The Leadless AV Versus DDD Pacing Study (LEAVE DDD)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Pacemaker
• Intervention / Treatment: Device: Conventional pacemaker DDD; Device: Leadless pacemaker Micra AV

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Andreas Häberlin, MD; Phone Number: +41 31 664 06 74; Email: Andreas.Haeberlin@insel.ch

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Recruiting
    • Inselspital, Bern University Hospital
    • Contact: Andreas Häberlin, MD; Phone Number: +41 31 664 06 74; Email: Andreas.Haeberlin@insel.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Collaborators: University of Bern
• Investigators: Principal Investigator: Andreas Häberlin, MD, Inselspital, Bern University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2022
• Primary Completion (Estimated): May 31, 2024
• Study Completion (Estimated): February 28, 2026

Study Registration Dates

• First Submitted: August 3, 2022
• First Submitted That Met QC Criteria: August 8, 2022
• First Posted (Actual): August 12, 2022

Study Record Updates

• Last Update Posted (Actual): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Bradyarrhythmias; Leadless pacemaker; Atrioventricular conduction block; Micra
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac
• Other Study ID Numbers: 2021-D0050

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No