The Leadless AV Versus DDD Pacing Study

Cardiovascular Diseases Clinical Trial

— LEAVE DDD  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05498376
• Other study ID #: 2021-D0050
• Status: Recruiting
• Phase: Phase 4
• Start date: August 23, 2022
• Est. completion date: February 28, 2026

Study information

• Verified date: December 2023
• Source: Insel Gruppe AG, University Hospital Bern
• Contact: Andreas Häberlin, MD
• Phone: +41 31 664 06 74
• Email: Andreas.Haeberlin[@]insel.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: February 28, 2026
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arrhythmias, Cardiac
• Cardiac Pacemaker
• Cardiovascular Diseases
• Heart Diseases

Intervention

Device:
• Conventional pacemaker DDD
Implantation of a conventional cardiac pacemaker
• Leadless pacemaker Micra AV
Implantation of a leadless cardiac pacemaker

Locations

Country	Name	City	State
Switzerland	Inselspital, Bern University Hospital	Bern

Sponsors (2)

Lead Sponsor	Collaborator
Insel Gruppe AG, University Hospital Bern	University of Bern

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Exercise capacity	Exercise capacity (VO2 at anaerobic threshold) as assessed by spiroergometry	Month 3 post implantation
Secondary	Total implantation time	Total implantation time	During implantation on day 0
Secondary	Total fluoroscopy time	Total fluoroscopy time during implantation	During implantation on day 0
Secondary	Total fluoroscopy dosage	Total fluoroscopy dosage during implantation	During implantation on day 0
Secondary	Pacing thresholds	Pacing thresholds of the implanted pacemaker	Days 0,1 and months 1,3,12 and 24 post implantation
Secondary	Sensing values	Sensing values of the implanted pacemaker	Days 0,1 and months 1,3,12 and 24 post implantation
Secondary	Impedance values	Impedance values of the implanted pacemaker	Days 0,1 and months 1,3,12 and 24 post implantation
Secondary	Duration of exercise	Duration of exercise until exhaustion assessed by spiroergometry	Month 3 post implantation
Secondary	VO2max	VO2max assessed by spiroergometry	Month 3 post implantation
Secondary	VE/VCO2	VE/VCO2 assessed by spiroergometry	Month 3 post implantation
Secondary	VE/VO2	VE/VO2 assessed by spiroergometry	Month 3 post implantation
Secondary	Maximum atrial heart rate	Maximum atrial heart rate as assessed by spiroergometry	Month 3 post implantation
Secondary	Left ventricular ejection fraction (LVEF)	LVEF as assessed by echocardiography	Day 0 and months 3, 12 and 24 post implantation
Secondary	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
Secondary	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
Secondary	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
Secondary	AV synchrony		Day 1 and months 1,3,12 and 24 post implantation
Secondary	Laboratory	NT-proBNP	Day 0 and month 3 post implantation
Secondary	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 >2000O), 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