Post-market Clinical Follow-up Study Evaluating the Efficacy and Safety of LifeVest in Real-life Settings in France
Conditions: Sudden Cardiac Death, Left Ventricular Dysfunction, Cardiac Event, Cardiac Arrythmias
Sponsor: Zoll Medical Corporation

90D0130: LifeVest Safety and Efficacy in Real 
Life Settings in France 
 
NCT03319160 
 
10/2016 
 

 
WEARIT France Protocol 
 
Structured according to EN ISO 14155:2011/AC:2011 
Study Title: 
Post-market clinical follow-up study evaluating the efficacy and safety of 
LifeVest in real-life settings in France 
Reference code 
WEARIT France 
Study type 
This post-market study is an observational study evaluating the efficacy and 
safety of the LifeVest in real-life settings. 
Investigators: 
Multicenter in France 
Sponsor: 
ZOLL 
121 Gamma Drive 
Pittsburgh, PA, 15238 
USA 
Coordinating Investi-
gators: 
Dr. Nicolas Combes, Clinique Pasteur, Toulouse, France (Chief investigator) 
Dr. Eloi Marijon, Hôpital Georges Pompidou, Paris, France 
Contract Research 
Organisation: 
ClinSearch, Malakoff, France wearit-france@clinsearch.net 
 
Version control: 
Amendment 2 version, dated October 10th, 2016 
All information in this protocol including attachments provided to you as investigator, potential investiga-
tor, co-investigator or committee member must be treated confidentially. The right to use this information 
is limited to you, your staff, members of the relevant committees or entitled authorities. The objectives 
and the content of this study, as well as its results, must be treated confidentially and may not be made 
available to third parties at any time before, during and after the study without written approval of the 
sponsor except to the extent necessary to get informed consent from patients. This applies to investiga-
tors and all supporting staff involved in the study. Transmission, duplication or use for publication is 
permitted only with the written agreement of the sponsor. 
This study protocol has been written in accordance with current applicable guidelines, in particular the 
ISO 14155:2011/AC:2011 was used as guidance for the structure of the protocol. 
Confidentially 
 
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Table of Contents 
1. 
General ................................................................................................................................................. 4 
1.1 Introduction .................................................................................................................................... 4 
1.2 Sponsor ......................................................................................................................................... 5 
1.3 Coordinating investigators and investigation site(s) ..................................................................... 5 
1.4 Rationale and Aims of the study ................................................................................................... 5 
2. 
Justification for the design of the investigation ..................................................................................... 6 
3. 
Risks and benefits of the investigation ................................................................................................. 6 
4. 
Objectives and hypotheses of the investigation ................................................................................... 6 
4.1 Objectives ...................................................................................................................................... 6 
5. 
Design of the investigation .................................................................................................................... 7 
5.1 General .......................................................................................................................................... 7 
5.1.1 Description of investigation .............................................................................................. 7 
5.1.2 Description of the measures to be taken to minimize or avoid bias, including 
randomization and blinding/masking ................................................................................ 7 
5.1.3 Main Definitions and criteria for evaluating efficacy and safety ....................................... 8 
5.1.4 Methods and timing for assessing, recording, and analysing variables. .......................... 9 
5.1.5 Any procedures for the replacement of subjects. ............................................................. 9 
5.2 Subjects ....................................................................................................................................... 10 
5.2.1 Inclusion criteria for subject selection. ........................................................................... 10 
5.2.2 Exclusion criteria for subject selection. .......................................................................... 10 
5.2.3 Criteria and procedures for subject withdrawal or discontinuation................................. 10 
5.2.4 Participating centers and point of enrolment: ................................................................. 10 
5.2.5 Personal Data and Data Protection ................................................................................ 11 
5.2.6 Data Handling and Record Keeping ............................................................................... 11 
5.2.7 Total expected duration of the clinical investigation: ...................................................... 12 
5.2.8 Expected duration of each subject's participation .......................................................... 12 
5.2.9 Number of subjects required to be included in the clinical investigation. ....................... 12 
5.2.10 Estimated time needed to select this number (i.e. enrolment period). ........................... 12 
5.3 Procedures .................................................................................................................................. 12 
5.3.1 Description of all the clinical-investigation-related procedures that subjects undergo 
during the clinical investigation....................................................................................... 12 
5.3.2 Description of activities performed by sponsor representatives (excluding monitoring) 14 
5.3.3 Any known or foreseeable factors that may compromise the outcome of the clinical 
investigation or the interpretation of results ................................................................... 14 
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5.4 Monitoring plan ............................................................................................................................ 14 
6. 
Statistical considerations and methods .............................................................................................. 15 
6.1 Sample size ................................................................................................................................. 15 
7. 
Procedures used for data review, database cleaning, and issuing and resolving data queries ......... 16 
7.1 Procedures for verification, validation and securing of electronic clinical data systems, if 
applicable. ................................................................................................................................... 16 
8. 
Amendments to the study protocol ..................................................................................................... 17 
9. 
Deviations from study protocol ........................................................................................................... 17 
10. Statements of compliance .................................................................................................................. 17 
10.1 Statement specifying that the clinical investigation shall be conducted in accordance with the 
ethical principles that have their origin in the Declaration of Helsinki ......................................... 17 
10.2 Statement specifying compliance with this International Standard and any regional or national 
regulations, as appropriate. ......................................................................................................... 17 
10.3 Statement specifying that the study protocol will be sent for comment to the EC ...................... 18 
10.4 Statement specifying the type of insurance that shall be provided for subjects, if appropriate. . 18 
11. Informed consent process .................................................................................................................. 18 
12. Adverse events, adverse device effects and device deficiencies ....................................................... 18 
13. Clinical Event Committee .................................................................................................................... 19 
14. Study limitations .................................................................................................................................. 19 
15. Quality control & Quality assurance .................................................................................................... 19 
16. Publication policy ................................................................................................................................ 19 
16.1 Statement indicating whether the results of the clinical investigation will be submitted for 
publication. .................................................................................................................................. 19 
16.2 Statement indicating the conditions under which the results of the clinical investigation will be 
offered for publication. ................................................................................................................. 19 
17. Bibliography ........................................................................................................................................ 20 
18. Signatures ........................................................................................................................................... 22 
 
 
 
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1. General 
1.1 
Introduction 
Sudden cardiac death (SCD) is a major cause of mortality throughout the world, accounting for approxi-
mately 300,000 deaths per year in the United States.1 SCD accounts for about 50% of all heart related 
deaths. Studies of patients who suffer SCD suggest that ventricular tachyarrhythmias are the dominant 
cause of this rapid terminal event although asystole due to heart block or sinus arrest can account for 
approximately 10-15% of the sudden deaths. However, these are most often electrical signs of a dying 
heart or electro-mechanical dissociation. The introduction of the implantable cardiac defibrillator (ICD) in 
the 1980s resulted in subsequent clinical trials showing a significant reduction in SCD with ICD therapy in 
at-risk cardiac patients. 
However,2-4 not all high-risk patients are candidates for the ICD for a variety of reasons. These are: 
transient nature of the high-risk for SCD; patients who do not meet current guideline indications for an 
ICD;5 high-risk cardiac patients who had previously received an ICD but had it removed because of 
complications or malfunction; patients who refuse an ICD; age-related factors; and a variety of other 
medical and ethical considerations. 
The use of automatic external defibrillator (AED) in acute cardiac arrest in the home, school, workplace, 
airplanes, and locations where there is a high density of people such as airports and sporting events has 
limited effectiveness in saving lives.6  Successful resuscitation with utilization of the AED is dependent on 
a short time-interval of just a few minutes between the witnessed cardiac arrest and the AED interven-
tion. The rate of successful resuscitation for out-of-hospital cardiac arrest with the AED with full recovery 
to a normal neurologic state is not more than 8%. 
The Wearable Cardioverter-Defibrillator (WCD) gives the patient’s physician time to assess the long-term 
arrhythmic risk in cases when the risk of life-threatening arrhythmias may only be temporary and to make 
appropriate plans.  Thus, the WCD can be used as a risk stratification tool. It provides continuous ar-
rhythmia monitoring, detection of life-threatening ventricular arrhythmias, and provides automatic defibril-
lation within a minute of detection of the potentially fatal ventricular tachyarrhythmia, unless the patient 
withholds the shock delivery. The safety and effectiveness of the WCD in saving lives has been docu-
mented in several publications including the first report in 1998,7 WEARIT/BIROAD study in 2004,8 and 
the US and German experience report in 2013.9-12 
Currently, there is only one approved WCD device on the world-wide market. This is the LifeVest®, 
produced by ZOLL, Pittsburgh, PA, USA. During the past few years, there has been an increased use of 
the WCD to more than 100.000 patients (personal information from ZOLL, Pittsburgh, PA, USA) having a 
spectrum of at-risk cardiac conditions, with use of the WCD averaging over 21 hours per day for periods 
of 1 to 6 months, or even longer. 
The WCD is a therapeutic option, listed along with implantable cardioverter-defibrillators (ICDs), in the 
ACC/AHA/ESC Guidelines for the Management of Patients with Ventricular Arrhythmias and the Preven-
tion of Sudden Cardiac Death13. It is also a Class I recommendation in the International Society for Heart 
and Lung Transplantation Guidelines for the Care of Cardiac Transplant Candidates14. 
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1.2 
Sponsor 
ZOLL  
121 Gamma Drive  
Pittsburgh, PA 15238 
USA 
1.3 
Coordinating investigators and investigation site(s) 
a) Name and address of the coordinating investigators. 
Dr. Nicolas Combes (Chief investigator) 
Clinique Pasteur, Toulouse, France 
 
Dr. Eloi Marijon (Coordinating investigator) 
Hôpital Georges Pompidou, Paris, France 
 
b) Name and address of the investigation site(s) in which the clinical investigation will be conducted. 
A list of investigational sites is maintained in the Trial Master File. 
c) Name(s) and address (es) of other institutions involved in the clinical investigation. 
N.a. 
1.4 
Rationale and Aims of the study 
LifeVest is a wearable cardioverter defibrillator (WCD) that has been recently approved for reimburse-
ment by the HAS. LifeVest has obtained coverage for 4 indications: (i) implantable cardiac defibrillator 
(ICD) removal due to cardiac device infections, (ii) a bridge to heart transplantation, (iii) in the early post-
MI period with left ventricular (LV) dysfunction (LVEF <30%), (iv) and a recent coronary revascularization 
with LV dysfunction (LVEF < 30%). There is no current comparator to LifeVest. In France, patients at 
high risk for sudden cardiac arrest (SCD) and waiting for heart transplant or ICD are hospitalized or 
discharged home without any particular ECG monitoring. LifeVest has been demonstrated to automati-
cally detect and terminate rapid ventricular arrhythmias. Introduction of LifeVest into the current patient 
management would definitely improve the clinical outcomes and benefit the patients with temporary risk 
of SCD. The use of LifeVest was shown to be effective in protecting patients against SCD in the United 
States. However, the clinical impact of using LifeVest in France remains unassessed. Therefore, this 
post-market study in France will provide efficacy and safety data for the reimbursement dossier renewal 
before September 2018. 
Identification and description of the investigational device 
The Wearable Cardioverter-Defibrillator (WCD) [LifeVest ®] is an external defibrillator, guided by an 
algorithm to detect ventricular tachyarrhythmic events, recorded by non-adhesive ECG electrodes (two 
leads). The WCD delivers up to 5 biphasic, high-voltage electrical shocks unless shock delivery is with-
held intentionally by a conscious patient. The WCD comprises also a continuous ECG monitoring sys-
tem, which transmits ECG data and other information (such as recorded arrhythmic events and alerts, 
details of the shock delivery episode, appropriate WCD use, daily wearing time, correct ECG monitoring, 
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battery charging and electrode connection/electrode noise) directly from the LifeVest to a central ECG 
and data server in the USA, Pittsburgh. The patient’s physician is able to check the history of recorded 
arrhythmic events, details of the shock delivery episode, appropriate WCD use, daily wearing time and 
correct ECG monitoring via a password protected web-accessed to the ECG and data server. 
The WCD has CE certification and is FDA approved since 2002. 
2. Justification for the design of the investigation 
In general, patients considered having high, long term risk of sudden arrhythmic death (SCD) receive 
implantable cardioverter-defibrillators (ICD). 
Risk assessment in patients that are candidates for ICD therapy is difficult and time consuming, though. 
In order to bridge the time period necessary to identify the patient who will need an ICD or in whom ICD 
therapy is unnecessary, a tool is mandatory that protects the patient during this time period from dying 
suddenly and to provide continuous ECG monitoring which is necessary for the risk assessment.  
The device that is able to fulfill these characteristics is the wearable cardioverter-defibrillator (WCD). The 
WCD has CE certification and is FDA approved since 2002. Currently, only observational studies with the 
WCD are available. Prospective randomized studies in patients that are already considered carrying a 
high risk of sudden death are difficult, if not impossible to perform, mainly due to ethical reasons. 
Currently available data with the WCD demonstrate that the WCD is safe and effective. Detected ventric-
ular tachyarrhythmias are terminated with the first shock in 98% of all cases; inappropriate defibrillator 
discharges (not occurring on sustained VT or VF) may occur in <1% per month of WCD wearing9. 
3. Risks and benefits of the investigation 
Patients participating in the post-market clinical follow-up study in France will have neither additional 
risks due to participation in the study compared to clinical routine care nor individual benefits, because of 
its purely observational character. 
4. Objectives and hypotheses of the investigation 
4.1 
Objectives 
a) Primary Objective: 
1.  Appropriate shocks as measured by shocks delivered for adjudicated sustained ventricular tachy-
cardia (VT) or ventricular fibrillation (VF) episodes.  
2.  Inappropriate shocks as measured by shocks delivered for all episodes that are not adjudicated 
sustained VT or VF episodes.  
The frequency and rate of appropriate and inappropriate shocks will be measured. The risk of receiving 
an inappropriate shock will be analyzed. The risk of not receiving appropriate shocks when necessary 
will also be analyzed.  
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b) Secondary Objectives 
1.  Overall survival as measured by the ratio of the number of patients that are alive at the end of the 
use of the WCD to the total population of patients prescribed the LifVest. 
2.  Quality of life relative to health state as measured through the administration of a patient quality of 
life survey.  This survey has been used previously in a published study of patient quality of life. 
5. Design of the investigation 
5.1 
General 
5.1.1 
Description of investigation 
France post marketing protocol is an observational study of patients with a prescribed WCD during the 
time of risk assessment for future potential ICD therapy. Patients who are prescribed a WCD will be 
asked to participate in the prospective cohort of the study. Patients who have already completed use of 
LifeVest before start of the study in the corresponding study site can also be asked to consent for use of 
their clinical data to be included in the retrospective cohort of the study. The retrospective cohort of 
patients will be analysed separately compared to prospectively included study patients for any variables 
that are not available for both cohorts, such as the patient survey. Mean WCD wearing time is anticipated 
to be three months. However, some indications for wearing the WCD may be longer (up to 6 months) or 
shorter (only one month). For patients who are listed for heart transplantation, the wearing time is sched-
uled until heart transplantation is performed, or an ICD will be implanted.  
5.1.2 
Description of the measures to be taken to minimize or avoid bias, including randomization 
and blinding/masking 
There is no randomization of patients enrolled into the study. All consenting patients with a routinely 
prescribed WCD in the study participating centers will be evaluated, regardless of the length of WCD 
wearing, including patients who have already completed use of LifeVest before start of the study in the 
corresponding study site.  
The selection bias is limited by the protocol comprehensiveness. There will be no selection, the study will 
be proposed to all patients receiving LifeVest. In addition, all centres performing implantation of the 
device will be asked to participate. “Non-participants” will be described. 
The attrition bias is also limited (non-existent) as at the end of LifeVest utilization, all material provided to 
the patient should be returned systematically. Furthermore, the patients follow- up is completely identical 
to the routine clinical practice. This means that we don’t expect to have any difference between the data 
collected retrospectively and those collected prospectively. However, only patients included prospectively 
will be asked to complete the quality of life questionnaire.  
The prospective cohort of patients will be analysed separately for variables not available for the patients 
in the retrospective cohort, such as the patient survey. 
Patients who have worn WCD for at least 8 days (i.e. longer than 1 week) will be evaluated separately in 
an “on-treatment” efficacy analysis, because it is assumed from clinical experience that the WCD wear-
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ing time will only for those patients be long enough to reliably compare their long-term outcome in a 
cohort of patients who have had the WCD for several months (even six or more months in some indica-
tions).  
5.1.3 
Main Definitions and criteria for evaluating efficacy and safety 
Efficacy will be evaluated using the success rate of appropriate shocks. In order for a shock to be appro-
priate, it must be administered while a patient is experiencing either sustained VT or VF. Otherwise, the 
shock is inappropriate. 
The risk associated with the use of LifeVest will be assessed in terms of inappropriate shocks. Any shock 
administered to a patient who is not experiencing either VF or sustained VT at the time of administration 
is an Inappropriate Shock. Even if the patient experiences VT or VF and the condition resolves by itself 
or bystanders intervention just prior to administration of the shock, it would be classified as Inappropriate. 
The classification of individual shocks into the categories of Appropriate and Inappropriate is quite un-
ambiguous, so long as the ECG signal is of sufficient strength to be able to accurately determine the 
heart rhythm. If the signal is obscured by noise and it is not possible to unambiguously determine the 
rhythm the shock is generally categorized as Inappropriate, because the noise is generally the cause of 
the false detection. 
All appropriate and inappropriate WCD shock deliveries, as well as VT/VF events will be recorded and 
analyzed by means of precise ECG recording, provided the VT/VF exceeds the programmed rate 
threshold for event detection by the WCD. ECG recordings are retrievable from a central server to which 
all WCD data and ECGs will be transmitted automatically. Similarly, all shock-withhold VT/VF events or 
VT/VF events that terminated spontaneously will be recorded and counted. All potential bradyarrhythmic 
or asystole events will be recorded. The device is programmed to record events which are slower than 
20 beats per minute or have a QRS amplitude less than 200 microvolts (peak to peak), provided the 
patient does not respond to alarms. 
There will be assessment of all ventricular tachyarrhythmic events, either treated by WCD-shock or with 
shock withheld by the patient. Furthermore, the assessment of the overall outcome (death) and of clinical 
events (cardiac and non-cardiac), such as hospitalization, heart failure status, ischemic events, ICD 
implantation, Pacemaker implantation, surgical interventions (CABG or valve replacement) during the 
period of WCD wearing. 
The assessment and classification of the type of arrhythmic events will be carried out by an independent 
Clinical Event Committee (CEC) by evaluating the ECG data provided by the WCD during wearing and 
recorded on the central ECG and WCD data server. Members of the CEC are listed in Appendix A. 
Events will be separately reviewed by at least two CEC members. A third reviewer will review events for 
which there is not agreement between the first two reviews. 
Primary parameters to be assessed during follow-up: 
1. Arrhythmic (VT/VF) events and type of event 
2. Appropriateness of shock delivery 
3. All-cause mortality 
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4. Hospitalization  
5. Cardiac events  
6. Non-cardiac events (e.g. stroke, renal failure) 
Secondary parameters to be assessed: 
1. Analysis of primary outcome parameters (see above) in sub-groups according to their clinical pro-
file at baseline (age, gender, disease etiology, type of inherited arrhythmia syndrome, etc.) 
2. LV-EF at time of WCD end of use  
3. Type and character of arrhythmic events 
4. Type and character of cardiac events 
5.1.4 
Methods and timing for assessing, recording, and analysing variables. 
During wearing of the WCD the responsible physician in the participating centers is able to check the 
event history, appropriate use of the WCD, compliance of the patient and potential complications of the 
WCD by means of a password protected access to the central server. The patient’s ECGs in case of 
detection of arrhythmias and all wearing data are automatically transmitted from the WCD to the server. 
After an arrhythmic event, the patient is instructed to inform not only the emergency ambulance but also 
the responsible physician and the ZOLL Company about the event.  The responsible physician is able to 
analyze the event and will document all available data in the e-CRF system. The ECG recording during 
the event is also stored and retrievable from the server. 
All arrhythmia and clinical events as well as the clinical status (including measurement of LV-EF) of the 
patient during the WCD wearing period are documented in the e-CRF by the responsible physician. All 
arrhythmia episodes detected by the WCD will be reviewed and evaluated by an independent Clinical 
Event Committee. All patient data from France post marketing study will be gathered by CRI on e-CRFs. 
After the first month of use, all participating patients will be surveyed confidentially to assess their quality 
of life related to their health status and use of the WCD. Because patients who are prescribed a LifeVest 
are typically in an acute episode of care involving a hospitalization (e.g., ICD explant procedure due to 
infection, post-MI,etc.), the Science Committee felt that a general population QoL survey, such as the 
SF-12 or EQ5D would not be as useful in this study. Other more relevant QoL instruments that have 
been validated are generally condition-specific are not applicable across the entire study population. 
Therefore, a patient survey developed specifically for LifeVest patients will be used for this study. This 
instrument has been used in published, peer reviewed research.16 Specific detail on survey content can 
be found in Section 6.2 of the analysis description. Study coordinators will administer the survey.  Pa-
tients who have not responded to the initial survey request will be reminded to participate approximately 
seven days after the initial invitation. 
5.1.5 
Any procedures for the replacement of subjects. 
The investigator is encouraged to try to enrol all patients to whom the WCD has been prescribed (provid-
ed informed consent is given by the patient). This includes also those patients who have already com-
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pleted use of LifeVest before start of the study in the corresponding study site. No replacement of pa-
tients is planned because of the observational nature of the study. 
5.2 
Subjects 
Study population will consist of patients at high risk for SCD and receiving LifeVest as a bridge therapy to 
heart transplantation, to ICD or to improvement of LV function. 
5.2.1 
Inclusion criteria for subject selection. 
 
Patients receiving a LifeVest prescription in clinical routine for the following indications: 
a) implantable cardiac defibrillator (ICD) removal due to cardiac device infections, 
b) a bridge to heart transplantation, 
c) in the early post-MI period with left ventricular (LV) dysfunction (LVEF <30%), 
d) a recent coronary revascularization with LV dysfunction (LVEF < 30%). 
 
Patients who have given their consent to participate. 
This includes also those patients who have already completed use of LifeVest before start of the study in 
the corresponding study site (retrospective inclusion). 
5.2.2 
Exclusion criteria for subject selection. 
There are no exclusion criteria for this study other than if the patient does not provide informed consent 
to participate.  All patients prescribed a LifeVest will be invited to participate. All patients that were previ-
ously prescribed a LifeVest before the start of this study will also be invited to participate by allowing 
access to their retrospective medical information. 
5.2.3 
Criteria and procedures for subject withdrawal or discontinuation. 
A low rate of lost-to-follow up is expected since the LifeVest is rented to patients and should be returned 
to ZOLL by the end of the prescription. In case a patient is lost to follow up, the CepiDC a French data-
base for automated coding of causes of death, will be interrogated to report if the patient is dead or alive, 
and if dead the cause of death. 
All patients enrolled into the study can withdraw at any time regardless of the reason. Patients may 
withdraw consent for use of data and exit the study at any time without prejudice to further treatment. 
Patients who have given consent to participate in the study but had the WCD for less than 8 days will be 
evaluated separately, but not withdrawn.  
5.2.4 
Participating centers and point of enrolment: 
Participating centers: The study will start along with the early-stage marketing of LifeVest. All approved 
ICD implant centers in France, who are using LifeVest in their routine practice, will be invited to partici-
pate to the study. A registry will be created to collect geographic information and type of centers (pub-
lic/private) refusing to participate. The reason for refusal will be reported in the registry. This registry will 
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be maintained by ClinSearch. Approved ICD implant centers in France who are not using LifeVest in their 
routine practice will be documented in the registry by ZOLL. 
Participating patients: All patients in participating centers receiving LifeVest, satisfying the inclusion and 
exclusion criteria and consenting to participate will be consecutively included in the study. ZOLL will 
maintain a registry of all patients screened but not included in the study, to verify the representativeness 
of patients by the end of the study. It will be listed in this registry all patients meeting the selection criteria 
and having received a LifeVest. Demographics, indication and the reason for non-inclusion will be col-
lected. 
Start of documentation is at the time when the patient signs and dates the informed consent form. Data 
from medical history will be documented. 
5.2.5 
Personal Data and Data Protection 
All data obtained in the context of the observational study are subject to data protection. This applies to 
patients' data as well as to investigators' personal data which may be included in any database of the 
sponsor or the CRO.  
The investigating physicians shall take care that patient documents (e.g. copies of reports on special 
findings) transmitted to the CRO or the sponsor contain no names, but only the year of birth and a rele-
vant patient study number. The storage of data for statistical analysis shall likewise be performed only 
under the patient’s study number. 
5.2.6 
Data Handling and Record Keeping 
a) Completion of Case Report Forms 
 
All medical data in this observational study are to be recorded directly in the e-CRFs. Documen-
tation on paper will be restricted to exceptional circumstances only.  
The investigator must ensure the accuracy, completeness and timeliness (and legibility in case of 
documentation on paper) of data. 
 
b) Archiving 
 
The investigator must maintain confidential all study documentation, and take measures to pre-
vent accidental or premature destruction of these documents. The investigator has to retain the 
study documents (i.e. investigator site file) after the completion or discontinuation of the study for 
the time period as required by national legislation. This especially applies to patients' signed in-
formed consent forms and the patient identification list. The patient identification list will be de-
stroyed at the end of the archiving period which is mandatory by national law as stated above. 
The investigator must notify the sponsor prior to destroying any essential study documents within 
the specified period following completion or discontinuation of the study. 
 
c) Confidentiality 
 
All information disclosed or provided by the sponsor (or any company / institution acting on his 
behalf), or produced during the study, including, but not limited to, the clinical study protocol, the 
e-CRFs and the results obtained during the course of the study, is confidential. The investigator 
or any person under his/her authority agrees to undertake to keep confidential and not to disclose 
the information to any third party without prior written approval of the sponsor. The sub-
investigators shall be bound by the same obligation as the investigator. The investigator shall in-
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form the sub-investigators of the confidential nature of the study. Both, the investigator and the 
sub-investigators shall use the information solely for the purposes of the study, to the exclusion of 
any use for their own or for a third party's account. 
 
 
5.2.7 
Total expected duration of the clinical investigation: 
The patient recruitment period will start along with the early-stage marketing of LifeVest. The inclusions 
will last for 2 years. The whole study duration will be of 24 months. Collected data will be analyzed and 
made available for the reimbursement dossier renewal (before April 2019). And final results will be sub-
mitted by the end of the study. 
5.2.8 
Expected duration of each subject's participation 
The patient will be included after being prescribed a LifeVest, and will be participating until LifeVest 
withdrawal. According to published data, the mean duration of participation will be about 3 months, 
depending on the indication. Accordingly patient participation will be about 3 months according to the 
indication. 
5.2.9 
Number of subjects required to be included in the clinical investigation. 
It is estimated that approximately 1,700 patients will receive LifeVest in clinical routine between May 
2015 and April 2018 (300 patients first year, 520 patients second year and 880 patients third year of 
marketing) in France. After obtaining all regulatory approvals, the study is expected to start in August 
2016. Between August 2016 and April 2018, 1,110 patients would receive LifeVest in clinical routine. 
Considering a participation rate of 50% related to centers participating in the study and consent given, 
around 550 patients will participate in this study. 
5.2.10 Estimated time needed to select this number (i.e. enrolment period). 
Enrollment period will last 20 months from March 2017 to December 2018. The period of clinical follow-
up will take about 3 months of wearing the WCD, depending on several factors, e.g. on the indication. 
5.3 
Procedures 
5.3.1 
Description of all the clinical-investigation-related procedures that subjects undergo during the 
clinical investigation 
Patients will not experience any particular tests or procedures that are not part of the clinical routine of 
adequate patient treatment according to their underlying disease. Participation in France Post Marketing 
Study does not require additional laboratory testing. 
5.3.1.1 
Informed Consent 
Before entering data into the clinical study, each patient shall be informed about the use of their data in 
the clinical study according to the requirements of data privacy regulations, i.e. consent to processing 
medical data of the patient to a central scientific database. Sufficient time will be allowed for the infor-
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mation to be read and for questions to be asked. The patient must be told that withdrawal of informed 
consent to use their data in the clinical study is possible at any time, without stating a reason and without 
prejudice, and does not cause any disadvantages. 
5.3.1.2 
Medical History 
 
Baseline demographic data  
 
Medical history of: 
 Coronary artery disease (CAD) 
 Myocardial infarction 
 PCI 
 CABG 
 Dilated Cardiomyopathy 
 Hypertrophic Cardiomyopathy 
 Heart Failure (NYHA II-IV)  
 Hospitalization for congestive heart failure 
 Cardiac arrest (CA)  
 Valve disease (aortic and mitral) 
 Stroke 
 Syncope  
 Atrial Fibrillation (A-Fib)  
 Inherited Arrhythmia Syndrome  
 Pacemaker Implantation  
 ICD Implantation  
 Congenital Heart Disease 
 Renal Disease 
5.3.1.3 
Symptoms and current status 
 Comorbidities 
 Concomitant treatments 
 Physical examination 
 Current cardiovascular symptoms 
 Estimation of the degree of heart failure (NYHA Class I-IV) 
 LV-EF at time of enrolment 
 Indication for LifeVest and duration of prescription 
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5.3.1.4 
At LifeVest end of use 
 The reason for end of use (death, ICD implantation, heart transplantation, LV function improve-
ment, patient’s wish, etc) 
 Reports on serious adverse events since the inclusion (ie: cardiac and non-cardiac death, hospi-
talization, heart surgery/revascularization, arrhythmic events and other cardiac events) 
5.3.1.5 
Data extracted from the LifeVest Network 
 Wear time (hours per day) 
 Description of all delivered treatments and associated ECG 
 Description of asystole, detected arrhythmia with no treatment (e.g., short run of VT) and associ-
ated ECGs 
 Information about any technical malfunctions and misuses, if applicable 
5.3.1.6 
Clinical Laboratory Tests 
Only data of laboratory tests will be documented that have been performed as routine procedures ac-
cording to clinical routine indications. All laboratory tests will be performed independently from participa-
tion in the France post marketing study. 
5.3.2 
Description of activities performed by sponsor representatives (excluding monitoring) 
Personnel of the ZOLL company will instruct and train the patients in the correct use of the WCD. ZOLL 
personnel are continuously controlling the correct use and function of the WCD during WCD wearing 
time. They automatically replace the WCD in case of technical problems with the device. These activities 
by ZOLL company personnel are part of their routine obligations accompanying the use of the WCD 
(LifeVest ®), and are independent of this study. 
5.3.3 
Any known or foreseeable factors that may compromise the outcome of the clinical investiga-
tion or the interpretation of results 
Only patients will receive the WCD if they are considered by their physician to be able to handle and use 
the WCD correctly. 
5.4 
Monitoring plan 
Authorized, qualified representatives of the sponsor will accomplish on-site monitoring during the study. 
The accuracy and completeness of core CRF data of a sufficient number of patients will be checked on 
site against source documents. Details will be given in a risk based monitoring plan. 
Quality management will assure that medical data are subject of continuous plausibility checks and data 
cleaning. The primary outcome parameters consist of follow-up and arrhythmic event raw data which are 
directly transmitted in clinical routine from the WCD device to a central database to which the treating 
physician has access via an internet platform enabling him to review any potential arrhythmic event 
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detected by the device. These data are not modified by human interactions, thus being per se valid and 
do not require source data verification. 
6. Statistical considerations and methods 
This is a nonrandomized, multicenter observational study.  All consecutive LifeVest patients will be asked 
to participate.  Demographic data will reported on all consenting patients.  Thus, all patients in this study 
will receive LifeVest treatment.  Descriptive statistics will be used to report major clinical characteristics 
of consenting patients, and incidence and frequency of appropriate and inappropriate shocks. 
For the overall survival rate calculation, the population of reference will correspond to the total number of 
patients enrolled who were prescribed the LifeVest. 
Standard methods will be used to calculate adjusted survival rates.  Kaplan Meier survival curves will be 
used to report total mortality and wear time. The time to event and census are defined here after. 
All reasons for therapy discontinuation will be reported in tabular form.  
Event 
Decision 
Event date or census date 
Occurrence of the event  
Not censored 
Date of the event occurrence  
No event and patient followed 
until the study end  
Censored 
Date of WCD withdrawal 
Lost-to-follow-up  
Censored 
Date of the last visit or last contact 
 
It is common to use a significance threshold of 5%. This will be applied in this study. 
6.1 
Sample size  
This study is a post-inscription study designed to describe all patients treated by LifeVest in a compre-
hensive way. Thus this study will be proposed to all patients receiving LifeVest.  
No sample size calculation has been planned. All patients accepting to participate will be included. 
The LifeVest device is commercialized in France since approximatively 1 year, the number of subjects 
has been estimated based on the sales and the foreseen participation rate. 
It is estimated that approximately 1,700 patients will receive LifeVest in clinical routine between May 
2015 and April 2018 (300 patients first year, 520 patients second year and 880 patients third year of 
marketing) in France. After obtaining all regulatory approvals, the study is expected to start in August 
2016. Between August 2016 and April 2018, 1,110 patients would receive LifeVest in clinical routine. 
Considering a participation rate of 50% related to centers participating in the study and consent given, 
around 550 patients will participate in this study. 
According to most recent data, the frequency of shock delivery is expected to be between 1% and 5 %. 
In this present study, 550 patients will allow for assessing a treatment rate ranging between 1%-5% with 
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an absolute precision < 2% (0.8 for 1% and 1.8 for 5%). Therefore, this sample size would be sufficient 
to answer the research questions.  
6.2 
Patient Survey  
All survey data will be included in the analysis as long as the patient answered at least one item on the 
survey. In other words, no exclusion criteria will be used based on survey response completeness. 
Overall survey statistics will be presented for the survey data results including overall response rate, item 
level response rate, Survey responses for all items will be analyzed and reported. The majority of the 
items on the survey ask the patient to indicate their agreement using the 5-point Likert agreement re-
sponse scale (Strongly agree, Agree, Neither agree not disagree, Disagree, Strongly disagree) with the 
following topics regarding their use of the LifeVest: 
• 
Ease of use 
• 
Peace of mind 
• 
Worry 
• 
Worry about being alone 
• 
Confidence in physician knowledge about managing condition 
• 
Sleep quality 
• 
Confidence returning to activities of daily living (screened) 
• 
Confidence to exercise or perform cardiac rehabilitation (screened) 
• 
Improved self-care 
• 
Taking condition seriously 
• 
Family and caregiver peace of mind 
• 
Family and caregiver sleep quality 
 
Patient information collected on the survey will include basic demographic information for subgroup 
analyses as well as patient self-reported health status from the SF-12. Consistent with previous publica-
tion, survey responses for items using the 5-point Likert agreement response scale will be presented as 
the top two box or the percentage of patients that either Strongly agree or Agree with the statement in 
the survey item. 
7.  Procedures used for data review, database cleaning, and issuing and resolv-
ing data queries 
All medical data in this study are to be recorded directly in an e-CRF system (MARVIN) running on a 
single central server. The e-CRF system is available for all participants based on individual access codes 
(numerical code) according to their duties and responsibilities in the project 24 hours/7 days. The investi-
gator must ensure the accuracy, completeness and timeliness of data. 
Plausibility rules and alert levels for parameters are programmed in the e-CRF system ensuring an 
optimized level of first-line data quality. Manual data queries based on repetitive statistical analyses will 
additionally improve data completeness and quality. 
7.1 
Procedures for verification, validation and securing of electronic clinical data systems, if 
applicable. 
The e-trial management system MARVIN used in this study is a GCP and 21 CFR 11 compliant EDC and 
CDM system based on the CDISC ODM data standard. 
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Any change or correction to an e-CRF will automatically be tracked (Audit Trail), recording the account ID 
of the person being logged in as well as the time stamp of the change. The e-CRF system will not accept 
changes without given reason. The history of changes to a single item including original entries is always 
available.  
8. Amendments to the study protocol 
Any amendment to the study protocol must be approved by the Sponsor. A study protocol amendment 
may not be implemented until after it has been sent for comment to the IEC responsible for the principal 
investigator. Since the study comprises only procedures routinely undertaken, no immediate implementa-
tion of changes necessary for patient safety are expected. 
9. Deviations from study protocol 
Deviations from the study protocol are not to be expected, because this is only an observational study 
without predefined procedures: 
10. Statements of compliance 
10.1 Statement specifying that the clinical investigation shall be conducted in accordance 
with the ethical principles that have their origin in the Declaration of Helsinki  
The procedures set out in this study protocol are designed to ensure that the Sponsor and the Investiga-
tor abide by the principles of ISO 14155:2011 and the Declaration of Helsinki (latest version) concerning 
the conduct, evaluation and documentation of the clinical investigation. 
10.2 Statement specifying compliance with this International Standard and any regional or 
national regulations, as appropriate. 
The study procedures will also be performed adhering to the local legal conditions and regulations and to 
the applicable regulatory requirements Each Investigator must confirm this by signing the study protocol. 
The text of the applicable version of the Declaration of Helsinki will be provided by the Sponsor. 
This study is within the scope of Chapter IX, relating to the treatment of personal data for research pur-
pose in the field of health, of the French Law No. 2004-801 of 6 August 2004 amending laws No. 78-17 
of 6 January 1978 and No. 94-548 of 1 July 1994 relating to information technology, files and freedoms. 
The protocol will be submitted for review to the Advisory Committee on Information Processing in Re-
search in the Field of Health (Comité Consultatif sur le Traitement de l’Information en Matière de Re-
cherche dans le Domaine de la Santé - CCTIRS), then for approval to the French Data protection Author-
ity (Nationale Informatique et Liberté - CNIL) before any data collection.  
The participating investigators receiving financial compensation for the conduct of the study, the protocol 
and the financial agreement will be sent for review to the French Medical Council (Conseil National de 
l’Ordre des Médecins - CNOM) in accordance with the Article L.4113-6 of the French Code of Public 
Health. 
 
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10.3 Statement specifying that the study protocol will be sent for comment to the EC  
In accordance with the French legislation (Articles L.1121-1 and following of the French Code of Public 
Health), given that the physician-patient relationship is not changed and that no examination or consulta-
tion is specific to the observatory, the study will not be subject to the opinion of a French Ethics Commit-
tee (Comité de Protection des Personnes, CPP). 
10.4 Statement specifying the type of insurance that shall be provided for subjects, if appro-
priate. 
No insurance is required because this study is purely observational. All medical treatment is decided and 
provided in clinical routine. The clinical routine insurance of the product will therefore cover all risk. 
11. Informed consent process 
Before entering into the study, information about the intention and nature of the study will be provided to 
each potentially eligible patient by the prescribing responsible physician of each participating center. 
Each patient will be informed about the use of his medical data in the clinical study according to the 
requirements data privacy regulations, i.e. consent to processing medical data of the patient to a central 
scientific database. Sufficient time will be allowed for the information to be read and for questions to be 
asked. Only subjects able to give their informed consent will be enrolled in this clinical study. 
The patient must be told that withdrawal of informed consent to use their data in the clinical study is 
possible at any time, without stating a reason and without prejudice, and does not cause any disad-
vantages. 
The patient will in any case receive detailed training on the use of the WCD by the ZOLL Company 
personnel. This will give the patient the opportunity to raise further questions about the device and data 
handling to the ZOLL personnel and the responsible physician. 
12. Adverse events, adverse device effects and device deficiencies 
Serious adverse events, i.e. cardiac and non-cardiac death, hospitalization, heart surgery, will be docu-
mented in the e-CRF. Adjudication of SAEs and second assessment of safety aspects will be performed 
by the sponsor.  
Non-serious adverse events and adverse device effects as well as serious adverse device effects and 
other device deficiencies, as defined by good clinical practice and other relevant regulations, will be 
reported according to clinical routine procedures. For all legal reporting requirements, the sponsor re-
mains fully responsible in the frame of his regular routine processes of reporting concerning his market 
authorization. Therefore, the sponsor’s assessment and reporting responsibilities are not affected by this 
study. 
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WEARIT France, an ZOLL study 
 
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13. Clinical Event Committee 
The Clinical Event Committee will be composed of three experts. These experts will adjudicate, in an 
independent blinding manner, the occurrence of treatments and their classification (appropri-
ate/inappropriate shocks), and will review the detected arrhythmia where no treatment was given. 
14. Study limitations 
Study limitations include mainly the observational nature of the design and the lack of control group. 
The number of included patients could also be a limitation. As the study will start along with the early-
stage launch of LifeVest, the number of patient inclusions will depend on the commercialization activities 
and is expected to increase over time. 
15. Quality control & Quality assurance 
The accuracy and completeness of the CRF entries will be monitored and checked against source doc-
uments according to a risk based monitoring plan. 
Quality control procedures will be implemented to ensure the relevance and consistency of datasets. 
16. Publication policy 
16.1 Statement indicating whether the results of the clinical investigation 
will be submitted for publication. 
The results of the study will be published by the principal investigator and other co-authors. The principal 
investigator will communicate the results of the observational study to the investigators. Prior to the 
communication or any publication, the sponsor will have the opportunity to have complete insight into the 
results and publication and to issue a statement. All relevant measures for transparency of clinical trials, 
and especially the recommendations of the editors of the major medical journals, will be met. 
16.2 Statement indicating the conditions under which the results of the 
clinical investigation will be offered for publication. 
The results of this study will be published by the principal investigator, but are the property of the spon-
sor. All publications (manuscripts, abstracts or other modes of presentation) shall be published freely but 
not before the sponsor had the opportunity to review and issue a statement, in advance of submission. 
Co-authorship with any sponsor personnel will be discussed and mutually agreed upon before submis-
sion of a manuscript to a publisher. 
 
 
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17. Bibliography 
1) Myerburg RJ. Sudden cardiac death: exploring the limits of our knowledge. J Cardiovasc 
Electrophysiol 2001;12:369-81. 
2) Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for 
congestive heart failure. N Engl J Med 2005;352:225-37. 
3) Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients 
with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator 
Implantation Trial Investigators. N Engl J Med 1996;335:1933-40. 
4) Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with 
myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877-83. 
5) Epstein AE, Dimarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 Guidelines for device-based 
therapy of cardiac rhythm abnormalities. Heart Rhythm 2008;5:e1-62. 
6) Bardy GH, Lee KL, Mark DB, et al. Home use of automated external defibrillators for sudden cardiac 
arrest. N Engl J Med 2008;358:1793-804. 
7) Auricchio A, Klein H, Geller CJ, Reek S, Heilman MS, Szymkiewicz SJ. Clinical efficacy of the 
wearable cardioverter-defibrillator in acutely terminating episodes of ventricular fibrillation. Am J 
Cardiol 1998;81:1253-6. 
8) Feldman AM, Klein H, Tchou P, et al. Use of a wearable defibrillator in terminating tachyarrhythmias 
in pati ents at high risk for sudden death: results of the WEARIT/BIROAD. Pacing Clin 
Electrophysiol 2004;27:4-9. 
9) Chung MK, Szymkiewicz SJ, Shao M, et al. Aggregate national experience with the wearable 
cardioverter-defibrillator: event rates, compliance, and survival. J Am Coll Cardiol 2010;56:194-203. 
10) Klein HU, Meltendorf U, Reek S, Smid J, Kuss S, Cygankiewicz I, Jons C, Szymkiewicz S, Buhtz F, 
Wollbrueck A, Zareba, W, Moss,AJ. Bridging a temporary high risk of sudden arrhythmic death. 
Experience with the Wearable Cardiverter Defibrillator (WCD). Pacing Clin Electrophysiol 2010; 
33:353-67 
11) Adler A, Halkin A, Viskin S. Wearable Cardioverter-Defibrillators. Circulation 2013;127:854-860 
12) Klein HU, Goldenberg I, Moss, AJ. Risk stratification for implantable cardioverter defibrillator thera-
py: the role of the wearable cardioverter-defibrillator. Eur Heart J 2013; doi: 
10.1093/eurheartj/eht167 
13) Zipes DP, Camm AJ, Borggrefe M, Buxton AE, Chaitman B, Fromer M, Gregoratos G, Klein G, 
Moss AJ, Myerburg RJ, Priori SG, Quinones MA, Roden DM, Silka MJ, Tracy C. ACC/AHA/ESC 
2006 guidelines for management of patients with ventricular arrhythmias and the prevention of 
sudden cardiac death: a report of the American College of Cardiology/American Heart Association 
Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing 
Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the 
Prevention of Sudden Cardiac Death). Europace 2006; 8 :746 – 837. 
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14) Gronda E, Bourge RC, Costanzo MR, Deng M, Mancini D, Martinelli L, Torre-Amione G. Heart 
Rhythm Considerations in Heart Transplant Candidates and Considerations for Ventricular Assist 
Devices: International Society for Heart and Lung Transplantation Guidelines for the Care of Cardiac 
Transplant Candidates—2006. J Heart Lung Transplant 2006;25(9):1043-1056. 
15) Al-Khatib SM, Hellkamp A, Curtis J, Mark D, Peterson E, Sanders GD, Heidenreich, PA, 
Hernnandez AF, Curtis LH, Hammill S. Non-evidence-based ICD implantations in the United States. 
JAMA 2011;305:43-49. 
16) Whiting JT, Simon M. Health and lifestyle benefits resulting from wearable cardioverter defibrillator 
use. J Inn Card Rhythm Mgmt 2012;1-2. 
 
 
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APPENDIX A. Clinical Evaluation Committee Members 
Pr Pascal Defaye 
pdefaye@chu-grenoble.fr 
Responsable de l'Unité de Rythmologie 
Clinique de cardiologie 
CHU de Grenoble site Nord - Hôpital Albert Michallon 
Boulevard de la Chantourne - CS10217 
38043 GRENOBLE CEDEX 9 
FRANCE 
 
Dr. Daniel Gras 
DANGRAS@aol.com 
Nouvelles Cliniques Nantaises, 
Rue Eric Tabarly, 44277 Nantes 
FRANCE 
 
Pr Nicolas Sadoul 
n.sadoul@chu-nancy.fr 
Service de cardiologie 
CHU de Nancy - Hôpital de Brabois 
Rue du Morvan 
54511 VANDOEUVRE-LÈS-NANCY CEDEX 
FRANCE 
 
 
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STATISTICAL ANALYSIS PLAN 
OF 
WEARIT France 
Post-market clinical observational study evaluating the efficacy and safety of LifeVest 
in real-life settings in France. 
 
 
 
 
Authors: D. Schmidbauer, M. Wolf 
Reviewed by: T. Fetsch 
 
 
Version: November 13th, 2018 
 
 
 
 
 
 
 
 
 
 
 
The information contained herein is the property of ZOLL and may not be reproduced, published or disclosed 
to others without written authorization of the sponsor. The information provided in this document is strictly 
confidential and is available for review to investigators, potential investigators, health authorities and 
appropriate Ethics Committees. No disclosure should take place without written authorization from the 
sponsor except to the extent necessary to obtain informed consent from potential subjects. Once signed, the 
terms of this protocol are binding for all. 
 
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Page 2 of 15 
CHIEF INVESTIGATORS 
Dr. Nicolas Combes, MD, Toulouse, France  
Pr. Eloi Marijon, MD, Paris, France 
 
SPONSOR 
ZOLL, 
121 Gamma Drive, 
Pittsburgh, PA, 15238, 
USA 
 
CONTRACT RESEARCH ORGANISATIONS (CROs) 
ClinSearch, 
110 Avenue Pierre Brossolette, 
92240 Malakoff, 
France 
Email: tony.toulorge@clinsearch.net 
 
Tasks: 
 
Lead CRO 
 
Management of study sites 
 
Clinical monitoring and source data verification 
 
CRI – The Clinical Research Institute GmbH 
Arnulfstr. 19 
80335 Munich, 
Germany 
Email: wearit-france@cri-muc.eu 
 
Tasks: 
 
Setup and technical management of MARVIN CTMS and eCRF 
 
Data cleaning and data management 
 
Statistical analyses 
 
STATISTICS 
CRI – The Clinical Research Institute GmbH 
Xiaoling Zhang, Statistician 
Arnulfstr. 19, 
80335 Munich, 
Germany 
Email: x.zhang@cri-muc.eu 
 
 
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Page 3 of 15 
 
Table of Content 
1. 
Abbreviations ................................................................................................................................... 4 
2. 
Signature page ................................................................................................................................. 5 
3. 
General Information ......................................................................................................................... 6 
4. 
Principles of the study ...................................................................................................................... 6 
4.1 
Primary study objectives ........................................................................................................ 6 
4.2 
Secondary study objectives ................................................................................................... 6 
5. 
Sample size and Power ................................................................................................................... 7 
6. 
Analysis populations ........................................................................................................................ 7 
6.1 
Intention to treat population (ITT) .......................................................................................... 7 
6.2 
On-treatment population ........................................................................................................ 8 
7. 
Analysis datasets ............................................................................................................................. 8 
7.1 
Final dataset .......................................................................................................................... 8 
7.2 
Dataset for interim analysis ................................................................................................... 8 
8. 
General methodology ...................................................................................................................... 8 
9. 
Demographics and characteristics of ITT population ...................................................................... 8 
9.1 
Baseline ................................................................................................................................. 8 
9.2 
Follow-up data (wearing period) of ITT population .............................................................. 11 
10. Primary analysis on ITT population ............................................................................................... 12 
11. Secondary analysis on ITT population .......................................................................................... 12 
12. Efficacy and safety analysis on ITT population ............................................................................. 13 
12.1 Primary parameters ............................................................................................................. 13 
12.2 Secondary parameters ........................................................................................................ 13 
13. On-treatment efficacy analysis ........................................................................................................ 14 
14. Analysis of WCD usage on ITT population ...................................................................................... 14 
15. Missing values ................................................................................................................................. 14 
16. Applied software .............................................................................................................................. 14 
17. Literature.......................................................................................................................................... 14 
 
 
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1. Abbreviations 
ARA2 
Angiotensin receptor II antagonist 
BMI 
Body Mass Index 
DCM 
Non-ischaemic dilated cardiomyopathy 
EOS 
End of study 
HCM 
Hypertrophic cardiomyopathy 
ICD 
Implantable cardiac defibrillator 
IEC 
Inhibitor of Angiotensin converting enzyme 
ITT 
Intention-to-treat 
LifeVest 
External wearable cardioverter defibrillator 
LV-EF or LVEF 
Left ventricular ejection fraction 
LPLV 
Last patient last visit 
NYHA 
New York Heart Association 
PCI 
Percutaneous coronary intervention 
SAP 
Statistical analysis plan 
SCD 
Sudden cardiac death 
SD 
Standard deviation 
VF 
Ventricular fibrillation 
VT 
Ventricular tachycardia 
WCD 
Wearable Cardioverter-Defibrillator 
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2. Signature page 
Date 
Signature 
 
___________________ 
_____________________________________ 
 
Dr. Nicolas Combes 
 
(Chief Investigator) 
___________________ 
_____________________________________ 
 
Pr. Eloi Marijon 
 
(Chief Investigator) 
___________________ 
_____________________________________ 
 
Kent Volosin  
 
(Sponsor representative) 
___________________ 
_____________________________________ 
 
Xiaoling Zhang 
 
(Study statistician, CRI) 
 
 
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3. General Information 
This Statistical Analysis Plan (SAP) is based on the study protocol version 05.10.2015, amended on 
10.10.2016 (Amendment No. 2). 
This SAP aims to specify definitions, procedures and statistical methods to be applied for the final 
analysis of the study data. 
4. Principles of the study 
Sudden cardiac death (SCD) is a major cause of mortality throughout the world, accounting for 
approximately 300,000 deaths per year in the United States [1]. SCD accounts for about 50 % of all 
heart related deaths. Studies of patients who suffer SCD suggest that ventricular tachyarrhythmias are 
the dominant cause of this rapid terminal event although asystole due to heart block or sinus arrest 
can account for approximately 10-15 % of the sudden deaths. However, these are most often electrical 
signs of a dying heart or electro-mechanical dissociation. The introduction of the implantable cardiac 
defibrillator (ICD) in the 1980s resulted in subsequent clinical trials showing a significant reduction in 
SCD with ICD therapy in at-risk cardiac patients. 
However, not all high-risk patients are candidates for the ICD for a variety of reasons [2-4]. These are: 
transient nature of the high-risk for SCD; patients who do not meet current guideline indications for an 
ICD; high-risk cardiac patients who had previously received an ICD but had it removed because of 
complications or malfunction; patients who refuse an ICD; age-related factors; and a variety of other 
medical and ethical considerations [5]. 
The Wearable Cardioverter-Defibrillator (WCD) LifeVest by ZOLL, Pittsburgh, PA, USA is an external 
defibrillator, guided by an algorithm to detect ventricular tachyarrhythmic events and gives the patient’s 
physician time to assess the long-term arrhythmic risk in cases when the risk of life-threatening 
arrhythmias may only be temporary and to make appropriate plans. 
4.1 
Primary study objectives 
1. Appropriate shocks as measured by shocks delivered for adjudicated sustained ventricular 
tachycardia (VT) or ventricular fibrillation (VF) episodes.  
2. Inappropriate shocks as measured by shocks delivered for all episodes that are not adjudicated 
sustained VT or VF episodes. 
The frequency and rate of appropriate and inappropriate shocks will be measured. The risk of 
receiving an inappropriate shock will be analyzed. The risk of not receiving appropriate shocks when 
necessary will also be analyzed.  
4.2 
Secondary study objectives 
1. Overall survival as measured by the ratio of the number of patients that are alive at the end of the 
use of the WCD to the total population of patients prescribed the LifeVest.  
2. Quality of life relative to health state as measured through the administration of a patient quality of 
life survey. This survey has been used previously in a published study of patient quality of life. 
LifeVest has been recently approved for reimbursement by the HAS. LifeVest has obtained coverage 
for 4 indications: (i) implantable cardiac defibrillator (ICD) removal due to cardiac device infections, (ii) 
a bridge to heart transplantation, (iii) in the early post-MI period with left ventricular (LV) dysfunction 
(LVEF <30 %), (iv) and a recent coronary revascularization with LV dysfunction (LVEF < 30 %). There 
is no current comparator to LifeVest. In France, patients at high risk for sudden cardiac arrest and 
waiting for heart transplant or ICD are hospitalized or discharged home without any particular ECG 
monitoring. LifeVest has been demonstrated to automatically detect and terminate rapid ventricular 
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arrhythmias. Introduction of LifeVest into the current patient management would definitely improve the 
clinical outcomes and benefit the patients with temporary risk of SCD. The use of LifeVest was shown 
to be effective in protecting patients against SCD in the United States. However, the clinical impact of 
using LifeVest in France remains unassessed. Therefore, this post-market study in France will provide 
efficacy and safety data for the reimbursement dossier renewal before September 2018. 
5. Sample size and Power 
This study is a post-inscription study designed to describe all patients treated by LifeVest in a 
comprehensive way. Thus this study will be proposed to all patients receiving LifeVest.  
No sample size calculation has been planned. All patients accepting to participate will be included.  
The LifeVest device is commercialized in France since approximatively 3 years, the number of 
subjects has been estimated based on the sales and the foreseen participation rate.  
It was estimated that approximately 1,700 patients will receive LifeVest in clinical routine between May 
2015 and April 2018 (300 patients first year, 520 patients second year and 880 patients third year of 
marketing) in France. After obtaining all regulatory approvals, the study started in August 2016. 
Between August 2016 and April 2018, 1,110 patients were expected to receive LifeVest in clinical 
routine. Considering a participation rate of 50 % related to centers participating in the study and 
consent given, around 550 patients were considered to participate in this study.  
Due to an observed recruitment rate exceeding the initial expectations, the recruitment goal was 
reached prematurely with an estimated enrollment of about 1,200 patients until 31st March 2018. After 
the end of recruitment, follow-up of patients is planned until 31st march 2019 (LPLV). 
According to most recent data from literature, the frequency of ventricular tachyarrhythmic events with 
shock delivery within the spectrum of indications for the LifeVest device and within the associated 
wearing periods was estimated between 1% and 5% [6]. In this present study, a population of 550 
patients was expected as primary assumption, allowing to observe a shock delivery rate ranging 
between 1%-5% with an absolute precision below 2% (0.8 for 1% and 1.8 for 5%). This sample size 
was considered to be statistically sufficient to answer the pre-defined research questions, however, 
the expected final population in the study of about 1,200 patients will increase the level of precision. 
6. Analysis populations 
6.1 
Intention to treat population (ITT) 
ITT analysis in general includes every subject who is randomised according to randomised treatment 
assignment [7]. Since this is an observational study without randomisation, the equivalent, 
fundamental claim of “intention-to-treat” is the fulfilment of in- and exclusion criteria after giving 
informed consent on the use of medical data. 
All consenting patients with a routinely prescribed WCD in study participating centers will be 
evaluated, regardless of the length of WCD wearing. This may include patients who have already 
completed use of LifeVest before start of the study in the corresponding study site. 
Patients with missing outcome data are not considered in the outcome analysis [8]. 
The retrospective cohort of patients will be analyzed separately compared to prospectively included 
study patients for any variables that are not available for both cohorts, such as the patient survey. 
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6.2 
On-treatment population 
Patients who have worn WCD for at least 8 days (i.e. longer than 1 week) will be evaluated separately 
in an “on-treatment” efficacy analysis, because it is assumed from clinical experience that the WCD 
wearing time will only be long enough for those patients to reliably compare their long-term outcome in 
a cohort of patients who have had the WCD for several months (even six or more months in some 
indications). 
7. Analysis datasets 
7.1 
Final dataset 
Dataset at time of study database closure (= after date of last visit and end of data cleaning = date of 
end of study EOS). No further changes of clinical data will be possible, neither by sites nor by CROs. 
7.2 
Dataset for interim analysis 
An interim analysis is planned for reimbursement dossier renewal latest in September 2018. For this 
purpose a dataset for interim analyses will be generated at a specific point in time defined by the 
sponsor. The dataset for interim analysis is a data snapshot and will partially consist of uncleaned data 
because data documentation and cleaning are ongoing at this point in time. 
8. General methodology 
Continuous variables will be summarized as means (standard deviations [SDs]), quartiles (25 %, 50 % 
and 75 %), and minimum and maximum value. The number and percentage of patients in each 
category will be presented for nominal variables. For graphical representation distribution plots, 
histograms, boxplots and bar charts will be used, as appropriate. 
Comparisons of continuous variables will be performed using the Student´s t-test and if assumptions 
are not met Wilcoxon rank-sum test, and comparisons of nominal variables will be performed using the 
Pearson’s chi-square test or Fisher’s exact test, as appropriate. 
For time-to-event data, the Cox proportional hazards model will be used unless specified otherwise. 
Survival estimates will be illustrated in Kaplan-Meier plots. 
For comparing groups with respect to binary outcomes, logistic regression or analysis of covariance 
(ANCOVA) will be used as specified. 
Statistical comparisons will be performed using two-sided significance tests with alpha=0.05 unless 
otherwise noted. 
9. Demographics and characteristics of ITT population 
9.1 
Baseline 
The following demographic and baseline characteristics will be described: 
 
Patient characteristics, additionally subgrouped by WCD indication: 
 Gender 
 Age 
 BMI 
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 Heart rate at rest 
 Most recent LV-EF value 
 LV-EF in groups  
- 
≤ 25%  
- 
> 25% ≤ 35% 
- 
> 35% ≤ 45% 
- 
> 45% 
 and 
- 
< 30% 
- 
>= 30 – 35% 
- 
> 35% 
 NYHA classification for heart failure 
 ICD removal 
 Currently implanted cardiac pacemaker  
 WCD indication 
 
Medical history, additionally subgrouped by WCD indication 
 Documented atrial fibrillation 
 Coronary heart disease 
 Myocardial infarction 
 PCI (intervention e.g. balloon, stent, not only angiography) 
 Bypass surgery (CABG) 
 Heart failure (ever classified as NYHA II - IV) 
 Cardiomyopathy, divided into dilated, non-ischemic cardiomyopathy (DCM) or hypertrophic 
cardiomyopathy (HCM) 
 Congenital heart disease 
 Cardiac valve disease, divided into aortic or mitral valve disease 
 Hospitalisation during the last year due to aggravation of heart failure 
 Cardiac arrest or resuscitation 
 Inherited arrhythmia syndrome by type 
 Previous renal disease requiring therapy 
 Stroke 
 Syncope 
 
Current cardiovascular symptoms, additionally subgrouped by WCD indication 
 Angina pectoris 
 Chest pain 
 Increased heart rate 
 Nausea 
 Palpitations 
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 Shortness of breath 
 Sweating 
 Weakness, dizziness 
 Other current cardiac symptoms 
 
Current medication: 
 Antiarrhythmics (amiodarone, flecainide, sotalol, other) 
 Oral anticoagulants 
 Antiplatelet agents 
 Beta blockers 
 Diuretics 
 IEC/ARA2 
 Statines 
 
WCD activation/programming, additionally subgrouped by WCD indication 
 WCD activation 
 Prescription period 
 Shock energy of first shock 
 VF threshold heart rate 
 VT shock delay 
 VT threshold heart rate 
 
Patient questionnaires: 
All patient questionnaire data will be included in the analysis as long as the patient answered at 
least one item on the survey. In other words, no exclusion criteria will be used based on survey 
response completeness. Overall statistics will be presented for survey data results including 
 overall response rate, i.e. availability of surveys of prospective patients in % 
 item level response rate, i.e. availability of items in % and 
 survey responses for all items, i.e. frequency of answers per item in % 
For the majority of items in the questionnaires patients were asked to indicate their agreement 
using the 5-point Likert agreement response scale (strongly agree, agree, neither agree nor 
disagree, disagree, strongly disagree) with the following topics regarding their use of the LifeVest:  
 Peace of mind  
 Worry  
 Sleep quality  
 Confidence returning to activities of daily living (screened)  
 Confidence to exercise or perform cardiac rehabilitation (screened)  
 Taking condition seriously  
 Improved self-care  
 Confidence in LifeVest. 
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9.2 
Follow-up data (wearing period) of ITT population 
The following follow-up data will be described: 
 
Serious adverse events since inclusion by number of events in groups of 
 Type of event 
- 
Cardiac arrhythmic 
- 
Cardiac non-arrhythmic 
- 
Vascular non-cardiac (including stroke) 
- 
Cardiovascular without clearly defined other cause 
- 
Non-cardiovascular 
 Related hospital stay/prolongation of existing hospital stay 
 Causal relationship to WCD 
 Intensity 
 Outcome 
 Criteria for seriousness 
 
Time to first hospitalization 
 
Death 
 Cardiovascular  
- 
Cardiac 
- 
Vascular non-cardiac (including stroke) 
- 
Cardiovascular without clearly defined other cause 
 Non-cardiovascular 
 Death during prescription duration 
 Death while wearing the WCD 
 Death related to arrhythmic event 
 Death related to WCD dysfunction 
 
WCD events 
WCD events/patients with WCD events with following event parameters: 
 Type of event 
 Termination of event 
 Response button pressed 
 Shock delivered 
 Shock appropriate/inappropriate 
 
Occurrence of technical and non-technical problems during the wearing period 
 
Return of WCD device (end of therapy) due to: 
 Death 
 ICD implantation 
 Heart transplantation 
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 LV function improvement 
 Patient’s wish 
 Other reason 
 
Clinical status on WCD return: Most recent LV-EF value, NYHA classification, risk assessment 
and if patient is still listed for heart transplantation 
 
Planned therapy after wearing period: 
 ICD implantation 
 PCI (Angioplasty, Stent) 
 Bypass surgery 
 Implantation of cardiac pacemaker 
 Heart transplantation 
 Implantation LVAD (left ventricular assist device) 
 Therapy with anti-arrhythmic agents 
 Other planned cardiac therapy 
 
Medication on WCD return 
10. Primary analysis on ITT population 
1. Appropriate shocks as measured by shocks delivered for adjudicated sustained ventricular tachy-
cardia (VT) or ventricular fibrillation (VF) episodes. 
 Quantitative analysis of appropriate shocks 
 Analysis of the risk of not receiving appropriate shocks when necessary, calculated as number 
of non-terminated VT/VF events without shock delivery and without response button pressed/ 
number of VT/VF events 
2. Inappropriate shocks as measured by shocks delivered for all episodes that are not adjudicated 
as sustained VT or VF episodes. 
 Quantitative analysis of inappropriate shocks 
 The risk of receiving an inappropriate shock, calculated as number of inappropriate shocks/ 
non VT/VF events  
11. Secondary analysis on ITT population 
Overall survival as measured by the ratio of the number of patients that are alive at the end of the use 
of the WCD compared to the total ITT population. 
Survival analysis using Kaplan-Meier curves and cox proportional hazard models will be performed to 
identify impacts on survival and the occurrence of WCD events will be displayed in tables in the 
following subgroups : 
 indication for the WCD, 
 medical history, and 
 disease etiology: heart failure according to ESC guidelines 
- 
no HF (LV-EF >= 50%) 
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- 
intermediate HF (LV-EF >= 40 – < 50%) 
- 
HF (LV-EF < 40%) 
12. Efficacy and safety analysis on ITT population 
12.1 Primary parameters 
 
Arrhythmic (VT/VF) events and characterization of event: 
 Number of WCD shocks until termination of the tachycardia event 
 Cardiac arrest immediately after shock delivery 
 Asystole after VT/VF event 
 Maximum heart rate during ventricular tachycardia 
 Polymorphic VT event 
 Immediate ventricular fibrillation (VF) 
 Ventricular tachycardia degenerating into ventricular fibrillation (VF) 
 
Efficacy will be evaluated using the success rate of appropriate shocks: Number of VT/VF events 
terminated by shocks/VT/VF events with shock delivery 
 
Rate of treated VT/VF episodes calculated as shocked VT and VF events/ all VT and VF events 
 
Cumulative probability of sustained VT/VF, determined according to the Kaplan-Meier method in 
function of time 
 
Number of arrhythmic events and shocked events 
 Within 30 days from activation date 
 Within 90 days from activation date 
12.2 Secondary parameters 
 
Analysis of primary outcome parameters (section 12.1) in sub-groups according to their clinical 
profile at baseline: 
 Age: 
- 
< 40 years 
- 
>= 40 - < 65 years 
- 
>= 65 - < 75 years 
- 
>= 75 years 
 Gender 
 Indication of WCD: 
- 
implantable cardiac defibrillator (ICD) removal due to cardiac device infections, 
- 
a bridge to heart transplantation, 
- 
in the early post-MI period with left ventricular (LV) dysfunction (LVEF <30%), 
- 
a recent coronary revascularization with LV dysfunction (LVEF < 30%). 
 Type of inherited arrhythmia syndrome: 
- 
Long-QT syndrome (LQTS) 
- 
Brugada syndrome  
- 
Catecholaminergic polymorphous ventricular tachycardia (CPVT)  
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- 
Arrhythmogenic right ventricular cardiomyopathy 
- 
Other 
- 
Unknown 
 
In addition the following parameters will be analysed in the mentioned subgroups: 
 
Cause of death (as assessed by CEC) 
 
Hospitalization 
 
Type of SAE 
LV-EF at baseline and at time of WCD end of use  
13. On-treatment efficacy analysis 
For on-treatment efficacy analysis, tables on baseline characteristics and outcome will be shown 
comparing patient group on-treatment to not on-treatment (for definitions refer to 6.3). 
14. Analysis of WCD usage on ITT population 
Analysis of usage patterns will be done by: 
 
Description of WCD wearing profile: 
 Average prescription period 
 Average wearing period (date of activation to date of end of use) 
 Average wearing period by gender 
 Description and analysis of compliance of WCD wearing: WCD device in use during wearing 
period (days in use / number of days of wearing period) Average daily WCD usage (hours) 
 
Regression model/ANOVA evaluating factors influencing the non-compliance of patients with 
prescribed WCD (age, gender, neurologic function, co-morbidities etc.)  
 
Distribution of reasons for end of WCD usage 
 
Kaplan-Meier curves for time to end of WCD usage. 
15. Missing values 
Missing data will not be replaced by any algorithm. 
16. Applied software 
R (version 3.3.3 or later) 
17. Literature 
 
1) Myerburg RJ. Sudden cardiac death: exploring the limits of our knowledge. J Cardiovasc 
Electrophysiol 2001; 12:369-81. 
2) Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for 
congestive heart failure. N Engl J Med 2005; 352:225-37. 
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3) Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients 
with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator 
Implantation Trial Investigators. N Engl J Med 1996; 335:1933-40. 
4) Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with 
myocardial infarction and reduced ejection fraction. N Engl J Med 2002; 346:877-83. 
5) Epstein AE, Dimarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 Guidelines for device-based 
therapy of cardiac rhythm abnormalities. Heart Rhythm 2008; 5:e1-62. 
6) Klein HU, Goldenberg I, Moss AJ. Risk stratification for implantable cardioverter defibrillator 
therapy: the role of the wearable cardioverter-defibrillator. Eur Heart J 2013; 34(29):2230-42 
7)  Gupta SK. Intention-to-treat concept: A review. Perspect Clin Res. 2011, 2(3):109-12 
8)  Alshurafa M, Briel M, Akl EA, et al. Inconsistent definitions for intention-to-treat in relation to 
missing outcome data: systematic review of the methods literature. PLoS ONE 2012, 
7(11):e49163 
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