Micra Atrial TRacking Using A Ventricular AccELerometer 2

Study Overview
=================
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.

Official Title
-----------------
Micra Atrial TRacking Using A Ventricular AccELerometer 2

Conditions
-----------------
Atrioventricular Conduction Block

Intervention / Treatment
-----------------
* Device: MARVEL 2 Algorithm Monitor Mode then Adaptive Mode


Participation Criteria
=================
Eligibility Criteria
-----------------
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 exclusion criteria required by local law (age or other).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional 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).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MARVEL 2 Algorithm Monitor Mode, Then MARVEL 2 Adaptive Mode<br>Participants first received MARVEL 2 algorithm monitor mode which provides standard VVI pacing for approximately 20 minutes followed by MARVEL 2 algorithm adaptive mode for approximately 2 hours which provides VDD pacing. | Device: MARVEL 2 Algorithm Monitor Mode then Adaptive Mode<br>* Software download into implanted Micra device and programmed to MARVEL 2 Monitor Mode then MARVEL 2 Adaptive Mode<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 40 Minutes | 
| 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: Cardiac pauses lasting longer than 2 cardiac cycles (where cardiac cycle length is defined by the programmed lower rate interval of the pacemaker), OR 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. | Through study completion an average of one day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 12 cardiac cycles |