Optimal Anti-tachycardia Therapy in Implantable Cardioverter-defibrillator (ICD) Patients Without Pacing Indications

Study Overview
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Brief Summary
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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
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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.

Official Title
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Optimal Antitachycardia Therapy in ICD Patients Without Pacing Indications

Conditions
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Tachycardia

Intervention / Treatment
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* Device: Ovatio DR 6550
* Device: OVATIO DR 6550


Participation Criteria
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Eligibility Criteria
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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

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: 1<br>Dual-chamber detection and activated treatment (at least ATP) in the slow VT-zone plus activated AAIsafeR pacing (basic rate 60 bpm). | Device: Ovatio DR 6550<br>* Dual-chamber ICD therapy with minimized ventricular pacing<br>|
| Experimental: 2<br>Single-chamber ICD following clinical practice but with a monitoring zone active to allow the documentation of all occurring ventricular arrhythmias | Device: OVATIO DR 6550<br>* Single-chamber device therapy with settings which are common in clinical practice.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  | implant, 3 months, 9 months, 15 months, 21 months and 27 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| all cause mortality and cardio-vascular related mortality |  | 27 months follow up | 
| Hospitalizations due to cardio-vascular event (specified for each type of event) |  | 27 months follow up | 
| Time to first occurrence of inappropriate ICD shock therapy |  | 27 months follow up | 
| Evaluation of the impact of the different therapies on quality of life and heart failure status |  | 27 months follow up | 
| Sensitivity and specificity for VT/SVT discrimination for the first 100 patients in each group. |  | 27 months | 
| Inappropriate overall device reactions defined by inappropriate shock and/or ATP therapy or inappropriate therapy delay/inhibition > 2 minutes on VTs |  | 27 months | 
| time to first documented AF occurrence and number of patients moving into permanent or persistent AF |  | 27 months follow up | 
| Cardiac dimensions obtained by echo evaluation for a subset of patients of both groups |  | Baseline and 27 months | 
| Slow VT incidence |  | 27 months | 
| Unscheduled visits and hospitalizations due to slow VT |  | 27 months follow up | 
| System related complications including lead dislodgements, exit block, oversensing which requires programming corrections, infections, complications which require reintervention |  | 27 months follow up | 
| Cumulative percentage of ventricular pacing and proportion of patients with 0% V pacing. |  | 27 months follow up | 
| Overall success rate of ATP in the FVT zone |  | 27 months | 
| Cost effectiveness of applied ICD therapy |  | 27 months | 
| PPV and NPV for Tvar risk stratification |  | 27 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ICD, Minimized, ventricular, pacing, indication, Clinical outcome, Inappropriate shock