Comparison of CRT-D and CRT-DX Systems (CRT-NEXT)

Study Overview
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Brief Summary
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The principal objective is to test non-inferiority of the CRT-DX system as compared to a conventional CRT-D system, in terms of the combined endpoint of mortality, hospitalizations due cardiovascular causes, any complication leading to loss of lead functionality, in the subset of patients without evidence of sinus dysfunction on optimal therapy.

Detailed Description
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Resting heart rate is strongly associated with incident worsening Heart Failure (HF) and mortality. Current devices for cardiac resynchronization (CRT-D) normally provide atrio-ventricular (AV) sequential pacing modes during resynchronization, but the best pacing programming strategy is not clear. On the one hand a basic rate of 50 to 70 bpm (optionally with some rate-responsive function) could be considered for therapy up-titration, specifically betablockers; on the other hand, increasing pacing rates may partially reduce benefits from resynchronization, reducing filling time and contractility reservoir. The Pegasus investigation is the only large randomized investigation comparing DDD with 70 bpm basic rate to DDD(R) @40 bpm. Results showed no difference in investigation endpoints, including mortality and HF-hospitalization. These results may support the use of a device implementing both a CRT function and a right ventricular single-lead with and an atrial sensing dipole (CRT-DX system). This system can track ventricular pacing and resynchronization following atrial sensing, even if it cannot provide atrial pacing support. It should be assessed whether such limitation is counterbalanced by the advantages related to the reduced number of necessary leads, with simplified implantation and less complications. The objective of the investigation is to assess whether atrial pacing support is really necessary in the subset of patients with indication to CRT-D and no evidence of sinus dysfunction on optimal therapy. The investigation will test the hypothesis that a CRT-DX system is not inferior to a conventional CRT-D system in this class of subjects.

Official Title
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Non-inferiority Randomized Clinical Investigation of CRT-DX Versus CRT-D Systems

Conditions
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Heart Failure, Cardiac Resynchronization Therapy

Intervention / Treatment
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* Device: Conventional 3-lead CRT defibrillator system implantation
* Device: 2-lead CRT defibrillator system implantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients ≥ 18 years old Patients willing to participate in the investigation and signing the Patient Informed Consent (PIC) Form; Indication to CRT-D implant according to current ESC Guidelines on cardiac pacing and cardiac resynchronization therapy Sinus rhythm at time of implant; Optimized medical therapy according to current ESC Guidelines Rest heart rate (HR) >45 bpm at baseline ECG, with betablocker therapy at optimal medical dosage; or, if rest HR<45 bpm: maximum heart rate at the 6- minute walking test >85 bpm. Exclusion Criteria: Any indication to atrial pacing according to current guidelines; Both: resting heart rate <45 bpm at baseline ECG, with betablocker therapy at optimal medical dosage and maximum heart rate at the 6-minute walking test <85 bpm; NYHA Class IV; Permanent Atrial Fibrillation Replacement of/upgrading from previously implanted pacing system; Dialysis patients; Pregnant or breast-feeding women.

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 |
| --- | --- |
| Active Comparator: 3-lead CRT implantation (CRT-D)<br>In the 3-lead CRT implantation (CRT-D) group, conventional 3-lead CRT defibrillator system implantation will be performed. The CRT-D system is composed by three leads, one in atrium and two in both ventricles | Device: Conventional 3-lead CRT defibrillator system implantation<br>* Conventional 3-lead(1 atrial and 2 ventricular leads) system implantation<br>|
| Experimental: 2-lead CRT implantation (CRT-DX)<br>In the 2-lead CRT implantation (CRT-DX) group, 2-lead CRT defibrillator system implantation will be performed. The CRT-DX system is composed by two ventricular leads, the right one is provided with a dipole for atrial sensing | Device: 2-lead CRT defibrillator system implantation<br>* 2-lead (2 ventricular leads with dipole for atrial sensing) DX system implantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined endpoint of Mortality, hospitalization due to cardiac causes and lead-related complications | It includes number of patients who experienced death, hospitalization due to cardiac causes, or any lead-related complication leading to loss of functionality (including lead dislodgement, conduction or insulation failure, loss of sensing or capture that couldn't resolved by reprogramming) | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of implant revisions | Rate of implant revisions to add, replace, reposition, and remove an atrial pacing lead. | 1 year | 
| Rate of inappropriate therapy of the device | Inappropriate detections and interventions of high rate ventricular episodes. | 1 year | 
| Atrial pacing percentage | In the conventional CRT-D group, atrial pacing percentage. | 1 year | 
| Exercise test | Six minute walking test distance at one year | 1 year | 
| Device detected AT | Incidence of atrial tachyarrhythmias (AT) | 1 year | 
| Incidence of appropriate Ventricular therapy | Incidence of Ventricular Arrhythmias (VA) requiring therapy delivery | 1 year | 
| Incidence of events due to short-long-short sequence | Incidence of both VA and AT due to bradycardia or short-long-short sequence | 1 year | 
| Implant failure | Impossibility to implant any component (leads and device) of the initially planned system | 1 year | 
| Procedure times | Skin-to-skin and fluoroscopy time | 1 year | 
| Atrial sensing amplitude measured by device | Atrial sensing amplitude measured by devices in both investigation arms | 1 year | 
| Far field oversensing incidence | Incidence of far field oversensing episodes in both investigation arms | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRT-D, CRT-DX, Atrial pacing