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U.S. Department of Health and Human Services

Post-Approval Studies (PAS) Database

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The FDA has the authority to require sponsors to perform a post-approval study (or studies) at the time of approval of a premarket approval (PMA), humanitarian device exemption (HDE), or product development protocol (PDP) application. Post-approval studies can provide patients, health care professionals, the device industry, the FDA and other stakeholders information on the continued safety and effectiveness (or continued probable benefit, in the case of an HDE) of approved medical devices. This database allows you to search Post-Approval Study information by applicant or device information.

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Micra AV Post Approval Study


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General
Study Status Progress Adequate
Application Number P150033 S061/ PAS001
Date Current Protocol Accepted 07/30/2020
Study Name Micra AV Post Approval Study
General Study Protocol Parameters
Study Design Comprehensive/Linked/RegistryBased Surveillance
Data Source Sponsor Registry
Comparison Group Objective Performance Criterion
Analysis Type Descriptive
Study Population Adult: >21
Detailed Study Protocol Parameters
Study Design Description The Micra AV PAS is a non-interventional observational study conducted within Medtronic’s Product Surveillance Registry (PSR) platform. Following consent and implant, patients will be followed per their center’s standard of care for a minimum of three years. As this study is designed to capture the real-world performance of the Micra AV system there are no device programming requirements.



Primary Objective: To characterize the rate of pacemaker syndrome resulting in a system revision at 3- years post-implant.



Secondary Objective #1: To estimate the acute major complication rate related to the Micra AV system and/or procedure.



Secondary Objective #2: To estimate the 3-year major complication rate related to the Micra AV system and/or procedure.



Ancillary Objectives:

To characterize the rate and severity of adverse events potentially related to AV synchrony loss

Summarize Micra AV system or procedure related adverse events

Characterize the implant procedure

Characterize electrical performance over time

Characterize A4 amplitude over time

Summarize quality of life as measured by the SF-36 v2 Standard and EQ-5D-5L questionnaires.



Study Population Description All patients who have successful implant of the Micra AV System will be included in the analysis of the primary objective and secondary objective #2. All patients who have an implant attempt will be included in the analysis of secondary objective #1. Any patient with a qualifying adverse event related to the Micra AV will be included in the analysis of the AV synchrony loss ancillary objective.
Sample Size Primary Objective:

For the primary objective, the goal is to size the study to estimate the pacemaker syndrome rate meeting the primary endpoint within a desired precision of at least 1.5% (distance from point estimate to the upper two-sided 95% confidence interval less than or equal to 1.5%). Table 1 displays the relationship between the assumed pacemaker syndrome rate requiring system revision and the estimated rate of precision for a sample size of 750 patients. As an example, if the true rate of pacemaker syndrome events requiring a pacing system upgrade is 2.0% at 3-years then a sample size of 750 patients will estimate the rate of this event within 1.5% with near certainty based on the following assumptions:

At least 750 patients will undergo an implant attempt with a Micra AV system.

Two thirds of pacemaker syndrome events requiring a pacemaker system upgrade will occur within 12-months of the implant attempt

Mortality rate not associated with major complications is 12% at 3-years (based on the mortality rate observed in 2667 dual chamber pacemaker patients from 6 prior Medtronic studies).

Premature exit rate for reasons other than death is 3% per year.

Premature exit and mortality not associated with pacemaker syndrome status are independent.

Event rate at 3-years computed using Kaplan-Meier methods



Table 1: Relationship Between Confidence Interval Width and Pacemaker Syndrome Requiring System Revision Rate at 3-Years Post-Implant for Sample Size of 750

Assumed Endpoint Rate at 3 Years Subjects Followed for 36-Months (95% MCCI) Observed Event Rate at 36-Months (95% MCCI) Median Upper Confidence

Boundary Percentage of Simulations where Distance to Upper CI <1.5%

0.5% 602 (584 – 619) 0.5% (0.1% - 0.9%) 1.0% >99.9%

1% 601 (582 – 618) 1.0% (0.4% - 1.7%) 1.8% >99.9%

2% 601 (584 – 619) 1.9% (1.2% - 2.9%) 3.0% >99.9%

3% 602 (583 – 620) 3.0% (1.9% - 4.0%) 4.2% 98.3%

Notes: Results based on 1000 simulated studies using based on assumptions described above.

R Program: H:\DocumentReviews\MicraAV\PostMarketScenarios\PAS\simulationMicraAVsingleArmStudy.R



Secondary Objective #1

For secondary objective #1, a final sample size of N = 750 patients with a Micra AV system implant attempt allows for an estimated 3% overall acute major complication rate with an expected precision (distance from upper two-sided 95% confidence interval to point estimate) of approximately 1.6%. Individual acute major complication rate occurring at a rate of 1.0% will be estimated with a precision of approximately 1.1%.



Secondary Objective #2

For secondary objective #2, a sample size of N = 750 will enable estimation of the 3-year post-implant complication rate within 2.0%, with a probability around 99%, based on assumptions identical to those of the primary objective (listed above). It is known that the Micra AV system has the same implant procedure and form factor as the predicate VR system, so it is assumed the long-term safety profile of the Micra AV system will be similar. It is also assumed that most Micra AV patients will have atrioventricular (AV) block with normal sinus function and may be more susceptible to pacemaker syndrome during periods of low AV synchrony. The MARVEL 2 clinical study (IDE #G180277) shows Micra AV may have an elevated risk for major complications through 3-year post implant, relative to Micra-VR, due to pacing intolerance. The risk for major complications through 3-year post-implant associated with the Micra VR system suggests the rate of major complications at 3-year post implant for the Micra AV system may be 6.0%.



Ancillary Objectives

For the ancillary objectives, a sample size of 750 enrolled patients with an attempted Micra AV system implant provides sufficient precision in which to estimate the event rates associated with the prim
Data Collection Main Effectiveness and Safety Endpoints:

The primary objective is to characterize the rate of pacemaker syndrome resulting in a system revision at 3-years post-implant. Pacemaker syndrome resulting in system revision is defined as a Micra AV system revision where the investigator indicates the reason for system revision is pacemaker syndrome and the Micra AV system is replaced with a new or upgraded dual chamber pacemaker system. This includes revisions where the Micra AV device is abandoned electrically (i.e. programmed to OOO on a permanent basis) and replaced with a new or upgraded dual chamber pacemaker.



Additionally, for a pacemaker syndrome event to meet the primary endpoint it must occur within 3-years (1095 days) of the Micra AV implant procedure.



Secondary Endpoint #1:

Secondary objective #1 is to estimate the acute major complication rate related to the Micra AV system and/or procedure. For an adverse event to meet the endpoint, the event must have occurred within 30 days (inclusive) of a Micra AV system implant attempt and be adjudicated by the Clinical Events Committee (CEC) as being a major complication related to the Micra AV system and/or procedure. Major complications are complications that result in one or more of the following:

Death

Permanent loss of device function due to mechanical or electrical dysfunction of the device (e.g. pacing function disabled, leaving device abandoned electrically)

Hospitalization

Prolonged hospitalization by at least 48 hours

System revision (reposition, replacement [including replacement with any transvenous pacing system], or explant)



Secondary Endpoint #2:

Secondary objective #2 is to estimate the 3-year major complication rate related to the Micra AV system and/or procedure. For an adverse event to meet the endpoint, the event must have occurred within 3-years (1095 days) of a Micra AV system implant attempt and be adjudicated by the Clinical Events Committee (CEC) as being a major complication related to the Micra AV system and/or procedure.

Follow-up Visits and Length of Follow-up 3 years (1095 days).
Interim or Final Data Summary
Interim Safety Information As of the visit cutoff date for this report (September 08, 2020), 44 patients have undergone a Micra AV implant procedure at 21 investigational sites in the US. All 44 implants were successful. The first patient was enrolled February 17, 2020. No adverse events have been reported. Study

enrollment has been slower than initially planned due to restrictions on elective procedures and clinical research at many participating institutions due to the COVID-19 pandemic. However, the firm expects the enrollment rate to increase as COVID-19 vaccines become more widely available

and stress on healthcare systems eases.
Actual Number of Patients Enrolled Forty-four (44) subjects enrolled
Actual Number of Sites Enrolled Twenty-one (21) sites enrolled.
Patient Follow-up Rate 10 % follow-ups < 6 months post-implant of 0 expected for this time frame.
Study Strengths & Weaknesses Enrollment rates are slower than expected


Micra AV Post Approval Study Schedule

Report Schedule
Report
Date Due
FDA Receipt
Date
Applicant's Reporting Status
six month report 07/15/2020 07/07/2020 On Time
one year report 01/14/2021 01/19/2021 Overdue/Received
18 month report 07/15/2021    
two year report 01/14/2022    
three year report 01/14/2023    


Contact Us

Mandated Studies Program
Food and Drug Administration
10903 New Hampshire Ave.
Silver Spring, MD 20993-0002
Email: MandatedStudiesPrograms@fda.hhs.gov

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