 Month Visit (+14 days)
Baseline Visit
(≤ 30 dMys PRIOR Po SJM CRT MP 
implMnP)
*IMPLANT ATTEMPTED?
(Quad LV Lead introduced into vasculature)
Re-attempt 
implant?
NO
Re-attempt 
successful?
Collow subject for 
30 Days, then 
Withdraw
YES
NO
YES
NO
Implant successful?
YES
PMPienP Enrolled in SPudy
YES
PMPienP NoP Enrolled in SPudy – 
no furPher McPion required
NO
*The implant procedure is not considered part of the research study.
 
 
                                                                                                                       Page 6 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
1.2 STUDY CONTACTS 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                                                                                                       Page 7 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 BACKGROUND AND JUSTIFICATION FOR CLINICAL STUDY 
2.0
Heart failure (HF) is a major threat to public health affecting an estimated 5.7 million individuals in the 
United States. It is estimated that 50% of people diagnosed with HF will die within 5 years.1  In 2007, 
the direct and indirect cost for HF in the United States was estimated at $33.2 billion.2, 3 HF is a varied 
clinical syndrome with complex pathophysiology, which continues to be defined, and often begins with 
a primary insult to the myocardium. Patients with HF experience decreased exercise capacity, inability 
to perform activities of daily living, diminished quality of life and an increased early mortality. 
 
Cardiac resynchronization therapy (CRT) using biventricular (BiV) pacing was developed to restore 
synchrony in HF patients with delayed ventricular activation, predominantly of the left ventricle (LV). 
Although a majority of treated patients show a benefit, up to 40% derive no benefit from CRT.  In the 
MIRACLE study, 34% of patients did not demonstrate an improvement in a HF clinical composite score 
(CCS) that combined all-cause mortality, HF related hospitalization, NYHA class and patient global 
assessment into an outcome measure.4 Birnie and Tang summarized various clinical studies that report 
CRT non-responder rates.5 Rates of non-response to cardiac resynchronization therapy are often quoted 
as 20-30% in the listed studies, but the authors suggest  the true non-responder rate may be as high as 
40-50%. This inconsistent CRT effectiveness may be due to incomplete resynchronization and the 
presence of intraventricular dyssynchrony. 
 
Although the cause for failed response to CRT is not completely understood, the consensus, supported 
by growing evidence, is  suboptimal LV lead placement accounts for a large percentage of patients who 
do not respond to CRT. Standard LV lead placement criteria for a stimulation electrode typically focuses 
on the location of mechanical stability, freedom from phrenic nerve stimulation, reasonable pacing 
thresholds, or the site of latest electrical activation.  However, ischemic cardiomyopathy can cause non-
uniform propagation of electrical activity over the myocardium due to scarred myocardial segments and 
density near the LV stimulation electrode.6 Thus, a site of latest electrical activation may not always 
yield the optimal response.  In such cases, the ability to pace from more than one left ventricular site 
may provide benefit.   
 
The St. Jude Medical family of quadripolar leads includes one tip electrode and three ring electrodes.  
The Quartet™ LV family of leads with the CRT device provides 10 - 14 different pacing vector options 
(VectSelect™) from the four pacing electrodes on the LV lead. Since this CRT device can provide 
quadripolar pacing, the device and Quartet™ LV lead will be referred to as the Quadripolar CRT device 
system in this protocol. 
 
Furthermore, this lead allows pacing from any two of the 10 - 14 available vectors that stimulate the LV 
in a multi-point fashion (MultiPoint™ pacing or MPP). In addition to the usual interventricular (RV-LV 
or V-V) timing that is currently available in a traditional CRT devices, MPP further allows timing 
between two LV lead pacing vectors termed ‘LV1-LV2 timing’ with programmable delays (5 – 80 ms). 
 
MultiPoint™ pacing (MPP) is a new pacing feature in the Quadripolar CRT system that allows  the LV 
with two pacing vectors compared to one vector in a traditional CRT system.  A combination of any two 
of the 10 – 14 available vectors can be used. Additionally, a delay can be introduced between the two 
LV pacing vectors.  
                                                                                                                       Page 8 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 
MPP via one LV lead has the potential to be an alternative to optimize LV lead placement non-
invasively, and it is feasible  the MPP feature may improve hemodynamics and the response to CRT. 
Studies showed simultaneously exciting a larger mass or volume of cardiac tissue results in faster 
depolarization velocity and shorter left ventricular trans-ventricular conduction times.7, 8 In addition, by 
capturing a larger volume of cardiac muscle, the site of latest intrinsic activation within the left ventricle 
may be more likely to be depolarized early, resulting in better synchronization and maximizing cardiac 
output.  
 
Since MPP delivers two pulses at programmable delays (LV1 and LV2) to two LV sites, the initial 
volume of excited cardiac tissue is increased. Additionally, by capturing more mass at the initial 
depolarization, there is a greater likelihood of pacing the site of latest systolic delay.  Both of these 
methods have shown to improve LV function9-20 and it is believed  this additional improvement in LV 
function may benefit those patients who are otherwise identified as non-responders to conventional BiV 
pacing.  
 
 
                                                                                                                       Page 9 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 STUDY DESIGN 
3.0
3.1 Purpose 
The purpose of this post market study is to characterize real-world use of MPP technology in 
patients indicated for a CRT device. 
3.2 Study Design and Scope 
This is a prospective, multicenter, non-randomized registry/observational study. All subjects who 
meet inclusion criteria, do not meet exclusion criteria, sign an IRB/EC approved informed consent, 
complete a Baseline visit prior to device implant and have an attempted implant of the SJM Quadra 
Allure MP, Quadra Assura MP, or newer SJM CRT MP device will be considered enrolled in the 
study. MPP programming guidelines are provided in Appendix I.  Patients will be followed for 12 
months after implant. Data will be collected at post-implant (within 30 days of successful CRT 
device implant), 3, 6, 12 months and during any unscheduled follow-up visit. At 12 months, the 
responder rate will be evaluated among the following groups: 
 
• MPP Group: MPP ON within 1 month post implant and then continuously programmed ON until 
12 months (i.e., MPP ON for months 1-12 continuously) 
• Treatment Strategy (BiV/MPP) Group: MPP ON at the 12-month study visit and for at least 3 
continuous months prior to 12-month assessment (i.e., BiV ON at some point in months 1-9 and 
MPP ON for months 10-12) 
• BiV Group: MPP OFF at the 12-month study visit and for at least three continuous months prior 
to 12-month assessment (i.e., BiV ON for months 10-12) 
• Other Pacing Group: Other pacing schemes not covered above (Retrospective categorization 
implemented based on the usage of MPP or BiV for 12 months)  
 
3.2.1 Number of subjects required to be included in the study 
The study will enroll up to 2,000 patients with successful SJM CRT MP device implant from 
up to 140 centers undergoing CRT implantation. Any patient who received a market 
approved SJM Quadra Allure MP, Quadra Assura MP, or newer SJM CRT MP device is 
eligible for enrollment in the study.  
 
3.2.2 Estimated time needed to enroll this subject population 
 
 
3.3 Objectives 
The objective of this post-market study is to understand the use of the MPP technology in real-
world clinical practice. The study should provide an understanding of the impact of MPP 
technology on: 
 
                                                                                                                       Page 10 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
• Overall CRT response rate measured by CCS. (A responder is defined as improved or 
unchanged from baseline and non-responder is defined as worsened from baseline.) 
• QOL, LVEF, if available and LVESV, if available 
• Programming timing and workflow 
• Rates of HF hospitalization events, cardiovascular hospitalizations, and HF 30-day 
hospitalization rates 
• Costs associated with HF-related healthcare utilizations 
• All-cause mortality 
3.4 Inclusion and Exclusion Criteria 
A subject, who meets all of the inclusion criteria, and none of the exclusion criteria, is eligible to 
participate in this study.  
 
3.4.1 Inclusion Criteria 
Eligible patients will meet all of the following: 
• Are scheduled to receive a new CRT implant or an upgrade from an existing 
ICD/Pacemaker implant (SJM CRT MP device and SJM QUAD Lead) with no prior LV 
lead placement 
• Have the ability to provide informed consent for study participation and are willing and 
able to comply with the prescribed follow-up tests and schedule of evaluations  
 
3.4.2 Exclusion Criteria 
 
Patients will be excluded if they meet any of the following: 
• Are expected to receive a heart transplant during the duration of the study 
• Have an epicardial ventricular lead system (Active or Inactive) 
• Are less than 18 years of age 
• Are currently participating in a clinical investigation including an active treatment arm 
and belong to the active arm 
• Are not expected to complete the study follow-up schedule or duration due to any health 
condition other than heart failure, such as malignancy, indication for heart transplant or 
hospice care. 
 
3.5 SUBJECT POPULATION  
3.5.1 Subject Screening 
All subjects presenting at the investigational site should be screened by a member of the 
investigational team previously trained on the CIP and delegated to do so. 
 
Subjects who do not meet the inclusion criteria or do meet the exclusion criteria will not be 
eligible to participate in this study. 
                                                                                                                       Page 11 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 
3.5.2 Point of Enrollment 
All subjects who meet inclusion criteria, do not meet exclusion criteria, sign an IRB/EC 
approved informed consent, complete a Baseline visit prior to device implant and have an 
attempted implant of the SJM Quadra Allure MP, Quadra Assura MP, or newer SJM CRT 
MP device will be considered enrolled in the study.  
 
3.6 INFORMED CONSENT PROCESS 
3.6.1 General process 
Prior to enrolling in the clinical study and conducting study-specific procedures, all subjects 
will be consented, as required by applicable regulations and the center’s IRB/EC.  Informed 
consent must be obtained from each subject prior to any study-related procedures. The 
consent form must be signed and dated by the subject and by the person obtaining the 
consent. 
 
The principal investigator or his/her authorized designee will conduct the Informed Consent 
Process. This process will include a verbal discussion with the subject on all aspects of the 
clinical study relevant to the subject’s decision to participate in the clinical study.  
 
The subject shall be provided with the informed consent form written in a language 
understandable to the subject and approved by the center’s IRB/EC.  Failure to obtain 
informed consent from a subject prior to study enrollment should be reported to St. Jude 
Medical within 5 working days and to the reviewing center’s IRB/EC consistent with the 
center’s IRB/EC reporting requirements.  
 DEVICE 
4.0
4.1 Device Description 
In this study, the Quartet™ LV family of leads will be implanted with the SJM CRT MP device. 
The SJM CRT MP devices are supported by the St. Jude Medical Merlin™ Patient Care System 
(Merlin™ PCS) with software Model 3330 version 21.1.1 rev 1 (or higher). 
 
The Quartet™ family of LV lead is a quadripolar, over–the-wire design that enables implantation 
using either a stylet or guidewire.  The lead has an open lumen and an opening at the lead tip to 
allow the use of a guidewire.  The body of the leads has Optim™ insulation. 
 
The titanium nitride (TiN) coated platinum/iridium (PtIr) tip electrode on the lead contains a 
molded ring that elutes steroid.  Additionally, the surface of the tip electrode is coated with a thin 
steroid film to provide immediate steroid release.  Three TiN-coated PtIr ring electrodes are located 
on the lead.  
                                                                                                                       Page 12 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 
The lead provides pace/sense capability from 4 electrodes (tip and 3 rings):  
 
• Distal Tip (D1) 
• Mid 2 (M2)  
• Mid 3 (M3) 
• Proximal 4 (P4)  
 
The Quartet™ family of LV leads can be programmed with a combination of 10 – 14 possible 
pacing vectors using the Merlin™ PCS programmer. Vectors are presented as cathode-anode 
(Figure 1) 
 
Figure 1: SJM CRT MP Device with Quadripolar Technology: LV Lead Vector (10 CRT-D or 
14 CRT-P VectSelect Quartet™ Vectors) 
 
 
 
 
Please note Vector numbering is for protocol use only and is not reflected on the Merlin™ 
programmer screen. 
 
                                                                                                                       Page 13 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
The user has the option to program the device to MPP in addition to BiV pacing. MPP consists of 
delivering two sequential LV pulses (LV1 and LV2) in addition to the standard RV pulse as 
follows: 
• RV first: RV
→
1
D
LV1
→

2
D
LV2 
• LV first: LV1
→
1
D
LV2
→
2
D
RV 
 
LV1 and LV2 configurations can be chosen from any of the 1 – 14 pacing vectors listed in Figure 1 
with independent pacing characteristics. Additionally, the timing delay 1 (D1) can be programmed 
from 5ms to 80ms with 5ms steps and the timing delay 2 (D2) can be programmed from 5ms to 
50ms with 5ms steps, respectively. 
 
4.2 Device Handling & Storage 
Instructions for use, storage and handling instructions, preparation for use and any precautions can 
be found in the User’s Manuals for each of the market-released devices and leads. 
 
 
                                                                                                                       Page 14 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 PROCEDURES 
5.0
5.1 Study Flow Chart 
Figure 2: Flow Chart 
 
 
6 Month Visit (+ 30 days)
12 Month Visit (+ 45 days)
Post Implant Visit
≤ 30 days POST successful SJM 
CRT MP implant)
3 Month Visit (+14 days)
Baseline Visit
(≤ 30 dMys PRIOR Po SJM CRT MP 
implMnP)
*IMPLANT ATTEMPTED?
(Quad LV Lead introduced into vasculature)
Re-attempt 
implant?
NO
Re-attempt 
successful?
Collow subject for 
30 Days, then 
Withdraw
YES
NO
YES
NO
Implant successful?
YES
PMPienP Enrolled in SPudy
YES
PMPienP NoP Enrolled in SPudy – 
no furPher McPion required
NO
*The implant procedure is not considered part of the research study.
 
                                                                                                                       Page 15 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
5.2 Evaluation of responder status 
Patients’ responder status will be assessed at 3, 6 and 12 months post implant using the CCS. The 
CCS includes four components: NYHA class, Patient Global Assessment (PGA), HF events, and 
cardiovascular death.21   
 
The NYHA Class assessment and PGA are determined by a designated assessor interviewing 
patients about their symptoms. Specifically, the PGA will be a single interview question asking the 
patient to categorize how they feel compared to their previous visits as either: 
 
• Markedly better 
• Better 
• No change 
• Worse 
• Markedly worse 
 
At the 3, 6 and 12-month visits, a PGA will be conducted to evaluate how the patient feels 
compared before having the CRT system implanted. 
 
In this trial, a HF event is defined as any one of the following when the subject has symptoms 
and/or signs consistent with congestive heart failure:  
• Hospitalization for HF ≥ 24 hours 
• Clinic or hospital visit for HF<24 hours (i.e. outpatient treatment, observational care, ER, Urgent 
Care and physician’s office visit) requiring administration of IV diuretics, inotropes, and/or 
vasodilators 
 
Finally, cardiovascular death is defined as sudden unexpected death; heart failure death; 
myocardial infarction related death; or ‘other’ death, such as deaths due to pulmonary embolism, 
peripheral thromboembolism, stroke, vascular procedure, or other major cardiovascular event.  
 
Using the CCS and decision algorithm described in section 5.2.1 patients are categorized as 
Improved, Worsened or Unchanged based on the following rules:  
• “Improved” – patients demonstrating: 
o 
At least a one-class improvement in NYHA Class OR improvement by 
PGA (“better” or “markedly better”) 
AND 
o 
No HF events as described above 
AND 
o 
No cardiovascular death 
 
•  “Worsened” – patients demonstrating: 
o 
Worsening in NYHA Class OR worsening by PGA (“worse” or “markedly 
worse”) 
OR 
                                                                                                                       Page 16 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
o 
Presence of HF events as described above 
OR 
o 
Cardiovascular death 
 
• “Unchanged” – patients neither “Improved” nor “Worsened”. 
 
Patients who are “Improved” or “Unchanged” using the above definition will be grouped together 
as Responders.  Patients classified as “Worsened” will be considered Non-Responders. 
 
5.2.1 Decision algorithm to classify response to CRT treatment 
Has the patient experienced a heart failure event as 
described in section 5.2 ?
WORSENED
Has the NYHA functional class worsened or the 
patient’s global assessment worsened (“moderately 
worse” or “markedly worse”)?
WORSENED
Has the NYHA functional class improved or the 
patient’s global assessment improved (“moderately 
better” or “markedly better”)?
UNCHANGED
IMPROVED
NO
NO
NO
YES
YES
YES
Did the patient have a cardiovascular death as 
described in section 5.2 ?
YES
NO
WORSENED
 
 
5.3 PROCEDURES 
The clinical study will be conducted in accordance with the CIP.  All parties participating in the 
conduct of the clinical study will be qualified by education, training, or experience to perform their 
tasks and this training will be documented appropriately. 
 
The clinical study will not commence until St. Jude Medical receives written approval from the 
IRB/EC and relevant regulatory authorities and all required documents have been collected from the 
site(s). 
 
 
 
                                                                                                                       Page 17 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 
Table 1: List of all study specific activities/procedures 
 
Evaluation 
Baseline* 
Post-
Implant** 
3-month 
Visit 
6-month 
visit 
12-month 
visit 
Inclusion/Exclusion 
Evaluation and Informed 
Consent 
√ 
 
 
 
 
NYHA class  
√ § 
√ 
√ 
√ 
Patient Global Assessment 
 
√ 
√ 
√ 
MLWHF and EQ-5D 
questionnaires 
√ 
 
√ 
√ 
√ 
LVEF (if available) and 
LVESV (if available) 
√ 
 
√ 
√ 
√ 
Cardiac Medications List 
√ 
 
 
 
 
HF events 
 
√ 
√ 
√ 
√ 
LV lead capture threshold 
testing and pacing lead 
impedance 
 
√ 
Testing of 
programmed 
LV lead 
vector(s) 
required 
√ 
Testing of 
programmed 
LV lead 
vector(s) 
required 
√ 
Testing of 
programmed 
LV lead 
vector(s) 
required 
√ 
Testing of 
programmed 
LV lead 
vector(s) 
required 
RA, RV capture threshold, 
signal amplitude and 
pacing lead impedance 
testing 
 
√ 
√ 
√ 
√ 
Device Session Records 
 
√ 
√ 
√ 
√ 
* Baseline visit should be completed up to 30 days before device implant to be enrolled in the study 
** Post-implant visit can occur up to 30 days post successful SJM CRT MP device implant 
§ At Baseline visit, NYHA used for device eligibility will be collected on the CRF 
 
5.4 ENROLLMENT  
5.4.1 Baseline visit 
Patients will undergo screening evaluations as outlined by the inclusion/exclusion criteria. 
The principal investigator or delegated study personnel are responsible for screening all 
potential patients to determine eligibility for the study.  
 
All patients will complete a Baseline visit within 30 days prior to implant. During this visit, 
eligible patients will sign an IRB/EC-approved informed consent form. NYHA class used to 
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Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
determine device eligibility will be collected on the Case Report Form (CRF). All patients 
will also complete QOL questionnaires (MLWHF and EQ-5D) at this visit prior to device 
implant. If a 2D-Echocardiogram was conducted as part of patient’s standard of care, LVEF 
and LVESV values will be collected on the CRF. 
 
Baseline, Medication, MLWHF and EQ-5D questionnaire CRFs will be submitted to St. Jude 
Medical using the EDC system.  
5.4.2 Implant procedures 
The implant procedure will be performed according to standard of care and is not considered 
part of the research study. The User's Manual must be consulted for implantation guidelines, 
appropriate lead/device connections and general handling information.  
All subjects who meet inclusion criteria, do not  meet exclusion criteria, sign an IRB/EC-
approved informed consent, complete a Baseline visit prior to device implant and have an 
attempted implant of the SJM Quadra Allure MP, Quadra Assura MP, or newer SJM CRT 
MP device will be considered enrolled in the study. An implant attempt is defined as 
insertion of the Quadripolar LV lead into the vasculature for positioning. There are no 
protocol-specific requirements for the implant procedure and a CRF is not required to be 
completed within the EDC system. 
5.4.3 Unsuccessful Implant 
Patients who have an unsuccessful implantation of the SJM Quadripolar CRT MP device 
system will be followed for a period of 30 days for adverse events and then withdrawn from 
the study, unless the implant will be re-attempted.   All explanted devices and leads should be 
returned to St. Jude Medical to the address below:  
  
 
 
An Out of Service (if applicable) CRF must be completed using the EDC system.   
After 30 days, if the patient will not have an implant re-attempted, a Withdrawal CRF 
and Adverse Event CRF (if applicable) should be completed using the EDC system.  
The physician may re-attempt the implantation of the SJM CRT MP device system per their 
discretion. If the physician chooses to re-attempt the implantation of the SJM Quadripolar 
CRT MP device system, a System Revision CRF (if applicable), an Adverse Event CRF (if 
applicable) and Product Out of Service CRF (if applicable) should be completed.  All forms 
should be submitted to St. Jude Medical using the EDC system. 
5.4.4 Post-implant visit 
In order to be enrolled in the study, patients must meet inclusion criteria, not meet exclusion 
criteria, sign an IRB/EC-approved informed consent, complete a Baseline visit prior to 
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Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
device implant, and have an attempted implant of the SJM Quadra Allure MP, Quadra Assura 
MP, or newer SJM CRT MP device.   
 
All patients who undergo a successful implant of the SJM CRT MP device system will 
proceed to complete a Post-implant visit. This visit may be completed on the same day as 
device implant, during pre-discharge, during an in-office wound check or any day following 
the implant, as long as it is completed within 30 days of successful implant. 
 
During this visit, the following device testing will be conducted:  
 
• 
RV-LV conduction tests using both RV sense and RV pace configurations 
 
*Note: If patient is pacemaker dependent, conduction tests using RV sense are not required. 
 
For the RA and RV leads: 
• 
Capture threshold testing  
• 
Lead impedance  
• 
Signal amplitude 
  
 
  
*Note: If patient is in atrial fibrillation or atrial flutter, RA electrical measurements are not 
required. 
 
*Note: If patient is in complete heart block or is pacemaker dependent, RV sensing 
amplitude is not required. 
 
For the LV lead: 
The following testing must be performed for the programmed LV lead vector(s)- 
• 
Capture threshold testing 
• 
Lead impedance 
 
The following device session records must be downloaded and sent to St. Jude Medical using 
the EDC system. 
• 
Initial and Final Programmed Parameters 
• 
Real-Time Measurements and Trends for all implanted leads  
• 
Capture threshold testing results for RA, RV and LV lead 
• 
All “new" stored IEGM(s) since previous session 
Once the new IEGM(s) are downloaded and exported, clear all IEGM(s) and diagnostics 
 
Post-Implant Case Report Form (CRF) will be submitted to St. Jude Medical, using the EDC 
system. 
 
5.5 SCHEDULED FOLLOW-UPS 
The schedule of follow-up visits is based on the date of successful SJM CRT MP system implant.  
 
                                                                                                                       Page 20 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
Table 3.0 outlines the time window permitted for each of the study visits. 
 
Table 3: Study Time Interval Windows 
3 Months 
6 Months 
12 Months 
± 14 days 
± 30 days 
± 45 days 
 
All subjects will be followed at 3, 6 and 12 months after the date of successful implant. During each 
follow-up visit, NYHA class and Patient Global Assessment (PGA) will be completed. Refer to 
section 5.2.  All patients will also complete QOL questionnaires (MLWHF and EQ-5D) during each 
scheduled follow-up visit. If a 2D-Echocardiogram was conducted as part of the patient’s standard 
of care since the last visit, LVEF and LVESV values will be collected on the Follow-up CRF. 
 
The following  device testing will be conducted: 
 
• 
RV-LV conduction tests using both RV sense and RV pace configurations 
 
*Note: If patient is pacemaker dependent, conduction tests using RV sense are not required. 
 
For the RA and RV leads: 
• 
Capture threshold testing  
• 
Lead impedance  
• 
Signal amplitude 
 
 
 
  
*Note: If patient is in atrial fibrillation or atrial flutter, RA electrical measurements are not 
required. 
 
*Note: If patient is in complete heart block or is pacemaker dependent, RV sensing amplitude is 
not required. 
 
For the LV lead: 
The following testing must be performed for the programmed LV lead vector(s)- 
• 
Capture threshold testing 
• 
Lead impedance 
 
Final BiV and MPP programming at all visits is per physician’s discretion. MPP programming 
guidelines are provided in Appendix I. 
 
A Follow-up CRF, MLWHF and EQ-5D questionnaires should be completed using the EDC 
system. If a patient had an inpatient hospital stay, ER visit, observational visit, outpatient visit, 
urgent care visit, or unscheduled office visit for cardiovascular reasons only since the last visit, 
                                                                                                                       Page 21 of 58 
 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
a Health Care Utilization / Hospitalization CRF should be completed. All forms should be 
submitted to St. Jude Medical using the EDC system. 
 
The following device session records must be downloaded and sent to St. Jude Medical using the 
EDC system. 
 
• Initial and Final Programmed Parameters 
• Real-Time Measurements and Trends for all implanted leads  
• Capture threshold testing results for RA, RV and LV lead 
• All “new" stored IEGM(s) since previous session 
 
Once the new IEGM(s) are downloaded and exported, clear all IEGM(s) and diagnostics. 
 
5.6 UNSCHEDULED VISITS 
An unscheduled visit is defined as a visit between two specified study visits during  where device 
interrogation and reprogramming associated with the Quadripolar LV lead takes place. 
Device session records should be downloaded and sent to St. Jude Medical using the EDC system.                      
A Follow-up CRF, and any other applicable CRF should be completed and submitted to St. Jude 
Medical using the EDC system. 
 
 CLINICAL EVENTS/ HOSPITALIZATIONS  
6.0
Any clinical event resulting in an inpatient hospital stay, ER visit, observational visit, outpatient 
visit, or urgent care visit for cardiovascular reasons must be reported to St. Jude Medical. Detailed 
source documentation surrounding the clinical event should also be sent to St. Jude Medical using 
the EDC system. This may include: 
 
• 
Emergency department notes 
• 
Physician consultation notes 
• 
Medication records and logs 
• 
Admission notes 
• 
Laboratory results and summary details 
• 
Discharge summary 
• 
Operative notes 
• 
Clinician progress notes 
• 
X-ray reports 
• 
Diagnostic test reports 
 
A Health Care Utilization /Hospitalization CRF and Medication CRF (if applicable) should be 
completed for each clinical event/ hospitalization and submitted along with supporting 
documentation to St. Jude Medical using the EDC system.  
 
 
                                                                                                                       Page 22 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
6.1 HEALTH CARE ECONOMIC DATA 
To assess potential differences in costs for heart failure-related health care utilizations among the 
groups described in section 3.2, billing records (i.e., UB-04 and CMS-1500 for centers in the United 
States) will be collected on a Health Care Utilization/ Hospitalization CRF. 
 
6.2 SUBJECT STUDY COMPLETION 
When the subject’s participation in the clinical study is completed, the subject will return to the 
medical care as per physician’s recommendation. 
 
6.3 CRITERIA AND PROCEDURES FOR SUBJECT WITHDRAWAL OR 
DISCONTINUATION 
Subjects must be informed about their right to withdraw from the study at any time and for any 
reason without sanction, penalty or loss of benefits to which the subject is otherwise entitled and 
withdrawal from the study will not jeopardize their future medical care or relationship with the 
investigator. Subjects will be asked to specify the reason for the termination, but have the right not 
to answer. 
 
The investigator may decide to withdraw a subject from the study at any time with reasonable 
rationale. The subject’s future care will not be influenced by a decision, voluntary or otherwise, to 
withdraw from the study. All reasonable efforts should be made to retain the subject in the clinical 
study until completion of the study. 
 
Reasons for subject’s withdrawal include, but are not limited to: 
 
• Subject refuses to continue participating in the study 
• Subject does not meet the inclusion/exclusion criteria and does not require additional follow-
up for safety reasons. 
• Subject is deceased (Complete Death Form) 
• Subject’s non-compliance 
• Subject’s participation is terminated by the PI or investigator, although the subject consented, 
since participation is no longer medically appropriate 
• Subject is ‘lost to follow up’: Subject does not adhere to the scheduled follow up visits but has 
not explicitly requested to be withdrawn from the clinical study. Site personnel should at all 
times make all reasonable efforts to locate and communicate with the subject in order to 
achieve subject compliance to the scheduled follow up visits: 
1.  A subject will be considered ‘Lost to Follow Up’ after a minimum of 2 phone calls of a 
physician or delegate at the investigational site to the subject or contact. These 2 phone 
calls need to be documented in the subject’s hospital records. 
2.  If these attempts are unsuccessful, a letter should be sent to the subject’s last known 
address or general practitioner (GP) and a copy of this letter should be maintained in the 
subject’s hospital records. 
 
                                                                                                                       Page 23 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
Note: If a subject misses one or more of the scheduled follow up visits (inclusive of the assigned 
visit windows), this will be considered as a missed visit requiring submission of a Protocol 
Deviation Form. The subject may therefore still return for subsequent visits and will not be 
excluded from the study. 
 
If a subject withdraws from the clinical study, the site will record the subject’s reasons for 
withdrawal, on a Withdrawal CRF. 
 
When subject withdrawal from the clinical study is due to an adverse event the subject will be 
followed until resolution of that adverse event or determination that the subject’s condition is 
stable. The status of the subject’s condition should be documented at the time of withdrawal.   
 
 COMPLIANCE TO CIP 
7.0
7.1 STATEMENTS OF COMPLIANCE 
The investigator will not start enrolling subjects or requesting informed consent from any subject 
prior to obtaining IRB/EC approval and Competent Authority approval, if applicable, and 
authorization from the sponsor in writing for the study. 
 
In case additional requirements are imposed by the IRB/EC, those requirements will be followed, if 
appropriate. If any action is taken by an IRB/EC, and regulatory requirements with respect to the 
study, that information will be forwarded to St. Jude Medical. 
 
7.2 ADHERENCE TO THE CLINICAL INVESTIGATION PLAN 
A deviation is defined as an event where the clinical investigator, site personnel, sponsor or sponsor 
representative did not conduct the clinical study according to the Clinical Investigational Plan, 
IRB/EC requirements or the Investigator Agreement. The investigator is not allowed to deviate 
from the CIP, except as specified under emergency circumstances.   
 
In some cases, failure to comply with the CIP may be considered failure to protect the rights, safety 
and well-being of subjects, since the non-compliance exposes subjects to unreasonable risks. For 
example, failure to adhere to the inclusion/exclusion criteria: these criteria are specifically defined 
by the Sponsor to exclude subjects for whom the device is not beneficial and the use involves 
unreasonable risks. This may be considered failure to protect the rights, safety and well-being of the 
enrolled subject. Similarly, failure to perform safety assessments intended to detect adverse events 
may be considered failure to protect the rights, safety and well-being of the enrolled subject. 
Investigators should seek minimization of such risks by adhering to the CIP. 
 
Simultaneously, in the event that adhering to the CIP might expose the subject to unreasonable 
risks, the investigator is also required to protect the rights, safety and well-being of the subject by 
intentionally deviating from the requirements of the CIP, so that subjects are not exposed to 
unreasonable risks.  
 
                                                                                                                       Page 24 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
It is the responsibility of the investigator to provide adequate medical care to a subject enrolled in a 
study. 
 
Regulations require that the PI maintain accurate, complete, and current records, including 
documents showing the date of and reason for every deviation from the Clinical Investigational 
Plan.  Relevant information for each deviation will be documented on a Deviation CRF. The site 
will submit the CRF to St. Jude Medical. 
 
Regulations require Investigators obtain approval from St. Jude Medical and the IRB/EC [as 
required] before initiating changes in or deviations from the protocol, except when necessary to 
protect the life or physical well-being of a subject in an emergency.   
 
Prior approval must be requested when the PI anticipates, contemplates, or makes a conscious 
decision to depart from the CIP, except when unforeseen circumstances are beyond the 
investigator’s control (e.g. a subject who fails to attend a scheduled follow-up visit, a subject is too 
ill to perform a CIP-required test, etc.).  All deviations, including those beyond the investigator’s 
control, must be reported on a CRF. 
 
To obtain approval, the Principal Investigator may call or email and discuss the potential deviation 
with St. Jude Medical or designee prior to initiating any changes.   
 
All deviations must be reported to appropriate regulatory authorities in specified timelines (if 
appropriate). 
 
Investigator will notify St. Jude Medical and the reviewing IRB/EC within 5 working days of: 
• Any deviation to protect the life or physical well-being of a subject in an emergency  
• Any failure to obtain informed consent 
 
Investigators or the designee must notify St. Jude Medical, Inc. as soon as possible and complete 
the Deviation CRF. 
 
The Investigator is required to adhere to local regulatory requirements for reporting deviations to 
IRB/EC. 
 
7.3 REPEATED AND SERIOUS NON-COMPLIANCE 
In the event of repeated non-compliance or a one-time serious non-compliance, as determined by 
the Sponsor, a Clinical Research Associate or clinical representative will attempt to secure 
compliance by one or more of the following actions:    
• Visiting the investigator 
• Contacting the investigator by telephone 
• Contacting the investigator in writing 
• Retraining of the investigator 
 
                                                                                                                       Page 25 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
If an investigator is found to be repeatedly non-compliant with the signed agreement, the CIP or 
any other conditions of the clinical study, the Sponsor will either secure compliance or, at its sole 
discretion, terminate the investigator’s participation in the clinical study. 
 
 RISKS AND BENEFITS OF THE CLINICAL STUDY 
8.0
The risks associated with the use of the SJM CRT MP device system are anticipated to be comparable to 
those associated with the use of other currently available CRT devices, and leads.  Patients participating 
in this study are indicated for a CRT system as part of their standard medical management and are 
subject to the risks associated with these devices (refer to Section 6).  
 
MPP may consume battery voltage faster than conventional BiV pacing.  Should MPP not be beneficial 
to a specific patient, the feature can be disabled, thereby minimizing the effect on battery longevity in 
that patient. 
 
Patients enrolled in this investigation may benefit as it is expected that the MPP feature will increase the 
volume of excited cardiac tissue and by capturing more mass at the initial depolarization, there is a 
greater likelihood of pacing the site of latest systolic delay. Both of these methods have been shown to 
improve LV function8, 9 and it is believed that this additional improvement in LV function may benefit 
those patients who are otherwise identified as non-responders to conventional BiV pacing. 
 ADVERSE EVENT, ADVERSE DEVICE EFFECT, DEVICE COMPLAINTS 
9.0
9.1 DEFINITIONS 
9.1.1 Medical device 
Any instrument, apparatus, implement, machine, appliance, implant, software, material or 
other similar or related article 
• Intended by the manufacturer to be used, alone or in combination, for human beings for 
one or more of the specific purpose(s) of 
o Diagnosis, prevention, monitoring, treatments or alleviation of disease, 
o Diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury, 
o Investigation, replacement, modification, or support of the anatomy or of a 
physiological process, 
o Supporting or sustaining life, 
o Control of conception, 
o Disinfection of medical devices and 
• Which does not achieve its primary intended action in or on the human body by 
pharmacological, immunological or metabolic means, but which may be assisted in its 
intended function by such means 
 
9.1.2 Adverse Event (AE) 
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 investigational medical device under study. 
                                                                                                                       Page 26 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 
This definition includes events related to the investigational medical device or the 
comparator. 
This definition includes events related to the procedures involved. 
 
9.1.3 Serious Adverse Event (SAE) 
An adverse event that led to: 
• Death 
• A serious deterioration in the health of the subject, that either resulted in: 
o A life-threatening illness or injury OR 
o A permanent impairment to a body structure or a body function OR 
o An in-patient or prolonged hospitalization OR 
o A medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body OR 
o A malignant tumor 
• Fetal distress, fetal death or a congenital abnormality or birth defect 
 
A planned hospitalization for a pre-existing condition, or a procedure required by the CIP is 
not considered a serious adverse event. 
 
9.1.4 Adverse Device Effect (ADE) 
An adverse event related to the use of an investigational medical device. 
 
This definition includes adverse events resulting from insufficient or inadequate instructions 
for use, deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device. 
 
This definition includes any event resulting from the use error or from intentional misuse of 
the investigational medical device. 
 
9.1.5 Serious Adverse Device Effect (SADE) 
Adverse device effect that has resulted in any of the consequences characteristic of a serious 
adverse event. 
 
9.2 PROCEDURE FOR ASSESSING, RECORDING, AND REPORTING ADVERSE 
EVENTS, DEVICE COMPLAINTS, ADVERSE DEVICE EFFECTS, SERIOUS 
ADVERSE EVENTS, AND SERIOUS ADVERSE DEVICE EFFECTS:  
Safety surveillance within this study and the safety reporting both performed by the 
investigator, starts as soon as the subject is enrolled in this study (date of attempted implant). 
The safety surveillance and the safety reporting will continue until the last investigational 
visit has been performed, the subject is deceased, the subject/investigator concludes his 
                                                                                                                       Page 27 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
participation into the study or the subject/investigator withdraws the subject from the study, 
except as otherwise specified in the CIP. 
 
Potential adverse events associated with the use of for all CRT systems, including the 
Quadripolar CRT MP device system (device and lead) include but not limited to: 
 
• Allergic reaction to contrast media 
• AV nodal reentrant tachycardia 
• Bodily rejection phenomena 
• Cardiac/coronary sinus dissection 
• Cardiac/coronary sinus perforation 
• Cardiac tamponade 
• Coronary sinus or cardiac vein thrombosis 
• Endocarditis 
• Excessive bleeding  
• Hematoma/seroma 
• Induced atrial or ventricular arrhythmias 
• Infection 
• Lead dislodgement 
• Lead/port damage 
• Local tissue reaction; formation of fibrotic tissue 
• Loss of pacing and/or sensing due to dislodgement or mechanical malfunction of the 
pacing lead 
• Myocardial irritability 
• Myopotential sensing 
• Pectoral/diaphragmatic/phrenic nerve stimulation 
• Pericardial effusion 
• Pericardial rub 
• Pneumothorax/ hemothorax 
• Prolonged exposure to fluoroscopic radiation 
• Pulmonary edema 
• Renal failure from contrast media used to visualize coronary veins 
• Rise in threshold and exit block 
• Thrombolytic or air embolism 
• 
Valve damage 
 
Records relating to the subject’s subsequent medical course must be maintained and 
submitted (as applicable) to the Sponsor until the event has subsided or, in case of permanent 
impairment, until the event stabilizes and the overall clinical outcome has been ascertained. 
Adverse events will be monitored until they are adequately resolved.  The status of the 
subject’s condition should be documented at each visit.   
 
The investigator will report the event to the IRB/EC per their reporting requirements.  
                                                                                                                       Page 28 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 
Reportable events to sponsor are considered:  
• All Adverse Device Effects 
• All Serious Adverse Effects (whether or not the event is considered device or procedure 
related) 
 
All above events will be reported to the Sponsor, as soon as possible, but no later than 10 
days of first learning of the event. 
 
Observable Adverse Event: 
An observable AE is defined as an adverse event related to the implant procedure that is 
expected to occur for a projected duration in all subjects. Observable AE’s are not reportable 
unless the condition worsens or continues beyond the time frame listed below. 
 
 
Observable AEs related to the Implant Procedure 
Event 
Time Frame 
post-Implant 
Anesthesia related nausea/vomiting 
<24 hours 
Low-grade fever (<100 degree Fahrenheit 
fever or < 37.8 degree Celsius 
< 48 hours 
Percutaneous access pain 
< 72 hours 
Mild to moderate bruising/ecchymosis at 
percutaneous access site 
< 72 hours 
Sleep problems (insomnia) 
< 72 hours 
Back pain related to laying on the table 
< 72 hours 
 
The Sponsor will ensure that all events are reported to the relevant authorities as per 
regulations.  
 
Additional information may be requested, when required, by the Sponsor in order to support 
the reporting of AEs to regulatory authorities. 
 
The investigator must notify the IRB/EC, if appropriate, in accordance with national and 
local laws and regulations, of the AEs reported to the Sponsor. 
 
 
 
 
 
 
                                                                                                                       Page 29 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
9.3 SUBJECT DEATH 
9.3.1 Procedure for recording and reporting subject death 
• All subject deaths are to be documented and reported to the sponsor as soon as possible but 
no later than 10 days after becoming aware of the event. Notification of death should include 
a detailed statement of the pertinent events and be signed by the investigator in addition to 
the appropriate case report forms (Death , Withdrawal, and Product Out of Service CRFs). It 
is the investigator’s responsibility to notify the IRB/EC per the IRB/EC policy. Details of 
death and the following information, if available, should be provided in a letter to St. Jude 
Medical by the investigator summarizing the patient’s course since enrollment in the study: 
• Date and time of death 
• Place death occurred (e.g. hospital, nursing home, patients home) 
• If death was witnessed 
• Identification of the rhythm at the time of death, if known (include any available 
documentation) 
• Cause of death 
• Any other circumstances surrounding the death 
• Approximate time interval to death from the initiating event. 
• Autopsy report (if performed) 
• Whether it was device and/or procedure related 
• Whether it was related to the study 
• Device configuration at the time of death 
 
Provide clinical notes and witness statements. If possible, interrogate the pulse generator. 
Retrieve and print all episode diagnostics, IEGMs, and programmed parameters. If 
applicable, the pulse generator should then be programmed OFF.  
 
Every attempt should be made to explant the pulse generator and/or leads intact. Any 
explanted devices or leads should be returned to St. Jude Medical for analysis promptly. In 
the event that the device is not explanted, the above procedure must be followed to retrieve 
the data. The reason the pulse generator and/or lead(s) are not being returned to St. Jude 
Medical must be stated clearly on the case report form. 
 
9.4 DEVICE COMPLAINTS  
A device complaint is defined as any written, electronic, or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, safety, effectiveness or 
performance of a device after it is released for distribution. 
  
Device complaints include malfunctions, use errors and inadequate labeling. 
 
Device complaints in St. Jude Medical market-released products must be reported per St. 
Jude Medical product surveillance process. Please notify SJM Tech Service via email at 
. 
 
                                                                                                                       Page 30 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 DATA MANAGEMENT 
10.0
Overall, the Sponsor will be responsible for the data handling. 
 
The sponsor and/or its affiliates will be responsible for compiling and submitting all required 
reports to governmental agencies. 
 
Data will be analyzed by the Sponsor and may be transferred to the Sponsor’s locations outside of 
US and/or any other worldwide regulatory authority in support of a market-approval application. 
 
St. Jude Medical respects and protects personally identifiable information that we collect or 
maintain. As part of our commitment, St. Jude Medical is certified to the U.S. - European Union 
Framework and U.S. – Swiss Safe Harbor Framework Agreements regarding human resources and 
subject clinical trial personal information. The privacy of each subject and confidentiality of 
his/her information will be preserved in reports and when publishing any data. Confidentiality of 
data will be observed by all parties involved at all times throughout the clinical study.  All data 
will be secured against unauthorized access. 
 
Data and additional source documents will be submitted through EDC.   
 
The Principal Investigator or institution will provide direct access to source data during and after 
the clinical study for monitoring, audits, IRB/EC review and regulatory authority inspections.  As 
required, the Principal Investigator or institution will obtain permission for direct access to source 
documents from the subject, hospital administration and national regulatory authorities before 
starting the clinical study. 
 
10.1 DATA MANAGEMENT PLAN 
A detailed Data Management Plan will be established to ensure consistency of the data. This 
document will include procedures used for data review, database cleaning, and issuing and 
resolving data queries. If appropriate, the DMP may be updated throughout the study duration. All 
revisions will be tracked and document controlled. 
 
CRF data will be captured in a validated electronic database management system hosted by St. Jude 
Medical.  
 
Only authorized site personnel will be permitted to enter the CRF data through the electronic data 
capture (EDC) system deployed by St. Jude Medical. An electronic audit trail will be used to track 
any subsequent changes of the entered data. 
 
10.2 DOCUMENT AND DATA CONTROL 
10.2.1 Traceability of documents and data 
The investigator will ensure accuracy, completeness, legibility and timeliness of the data 
reported to the sponsor on the CRFs and in all required reports.  
 
                                                                                                                       Page 31 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
10.2.2 Recording data 
Source documents will be created and maintained by the investigational site team throughout 
the clinical study. 
 
The data reported on the CRFs will be derived from, and be consistent with, these source 
documents, and any discrepancies will be explained in writing. 
 
The CRFs will be signed and validated by the authorized site personnel.  
 MONITORING  
11.0
Centralized monitoring will occur through routine internal data review.  This monitoring is 
designed to identify missing and inconsistent data, data outliers, and potential protocol deviations 
that may be indicative of site non-compliance. On site monitoring may occur at the discretion of 
the sponsor.  
 
STATISTICAL CONSIDERATIONS 
12.0
The following section describes the statistical methods for the clinical investigation design. 
12.1 STATISTICAL DESIGN, HYPOTHESES, METHOD AND ANALYTICAL 
PROCEDURES 
This is a prospective, multicenter, non-randomized registry/observational study. Analysis of 
the study objectives will be summarized using data collected upon 12-month follow-up visit 
by the groups defined in section 3.2.  The objectives of this study will be summarized as the 
follows: 
• Overall CRT response rate at 12 months will be summarized by percentages with a 95% 
confidence interval using exact method for binomial distribution. 
• QOL, LVEF, and LVESV at baseline, 3, 6, and 12 months will be summarized by means 
(± standard deviation), median and range. 
• Programming timing and workflow between implant and 12 months will be summarized 
by frequency and percentage for categorical data.  
• Rates of heart failure (HF) hospitalization events at 12 months, cardiovascular 
hospitalizations at 12 months, and HF 30-day hospitalization rates will be summarized 
using Kaplan-Meier method. 
• Costs associated with HF-related health care utilizations at 12 months will be 
summarized by means (± standard deviation), median and range. 
• All-cause mortality at 12 months will be summarized using Kaplan-Meier method. 
 
12.2 SAMPLE SIZE 
 
 
 
                                                                                                                       Page 32 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
12.3 MAXIMUM NUMBER OF SUBJECTS TO BE INCLUDED FOR EACH CENTER 
The maximum number of subjects that each center can enroll is 300.   
 
DOCUMENT RETENTION 
13.0
St. Jude Medical and the Principal Investigators will maintain the clinical study documents as 
required by St. Jude Medical, Inc. and applicable regulatory requirements.  They will take 
measures to prevent accidental or premature destruction of these documents.  The Principal 
Investigator or St. Jude Medical may transfer custody of records to another person/party and 
document the transfer at the investigational site or at St. Jude Medical’s facility. 
 
These documents must be retained by the investigational site for a period of 2 years after clinical 
study conclusion and made available for monitoring or auditing by St. Jude Medical’s 
representative or representatives of the FDA and other applicable regulatory agencies.  The 
Principal Investigator must ensure the availability of source documents from which the 
information on the case report forms was derived. 
 
AMENDMENTS TO CLINICAL INVESTIGATIONAL PLAN 
14.0
Study related documents such as CIP, CRFs, Informed Consent form and other subject 
information, or other clinical study documents will be amended as needed throughout the clinical 
study, and a justification statement will be included with each amended section of a document. 
The version number and date of amendments will be documented. 
 
The amendments to the CIP and the subject’s Informed Consent must be provided to and 
approved by the IRB/EC when required. Any amendment affecting the subject requires that the 
subject be informed of the changes and a new consent be signed and dated by the investigator at 
the subject’s next follow up visit. Sites must follow their IRB/EC’s policy regarding consenting 
subjects following a CIP amendment. 
 
 STUDY COMMITTEES  
15.0
15.1 STEERING COMMITTEE (SC) 
The Steering Committee may be used to advise the sponsor during the conduct of the study, 
during data analysis and/or presentation/publication of the study results.  Membership may 
include site investigators for the study under review. 
 
 INVESTIGATION SUSPENSION OR TERMINATION 
16.0
16.1 PREMATURE TERMINATION OF THE WHOLE CLINICAL STUDY OR OF THE 
CLINICAL STUDY IN ONE OR MORE INVESTIGATIONAL SITES 
The Sponsor reserves the right to stop the study at any stage, with appropriate written notice 
to the investigator.  
 
                                                                                                                       Page 33 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
Possible reasons for early termination of the study by the sponsor, either at local, national or 
international level, may include, but are not limited to: 
 
• The device /  therapy fails to perform as intended 
• Sponsor’s decision 
• Recommendation from DSMB to Steering committee and Sponsor 
• Request from Regulatory bodies 
• Request of Ethics Committee(s)  
• Concern for subject safety and welfare 
• Failure to secure subject Informed Consent prior to any investigational activity 
• Failure to report unanticipated adverse device effects within 72 hours to St. Jude 
Medical and the EC 
• Repeated non-compliance with this CIP or the Clinical Trial Agreement 
• Inability to successfully implement this CIP 
• Violation of the Declaration of Helsinki 2008 (refer to Appendix C) 
• Violation of applicable national or local laws and regulations 
• Falsification of data, or any other breach of ethics or scientific principles 
• Loss of or unaccounted use of investigational device inventory 
 
The study will be terminated according to applicable regulations. 
 
The investigator may also discontinue participation in the clinical study with appropriate 
written notice to the Sponsor. 
 
Should either of these events occur, the investigator will return all documents to the sponsor; 
provide a written statement as to why the premature termination has taken place and notify 
the IRB/EC and/or the Competent Authority (if applicable). Follow-up for all enrolled 
subjects will be as per CIP requirements. 
 
A Principal Investigator, IRB/EC or regulatory authority may suspend or prematurely 
terminate participation in a clinical study at the investigational sites for which they are 
responsible.   
 
If suspicion of an unacceptable risk to subjects arises during the clinical study or when so 
instructed by the IRB/EC or regulatory authority, St. Jude Medical may suspend the clinical 
study as appropriate while the risk is assessed.  St. Jude Medical will terminate the clinical 
study if an unacceptable risk is confirmed.   
 
St. Jude Medical will consider terminating or suspending the participation of a particular 
investigational site or investigator in the clinical study if monitoring or auditing identifies 
serious or repeated deviations on the part of an investigator.   
 
If suspension or premature termination occurs, the terminating party will justify its decision 
in writing and promptly inform the other parties with whom they are in direct 
                                                                                                                       Page 34 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
communication.  The Principal Investigator and St. Jude Medical will keep each other 
informed of any communication received from IRB/EC or regulatory authority.   
 
If for any reason St. Jude Medical suspends or prematurely terminates the study at an 
individual investigational site, St. Jude Medical will inform the responsible regulatory 
authority, as appropriate, and ensure that the IRB/EC are notified, either by the Principal 
Investigator or by St. Jude Medical.  If the suspension or premature termination was in the 
interest of safety, St. Jude Medical will inform all other Principal Investigators.   
 
If suspension or premature termination occurs, St. Jude Medical will remain responsible for 
providing resources to fulfill the obligations from the CIP and existing agreements for 
following up the subjects enrolled in the clinical study, and the Principal Investigator or 
authorized designee will promptly inform the enrolled subjects at his/her investigational site, 
if appropriate.   
 
 
16.2 RESUMING THE STUDY AFTER TEMPORARY SUSPENSION 
When St. Jude Medical concludes an analysis of the reasons for the suspension, implements 
the necessary corrective actions, and decides to lift the temporary suspension, St. Jude 
Medical will inform the Principal Investigators, IRB/EC, or regulatory authority, where 
appropriate, of the rationale, providing them with the relevant data supporting this decision.   
 
Concurrence will be obtained before the clinical study resumes from the IRB/EC or 
regulatory authority where appropriate.   
 
If subjects have been informed of the suspension, the Principal Investigator or authorized 
designee will inform them of the reasons for resumption. 
 
16.3 STUDY CONCLUSION 
The study will be concluded when: 
• All sites are closed AND 
• The Final report generated by St. Jude Medical has been provided to sites or St. Jude 
Medical has provided formal documentation of study closure 
 
 
PUBLICATION POLICY 
17.0
The results of the clinical study will be submitted, whether positive or negative for publication.  
 
A ‘Publication Agreement’ will be signed between the Principal Investigator and the Sponsor 
either as a separate Publication Agreement or within the Clinical Trial Agreement. 
 
For more information on publication guidelines, please refer to the International Committee of 
Medical Journal Editors (ICMJE) on www.icmje.org. 
 
                                                                                                                       Page 35 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
This study will be posted on ClinicalTrials.gov and results will be posted on ClinicalTrials.gov 
as required.  
 
 
                                                                                                                       Page 36 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 
BIBLIOGRAPHY  
18.0
 
1. 
Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Carnethon MR, Dai S, de 
Simone G, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Greenlund KJ, Hailpern SM, Heit JA, Ho 
PM, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, 
Marcus GM, Marelli A, Matchar DB, McDermott MM, Meigs JB, Moy CS, Mozaffarian D, 
Mussolino ME, Nichol G, Paynter NP, Rosamond WD, Sorlie PD, Stafford RS, Turan TN, 
Turner MB, Wong ND, Wylie-Rosett J. Heart disease and stroke statistics--2011 update: A 
report from the american heart association. Circulation. 2011;123:e18-e209 
2. 
Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, Haase N, Ho M, Howard V, 
Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell CJ, 
Roger V, Rumsfeld J, Sorlie P, Steinberger J, Thom T, Wasserthiel-Smoller S, Hong Y. Heart 
disease and stroke statistics--2007 update: A report from the american heart association statistics 
committee and stroke statistics subcommittee. Circulation. 2007;115:e69-171 
3. 
Wang L, Lahtinen S, Lentz L, Rakow N, Kaszas C, Ruetz L, Stylos L, Olson WH. Feasibility of 
using an implantable system to measure thoracic congestion in an ambulatory chronic heart 
failure canine model. Pacing Clin Electrophysiol. 2005;28:404-411 
4. 
Pires LA, Abraham WT, Young JB, Johnson KM. Clinical predictors and timing of new york 
heart association class improvement with cardiac resynchronization therapy in patients with 
advanced chronic heart failure: Results from the multicenter insync randomized clinical 
evaluation (miracle) and multicenter insync icd randomized clinical evaluation (miracle-icd) 
trials. Am Heart J. 2006;151:837-843 
5. 
Birnie DH, Tang AS. The problem of non-response to cardiac resynchronization therapy. Curr 
Opin Cardiol. 2006;21:20-26 
6. 
Butter C, Auricchio A, Stellbrink C, Fleck E, Ding J, Yu Y, Huvelle E, Spinelli J. Effect of 
resynchronization therapy stimulation site on the systolic function of heart failure patients. 
Circulation. 2001;104:3026-3029 
7. 
Lloyd MS, Heeke S, Lerakis S, Langberg JJ. Reverse polarity pacing: The hemodynamic benefit 
of anodal currents at lead tips for cardiac resynchronization therapy. J Cardiovasc 
Electrophysiol. 2007;18:1167-1171 
8. 
Theis C, Bavikati VV, Langberg JJ, Lloyd MS. The relationship of bipolar left ventricular pacing 
stimulus intensity to cardiac depolarization and repolarization in humans with cardiac 
resynchronization devices. J Cardiovasc Electrophysiol. 2009;20:645-649 
9. 
Leclercq C, Gadler F, Kranig W, Ellery S, Gras D, Lazarus A, Clementy J, Boulogne E, Daubert 
JC. A randomized comparison of triple-site versus dual-site ventricular stimulation in patients 
with congestive heart failure. J Am Coll Cardiol. 2008;51:1455-1462 
10. 
Lenarczyk R, Kowalski O, Kukulski T, Pruszkowska-Skrzep P, Sokal A, Szulik M, Zielinska T, 
Kowalczyk J, Pluta S, Sredniawa B, Musialik-Lydka A, Kalarus Z. Mid-term outcomes of triple-
site vs. Conventional cardiac resynchronization therapy: A preliminary study. Int J Cardiol. 
2009;133:87-94 
11. 
Forleo GB, Santini L, Potenza D, Stolfo GD, Locatelli A, Baracca E. Impact of multipoint left 
ventricular pacing on qrs duration and left ventricular ejection fraction: Preliminary results from 
a multicenter prospective study. Heart Rhythm. 2015;12:S388-S389 
                                                                                                                       Page 37 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
12. 
Gluteben K, Kranig W, Barr C, Morgenstern M, Simon M, Lee K. Multisite left ventricular 
pacing is safe and improves cardiac hemodynamic in heart failure patients - results from 1-month 
follow-up study. Heart Rhythm. 2012;9:S163 
13. 
Menardi E, Ballari GP, Goletto C, Rossetti G, Vado A. Characterization of ventricular activation 
pattern and acute hemodynamics during multipoint left ventricular pacing. Heart Rhythm. 
2015;12:1762-1769 
14. 
Osca J, Alonso P, Cano O, Andres A, Melero J, Sancho-Tello MJ, Olaque J. Multipoint pacing in 
left ventricle with a quadripolar lead improves cardiac dysynchrony and hemodynamics in 
comparison to conventional pacing. Heart Rhythm. 2015;12:S220 
15. 
Pappone C, Calovic Z, Vicedomini G, Cuko A, McSpadden LC, Ryu K, Jordan CD, Romano E, 
Baldi M, Saviano M, Pappone A, Vitale R, Catalano C, Ciaccio C, Giannelli L, Ionescu B, 
Petretta A, Fragakis N, Fundaliotis A, Tavazzi L, Santinelli V. Improving cardiac 
resynchronization therapy response with multipoint left ventricular pacing: Twelve-month 
follow-up study. Heart Rhythm. 2015;12:1250-1258 
16. 
Pappone C, Calovic Z, Vicedomini G, Cuko A, McSpadden LC, Ryu K, Romano E, Baldi M, 
Saviano M, Pappone A, Ciaccio C, Giannelli L, Ionescu B, Petretta A, Vitale R, Fundaliotis A, 
Tavazzi L, Santinelli V. Multipoint left ventricular pacing in a single coronary sinus branch 
improves mid-term echocardiographic and clinical response to cardiac resynchronization 
therapy. J Cardiovasc Electrophysiol. 2015;26:58-63 
17. 
Pappone C, Calovic Z, Vicedomini G, Cuko A, McSpadden LC, Ryu K, Romano E, Saviano M, 
Baldi M, Pappone A, Ciaccio C, Giannelli L, Ionescu B, Petretta A, Vitale R, Fundaliotis A, 
Tavazzi L, Santinelli V. Multipoint left ventricular pacing improves acute hemodynamic 
response assessed with pressure-volume loops in cardiac resynchronization therapy patients. 
Heart Rhythm. 2014;11:394-401 
18. 
Rinaldi CA, Kranig W, Leclercq C, Kacet S, Betts T, Bordachar P, Gutleben KJ, Shetty A, Keel 
A, Ryu K, Farazi TG, Simon M, Naqvi TZ. Acute effects of multisite left ventricular pacing on 
mechanical dyssynchrony in patients receiving cardiac resynchronization therapy. J Card Fail. 
2013;19:731-738 
19. 
Thibault B, Dubuc M, Khairy P, Guerra PG, Macle L, Rivard L, Roy D, Talajic M, Karst E, Ryu 
K, Paiement P, Farazi TG. Acute haemodynamic comparison of multisite and biventricular 
pacing with a quadripolar left ventricular lead. Europace. 2013;15:984-991 
20. 
Zanon F, Baracca E, Pastore G, Marcantoni L, Fraccaro C, Lanza D, Picariello C, Aggio S, 
Roncon L, Dell'Avvocata F, Rigatelli G, Pacetta D, Noventa F, Prinzen FW. Multipoint pacing 
by a left ventricular quadripolar lead improves the acute hemodynamic response to crt compared 
with conventional biventricular pacing at any site. Heart Rhythm. 2015;12:975-981 
21. 
Packer M. Proposal for a new clinical end point to evaluate the efficacy of drugs and devices in 
the treatment of chronic heart failure. J Card Fail. 2001;7:176-182 
 
 
 
                                                                                                                       Page 38 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
APPENDIX A: ABBREVIATIONS 
 
Select or add abbreviations used 
Abbreviation 
Term 
ADE 
AE 
CA 
CIP 
CRF 
DD 
DMP 
ECG 
eCRF 
EDC 
EC 
ICMJE 
IRB 
ISB 
MP 
NA 
PI 
RDC 
SADE 
SAE 
SC  
SJM 
Adverse Device Effect 
Adverse Event 
Competent Authority 
Clinical Investigational Plan 
Case Report Form 
Device Deficiency 
Data Management Plan 
Electrocardiogram 
Electronic Case Report Form 
Electronic Data Capture 
Ethics Committee 
International Committee of Medical Journal Editors 
Institutional Review Board 
Investigator Site Binder 
Monitoring Plan 
Not Applicable 
Principal Investigator 
Remote Data Capture 
Serious Adverse Device Effect 
Serious Adverse Event 
Steering Committee 
St. Jude Medical 
 
 
 
                                                                                                                       Page 39 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
APPENDIX B: CIP REVISION HISTORY 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                                                                                                       Page 40 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
APPENDIX C: DECLARATION OF HELSINKI 
The most current version of the document will be followed. 
 
 
                                                                                                                       Page 41 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
APPENDIX D: LIST OF CLINICAL INVESTIGATION SITES AND IRB/EC 
A list of Clinical Investigational sites and IRB/EC will be kept under a separate cover and is available 
upon request.  
 
 
                                                                                                                       Page 42 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
  
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
                                                                                                                       
 
 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
• 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
                                                                                                                       
 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
   
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
                                                                                                                       
 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
• 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
                                                                                                                       
 
 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 
 
 
 
 
 
 
 
 
    
 
 
 
 
 
 
 
 
 
   
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
                                                                                                                       
 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 
 
   
 
  
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
   
 
 
 
 
 
   
 
 
  
 
 
   
 
 
 
 
 
 
 
 
 
                                                                                                                       
 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 
 
 
 
 
 
  
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
                                                                                                                       
 
, disclosed 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 
 
 
   
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                                                                                                       
 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
APPENDIX F: CASE REPORT FORMS 
Case Report Forms will be kept under a separate cover, and are available upon request.  
 
 
                                                                                                                       Page 51 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
APPENDIX G: MINNESOTA LIVING WITH HEART FAILURE QUESTIONNAIRE 
 
Instructions for use: 
 
1. 
Patients should respond to the questionnaire prior to other assessments and interactions that may 
bias responses. You may tell the patient that you would like to get his or her opinion before 
performing other medical assessments. 
 
2. 
Ample, uninterrupted time should be provided for the patient to complete the questionnaire. 
 
3. 
The following instructions should be given to the patient each time the questionnaire is completed. 
 
 
a. 
Read the introductory paragraph at the top of the questionnaire to the patient. 
 
 
b. 
Read the first question to the patient - "Did your heart failure prevent you from living as you 
wanted during the last month by causing swelling, for example, in your ankles, legs"? Tell 
the patient, "If you did not have any ankle or leg swelling during the last month you should 
circle nought after this question to indicate that swelling was not a problem during the last 
month". Explain to the patient that if he or she did have swelling that was caused by a 
sprained ankle, or some other cause that was definitely not related to heart failure, he or she 
should also circle nought. Tell the patient, "If you are not sure why you had the swelling or 
think it was related to your heart condition, then rate how much the swelling prevented you 
from doing things you wanted to do and from feeling the way you would like to feel". In 
other words, how bothersome was the swelling? Show the patient how to use the 1 to 5 scale 
to indicate how much the swelling affected his or her life during the last month - from very 
little to very much. 
 
4. 
Let the patient read and respond to the other questions. The entire questionnaire may be read 
directly to the patient, being careful not to influence responses by verbal or physical cues. 
 
5. 
Check to make sure the patient has responded to each question and that there is only one answer 
clearly marked for each question. If a patient elects not to answer a specific question(s) indicate so 
on the questionnaire. 
 
6. 
Score the questionnaire by adding the responses to all 21 questions. In addition, physical (items 2, 3, 
4, 5, 6, 7, 12 and 13) and emotional (items 17, 18, 19, 20, and 21) dimensions of the questionnaire 
have been identified by factor analysis, and may be examined to further characterize the effect of 
heart failure on a patient's life. 
 
 
 
 
 
 
 
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Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 
 
LIVING WITH HEART FAILURE QUESTIONNAIRE 
 
These questions concern how your heart failure (heart condition) has prevented you from living as you wanted during the last 
month. The items listed below describe different ways some people are affected. If you are sure an item does not apply to you or is 
not related to your heart failure, then circle 0 (No) and go on to the next item. If an item does apply to you, then circle the number 
relating to how much it prevented you from living as you wanted. 
 
Did your heart failure prevent you from 
living as you wanted during the last 
month by: 
 
 
No 
Very 
little 
 
 
 
Very 
much 
1. 
Causing swelling, for example, in your 
ankles, legs? 
0 
1 
2 
3 
4 
5 
2. 
Making you sit or lie down to rest during the 
day? 
0 
1 
2 
3 
4 
5 
3. 
Making it difficult to walk about or climb 
stairs? 
0 
1 
2 
3 
4 
5 
4. 
Making it difficult to work around the house 
or in the garden? 
0 
1 
2 
3 
4 
5 
5. 
Making it difficult to go anywhere away from 
home? 
0 
1 
2 
3 
4 
5 
6. 
Making it difficult to sleep well at night? 
0 
1 
2 
3 
4 
5 
7. 
Making it difficult to have relationships or do 
things with your friends or family? 
0 
1 
2 
3 
4 
5 
8. 
Making it difficult to work to earn a living? 
0 
1 
2 
3 
4 
5 
9. 
Making your recreational pastimes, sports or 
hobbies difficult? 
0 
1 
2 
3 
4 
5 
10. Making your sexual activities difficult? 
0 
1 
2 
3 
4 
5 
11. Making you eat less of the foods you like? 
0 
1 
2 
3 
4 
5 
12. Making you short of breath? 
0 
1 
2 
3 
4 
5 
13. Making you tired, fatigued, or lacking in 
energy? 
0 
1 
2 
3 
4 
5 
14. Making you stay in hospital? 
0 
1 
2 
3 
4 
5 
15. Costing you money for medical care? 
0 
1 
2 
3 
4 
5 
16. Giving you side effects from medication? 
0 
1 
2 
3 
4 
5 
17. Making you feel you are a burden to your 
family or friends? 
0 
1 
2 
3 
4 
5 
18. Making you feel a loss of self-control in your 
life? 
0 
1 
2 
3 
4 
5 
19. Making you worry? 
0 
1 
2 
3 
4 
5 
20. Making it difficult for you to concentrate or 
remember things? 
0 
1 
2 
3 
4 
5 
21. Making you feel depressed? 
0 
1 
2 
3 
4 
5 
Copyright University of Minnesota 1986 
 
                                                                                                                       Page 53 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
APPENDIX H: EQ-5D QUALITY OF LIFE QUESTIONNAIRE 
 
                                                                                                                       Page 54 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 
 
                                                                                                                       Page 55 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
APPENDIX I: MULTIPOINT PACING PROGRAMMING GUIDANCE 
 
This appendix describes the suggested MultiPoint Pacing programming guidance.  
 
MPP consists of delivering two sequential LV pulses (LV1 and LV2) in addition to the standard RV 
pulse as follows: 
• RV first: RV
→
1
D
LV1
→
2
D
LV2 
• LV first: LV1
→
1
D
LV2
→

2
D
RV 
 
LV1 and LV2 configurations can be chosen from any of the 10 – 14 pacing vectors listed in Table 4.  
The timing delay D1 can be programmed from 5ms to 80ms with 5ms step 
The timing delay D2 can be programmed from 5ms to 50ms with 5ms step 
 
Table 4: 10 VectSelect™ pacing configurations available in the SJM Quadripolar CRT System.  D1 = Distal tip, M2 = 
middle ring 2, M3 = middle ring 3, P4 = proximal ring, RVC = RV coil 
Configuration # Vector (Cathode – Anode) 
1 
D1 – M2 
2 
D1 – P4 
3 
D1 – RVC 
4 
M2 – P4 
5 
M2 – RVC 
6 
M3 – M2 
7 
M3 – P4 
8 
M3 – RVC 
9 
P4 – M2 
10 
P4 – RVC 
11 
D1 - Can 
12 
M2 - Can 
13 
M3 - Can 
14 
P4 - Can 
 
The recommendation for vector selection can be summarized in 2 main points: 
 
• MultiPoint Pacing configuration with the most separated LV1 and LV2 vectors (distal and 
proximal) resulted in better performances (in terms of LVdP/dtmax improvement19, less 
dyssynchrony18, contractility15, 17 and stroke volume17) or at least not inferior performances (in 
terms of AoVTI) compared to BiV simultaneous or other tested programmed delays 
 
 
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Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
• MultiPoint Pacing configurations with minimum timing delays between RV-LV and between 
LV1-LV2 resulted in not inferior performances (in terms of LVdP/dtmax improvement, stroke 
volume and  AoVTI) compared to BiV Simultaneous or longer programmed delays 
 
Based on the results from Thibault et al19 and other acute and chronic studies summarized in the 2 points 
above, the following general MPP programming guidance is recommended: 
 
• MPP vector selection: Program the MPP feature to pace from the most distal and proximal 
electrode pairs (i.e., choose widest spacing: D1-M3 or D1-P4) 
• Timing Delays: use the minimum delays between LV1-LV2 and LV-RV of 5 ms 
 
 
As guidance, Table 5 lists 37 MPP vector combinations of the several options available for 
programming.  
 
The investigator can use this guidance to select the appropriate MPP configuration to be programmed.  
 
Within Table 5, the vector combinations are categorized in 6 groups based on cathode electrode 
selection for LV1 and LV2 pacing configuration. The pacing configurations (LV1 and LV2) can be 
interchanged.  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
                                                                                                                       Page 57 of 58 
 

Study Document No: SJM-CIP-10149 Ver. A 
Study Name: MultiPoint™ Pacing Post Market Study 
Clinical Investigational Plan  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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