Lead Evaluation for Defibrillation and Reliability in Left Bundle Branch Area Pacing (LEADR LBBAP)

I refer to section 3.1 of the Clinical Investigational plan version 2.0.

The purpose of this study is to confirm the safety and defibrillation efficacy
of the Next Generation ICD Lead when placed in the Left Bundle Branch Area
Pacing (LBBAP) location in an Implantable Cardioverter Defibrillator (ICD) or
Left Bundle Branch-Optimized Cardiac Resynchronization Therapy (LOT-CRT)
patient population.

The LEADR LBBAP study is a prospective, pre-market, pivotal, non-randomized,
multi-site, interventional, global study designed to allow controlled access of
the Next Generation ICD Lead for placement in a LBBAP application. The study is
expected to be conducted at up to 40 study sites. Participating geographies may
include but are not limited to: Australia, Mainland China, Japan, Hong Kong,
Malaysia, Europe, Middle East, and Africa (EMEA), Canada, and the United States.
Approximately 300 subjects, including a minimum of 150 LOT-CRT implant attempts
(no minimum requirement for ICD implant attempts), will be enrolled. Assuming
one lead is used per subject, as well as a 6% increase to account for system
revisions, sterility compromised products, etc., it is expected that
approximately 320 Next Generation ICD Leads will be used in the study.
Medtronic may decide to stop or pause ICD or LOT-CRT enrollments (in all or in
specific regions), for example to manage total (or per cohort) sample size. In
addition, Medtronic may decide to keep enrollments open in specific
regions/sites beyond 300 enrollments to address local needs. The final study
sample size will depend on enrollment rate and/or timing of official enrollment
closure (see section 15.10.1). A sample size of at least 160 subjects
completing the defibrillation protocol at implant with the Next Generation ICD
Lead placed in the LBBAP location will provide at minimum 90.4% power to test
the study*s primary efficacy objective provided the true defibrillation success
rate is at least 95.5%.
Subjects will be considered enrolled into the study upon signing the Informed
Consent Form (ICF) and will be followed prospectively from consent to implant,
3-months post-implant, 6-months post-implant, and at subsequent 6-month
intervals until study closure. Enrolled subjects from all geographies will be
followed until at least 3-months post-implant (ICD-indicated subjects) or
6-months post-implant (CRT-indicated subjects).
There is no minimum number of subjects to be enrolled per study site.
Enrollment parameters are included in the study to avoid introduction of bias
to the study results due to disproportionate enrollment. Enrollment should not
exceed 10% (i.e., 30 subjects if 300 subjects are enrolled) of the final sample
size at any individual site. Enrollment will be competitive across study sites.
The per-study site enrollment cap may be increased upon Sponsor approval.

The first enrollment is projected to occur in 2024. Successfully implanted
study subjects will be followed until study closure, with an Exit electronic
Case Report Form (eCRF) entered for each subject. Official study closure is
defined as when all enrolled subjects have been followed until at least 3
months (ICD-indicated subjects) or 6 months post-implant (CRT-indicated
subjects) or have been exited, and applicable regulatory authority agency or
governing body requirements have been satisfied per the Clinical Investigation
Plan (CIP) and/or by a decision by Medtronic or regulatory authority to stop or
close the study. The duration of individual subject participation will vary
based on timing of study site activation and their enrollment. The approximate
duration for each subject participant will be 1.5 to 3 years. The expected
study duration is approximately 3 years from first site activation until the
study closure criteria are met. Official study closure is anticipated in 2027.

Please see visit schedule overview in CIP section 9.2, table 7

Enrollment/Baseline visit - Visit 1
- Physical Exam - a general exam that will include height and weight
- Demographics: including age, gender, race, and ethnicity (if allowed per
local regulations)
- New York Heart Association (NYHA classification (assessment of heart failure)
and general cardiovascular and surgical medical history will be reviewed
- Assessment for an ICD or CRT-D implant, in the case of CRT-D, an
echocardiogram will be needed within 60 days of the baseline visit
- Quality of Life Survey

Implant visit - Visit 2
- Within about 30 days of the enrollment visit, the implant will be scheduled.
- Pregnancy test
- The Medtronic CRT-D or ICD device will be implanted
- In case the Next Generation ICD Lead is not attempted to be implanted or is
not implanted at completion during the Implant visit, the patient will be
exited from the study
- If a Next Generation ICD Lead implant is attempted, but not successfully
placed in the LBBAP location or the right ventricle (RV) location, the patient
will be exited from the study after monitoring for at minimum 30 days to ensure
there are no problems..

Following the successful implant, the following tests will be done:
- 12-Lead Electrocardiogram (ECG)
- Defibrillation testing may take place
- Moving X-ray
Defibrillation Testing During the Implant
-In case the device needs to be repositioned during defibrillation testing, the
patient may have additional fluoroscopy to get extra pictures of your
lead and device before repositioning the lead.
-In case the device does not successfully provide appropriate therapy (shock),
the device may be removed and replaced with another device from your body and
could be replaced with another lead

Pre-discharged checks from the hospital, the following procedures will be done:
-Electrical testing
-Chest x-rays

3 and 6-month follow-up visits - Visits 3 and 4
- Electrical testing of the device implanted
-Chest x-rays (at either the 3 or the 6-month visit, but not both)
-12-Lead ECG (6-month visit only)
- Quality of Life survey (6-month visit only)
In case the CRT-D device is done during the implant, the following procedures
are completed at the 6-month follow-up visit : Transthoracic echocardiogram
(TTE) (a test that uses sound waves to create pictures of your heart)

Long-term follow-up visits - Visit 5 and any additional visits beyond 5

Depending on when you were enrolled in this study you may have these visits at
12 months after the implant and every 6 months thereafter. These visits may be
in the office or as phone call visits.

At each of the long-term follow-up visits, the following will occur:
-Electrical testing (only be done at in-office visits)
-Information regarding the device and other problems that the patient is having
device-related or not will be collected

Unscheduled follow-up visits
- Electrical testing can be done
-Information regarding the device and other problems that the patient is having
device-related can be reviewed

Risk/Benefit rational CIP section 10.4:
In addition to the extensive pre-clinical testing, bench testing, and
computational modeling, a formal risk analysis and risk assessment for the Next
Generation ICD Lead was performed according to EN ISO 14971:2019 and were used
to ensure that the level of risk is acceptable prior to starting clinical
investigations. The risk management activities reduced the risks to as low as
possible and concluded that the residual risks associated with these hazards
are acceptable when weighed against the benefits. The risk management file for
the Next Generation ICD Lead will be updated periodically for impact to the
product*s overall residual risk for issues that are identified during the
clinical investigational study and following market release, in accordance with
EN ISO 14971:2019.
A risk management plan/report establishes the strategy for performing
systematic and comprehensive evaluation of potential safety risks associated
with the use or performance of the Next Generation ICD Lead for the
investigational study, in accordance with EN ISO 14971:2019.
The risk management plan describes inputs to the hazard analysis as well as the
structure of the hazard analysis activities performed for the Next Generation
ICD Lead project. The chosen strategy was to perform hazard analysis for the
therapy to capture potential risks associated with design inputs and then also
perform hazard analyses for the new lead to capture potential risks associated
with the design outputs (i.e., finished devices). The hazard analysis leverages
the relevant risk analysis inputs such as failure analysis and use error
analysis. Furthermore, the hazard analysis captures the pertinent risk controls
that serve to minimize the residual risk to as low as possible. This plan may
be updated in future phases of the device development lifecycle.
A systematic process is in place to continuously collect, analyze, and assess
data relevant to the safety performance of the system during human use.
Furthermore, the information gained during the investigational study will be
leveraged during the planning and execution of the risk management activities
throughout all phases for this project and for commercial release.
In summary, the anticipated risks of the Next Generation ICD Lead placed in the
LBBAP location are consistent with the risks of similar market-approved
transvenous ICD and catheter-delivered pacing leads. The potential benefits of
having the Next Generation ICD Lead implanted in the LBBAP location are also
consistent with the benefits of ICD therapy and similar market-approved
transvenous ICD leads. Additionally, due to the smaller lead diameter of the
Next Generation ICD Lead and the novel catheter delivery in tachycardia
application, potential benefits may be seen in long term reliability, the ease
of extraction and the potential to target specifically selected sites with the
use of a catheter delivery system. The Next Generation ICD Lead may also be an
alternative for subjects with small vasculature anatomies. Furthermore, the
benefits for pediatric subjects, described in detail in section 10.3, outweigh
the risks based on lower body mass. Therefore, it is concluded that the
potential benefits related to the use of the Next Generation ICD Lead placed in
the LBBAP location have been determined to outweigh any potential risks and
justify the implementation of this investigation.