Class I or II Indication for Implantation of a Single Chamber Ventricular Pacemaker According to ACC/AHA/HRS 2001 Guidelines and Any National Guidelines
Conditions
Keywords
pacemaker, leadless, single chamber
Brief summary
The purpose of this clinical study is to evaluate the safety and efficacy of the Micra Transcatheter Pacing System and to assess long term performance.
Detailed description
The study is being conducted in 56 sites located around the world, including 30 sites in the United States (U.S.). Up to 780 subjects were planned to be enrolled (i.e. consented) to allow up to 720 subjects to be implanted enabling at least 600 subjects to be followed for at least 12-months post-implant. There are two primary objectives in this study (one safety and one efficacy). The primary safety objective of the study is to evaluate major complications related to the Micra system or procedure. The primary safety endpoint was pre-specified to be evaluated at 6-months (183 days) post-implant. The primary efficacy objective, Micra pacing capture thresholds, was also pre-specified to be evaluated six months post-implant. This study also has a separate long term safety objective that will provide additional long-term safety data following potential regulatory submissions. All subjects will be followed until official study closure (official study closure is defined as when Medtronic and/or FDA requirements have been satisfied per the Clinical Investigational Plan and/or by a decision by Medtronic or regulatory authority). Additionally, the Micra Accelerometer Sensor Sub-Study (MASS) is being conducted at 4 centers already active in the Micra study in Austria, Spain, Hungary and France. Forty (40) subjects were enrolled in the Sub-Study, and enrollment in the Sub-Study was complete as of March 31, 2016. The purpose of the Sub-Study is to test feasibility for future enhancements in the Micra device functionalities. An algorithm was designed to sense the atrial contraction using the Micra accelerometer.
Interventions
DEVICEMicra Pacemaker Implant
Sponsors
Medtronic Cardiac Rhythm and Heart Failure
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects who have a Class I or II indication for implantation of a single chamber ventricular pacemaker according to ACC/AHA/HRS 2008 guidelines and any national guidelines * Subjects who are able and willing to undergo the study requirements and are expected to be geographically stable for the duration of the follow-up. * Subjects who are at least 18 years of age (or older, if required by local law).
Exclusion criteria
* Subjects who are entirely pacemaker dependent (escape rhythm \<30 bpm). (Please note: Subjects who are entirely pacemaker dependent (escape rhythm \<30 bpm) can now be included in the study. Medtronic notified all sites on July 23, 2014 that the restriction against pacemaker dependent subjects was lifted, following review of the Early Performance Assessment.) * Subject has an existing or prior pacemaker, ICD or CRT device implant. * Subject has unstable angina pectoris or has had an acute myocardial infarction (AMI) in the 30 days prior to eligibility assessment. * Subjects with current implantation of neurostimulator or any other chronically implanted device which uses current in the body. Note that a temporary pacing wire is allowed. * Subjects with a mechanical tricuspid valve, implanted vena cava filter, or left ventricular assist device (LVAD). * Subjects who are morbidly obese and physician believes telemetry communication of ≤5 inches (12.7 cm) could not be obtained with programmer head. * Subjects whose femoral venous anatomy is unable to accommodate a 23 French introducer sheath or implant on the right side of the heart (for example, due to obstructions or severe tortuosity) in the opinion of the implanter. * Subjects who are considered as unable to tolerate an urgent sternotomy * Subjects with a known intolerance to Nickel-Titanium (Nitinol) Alloy. * Subjects for whom a single dose of 1.0mg dexamethasone acetate may be contraindicated. * Subjects with a life expectancy of less than 12- months. * Subjects who are currently enrolled or planning to participate in a potentially confounding drug or device trial during the course of this study. Coenrollment in concurrent trials is only allowed when document pre-approval is obtained from the Medtronic study manager. * Pregnant women, or women of child bearing potential and who are not on a reliable form of birth control. * Subjects with
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Complications | Implant to 6 Months Post Implant | Micra system and/or procedure related major complication free rate at 6-months post-implant. |
| Pacing Capture Threshold | 6 Months Post Implant | Subjects that have an adequate pacing capture threshold (PCT) at the 6-month post-implant visit, which is defined as PCT \<=2 volts at 0.24 ms pulse width and the increase in PCT from implant to 6 months \<=1.5 volts. The pacing capture threshold is the minimal electrical stimulus required to produce consistent cardiac depolarization. It is the minimum amount of energy that is required for a pacemaker to pace the heart. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ventricular Capture Management Threshold | 6 Months Post Implant | Subjects that have a ventricular capture management threshold (VCMT) that is within 0.5 Volts of the manual (auto decrement) PCT (at 0.24 ms pulse width) at the 6-month post-implant visit. The VCMT is an automatically measured pacing capture threshold that is measured by the Micra device's pacing algorithm. In contrast, the manual (auto decrement) pacing capture threshold is measured by the clinician during a study visit. |
| Rate Response Operation of Micra | 3 Months and 6 Months Post Implant (combined analysis) | Assessment of whether the Micra sensor-indicated rate derived from the input of the accelerometer during the Minnesota Pacemaker Response Exercise Protocol (M-PREP) treadmill test conducted at the 3-month and 6-month follow-up visits was proportional to the workload. The sensor-indicated rate (in min\^-1) and workload (in METS) were normalized for each subject relative to their minimum and maximum possible values so the normalized values have a minimum possible value of zero and a maximum possible value of 1. These normalized values were used in a random effect linear regression model to assess the relationship between the sensor-indicated rate and workload via estimation of the Kay-Wilkoff slope parameter. The tests at 3-month and 6-month visits were combined in one analysis. |
Countries
Australia, Austria, Canada, China, Czechia, Denmark, France, Greece, Hungary, India, Italy, Japan, Malaysia, Netherlands, Serbia, South Africa, Spain, United Kingdom, United States
Participant flow
Recruitment details
The study enrolled 744 subjects at 56 centers in 19 countries worldwide between December 2013 and May 2015.
Pre-assignment details
Of the 744 subjects enrolled, 19 exited from the study without attempting Micra implant (7 did not meet inclusion / exclusion criteria, 12 due to other miscellaneous reasons), 6 attempted Micra implant but were unsuccessful, and the remaining 719 subjects were successfully implanted with a Micra device.
Participants by arm
| Arm | Count |
|---|---|
| Micra Study Enrollments All subjects enrolled in the Micra study | 744 |
| Total | 744 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Awaiting 6-month visit | 390 |
| Overall Study | Death | 23 |
| Overall Study | Implant unsuccessful | 6 |
| Overall Study | Missed 6-month visit | 4 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Micra Study Enrollments |
|---|---|
| Age, Continuous | 75.7 years STANDARD_DEVIATION 11 |
| Region of Enrollment Australia | 4 participants |
| Region of Enrollment Austria | 50 participants |
| Region of Enrollment Canada | 15 participants |
| Region of Enrollment China | 7 participants |
| Region of Enrollment Czech Republic | 43 participants |
| Region of Enrollment Denmark | 3 participants |
| Region of Enrollment France | 38 participants |
| Region of Enrollment Greece | 5 participants |
| Region of Enrollment Hungary | 56 participants |
| Region of Enrollment India | 19 participants |
| Region of Enrollment Italy | 17 participants |
| Region of Enrollment Japan | 38 participants |
| Region of Enrollment Malaysia | 21 participants |
| Region of Enrollment Netherlands | 37 participants |
| Region of Enrollment Serbia | 7 participants |
| Region of Enrollment South Africa | 3 participants |
| Region of Enrollment Spain | 54 participants |
| Region of Enrollment United Kingdom | 30 participants |
| Region of Enrollment United States | 297 participants |
| Sex/Gender, Customized Female | 309 participants |
| Sex/Gender, Customized Male | 434 participants |
| Sex/Gender, Customized Missing | 1 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 725 |
| serious Total, serious adverse events | 226 / 725 |
Outcome results
Primary
Major Complications
Micra system and/or procedure related major complication free rate at 6-months post-implant.
Time frame: Implant to 6 Months Post Implant
Population: All subjects who attempted Micra implant procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Micra Pacemaker Implant | Major Complications | 96.0 Kaplan-Meier survival probability (%) |
Comparison: Null hypothesis: Major complication free rate at 6 months post-implant is less than or equal to 83%.~Alternative hypothesis: Major complication free rate at 6 months post-implant is greater than 83%.p-value: <0.000198.66% CI: [93.3, 97.6]z-test, 1-sided
Primary
Pacing Capture Threshold
Subjects that have an adequate pacing capture threshold (PCT) at the 6-month post-implant visit, which is defined as PCT \<=2 volts at 0.24 ms pulse width and the increase in PCT from implant to 6 months \<=1.5 volts. The pacing capture threshold is the minimal electrical stimulus required to produce consistent cardiac depolarization. It is the minimum amount of energy that is required for a pacemaker to pace the heart.
Time frame: 6 Months Post Implant
Population: Subjects implanted with Micra who had paired implant and 6-month auto decrement PCT values (at 0.24 ms), or who had a system modification or alternative device implant prior to 6 months due to elevated threshold.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Micra Pacemaker Implant | Pacing Capture Threshold | 292 participants |
Comparison: Null hypothesis: Percentage of subjects with an adequate pacing capture threshold at 6-months post-implant is less than or equal to 80%.~Alternative hypothesis: Percentage of subjects with an adequate pacing capture threshold at 6-months post-implant is greater than 80%.p-value: <0.000198.66% CI: [95.4, 99.6]Exact Binomial test
Secondary
Rate Response Operation of Micra
Assessment of whether the Micra sensor-indicated rate derived from the input of the accelerometer during the Minnesota Pacemaker Response Exercise Protocol (M-PREP) treadmill test conducted at the 3-month and 6-month follow-up visits was proportional to the workload. The sensor-indicated rate (in min\^-1) and workload (in METS) were normalized for each subject relative to their minimum and maximum possible values so the normalized values have a minimum possible value of zero and a maximum possible value of 1. These normalized values were used in a random effect linear regression model to assess the relationship between the sensor-indicated rate and workload via estimation of the Kay-Wilkoff slope parameter. The tests at 3-month and 6-month visits were combined in one analysis.
Time frame: 3 Months and 6 Months Post Implant (combined analysis)
Population: Subjects implanted with Micra who had usable M-PREP test(s) at 3-month and/or 6-month visits.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Micra Pacemaker Implant | Rate Response Operation of Micra | 0.864 regression slope parameter |
Comparison: Null hypothesis: Kay-Wilkoff slope parameter is \< 0.65 or \> 1.35 Alternative hypothesis: Kay-Wilkoff slope parameter is between 0.65 and 1.35p-value: <0.00190% CI: [0.768, 0.961]t-test, 1 sided
Secondary
Ventricular Capture Management Threshold
Subjects that have a ventricular capture management threshold (VCMT) that is within 0.5 Volts of the manual (auto decrement) PCT (at 0.24 ms pulse width) at the 6-month post-implant visit. The VCMT is an automatically measured pacing capture threshold that is measured by the Micra device's pacing algorithm. In contrast, the manual (auto decrement) pacing capture threshold is measured by the clinician during a study visit.
Time frame: 6 Months Post Implant
Population: Subjects implanted with Micra who had paired ventricular capture management PCT and auto decrement PCT data available at the 6-month visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Micra Pacemaker Implant | Ventricular Capture Management Threshold | 279 participants |
Comparison: Null hypothesis: Percentage of subjects with VCMT within 0.5 Volts of auto decrement PCT at 6 months post-implant is less than or equal to 85%.~Alternative hypothesis: Percentage of subjects with VCMT within 0.5 Volts of auto decrement PCT at 6 months post-implant is greater than 85%.p-value: <0.000198.66% CI: [97.5, 100]Exact Binomial test