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Clinical Benefits of the Closed Loop Stimulation in Sinus Node Disease (B3)

Primary Purpose

Sinus Node Disease

Status
Active
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
DDD+CLS
DDD(R)
Sponsored by
Biotronik SE & Co. KG
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sinus Node Disease focused on measuring Closed Loop Stimulation, Atrial Fibrillation, Stroke, Heart Failure, Pacemaker, ICD

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Wuhan Asia Heart Hospital
  • The 2nd Affiliated Hospital of Harbin Medical University
  • Xuanwu Hospital Capital Medical University
  • Semmelweis University Heart and Vascular Center
  • Max Super Speciality Hospital
  • Ospedali Riuniti di Ancona
  • Ospedale Generale Regionale "F. Miulli"
  • Ospedale "Bolognini"
  • Presidio Ospedaliero Ospedale Sant'Anna
  • Ospedale Civile SS. Annunziata
  • Ospedale di Rho
  • Ospedale F. Ferrari
  • Ospedale Maria SS Addolorata
  • Ospedale Santa Maria della Stella
  • Ospedale di Conegliano
  • Azienda Ospedaliera Policlinico Consorziale
  • Ospedale Antonio Cardarelli
  • Azienda Ospedaliera di Caserta Sant'Anna e San Sebastiano
  • A.O.U. Policlinico Vittorio Emanuele
  • Ospedale Santa Maria Nuova
  • Ospedale Fabrizio Spaziani
  • ASST Valle Olona - Ospedale Sant'Antonio Abate
  • ASST RHODENSE - Ospedale Guido Salvini
  • Ospedale Ferdinando Veneziale
  • Ospedale Vito Fazzi
  • Nuovo Ospedale delle Apuane
  • Ospedale V. Monaldi
  • A.O.P. Federico II
  • A.O.U Maggiore della Carità di Novara
  • Azienda Ospedaliera di Padova
  • Ospedale S. Maria della Misericordia
  • Nuovo Ospedale Santo Stefano
  • Ospedale "Maria Paternò Arezzo"
  • Ospedale Infermi di Rimini
  • Policlinico Umberto I
  • Policlinico Casilino
  • Fondazione Policlinico Universitario Agostino Gemelli
  • Azienda Ospedaliera "S. Maria" di Terni
  • Ospedale di Treviso
  • Sejong General Hospital
  • Soon Chun Hyang University Hospital Bucheon
  • Seul National University Bundang Hospital
  • Korea University Anam Hospital
  • Seul National University Hospital
  • Pusan National University Yangsan Hospital
  • Hospital Serdang
  • National Heart Center Singapore
  • Tan Tock Seng Hospital
  • Hospital General Universitario de Alicante
  • Hospital Universitario 12 de Octubre
  • China Medical University Hospital
  • National Cheng Kung University Hospital
  • Chang Gung Memorial Hospital
  • National Taiwan University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Active group - CLS ON

Control group - CLS OFF

Arm Description

Device will be programmed in a dual-chamber DDD pacing mode with the Closed Loop Stimulation (CLS) function ON; Intervention: DDD+CLS

Device will be programmed in a dual-chamber DDD(R) pacing mode with the Closed Loop Stimulation (CLS) function OFF

Outcomes

Primary Outcome Measures

First event of Sustained Paroxysmal AF or Persistent AF or stroke or TIA, whichever comes first.

Secondary Outcome Measures

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

Full Information

First Posted
October 16, 2015
Last Updated
June 1, 2023
Sponsor
Biotronik SE & Co. KG
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1. Study Identification

Unique Protocol Identification Number
NCT02579889
Brief Title
Clinical Benefits of the Closed Loop Stimulation in Sinus Node Disease
Acronym
B3
Official Title
Clinical Benefits of the Closed Loop Stimulation in Sinus Node Disease - B3 Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 2015 (undefined)
Primary Completion Date
March 2023 (Actual)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biotronik SE & Co. KG

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sinus Node Disease
Keywords
Closed Loop Stimulation, Atrial Fibrillation, Stroke, Heart Failure, Pacemaker, ICD

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
1308 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active group - CLS ON
Arm Type
Experimental
Arm Description
Device will be programmed in a dual-chamber DDD pacing mode with the Closed Loop Stimulation (CLS) function ON; Intervention: DDD+CLS
Arm Title
Control group - CLS OFF
Arm Type
Active Comparator
Arm Description
Device will be programmed in a dual-chamber DDD(R) pacing mode with the Closed Loop Stimulation (CLS) function OFF
Intervention Type
Device
Intervention Name(s)
DDD+CLS
Intervention Description
Device will be programmed in a dual-chamber DDD pacing mode with the Closed Loop Stimulation (CLS) function ON
Intervention Type
Device
Intervention Name(s)
DDD(R)
Intervention Description
Device will be programmed in a dual-chamber DDD(R) pacing mode with the Closed Loop Stimulation (CLS) function OFF
Primary Outcome Measure Information:
Title
First event of Sustained Paroxysmal AF or Persistent AF or stroke or TIA, whichever comes first.
Time Frame
three years
Secondary Outcome Measure Information:
Title
Sustained Paroxysmal AF (SPAF)
Description
Assess the date of each events of SPAF occurred during the follow-up periods
Time Frame
Three years
Title
Persistent AF
Description
Assess the date of each events of peristent AF occurred during the follow-up periods
Time Frame
Three years
Title
Permanent AF
Description
Assess the date when AF is declared permanent
Time Frame
Three years
Title
Stroke/TIA
Description
Assess the date of each events of stroke/TIA occurred during the follow-up periods
Time Frame
Three years
Title
Worsening Heart failure Hospitalization (wHF-H)
Description
Assess the date of each events of wHF-H occurred during the follow-up periods
Time Frame
Three years
Title
All cause mortality
Time Frame
Three years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Wuhan Asia Heart Hospital
City
Wuhan
State/Province
Jinghan District
ZIP/Postal Code
430022
Country
China
Facility Name
The 2nd Affiliated Hospital of Harbin Medical University
City
Harbin
State/Province
Nangang District
Country
China
Facility Name
Xuanwu Hospital Capital Medical University
City
Beijing
State/Province
West City District
ZIP/Postal Code
100053
Country
China
Facility Name
Semmelweis University Heart and Vascular Center
City
Budapest
ZIP/Postal Code
1122
Country
Hungary
Facility Name
Max Super Speciality Hospital
City
New Delhi
ZIP/Postal Code
110017
Country
India
Facility Name
Ospedali Riuniti di Ancona
City
Torrette
State/Province
Ancona
ZIP/Postal Code
60126
Country
Italy
Facility Name
Ospedale Generale Regionale "F. Miulli"
City
Acquaviva Delle Fonti
State/Province
Bari
ZIP/Postal Code
70021
Country
Italy
Facility Name
Ospedale "Bolognini"
City
Seriate
State/Province
Bergamo
Country
Italy
Facility Name
Presidio Ospedaliero Ospedale Sant'Anna
City
San Fermo della Battaglia
State/Province
Como
ZIP/Postal Code
22020
Country
Italy
Facility Name
Ospedale Civile SS. Annunziata
City
Savigliano
State/Province
Cuneo
ZIP/Postal Code
12038
Country
Italy
Facility Name
Ospedale di Rho
City
Rho
State/Province
Italia
ZIP/Postal Code
20017
Country
Italy
Facility Name
Ospedale F. Ferrari
City
Casarano
State/Province
Lecce
Country
Italy
Facility Name
Ospedale Maria SS Addolorata
City
Eboli
State/Province
Salerno
ZIP/Postal Code
84025
Country
Italy
Facility Name
Ospedale Santa Maria della Stella
City
Orvieto
State/Province
Terni
ZIP/Postal Code
05018
Country
Italy
Facility Name
Ospedale di Conegliano
City
Conegliano
State/Province
Treviso
ZIP/Postal Code
31015
Country
Italy
Facility Name
Azienda Ospedaliera Policlinico Consorziale
City
Bari
Country
Italy
Facility Name
Ospedale Antonio Cardarelli
City
Campobasso
ZIP/Postal Code
86100
Country
Italy
Facility Name
Azienda Ospedaliera di Caserta Sant'Anna e San Sebastiano
City
Caserta
Country
Italy
Facility Name
A.O.U. Policlinico Vittorio Emanuele
City
Catania
Country
Italy
Facility Name
Ospedale Santa Maria Nuova
City
Firenze
ZIP/Postal Code
50122
Country
Italy
Facility Name
Ospedale Fabrizio Spaziani
City
Frosinone
Country
Italy
Facility Name
ASST Valle Olona - Ospedale Sant'Antonio Abate
City
Gallarate
Country
Italy
Facility Name
ASST RHODENSE - Ospedale Guido Salvini
City
Garbagnate
Country
Italy
Facility Name
Ospedale Ferdinando Veneziale
City
Isernia
ZIP/Postal Code
86170
Country
Italy
Facility Name
Ospedale Vito Fazzi
City
Lecce
ZIP/Postal Code
73100
Country
Italy
Facility Name
Nuovo Ospedale delle Apuane
City
Massa
ZIP/Postal Code
54100
Country
Italy
Facility Name
Ospedale V. Monaldi
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
A.O.P. Federico II
City
Napoli
Country
Italy
Facility Name
A.O.U Maggiore della Carità di Novara
City
Novara
ZIP/Postal Code
28100
Country
Italy
Facility Name
Azienda Ospedaliera di Padova
City
Padova
Country
Italy
Facility Name
Ospedale S. Maria della Misericordia
City
Perugia
Country
Italy
Facility Name
Nuovo Ospedale Santo Stefano
City
Prato
ZIP/Postal Code
59100
Country
Italy
Facility Name
Ospedale "Maria Paternò Arezzo"
City
Ragusa
ZIP/Postal Code
97100
Country
Italy
Facility Name
Ospedale Infermi di Rimini
City
Rimini
ZIP/Postal Code
47923
Country
Italy
Facility Name
Policlinico Umberto I
City
Roma
ZIP/Postal Code
00161
Country
Italy
Facility Name
Policlinico Casilino
City
Roma
ZIP/Postal Code
00169
Country
Italy
Facility Name
Fondazione Policlinico Universitario Agostino Gemelli
City
Rom
Country
Italy
Facility Name
Azienda Ospedaliera "S. Maria" di Terni
City
Terni
ZIP/Postal Code
05100
Country
Italy
Facility Name
Ospedale di Treviso
City
Treviso
ZIP/Postal Code
31100
Country
Italy
Facility Name
Sejong General Hospital
City
Bucheon
ZIP/Postal Code
14154
Country
Korea, Republic of
Facility Name
Soon Chun Hyang University Hospital Bucheon
City
Bucheon
Country
Korea, Republic of
Facility Name
Seul National University Bundang Hospital
City
Gyeonggi-do
Country
Korea, Republic of
Facility Name
Korea University Anam Hospital
City
Seoul
ZIP/Postal Code
02841
Country
Korea, Republic of
Facility Name
Seul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Pusan National University Yangsan Hospital
City
Yangsan
Country
Korea, Republic of
Facility Name
Hospital Serdang
City
Kajang
ZIP/Postal Code
43000
Country
Malaysia
Facility Name
National Heart Center Singapore
City
Singapore
ZIP/Postal Code
169609
Country
Singapore
Facility Name
Tan Tock Seng Hospital
City
Singapore
ZIP/Postal Code
308433
Country
Singapore
Facility Name
Hospital General Universitario de Alicante
City
Alicante
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
China Medical University Hospital
City
Taichung
ZIP/Postal Code
40447
Country
Taiwan
Facility Name
National Cheng Kung University Hospital
City
Tainan
Country
Taiwan
Facility Name
Chang Gung Memorial Hospital
City
Taipei
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei
Country
Taiwan

12. IPD Sharing Statement

Citations:
PubMed Identifier
14585254
Citation
Puglisi A, Altamura G, Capestro F, Castaldi B, Critelli G, Favale S, Pavia L, Pettinati G. Impact of Closed-Loop Stimulation, overdrive pacing, DDDR pacing mode on atrial tachyarrhythmia burden in Brady-Tachy Syndrome. A randomized study. Eur Heart J. 2003 Nov;24(21):1952-61. doi: 10.1016/j.ehj.2003.08.011.
Results Reference
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PubMed Identifier
18950302
Citation
Puglisi A, Favale S, Scipione P, Melissano D, Pavia L, Ascani F, Elia M, Scaccia A, Sagone A, Castaldi B, Musacchio E, Botto GL; Burden II Study Group. Overdrive versus conventional or closed-loop rate modulation pacing in the prevention of atrial tachyarrhythmias in Brady-Tachy syndrome: on behalf of the Burden II Study Group. Pacing Clin Electrophysiol. 2008 Nov;31(11):1443-55. doi: 10.1111/j.1540-8159.2008.01208.x.
Results Reference
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PubMed Identifier
22236222
Citation
Healey JS, Connolly SJ, Gold MR, Israel CW, Van Gelder IC, Capucci A, Lau CP, Fain E, Yang S, Bailleul C, Morillo CA, Carlson M, Themeles E, Kaufman ES, Hohnloser SH; ASSERT Investigators. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med. 2012 Jan 12;366(2):120-9. doi: 10.1056/NEJMoa1105575. Erratum In: N Engl J Med. 2016 Mar 10;374(10):998.
Results Reference
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PubMed Identifier
23723446
Citation
Russo V, Rago A, Papa AA, Golino P, Calabro R, Russo MG, Nigro G. The effect of dual-chamber closed-loop stimulation on syncope recurrence in healthy patients with tilt-induced vasovagal cardioinhibitory syncope: a prospective, randomised, single-blind, crossover study. Heart. 2013 Nov;99(21):1609-13. doi: 10.1136/heartjnl-2013-303878. Epub 2013 May 30.
Results Reference
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PubMed Identifier
12842643
Citation
de Cock CC, Giudici MC, Twisk JW. Comparison of the haemodynamic effects of right ventricular outflow-tract pacing with right ventricular apex pacing: a quantitative review. Europace. 2003 Jul;5(3):275-8. doi: 10.1016/s1099-5129(03)00031-x.
Results Reference
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PubMed Identifier
15189520
Citation
Lieberman R, Grenz D, Mond HG, Gammage MD. Selective site pacing: defining and reaching the selected site. Pacing Clin Electrophysiol. 2004 Jun;27(6 Pt 2):883-6. doi: 10.1111/j.1540-8159.2004.00551.x.
Results Reference
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PubMed Identifier
12063369
Citation
Lamas GA, Lee KL, Sweeney MO, Silverman R, Leon A, Yee R, Marinchak RA, Flaker G, Schron E, Orav EJ, Hellkamp AS, Greer S, McAnulty J, Ellenbogen K, Ehlert F, Freedman RA, Estes NA 3rd, Greenspon A, Goldman L; Mode Selection Trial in Sinus-Node Dysfunction. Ventricular pacing or dual-chamber pacing for sinus-node dysfunction. N Engl J Med. 2002 Jun 13;346(24):1854-62. doi: 10.1056/NEJMoa013040.
Results Reference
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PubMed Identifier
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Citation
Connolly SJ, Kerr CR, Gent M, Roberts RS, Yusuf S, Gillis AM, Sami MH, Talajic M, Tang AS, Klein GJ, Lau C, Newman DM. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. Canadian Trial of Physiologic Pacing Investigators. N Engl J Med. 2000 May 11;342(19):1385-91. doi: 10.1056/NEJM200005113421902.
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PubMed Identifier
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Citation
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Results Reference
result

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Clinical Benefits of the Closed Loop Stimulation in Sinus Node Disease

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