Atrioventricular Conduction Block
Conditions
Brief summary
The purpose of the Micra Atrial TRacking Using A Ventricular AccELerometer 2 (MARVEL 2) study is to demonstrate safe and effective operation of the MARVEL 2 features for providing AV synchronous pacing in patients with normal sinus node function and AV block
Detailed description
The MARVEL 2 study is an acute, prospective, global, multi-center, software-download clinical study. The study is planned to be conducted in US, Europe, and Asia. The study is expected to be conducted at approximately 15-20 centers in up to 100 subjects to obtain at least 70 usable Holter datasets to meet the objectives of the study. The expected total study duration (from first subject enrollment to the exit of the last subject) is approximately 6-months; this represents the time necessary to enroll the target sample size of at least 70 subjects with usable Holter datasets. Software will be downloaded into patients implanted with a Micra device to allow the new algorithm performance to be measured in patients where a Micra device has already been chosen as most appropriate for the patient. Most enrolled subjects will complete the study procedures during a single study visit. However, subjects enrolling in the study at the time of their Micra implant (anticipated to be approximately 10 subjects) will have the investigational algorithm downloaded following Micra implant, prior to hospital discharge, and approximately 1-month post-implant. This subset of subjects with de novo Micra implants will allow the MARVEL 2 features to be tested at multiple points in the device life cycle. Since the download algorithm running in a Micra device significantly increases current drain, a 2-4 hour acute study is used to limit the reduction in device longevity.
Interventions
DEVICEMARVEL 2 Algorithm Monitor Mode then Adaptive Mode
Software download into implanted Micra device and programmed to MARVEL 2 Monitor Mode then MARVEL 2 Adaptive Mode
Sponsors
Medtronic Cardiac Rhythm and Heart Failure
Study design
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Echocardiogram core lab will be masked to the individual patient subjects and MARVEL 2 algorithm mode.
Intervention model description
Subjects enrolled in the MARVEL 2 study. Enrolled subjects will have the MARVEL 2 algorithm downloaded into their implanted market released Micra device. Each subject will be tested during when the MARVEL 2 algorithm is in monitor mode (VVI pacing) and in adaptive mode (VDD pacing).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has been implanted with a Micra TPS (Model MC1VR01) with remaining device longevity of 6 years or more or is expected to be implanted with a Micra TPS. * Subject has history of AV block\* * Subject is ≥ 18 years old and as per required local law. * Subject (and/or witness as applicable per local regulations) provides signed and dated authorization and/or consent per institution and local requirements. * Subject is willing and able to comply with the protocol. \*This includes subjects with normal sinus function and persistent 3rd degree AV block and subjects with other forms of AV block.
Exclusion criteria
* Subject is currently enrolled or planning to participate in a potentially confounding drug or device trial during the study. Co-enrollment in concurrent trials is only allowed when documented pre-approval is obtained from the Medtronic Clinical Research Specialist. * Subject is pregnant (if required by local law, women of child-bearing potential must undergo a pregnancy test within seven days prior to MARVEL 2 study procedures). * Subject meets any
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Atrial Ventricular Pacing Synchrony Success During Rest | 40 Minutes | A subject will meet the primary endpoint if a paced or sensed ventricular beat is within 300 ms following an ECG confirmed P-wave for at least 70% of the ECG confirmed P-waves. The primary endpoint will be evaluated during the MARVEL 2 setup phase during MARVEL 2 Algorithm monitor mode (VDI pacing which is effectively VVI pacing) and during the 20-minute resting period in which the MARVEL 2 Algorithm is programmed to Adaptive mode (VDD pacing) |
| Number of Participants Free From Inappropriate Pacemaker Function Events | Through study completion an average of one day | A participant will meet the primary endpoint if they are free from the following MARVEL 2 software related events during the entire Holter monitoring period where the MARVEL 2 features are enabled. Inappropriate pacemaker function events are defined as: 1. Cardiac pauses lasting longer than 2 cardiac cycles (where cardiac cycle length is defined by the programmed lower rate interval of the pacemaker), OR 2. Pacemaker oversensing induced tachycardia exceeding 3-minutes, defined as oversensing of the pacemaker's accelerometer signal leading to a heart rate exceeding 100 beats per minute. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular Outflow Tract Velocity Time Integral | 12 cardiac cycles | The secondary endpoint is left ventricular outflow tract (LVOT) velocity time integral (VTI) as obtained from echocardiogram while the MARVEL 2 features are in adaptive mode (VDD pacing) and while the MARVEL 2 features are in monitor mode (VDI pacing which is effectively VVI pacing). This was measured by the echo core laboratory that was blinded to the study participant and MARVEL 2 algorithm mode. |
Countries
Austria, Belgium, Denmark, France, Hong Kong, Malaysia, Spain, United States
Participant flow
Recruitment details
Subjects were considered enrolled when they signed informed consent Subjects were enrolled between 22 January 2019 and 14 June 2019 at 12 study centers in 8 countries
Pre-assignment details
Following enrollment, the MARVEL 2 algorithm was downloaded into the subject's implanted Micra pacemaker. Following download subjects were programmed to MARVEL 2 Algorithm monitor mode followed by MARVEL 2 adaptive mode. Two subjects exited prior to MARVEL 2 download; one did not meet the study inclusion/exclusion and one withdrew consent.
Participants by arm
| Arm | Count |
|---|---|
| MARVEL 2 Monitor Mode Then MARVEL 2 Adaptive Participants were programmed to MARVEL 2 algorithm monitor mode which provides standard VVI pacing for approximately 20 minutes. Then the MARVEL 2 algorithm was programmed to adaptive mode which provides VDD pacing for approximately 2 hours. | 77 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | MARVEL 2 Monitor Mode Then MARVEL 2 Adaptive | — |
|---|---|---|
| Age, Continuous | 77.6 years STANDARD_DEVIATION 11.8 | — |
| Predominant heart rhythm Intact atrioventricular conduction | 18 Participants | — |
| Predominant heart rhythm Other rhythm | 15 Participants | — |
| Predominant heart rhythm Participant exited prior to software download | 2 Participants | — |
| Predominant heart rhythm Persistent 3rd degree AV block with normal sinus | 40 Participants | — |
| Predominant heart rhythm Rhythm indeterminate | 2 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Austria | 6 participants | — |
| Region of Enrollment Belgium | 20 participants | — |
| Region of Enrollment Denmark | 4 participants | — |
| Region of Enrollment France | 6 participants | — |
| Region of Enrollment Hong Kong | 11 participants | — |
| Region of Enrollment Malaysia | 15 participants | — |
| Region of Enrollment Spain | 1 participants | — |
| Region of Enrollment United States | 14 participants | — |
| Sex: Female, Male Female | 31 Participants | — |
| Sex: Female, Male Male | 45 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 75 |
| other Total, other adverse events | 3 / 75 |
| serious Total, serious adverse events | 3 / 75 |
Outcome results
Primary
Atrial Ventricular Pacing Synchrony Success During Rest
A subject will meet the primary endpoint if a paced or sensed ventricular beat is within 300 ms following an ECG confirmed P-wave for at least 70% of the ECG confirmed P-waves. The primary endpoint will be evaluated during the MARVEL 2 setup phase during MARVEL 2 Algorithm monitor mode (VDI pacing which is effectively VVI pacing) and during the 20-minute resting period in which the MARVEL 2 Algorithm is programmed to Adaptive mode (VDD pacing)
Time frame: 40 Minutes
Population: Participants with a predominant heart rhythm of 3rd degree atrioventricular block and normal sinus function during the study period.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MARVEL 2 Monitor Mode Then MARVEL 2 Adaptive | Atrial Ventricular Pacing Synchrony Success During Rest | Monitor Mode Success and Adaptive Mode Success | 0 Participants |
| MARVEL 2 Monitor Mode Then MARVEL 2 Adaptive | Atrial Ventricular Pacing Synchrony Success During Rest | Monitor Mode Failed and Adaptive Mode Success | 38 Participants |
| MARVEL 2 Monitor Mode Then MARVEL 2 Adaptive | Atrial Ventricular Pacing Synchrony Success During Rest | Monitor Mode Success and Adaptive Mode Fail | 0 Participants |
| MARVEL 2 Monitor Mode Then MARVEL 2 Adaptive | Atrial Ventricular Pacing Synchrony Success During Rest | Monitor Mode Fail and Adaptive Mode Fail | 2 Participants |
Comparison: The null hypothesis was that the probability of meeting the endpoint (Atrioventricular synchrony \>70%) was the same in MARVEL 2 Monitor Mode and MARVEL 2 Adaptive Mode. A sample size of 35 participants with a predominant rhythm of 3rd degree atrioventricular block and normal sinus function provided \>90% power at a type I error rate of 0.05 assuming the proportion of patients meeting the endpoint in one mode, but not the other exceeded 50% and 90% of these pairs favored the Adaptive mode.p-value: <0.001McNemar
Primary
Number of Participants Free From Inappropriate Pacemaker Function Events
A participant will meet the primary endpoint if they are free from the following MARVEL 2 software related events during the entire Holter monitoring period where the MARVEL 2 features are enabled. Inappropriate pacemaker function events are defined as: 1. Cardiac pauses lasting longer than 2 cardiac cycles (where cardiac cycle length is defined by the programmed lower rate interval of the pacemaker), OR 2. Pacemaker oversensing induced tachycardia exceeding 3-minutes, defined as oversensing of the pacemaker's accelerometer signal leading to a heart rate exceeding 100 beats per minute.
Time frame: Through study completion an average of one day
Population: Number of participants with the MARVEL 2 software downloaded onto their Micra implanted pacemaker
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MARVEL 2 Monitor Mode Then MARVEL 2 Adaptive | Number of Participants Free From Inappropriate Pacemaker Function Events | 75 Participants |
Comparison: The null hypothesis is that 87% or fewer participants will achieve the endpoint. The alternative hypothesis is that more than 87% of participants will achieve the endpoint. A sample size of 70 participants provides at least 90% power to test the null hypothesis assuming the true rate of meeting the endpoint in the population is 98% at a type I error rate of 2.5%.p-value: <0.00195% CI: [95.2, 100]Exact binomial test
Secondary
Left Ventricular Outflow Tract Velocity Time Integral
The secondary endpoint is left ventricular outflow tract (LVOT) velocity time integral (VTI) as obtained from echocardiogram while the MARVEL 2 features are in adaptive mode (VDD pacing) and while the MARVEL 2 features are in monitor mode (VDI pacing which is effectively VVI pacing). This was measured by the echo core laboratory that was blinded to the study participant and MARVEL 2 algorithm mode.
Time frame: 12 cardiac cycles
Population: Participants with paired LVOT VTI measurements during MARVEL 2 Adaptive mode (VDD pacing mode) and MARVEL 2 Monitor mode (VDI pacing which is effectively VVI pacing) with a predominant heart rhythm of persistent 3rd degree atrioventricular block and normal sinus rhythm
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MARVEL 2 Monitor Mode Then MARVEL 2 Adaptive | Left Ventricular Outflow Tract Velocity Time Integral | 1.7 cm |
Comparison: The null hypothesis is that the mean LVOT VTI during MARVEL 2 Adaptive mode equals the mean LVOT VTI during MARVEL 2 Monitor mode. A sample size of 35 participants with paired LVOT VTI measurements provides 89% power at a type I error rate of 5% to reject the null hypothesis assuming the true difference in LVOT VTI is 2.1 cm with a standard deviation of 3.8 cm.p-value: 0.00295% CI: [0.7, 2.7]t-test, 2 sided