Clinical trial NCT02579889: Clinical Benefits of the Closed Loop Stimulation in Sinus Node Disease
Official title: Clinical Benefits of the Closed Loop Stimulation in Sinus Node Disease - B3 Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Sinus Node Disease
Keywords: Closed Loop Stimulation
Atrial Fibrillation
Stroke
Heart Failure
Pacemaker
ICD
Lead sponsor: Biotronik SE & Co. KG
Sponsor class: INDUSTRY
First posted: 2015-10-20
Enrollment: 1390
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

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