Clinical trial NCT00729703: Optimal Anti-tachycardia Therapy in Implantable Cardioverter-defibrillator (ICD) Patients Without Pacing Indications
Official title: Optimal Antitachycardia Therapy in ICD Patients Without Pacing Indications
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Tachycardia
Keywords: ICD
Minimized
ventricular
pacing
indication
Clinical outcome
Inappropriate shock
Lead sponsor: LivaNova
Sponsor class: INDUSTRY
First posted: 2008-08-07
Enrollment: 462
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: This study evaluates the impact of a new pacing mode avoiding unnecessary ventricular stimulation in combination with advanced dual chamber detection with slow VT management on the clinical outcome for hospitalization and mortality and inadequate therapy in medically stable, ICD-indicated patients with impaired left ventricular function (LVEF ≤ 40%) who do not have pacing indications and no indication for Cardiac Resynchronization Therapy (CRT). It compares a new pacing mode avoiding ventricular stimulation when not needed combined with dual chamber detection with a pure ventricular back up pacing and single chamber detection criteria with pure ventricular back up pacing. Therapies are compared in a prospective, randomized, single-blinded, parallel trial with a 24-month randomized treatment period. Randomization follows a 1:1 ratio. ICD therapy is enabled for all patients throughout the study. All patients receive optimal drug therapy for arrhythmia and heart failure treatment.

Detailed description: All patients will receive an implantable cardioverter defibrillator OVATIO™ DR model 6550 or a later Sorin Group device offering the same functions. After Enrolment visit but before implant, patients will be randomized in two arms according to the parallel study design. Whenever possible before implant there will be the first Holter recording for the Tvar risk stratification procedure. In case Tvar recording could not be performed before implant it has to be performed before patient leaves the hospital post implant in unpaced rhythm.

The dual-chamber arm will be programmed to 3 detection zones with PARAD+ activated.

The TDI for the slow VT zone will be set to 500 ms (120 bpm - or in case the resting rate is higher than 90 bpm it is recommended to adjust this parameter to: resting rate + 30 bpm) and at least one ATP program activated as specified in table 1.

A VT zone with a TDI of 353 ms (170 bpm) in case of no history of VT or a TDI cycle length equalling slowest documented VT interval (spontaneous or induced) plus 50 ms is required. In this 2nd VT zone therapies need to be activated in this group.

AAIsafeR2 mode will be activated with a basic rate of 60 bpm. The single-chamber arm will be programmed to optimal detection with Acceleration (Onset), Stability and Long Cycle Search (VTLC) activated. A VT zone is requested in this group, with the same programming procedures as described above. Therapies will be set according to the clinical judgment of the participating investigators but a Slow VT-zone with TDI 500 ms in monitoring setting at least is required.

Eligibility criteria: Inclusion Criteria:

* Patient has been prescribed the implantation for an ICD system accordingly to the relevant currently-approved ACC/AHA guidelines 1 or ESC guidelines 35 or any relevant currently-approved local guidelines for the implantation of an ICD-system
* Impaired left ventricular function demonstrated by a left-ventricular ejection fraction (LVEF) ≤ 40 %, measured by angio-scintigraphy, echocardiography, or contrast ventriculogram.
* An optimal (as determined by the enrolling physician) medical regimen.
* Patient has received all relevant information on the study, and has signed and dated a consent form.

Exclusion Criteria:

* Any generally accepted indication for standard cardiac pacing, or any contraindication for standard cardiac pacing.
* Any indication for CRT accordingly to the relevant currently-approved ACC/AHA1 or ESC35 guidelines for the implantation of a CRT system.
* Any contraindication for ICD therapy and the implant of a dual chamber ICD.
* ICD replacement
* Chronic atrial arrhythmias or cardioversion for atrial fibrillation within the past month.
* A PR interval \> 250 ms or AR interval \> 300 ms measured at implant.
* Hypertrophic obstructive cardiomyopathy.
* Acute myocarditis.
* Unstable coronary symptoms or myocardial infarction within the last month.
* Recent (within the last month) or planned cardiac revascularization or coronary angioplasty.
* Recently performed (in the last month) or planned cardiac surgery
* Already included in another clinical study.
* Life expectancy less than 24 months.
* Inability to understand the purpose of the study or refusal to cooperate.
* Inability or refusal to provide informed consent and, if not part of the informed consent, a Health Insurance Portability and Accountability Act (HIPAA) authorization.
* Unavailability for scheduled follow-up at the implanting or cooperating center.
* Age of less than 18 years.
* Pregnancy

Primary outcomes:
measure: The first part is the time to first occurrence of inappropriate ICD shock therapy. The second part is the composite endpoint of time to first occurrence of death (all causes)or Hospitalizations due to cardio-vascular event.
timeFrame: implant, 3 months, 9 months, 15 months, 21 months and 27 months
Secondary outcomes:
measure: all cause mortality and cardio-vascular related mortality
timeFrame: 27 months follow up
measure: Hospitalizations due to cardio-vascular event (specified for each type of event)
timeFrame: 27 months follow up
measure: Time to first occurrence of inappropriate ICD shock therapy
timeFrame: 27 months follow up
measure: Evaluation of the impact of the different therapies on quality of life and heart failure status
timeFrame: 27 months follow up
measure: Sensitivity and specificity for VT/SVT discrimination for the first 100 patients in each group.
timeFrame: 27 months
measure: Inappropriate overall device reactions defined by inappropriate shock and/or ATP therapy or inappropriate therapy delay/inhibition > 2 minutes on VTs
timeFrame: 27 months
measure: time to first documented AF occurrence and number of patients moving into permanent or persistent AF
timeFrame: 27 months follow up
measure: Cardiac dimensions obtained by echo evaluation for a subset of patients of both groups
timeFrame: Baseline and 27 months
measure: Slow VT incidence
timeFrame: 27 months
measure: Unscheduled visits and hospitalizations due to slow VT
timeFrame: 27 months follow up
measure: System related complications including lead dislodgements, exit block, oversensing which requires programming corrections, infections, complications which require reintervention
timeFrame: 27 months follow up
measure: Cumulative percentage of ventricular pacing and proportion of patients with 0% V pacing.
timeFrame: 27 months follow up
measure: Overall success rate of ATP in the FVT zone
timeFrame: 27 months
measure: Cost effectiveness of applied ICD therapy
timeFrame: 27 months
measure: PPV and NPV for Tvar risk stratification
timeFrame: 27 months
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Piedmont Hospital Research Institute
state: Georgia
city: Decatur
country: United States
facility: Atlanta Va Medical Center
state: Georgia
city: Mandeville
country: United States
facility: Southern Medical Research, Llc
state: Louisiana
city: Jeffersonville
country: United States
facility: River City Cardiology
state: Ohio
city: Florence
country: United States
facility: Pee Dee Cardiology
state: South Carolina
city: Antwepen
country: Belgium
facility: Algemeen Ziekenhuis - Antwepen
city: Gent
country: Belgium
facility: Kliniek Maria Middelares - Gent
city: Hasselt
country: Belgium
facility: Heart Center Virga Jesse Ziekenhuis - Hasselt
city: Montreal
country: Canada
facility: CHUM Hotel-Dieu
city: Montreal
country: Canada
facility: Hôpital Sacré Coeur
city: Aix-en-Provence
country: France
facility: Centre Hospitalier General
city: Bordeaux
country: France
facility: CHU Le Haut L'Evêque
city: Grenoble
country: France
facility: CHU Hôpital Michallon Grenoble
city: Le Chesnay
country: France
facility: Clinique De Parly II
city: Le Mans
country: France
facility: Clinique les sources
city: Lomme
country: France
facility: CH ST Philibert
city: Lyon
country: France
facility: Hôpital St Joseph
city: Montpellier
country: France
facility: Hopital Arnaud De Villeneuve
city: Nantes
country: France
facility: CHU Nantes
city: Paris
country: France
facility: Clinique Bizet
city: Pau
country: France
facility: CH Pau
city: Rouen
country: France
facility: CHU Charles Nicolle
city: Toulouse
country: France
facility: Clinique Pasteur
city: Toulouse
country: France
facility: Hôpital Rangueil
city: Toulouse
country: France
facility: CHU Purpan Toulouse
city: Tours
country: France
facility: CHU Tours
city: Bad Bevensen
country: Germany
facility: Herzkreislaufklinik
city: Bad Nauheim
country: Germany
facility: Kerckhoff Klinik
city: Berlin
country: Germany
facility: Charite Campus Virchow
city: Bonn
country: Germany
facility: Universitätskliniken Bonn
city: Coburg
country: Germany
facility: Klinikum Coburg
city: Garmisch-Partenkirchen
country: Germany
facility: Klinikum Garmisch-Partenkirchen
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Homburg
country: Germany
facility: Universität des Saarlandes
city: Lübeck
country: Germany
facility: Universitatsklinikum Schleswig-Holstein Campus Lübeck
city: Munchen
country: Germany
facility: DHZ Munchen
city: Munchen
country: Germany
facility: Klinikum Bogenhausen
city: Munchen
country: Germany
facility: Klinikum rechts der Isar
city: Munster
country: Germany
facility: Uniklinik Munster
city: München
country: Germany
facility: Kardiologische Gemeinschaftspraxis
city: München
country: Germany
facility: Universitatsklinikum Grosshadern
city: Regensburg
country: Germany
facility: Klinikum der Universität Regensburg
city: Regensburg
country: Germany
facility: Krankenhaus der Barmherzigen Brüder
city: ULM
country: Germany
facility: Universitätsklinik Ulm
city: Desio
country: Italy
facility: Ospedale Civile
city: Negrar
country: Italy
facility: Ospedale Sacro Cuore Don Calabria
city: Pavia
country: Italy
facility: Casa Di Cura Citta Di Pavia
city: San Donato Milanese
country: Italy
facility: Ospedale Clinicizzato San Donato
city: San Donato
country: Italy
facility: Policlinico San Donato
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwen Gasthuis
city: Almada
country: Portugal
facility: Hospital Garcia de Orta
city: Guimaraes
country: Portugal
facility: Hospital Senhora da Oliveira
city: London
country: United Kingdom
facility: St Peters Hospital
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospltal
city: Worthing
country: United Kingdom
facility: Worthing And Southlands Hospital
Study officials:
affiliation: Deutsches Herzzentrum München
name: Kolb
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kolb C, Tzeis S, Sturmer M, Babuty D, Schwab JO, Mantovani G, Janko S, Aime E, Ocklenburg R, Sick P. Rationale and design of the OPTION study: optimal antitachycardia therapy in ICD patients without pacing indications. Pacing Clin Electrophysiol. 2010 Sep;33(9):1141-8. doi: 10.1111/j.1540-8159.2010.02790.x.
citation: Kolb C, Sturmer M, Sick P, Reif S, Davy JM, Molon G, Schwab JO, Mantovani G, Dan D, Lennerz C, Borri-Brunetto A, Babuty D. Reduced risk for inappropriate implantable cardioverter-defibrillator shocks with dual-chamber therapy compared with single-chamber therapy: results of the randomized OPTION study. JACC Heart Fail. 2014 Dec;2(6):611-9. doi: 10.1016/j.jchf.2014.05.015. Epub 2014 Oct 1.