The Leadless AV Versus DDD Pacing Study

Study Overview
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Brief Summary
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Cardiac pacemaker (PM) implantation is the established treatment for relevant bradyarrhythmias. Conventional PMs require 1-3 pacing leads to register the heart's intrinsic activity (sensing) and to deliver the electrical stimuli to the heart (pacing). These leads are responsible for the vast majority of morbidity after implantation and PM failures. Therefore, a leadless PM system (Micra TPS™, Medtronic, United States) has been introduced a few years ago. This system overcomes the limitations of leads, however, the first generation of the Micra TPS™ only allowed sensing and pacing in the right ventricle. More recently, an upgraded version has been introduced and gained market approval (Micra AV, Medtronic, United States). According to published results from several clinical trials, this device allows sensing the atrial activity and, thus, timing the delivery of the ventricular pacing impulse in a physiological manner similar to a conventional dual-chamber PM with two leads. Clinical feasibility and safety for this concept have been established already. However, it is unclear if this translates into a direct clinical benefit for patients in comparison to conventional PM systems. The aim of this trial is to compare the therapeutic efficacy of the Micra AV™ PM and conventional dual-chamber PM systems in patients with intermittent or permanent atrioventricular conduction block and a PM indication according to the latest European guidelines. Thus, patients will be randomized to either a conventional dual-chamber PM implantation or the implantation of a leadless Micra AV™ system. Patients will be stratified for gender (female/male) and a priori estimated physical exercise capacity (fit/unfit). The primary outcome will be the physical exercise capacity of the patients. The null hypothesis with regards to the primary endpoint is that the leadless pacemaker arm shows an inferior VO2 anaerobic threshold than the conventional pacemaker arm. Hence the alternative hypothesis postulates that the leadless pacemaker arm shows a non-inferior VO2 anaerobic threshold compared to the conventional pacemaker arm. Rejection of the null hypothesis is needed to conclude non-inferiority.

Official Title
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The Leadless AV Versus DDD Pacing Study: A Randomized Controlled Single-center Trial on Leadless Versus Conventional Cardiac Dual-chamber Pacing

Conditions
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Cardiac Pacemaker, Arrhythmias, Cardiac, Heart Diseases, Cardiovascular Diseases

Intervention / Treatment
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* Device: Conventional pacemaker DDD
* Device: Leadless pacemaker Micra AV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients (≥70y) undergoing a de-novo pacemaker implantation due to intermittent or permanent AV block, qualifying for a conventional or leadless pacemaker Written informed consent Exclusion Criteria: Permanent atrial fibrillation or atrial standstill Evidence of sinus node disease and need for right atrial pacing (not possible with Micra AV) LVEF <50% and permanent high-degree or total AVB (requiring CRT/His-Bundle/CSP pacing) Preoperative E/A ratio >1.5 in the echocardiography Any co-existing ICD indications (no leadless ICD systems available) Hemodialysis Presence of a mechanical tricuspid valve prosthesis Unwilling or unable to comply fully with study procedures and follow-up

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conventional pacemaker DDD<br>Implantation of a conventional dual-chamber PM | Device: Conventional pacemaker DDD<br>* Implantation of a conventional cardiac pacemaker<br>|
| Active Comparator: Leadless pacemaker Micra AV<br>Implantation of a leadless pacemaker system (Micra AV™) | Device: Leadless pacemaker Micra AV<br>* Implantation of a leadless cardiac pacemaker<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exercise capacity | Exercise capacity (VO2 at anaerobic threshold) as assessed by spiroergometry | Month 3 post implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total implantation time | Total implantation time | During implantation on day 0 | 
| Total fluoroscopy time | Total fluoroscopy time during implantation | During implantation on day 0 | 
| Total fluoroscopy dosage | Total fluoroscopy dosage during implantation | During implantation on day 0 | 
| Pacing thresholds | Pacing thresholds of the implanted pacemaker | Days 0,1 and months 1,3,12 and 24 post implantation | 
| Sensing values | Sensing values of the implanted pacemaker | Days 0,1 and months 1,3,12 and 24 post implantation | 
| Impedance values | Impedance values of the implanted pacemaker | Days 0,1 and months 1,3,12 and 24 post implantation | 
| Duration of exercise | Duration of exercise until exhaustion assessed by spiroergometry | Month 3 post implantation | 
| VO2max | VO2max assessed by spiroergometry | Month 3 post implantation | 
| VE/VCO2 | VE/VCO2 assessed by spiroergometry | Month 3 post implantation | 
| VE/VO2 | VE/VO2 assessed by spiroergometry | Month 3 post implantation | 
| Maximum atrial heart rate | Maximum atrial heart rate as assessed by spiroergometry | Month 3 post implantation | 
| Left ventricular ejection fraction (LVEF) | LVEF as assessed by echocardiography | Day 0 and months 3, 12 and 24 post implantation | 
| Degree of tricuspid valve regurgitation | Degree of tricuspid valve regurgitation assessed by trans-thoracic echocardiogram. The degree of tricuspid valve regurgitation will be classified as none, mild, moderate or severe | Day 0 and months 3, 12 and 24 post implantation | 
| Degree of mitral valve regurgitation | Degree of mitral valve regurgitation assessed by trans-thoracic echocardiogram. The degree of mitral valve regurgitation will be classified as none, mild, moderate or severe | Day 0 and months 3, 12 and 24 post implantation | 
| Quality of Life scores measured with the EQ-5D-5L Questionnaire | Quality of Life scores measured with the EQ-5D-5L Questionnaire Scores: mobility, self-care, usual activities, pain/discomfort and anxiety/depression, each with a 5-scale response option; current health state assessed with a number between 0 and 100 | Days 0,1 and months 1,3,12 and 24 post implantation | 
| AV synchrony |  | Day 1 and months 1,3,12 and 24 post implantation | 
| Laboratory | NT-proBNP | Day 0 and month 3 post implantation | 
| Safety outcomes | Major adverse events (death, cardiac tamponade, any surgical reintervention, pocket/groin problems, lead/device dislocations; electrode noise, pacing impedance out of range (<200 or >2000Ω), failure to capture at maximum output, infections and thrombosis/embolism); rate of pacemaker syndrome developed by patients; rate of device upgrades/revisions required | Days 0,1 and months 1,3,12 and 24 post implantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Micra, Leadless pacemaker, Atrioventricular conduction block, Bradyarrhythmias