Clinical trial NCT05498376: The Leadless AV Versus DDD Pacing Study
Official title: The Leadless AV Versus DDD Pacing Study: A Randomized Controlled Single-center Trial on Leadless Versus Conventional Cardiac Dual-chamber Pacing
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Cardiac Pacemaker
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Keywords: Leadless pacemaker
Atrioventricular conduction block
Bradyarrhythmias
Micra
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: University of Bern
First posted: 2022-08-12
Enrollment: 100
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Exercise capacity
timeFrame: Month 3 post implantation
Secondary outcomes:
measure: Total implantation time
timeFrame: During implantation on day 0
measure: Total fluoroscopy time
timeFrame: During implantation on day 0
measure: Total fluoroscopy dosage
timeFrame: During implantation on day 0
measure: Pacing thresholds
timeFrame: Days 0,1 and months 1,3,12 and 24 post implantation
measure: Sensing values
timeFrame: Days 0,1 and months 1,3,12 and 24 post implantation
measure: Impedance values
timeFrame: Days 0,1 and months 1,3,12 and 24 post implantation
measure: Duration of exercise
timeFrame: Month 3 post implantation
measure: VO2max
timeFrame: Month 3 post implantation
measure: VE/VCO2
timeFrame: Month 3 post implantation
measure: VE/VO2
timeFrame: Month 3 post implantation
measure: Maximum atrial heart rate
timeFrame: Month 3 post implantation
measure: Left ventricular ejection fraction (LVEF)
timeFrame: Day 0 and months 3, 12 and 24 post implantation
measure: Degree of tricuspid valve regurgitation
timeFrame: Day 0 and months 3, 12 and 24 post implantation
measure: Degree of mitral valve regurgitation
timeFrame: Day 0 and months 3, 12 and 24 post implantation
measure: Quality of Life scores measured with the EQ-5D-5L Questionnaire
timeFrame: Days 0,1 and months 1,3,12 and 24 post implantation
measure: AV synchrony
timeFrame: Day 1 and months 1,3,12 and 24 post implantation
measure: Laboratory
timeFrame: Day 0 and month 3 post implantation
measure: Safety outcomes
timeFrame: Days 0,1 and months 1,3,12 and 24 post implantation
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Inselspital, Bern University Hospital
Study officials:
affiliation: Inselspital, Bern University Hospital
name: Andreas Häberlin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, Breithardt OA, Cleland J, Deharo JC, Delgado V, Elliott PM, Gorenek B, Israel CW, Leclercq C, Linde C, Mont L, Padeletti L, Sutton R, Vardas PE; ESC Committee for Practice Guidelines (CPG); Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S; Document Reviewers; Kirchhof P, Blomstrom-Lundqvist C, Badano LP, Aliyev F, Bansch D, Baumgartner H, Bsata W, Buser P, Charron P, Daubert JC, Dobreanu D, Faerestrand S, Hasdai D, Hoes AW, Le Heuzey JY, Mavrakis H, McDonagh T, Merino JL, Nawar MM, Nielsen JC, Pieske B, Poposka L, Ruschitzka F, Tendera M, Van Gelder IC, Wilson CM. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J. 2013 Aug;34(29):2281-329. doi: 10.1093/eurheartj/eht150. Epub 2013 Jun 24. No abstract available.