Clinical Benefits of the Closed Loop Stimulation in Sinus Node Disease

Study Overview
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Brief Summary
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The study is designed as a multi-center, international, prospective, parallel, randomized, single blinded trial comparing the time to first primary endpoint event (Sustained Paroxysmal AF/Persistent AF or stroke/TIA) occurrence in a follow up period of 3 years, between Closed Loop Stimulation (CLS) ON versus OFF, on top of a DDD pacing in patients with pacemaker or ICD indication who require dual-chamber pacing due to sinus node disease (SND), with or without atrioventricular (AV) block.

Detailed Description
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The benefits of rate-responsiveness on top of dual-chamber pacing still need to be definitively assessed in Sinus Node Dysfunction (SND). Although many rate responsive (RR) sensors have been developed, no large clinical trials evaluated their benefits in terms of clinical endpoints such as clinically relevant atrial fibrillation (AF) and stroke. Electromechanical sensors (piezoelectric accelerometers) have been widely used for their simplicity and overall reliability. However there is some evidence indicating the Closed Loop Stimulation as one of the more efficient and physiological sensors. Two randomized clinical studies have been conducted so far, showing that in the Brady-Tachy Syndrome the CLS algorithm was associated with a significantly lower overall atrial arrhythmia burden as compared both with a DDDR mode based on a standard accelerometric sensor and an atrial overdrive approach. Both studies yielded consistent results, albeit with a parallel and intraindividual comparison designs, respectively. The atrial arrhythmic burden is an important but surrogate endpoint, not necessarily related to long-term clinical outcome. The CLS effects on AF (if any) should be investigated in terms of time to first new onset of clinically relevant AF. In the light of these considerations, it appears interesting to run a large randomized study coherently collecting data on the overall clinical benefit of CLS, primarily in terms of AF and stroke, in a population indicated for pacemaker or ICD and needing dual-chamber pacing due to SND.

Official Title
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Clinical Benefits of the Closed Loop Stimulation in Sinus Node Disease - B3 Study

Conditions
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Sinus Node Disease

Intervention / Treatment
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* Device: DDD+CLS
* Device: DDD(R)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Class I or II recommendations for permanent pacing due to SND, with or without AV block according to the current guidelines; Patients for whom dual-chamber pacing is indicated or preferred; Patients with an optimized and stable antiarrhythmic medical therapy at the time of enrolment; Closed Loop Stimulation function was not previously activated; No stroke events from implant; Patient implanted for the first time; Exclusion Criteria: Permanent AF (PermAF) NYHA Class IV Heart Failure Stage V kidney dysfunction Any indication to Cardiac Resynchronization Therapy (CRT) Life expectancy < 1 Minors Pregnant or breast-feeding patients Participation in another interventional trial Atrial fibrillation ablation (left pulmonary veins) or other cardiac surgery < 3 m

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active group - CLS ON<br>Device will be programmed in a dual-chamber DDD pacing mode with the Closed Loop Stimulation (CLS) function ON; Intervention: DDD+CLS | Device: DDD+CLS<br>* Device will be programmed in a dual-chamber DDD pacing mode with the Closed Loop Stimulation (CLS) function ON<br>|
| Active Comparator: Control group - CLS OFF<br>Device will be programmed in a dual-chamber DDD(R) pacing mode with the Closed Loop Stimulation (CLS) function OFF | Device: DDD(R)<br>* Device will be programmed in a dual-chamber DDD(R) pacing mode with the Closed Loop Stimulation (CLS) function OFF<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First event of Sustained Paroxysmal AF or Persistent AF or stroke or TIA, whichever comes first. |  | three years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Paroxysmal AF (SPAF) | Assess the date of each events of SPAF occurred during the follow-up periods | Three years | 
| Persistent AF | Assess the date of each events of peristent AF occurred during the follow-up periods | Three years | 
| Permanent AF | Assess the date when AF is declared permanent | Three years | 
| Stroke/TIA | Assess the date of each events of stroke/TIA occurred during the follow-up periods | Three years | 
| Worsening Heart failure Hospitalization (wHF-H) | Assess the date of each events of wHF-H occurred during the follow-up periods | Three years | 
| All cause mortality |  | Three years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ICD, Heart Failure, Pacemaker, Closed Loop Stimulation, Atrial Fibrillation, Stroke