Clinical Trial of the SonRtip Lead and Automatic AV-VV Optimization Algorithm in the PARADYM RF SonR CRT-D

Study Overview
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Brief Summary
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The objective of this study is to assess the safety and effectiveness of the automatic atrioventricular (AV) delay and interventricular (VV) delay optimization algorithm used in the PARADYM RF SONR Cardiac Resynchronization Therapy with Defibrillation (CRT-D) device (Model 9770) in combination with the SonRtip Lead, which includes a SonR sensor in the tip of the atrial pacing lead, and compatible SmartView programming software. This study will evaluate the effectiveness of the automatic optimization algorithm in increasing the rate of patients responding to the therapy as compared to an echocardiographic optimization method. This study will also evaluate the safety and effectiveness of the SonRtip atrial pacing lead.

Detailed Description
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Since the introduction of cardiac resynchronization therapy (CRT) on a large scale, it has been observed that approximately 30% of recipient patients are non-responsive to therapy. This non-responsiveness can be decreased by optimizing the device programming, particularly the stimulation rate, paced and sensed atrioventricular (AV) delay, and the interventricular (VV) delay. All CRT patients need a 100% rate of ventricular capture, but beyond this the achievement of therapy effectiveness requires the identification of the optimal pacing configuration, which varies among patients. The optimization of CRT systems, usually based on ultrasound imaging is time-consuming and the number of patients in need of multiple optimization procedures due to ventricular remodeling is growing rapidly. The mechanical effects of a more coordinated contraction result in a shortening of the isovolumetric contraction phase and the pre-ejection time, and an increase in LV dP/dt (change in left ventricular pressure over time. The concept of measuring contractility with an implantable accelerometer was first clinically validated through a multicenter study on a rate responsive pacing system (BEST - Living from SORIN Biomedica) in 1996. This study positively demonstrates that measurement of Peak Endocardial Acceleration signal (called PEA or SonR) is feasible and reliable in the long-term, both for the purpose of rate response and as a hemodynamic monitor of cardiac function. More recent clinical studies have demonstrated that optimal VV and AV Delays determined using algorithms based on SonR signal analysis (SonR method) are correlated with the highest hemodynamic improvement and lead to significant clinical benefit for the patients, thus reducing the rate of non-responsiveness to CRT therapy. Therefore, automatic AV and VV delay optimization in patients with CRT devices could benefit both the patient and physician.

Official Title
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Clinical Trial of the SonRtip Lead and Automatic AV-VV Optimization Algorithm in the PARADYM RF SonR CRT-D

Conditions
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Heart Failure NYHA Class III and Ambulatory IV

Intervention / Treatment
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* Device: PARADYM RF SONR
* Device: PARADYM RF SONR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient eligible with class I and IIa indication for implantation of a CRT-D device according to current available guidelines ; Modere,Severe HF (NYHA Class III or ambulatory IV) LVEF ≤ 35 % LBBB: QRS ≥ 120 ms ; non-LBBB : QRS ≥ 150 ms On a stable, optimal drug regimen Patient is in sinus rhythm at the time of enrollment; Signed and dated informed consent Exclusion Criteria: Ventricular tachyarrhythmia of transient or reversible causes such as acute myocardial infarction, digitalis intoxication, drowning, electrocution, electrolyte imbalance, hypoxia or sepsis, uncorrected at the time of the enrolment; Incessant ventricular tachyarrhythmia; Unstable angina, or acute MI, CABG, or PTCA within the past 4 weeks; Correctable valvular disease that is the primary cause of heart failure; Recent CVA or TIA (within the previous 3 months); Persistent or permanent atrial arrhythmias (or cardioversion for atrial fibrillation) within the past month; Post heart transplant (patients who are waiting for a heart transplant are allowed in the study); Renal failure (GFR<15 ml/min/1.73m2) or on dialysis Previous implant with a CRT/CRT-D device; Concurrent implant with another pacemaker or ICD (previously implanted pacemaker or ICD devices or RA leads should be removed prior to implant with the Paradym RF SONR CRT-D); Already included in another clinical study that could confound the results of this study; Life expectancy less than 1 year; Inability to understand the purpose of the study or to understand and complete the QOL questionnaire; Unavailability for scheduled follow-up or refusal to cooperate; Sensitivity to 1 mg dexamethasone sodium phosphate (DSP) Age of less than 18 years; Pregnancy Drug addiction or abuse Under guardianship

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SonR group<br>SonR CRT Optimization | Device: PARADYM RF SONR<br>* SonR CRT Optimization<br>* Other names: Automatic Hemodynamic CRT Optimization;|
| Active Comparator: ECHO group<br>Echocardiographic Optimization | Device: PARADYM RF SONR<br>* Echocardiography Optimization<br>* Other names: Echo Optimization;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of SonR CRT Optimization Effectiveness in terms of proportion of responders at 12 months. The investigational(SonR)and control groups(ECHO)will be compared in a non-inferiority context employing a clinically meaningful difference of 10%. | The analysis will be done on all patients implanted with the entire system who have been followed out to 12 months. The patients will be classified as improved, unchanged or worsened based on composite criteria(death/heart failure (HF) events,New York Heart association(NYHA) class), Quality of life (QOL). In the event that the non-inferiority test is met, a test of superiority will be conducted comparing the treatment and control groups. | 12 months | 
| Evaluation of Lead Safety: Acute SonRTipLead Complication-Free Rate (at 3 months) | SonRtip acute lead-related complication-free rate is defined as the proportion of patients not experiencing any complication related to the SonRtip lead within 3 months post-implant, relative to the total number of patients implanted with the lead.All patients who are successfully implanted with SonRtip lead will be included. | 3 months | 
| Evaluation of Lead Safety: Chronic SonRTipLead Complication-Free Rate (from 3 months to 12 months) | SonRtip lead-related complication-free rate is defined as the proportion of patients not experiencing any complication related to the SonRtip lead from 3 to 12 months post-implant.All patients who are successfully implanted with SonRtip lead will be included. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of CRT effectiveness and CRT Safety: evaluation of Mortality and HF hospitalizations at 12 months | This endpoint will compare treatment arms in a non-inferiority hypothesis test of the proportion of subjects that either died from any cause, or were hospitalized for heart failure | 12 months | 
| Evaluation of CRT effectiveness and CRT therapy: Proportion of patients worsened at 12 months | This endpoint will compare treatment arms in a non-inferiority hypothesis test of the proportion of subjects classified as worsened, in order to evaluate the potential detrimental effects of the optimization method | 12 months | 
| SonR tip lead pacing threshold | For all patients implanted with the SonRtip lead. | 24 months | 
| SonR tip lead sensing threshold | For all patients implanted with the SonRtip lead. | 24 months | 
| SonR tip lead pacing impedance | For all patients implanted with the SonRtip lead. | 24 months | 
| Evaluation of CRT effectiveness and CRT and System Safety: Report deaths for any cause | The report of the deaths occurred consists of the percentage of dead patients, the causes of death, the time to death, the survival curves. | 24 months | 
| Report Heart Failure-related events to assess CRT effectiveness | For all patients implanted it will be reported the percentage of patients with events, number of events for patients, event type, time to first occurence, survival curves) | 24 months | 
| Report Quality of life (QOL) improvement to assess CRT effectiveness (percentage of patients with improvements in QOL) | In all patients implanted the evaluation of the Quality of Life Score will consist of reporting the percentage of patients who showed improvement in their KCCQ Score at each follow-up post-implant | 24 months | 
| Report NYHA class improvement to assess CRT effectiveness (the percentage of patients with improved in NYHA class) | In all patients implanted the evaluation of the NYHA Classification will consist of reporting the percentage of patients who improved at least one NYHA class at each follow-up post-implant | 24 months | 
| Evaluation of CRT effectiveness: Report echocardiographic parameters trend at M12 | The intra-patient variations of the echocardiographic parameters measured at M12 as compared to those measured at baseline. The echo measures will be validated by an independent and blinded core lab | 12 months | 
| Evaluation of SonR CRT Optimization Effectiveness - Superiority by assessment the proportion of responder patients in SonR group | The analysis will be done on all patients implanted with the entire system. The patients will be classified as improved, unchanged or worsened based on composite criteria(death/heart failure events,NYHA class, Quality of life (QOL). | 18/24 months | 
| Evaluation of the time spent for CRT optimization by the physician on optimization in each group (sonR and ECHO) | The amount of time (mean, median, standard deviation, minimum, maximum)in each group will be evaluated in all patients implanted | 24 months | 
| Evaluation of the Number of re-optimizations performed in both groups (SonR and ECHO) | In all patients implanted will be evaluated the number of re-optimizations performed (mean, median, standard deviation, minimum, maximum) in each group (study and control). | 24 months | 
| Report Adverse Events for both group to assess CRT effectiveness / System Safety | For all patients enrolled all Adverse Events will be reported. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRT-D device, Severe HF (NYHA Class III or ambulatory IV), stable, optimal drug regimen, sinus rhythm