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| General |
| Study Status |
Ongoing |
Application Number /
Requirement Number |
P150033 S061/ PAS001 |
| Date Original Protocol Accepted |
01/15/2020
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| Date Current Protocol Accepted |
07/30/2020
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| Study Name |
Micra AV Post Approval Study
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| Device Name |
Micra Transcatheter Pacing System, Micra AV Application Software
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| General Study Protocol Parameters |
| Study Design |
Comprehensive/Linked/RegistryBased Surveillance
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| Data Source |
Sponsor Registry
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| Comparison Group |
Objective Performance Criterion
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| Analysis Type |
Descriptive
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| Study Population |
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
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.
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| Study Population |
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.
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| 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 primary and secondary objectives. For the quality of life assessment, it is anticipated 350 patients wil par
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| Key Study Endpoints |
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.
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| Follow-up Visits and Length of Follow-up |
3 years (1095 days).
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| Interim or Final Data Summary |
| Interim Results |
Safety Results
113 adverse events have been reported which occurred on or after a Micra AV implant attempt in 99 patients.
At the time of the database freeze, there were 113 events requiring CEC adjudication of which 108 (95.6%) have been adjudicated by
the CEC. Of the 108 adjudicated events, 96 were considered related to the Micra system or procedure and 12 were considered not
related. Of the 96 related events, 35 (in 33 patients) were classified as Micra System-related and/or procedure-related complications by
the CEC. The most comment events were cardiac tamponade, post procedural hematoma and pericardial effusion
73 study exits were reported. None were due to system explants.
108 patient deaths reported as of the cut-off.
One adjudicated death was related to the Micra system or procedure related it was a non-sudden cardiac death.
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| Actual Number of Patients Enrolled |
There are 801 patients enrolled (796 patients successfully implanted)
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| Actual Number of Sites Enrolled |
There are 97 study centers enrolled as of the cutoff date.
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| Patient Follow-up Rate |
Year 1 (6-18months) - 91.7% (638/696)
Year 2 (18-30months) – 94.6% (313/331)
Year 3 (30-42months)- 96.% (55/57)
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| Final Effect Findings |
The pacing capture thresholds for patients were reported.
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