Clinical Benefits of the Closed Loop Stimulation in Sinus Node Disease

Sinus Node Disease Clinical Trial

— B3  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02579889
• Other study ID #: BA104
• Status: Terminated
• Phase: N/A
• Start date: September 2015
• Est. completion date: December 2023

Study information

• Verified date: January 2024
• Source: Biotronik SE & Co. KG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1390
• Est. completion date: December 2023
• Est. primary completion date: March 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Sick Sinus Syndrome
• Sinus Node Disease

Intervention

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

Locations

Country	Name	City	State
China	Xuanwu Hospital Capital Medical University	Beijing	West City District
China	The 2nd Affiliated Hospital of Harbin Medical University	Harbin	Nangang District
China	Wuhan Asia Heart Hospital	Wuhan	Jinghan District
Hungary	Semmelweis University Heart and Vascular Center	Budapest
India	Max Super Speciality Hospital	New Delhi
Italy	Ospedale Generale Regionale "F. Miulli"	Acquaviva Delle Fonti	Bari
Italy	Azienda Ospedaliera Policlinico Consorziale	Bari
Italy	Ospedale Antonio Cardarelli	Campobasso
Italy	Ospedale F. Ferrari	Casarano	Lecce
Italy	Azienda Ospedaliera di Caserta Sant'Anna e San Sebastiano	Caserta
Italy	A.O.U. Policlinico Vittorio Emanuele	Catania
Italy	Ospedale di Conegliano	Conegliano	Treviso
Italy	Ospedale Maria SS Addolorata	Eboli	Salerno
Italy	Ospedale Santa Maria Nuova	Firenze
Italy	Ospedale Fabrizio Spaziani	Frosinone
Italy	ASST Valle Olona - Ospedale Sant'Antonio Abate	Gallarate
Italy	ASST RHODENSE - Ospedale Guido Salvini	Garbagnate
Italy	Ospedale Ferdinando Veneziale	Isernia
Italy	Ospedale Vito Fazzi	Lecce
Italy	Nuovo Ospedale delle Apuane	Massa
Italy	A.O.P. Federico II	Napoli
Italy	Ospedale V. Monaldi	Napoli
Italy	A.O.U Maggiore della Carità di Novara	Novara
Italy	Ospedale Santa Maria della Stella	Orvieto	Terni
Italy	Azienda Ospedaliera di Padova	Padova
Italy	Ospedale S. Maria della Misericordia	Perugia
Italy	Nuovo Ospedale Santo Stefano	Prato
Italy	Ospedale "Maria Paternò Arezzo"	Ragusa
Italy	Ospedale di Rho	Rho	Italia
Italy	Ospedale Infermi di Rimini	Rimini
Italy	Fondazione Policlinico Universitario Agostino Gemelli	Rom
Italy	Policlinico Casilino	Roma
Italy	Policlinico Umberto I	Roma
Italy	Presidio Ospedaliero Ospedale Sant'Anna	San Fermo della Battaglia	Como
Italy	Ospedale Civile SS. Annunziata	Savigliano	Cuneo
Italy	Ospedale "Bolognini"	Seriate	Bergamo
Italy	Azienda Ospedaliera "S. Maria" di Terni	Terni
Italy	Ospedali Riuniti di Ancona	Torrette	Ancona
Italy	Ospedale di Treviso	Treviso
Korea, Republic of	Sejong General Hospital	Bucheon
Korea, Republic of	Soon Chun Hyang University Hospital Bucheon	Bucheon
Korea, Republic of	Seul National University Bundang Hospital	Gyeonggi-do
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Seul National University Hospital	Seoul
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan
Malaysia	Hospital Serdang	Kajang
Singapore	National Heart Center Singapore	Singapore
Singapore	Tan Tock Seng Hospital	Singapore
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Universitario 12 de Octubre	Madrid
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Chang Gung Memorial Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Biotronik SE & Co. KG

Countries where clinical trial is conducted

China,  Hungary,  India,  Italy,  Korea, Republic of,  Malaysia,  Singapore,  Spain,  Taiwan, 

References & Publications (9)

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 — View 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. — View 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 M — View 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 Dysfunctio — View 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. — View 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. 200 — View 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 tachyar — View 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, c — View Citation

Toff WD, Camm AJ, Skehan JD; United Kingdom Pacing and Cardiovascular Events Trial Investigators. Single-chamber versus dual-chamber pacing for high-grade atrioventricular block. N Engl J Med. 2005 Jul 14;353(2):145-55. doi: 10.1056/NEJMoa042283. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	First event of Sustained Paroxysmal AF or Persistent AF or stroke or TIA, whichever comes first.		three years
Secondary	Sustained Paroxysmal AF (SPAF)	Assess the date of each events of SPAF occurred during the follow-up periods	Three years
Secondary	Persistent AF	Assess the date of each events of peristent AF occurred during the follow-up periods	Three years
Secondary	Permanent AF	Assess the date when AF is declared permanent	Three years
Secondary	Stroke/TIA	Assess the date of each events of stroke/TIA occurred during the follow-up periods	Three years
Secondary	Worsening Heart failure Hospitalization (wHF-H)	Assess the date of each events of wHF-H occurred during the follow-up periods	Three years
Secondary	All cause mortality		Three years