Physiological Ventricular Pacing Vs Managed Ventricular Pacing for Persistent AF Prevention in Prolonged AV Interval

Sinus Node Disease Clinical Trial

— PhysioVP-AF  

Official title:

Physiological Ventricular Pacing Versus Managed Ventricular Pacing for Persistent Atrial Fibrillation Prevention in Patients With Prolonged Atrioventricular Interval: a Multicenter RCT

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05367037
• Other study ID #: PhysioVP-AF
• Status: Recruiting
• Phase: N/A
• Start date: July 27, 2022
• Est. completion date: July 2027

Study information

• Verified date: September 2023
• Source: Quovadis Associazione
• Contact: Gianni Pastore, MD
• Phone: ?+39 (339) 754-4514?
• Email: gianni.pastore[@]aulss5.veneto.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: July 2027
• Est. primary completion date: July 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atrial Fibrillation
• Atrioventricular Block
• Sick Sinus Syndrome
• Sinus Node Disease

Intervention

Device:
• PhysioVP
The Physiological ventricular pacing is achieved by delivering a 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. A specialized delivery sheath for His-Purkinje system pacing with appropriate or standard leads will be used. The atrial leads will be implanted in the right atrial appendage and will connect the leads to the standard dual-chamber PM. By continuously recording a 12-lead ECG, we determine whether cardiac conduction structure, such as the bundle of His or left bundle branch of the His-Purkinje system, will be achieved.
• DDD-VPA
In dual-chamber pacing with the addition of algorithms for ventricular pacing avoidance, also called 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. Therefore, the RV leads will be implanted in the right ventricular myocardial sites (septum or apex) and standard bipolar active or passive fixation leads. In addition, the atrial leads will be implanted in the right atrial appendage and connect leads to the standard dual-chamber PM.

Locations

Country	Name	City	State
Italy	Elettrofisiologia, Cardiologia, Ospedale di Rovigo	Rovigo	Veneto

Sponsors (1)

Lead Sponsor	Collaborator
Quovadis Associazione

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PeAF Free	Freedom from persistent AF occurrences up to 36 months after the pacemaker (PM) implant.; The occurrence of PeAF is defined as the first AF / Atrial Flutter / Atrial Tachycardia episode lasting > 7 days, detected by the PM after a 1-month post PM lead-stabilization period. A day of AF is satisfied with a device-detected daily AF burden of = 23 hours. Device-detected AF may also be collected by remote monitoring tools, if available. The definition also includes the occurrence of episodes terminated by cardioversion, whatever its duration or undergoing AF ablation	36 months
Secondary	Hemodynamic performance, LV remodeling 1	Echocardiographic parameters: Left Ventriculi end-systolic volume (ml/m2).	12 months
Secondary	Hemodynamic performance, LV remodeling 2	Echocardiographic parameters: LVEF (%).	12 months
Secondary	Hemodynamic performance, Diastolic function 1	Echocardiographic parameters: E to A mitral wave amplitude ratio.	12 months
Secondary	Hemodynamic performance, Diastolic function 2	Echocardiographic parameters: E wave deceleration time (ms).	12 months
Secondary	Hemodynamic performance, Diastolic function 3	Echocardiographic parameters: pulsed-wave tissue Doppler early diastolic septal mitral annular velocity (e') (cm/s).	12 months
Secondary	Hemodynamic performance, Diastolic function 4	Echocardiographic parameters: E/e' ratio.	12 months
Secondary	Hemodynamic performance, Diastolic function 5	Echocardiographic parameters: Diastolic time (from onset E wave to end A wave) normalized for RR interval (ms).	12 months
Secondary	Hemodynamic performance, Left atrial volume	Echocardiographic parameters: Left atrial volume (ml/m2).	12 months
Secondary	Hemodynamic performance, Mitral regurgitation	Echocardiographic parameters: vena contracta (mm).	12 months
Secondary	Clinical evaluations, NYHA	NYHA class variation (I, II, III, IV).	12, 24, and 36 months
Secondary	Clinical evaluations, MLHFQ	Variation of Quality-of-Life assessment by Minnesota Living with Heart Failure questionnaire (MLHFQ).	12, 24, and 36 months
Secondary	Clinical evaluations	Number of cardiovascular diseases related to health structure access.	12, 24, and 36 months
Secondary	Clinical evaluations, HFH	Number of hospitalization for heart failure (HFH).	12, 24, and 36 months
Secondary	Safety endpoints, PRAE	Rate of all procedure-related adverse events (PRAE).	36 months
Secondary	Safety endpoints, Potentially harmful factor 1	Implantation/s procedure time (mm:ss).	36 months
Secondary	Safety endpoints, Potentially harmful factor 2	Fluoroscopy time (mm:ss).	36 months
Secondary	Safety endpoints, Incidence Rate of re-interventions	Rate of re-interventions for lead revision, replacement, or infection.	36 months
Secondary	Estimated battery longevity	Estimated residual battery longevity (time to end-of-life) by the implanted device every 6-months and/or when the primary endpoint is reached.	36 months