Clinical trial NCT05367037: Physiological Ventricular Pacing Vs Managed Ventricular Pacing for Persistent AF Prevention in Prolonged AV Interval
Official title: Physiological Ventricular Pacing Versus Managed Ventricular Pacing for Persistent Atrial Fibrillation Prevention in Patients With Prolonged Atrioventricular Interval: a Multicenter RCT
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Sinus Node Disease
Atrioventricular; Block, Second Degree (Types I and II)
Keywords: Sinus Node Disease
Paroxysmal AV-block
conduction system pacing
persistent atrial fibrillation
Lead sponsor: Quovadis Associazione
Sponsor class: OTHER
First posted: 2022-05-10
Enrollment: 640
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: a prospective, randomized study in a 1:1 ratio, single-blind with double-blind evaluation (the actual evaluator of the primary endpoint is the pacemaker device's internal diagnostic algorithm, without intervention by the Investigator)
Primary purpose: PREVENTION

Brief summary: A multicenter, prospective, randomized study in a 1:1 ratio, single-blind with double-blind evaluation to evaluate the superiority of physiological ventricular pacing (proposed modality) vs. managed ventricular pacing (control) for prevention of persistent AF (PeAF) occurrence in patients with prolonged atrioventricular interval (PR≥180 ms) and indication for pacing: sinus node disease and/or paroxysmal type 1 or 2-second degree AV block.

Detailed description: Study aim: Evaluate the superiority of physiological ventricular pacing (proposed modality) vs. managed ventricular pacing (control) for prevention of persistent AF (PeAF) occurrence in patients with prolonged atrioventricular interval (PR≥180 ms) and indication for pacing: sinus node disease and/or paroxysmal type 1 or 2-second degree AV block. If the efficacy superiority is confirmed, this pacing mode may be considered to reduce the occurrence of persistent atrial fibrillation in this group of patients.

Study design: Independent, multicenter, prospective, randomized study in a 1:1 ratio, single-blind with double-blind evaluation (the actual evaluator of the primary endpoint is the pacemaker device's internal diagnostic algorithm, without intervention by the Investigator). This study will use only CE-marked devices already part of clinical practice.

Groups:

* PhysioVP group: the Physiological Ventricular Pacing is achieved by delivering a pacing stimulus to a cardiac conduction structure, such as the bundle of His or left bundle branch of the His-Purkinje system, with a permanent lead. PhysioVP activates the heart through the native His-Purkinje conduction system, thus offering the most physiologic pacing approach to correct the PR interval and avoiding pacing-induced dyssynchrony.
* DDD-VPA group: In managed ventricular pacing, the right ventricular (RV) lead is implanted in the myocardial right ventricular (septum or apex). In this pacing mode, the ventricular pacing is minimized by using algorithms for right Ventricular Pacing Avoidance.

Devices used:

* PhysioVP group: a specialized delivery sheath for His-Purkinje system pacing with appropriate or standard leads will be used.
* DDD-VPA group: the RV leads will be implanted in the standard right ventricular myocardial sites (septum or apex) using standard bipolar active-fixation leads.

The atrial leads will be placed in the right atrial appendage in both groups. The 13 participating Italian Clinical Centers are proven experience in the PM implantation procedures used in the study.

Enrolled patients will be monitored by in-office clinical checks at 1, 12, 24, and 36 months and by home monitoring at 6, 18, and 30 months after implantation.

Eligibility criteria: Inclusion Criteria:

18 years older patients, able to express Informed Consent, with prolonged atrioventricular interval (PR\>180 ms) and one of the following indications for PM implantation according to current guidelines:

* Sinus node disease.
* Paroxysmal type1or 2 second-degree AV-block.

Exclusion Criteria:

* Candidacy for implantable cardioverter-defibrillator or cardiac resynchronization therapy device implantation.
* Severe grade mitral or aortic regurgitation/stenosis.
* Atrial fibrillation ablation (left pulmonary veins).
* Cardiac surgery \< 3 months before PM implantation.
* History of long-standing persistent AF.
* Permanent third-degree AV block.
* Participation in another clinical trial in the past 3 months.
* Pregnancy or intention to become pregnant.
* Life expectancy of \< 3 years.

Primary outcomes:
measure: PeAF Free
timeFrame: 36 months
measure: Clinical composite outcome
timeFrame: 36 months
Secondary outcomes:
measure: Hemodynamic performance, LV remodeling 1
timeFrame: 12 months
measure: Hemodynamic performance, LV remodeling 2
timeFrame: 12 months
measure: Hemodynamic performance, Diastolic function 1
timeFrame: 12 months
measure: Hemodynamic performance, Diastolic function 2
timeFrame: 12 months
measure: Hemodynamic performance, Diastolic function 3
timeFrame: 12 months
measure: Hemodynamic performance, Diastolic function 4
timeFrame: 12 months
measure: Hemodynamic performance, Diastolic function 5
timeFrame: 12 months
measure: Hemodynamic performance, Left atrial volume
timeFrame: 12 months
measure: Hemodynamic performance, Mitral regurgitation
timeFrame: 12 months
measure: Clinical evaluations, NYHA
timeFrame: 12, 24, and 36 months
measure: Clinical evaluations, MLHFQ
timeFrame: 12, 24, and 36 months
measure: Clinical evaluations
timeFrame: 12, 24, and 36 months
measure: Safety endpoints, PRAE
timeFrame: 36 months
measure: Safety endpoints, Potentially harmful factor 1
timeFrame: 36 months
measure: Safety endpoints, Potentially harmful factor 2
timeFrame: 36 months
measure: Safety endpoints, Incidence Rate of re-interventions
timeFrame: 36 months
measure: Estimated battery longevity
timeFrame: 36 months
Other outcomes:
Locations:
city: Rovigo
country: Italy
facility: Elettrofisiologia, Cardiologia, Ospedale di Rovigo
state: Veneto
Study officials:
affiliation: Cardiology Unit, "S.Maria della Misericordia" Hospital, Rovigo, Italy
name: Gianni Pastore, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pastore G, Bertini M, Bonanno C, Coluccia G, Dell'Era G, De Mattia L, Grieco D, Katsouras G, Maines M, Marcantoni L, Marinaccio L, Paglino G, Palmisano P, Ziacchi M, Zoppo F, Noventa F. The PhysioVP-AF study, a randomized controlled trial to assess the clinical benefit of physiological ventricular pacing vs. managed ventricular pacing for persistent atrial fibrillation prevention in patients with prolonged atrioventricular conduction: design and rationale. Europace. 2023 May 19;25(5):euad082. doi: 10.1093/europace/euad082.