Clinical Evaluation on Advanced Resynchronization

Study Overview
=================
Brief Summary
-----------------
The aim of the study is to compare clinical benefits of the cardiac resynchronisation (CRT) achieved by the PEA optimised pacing configuration and a CRT optimised by standard clinical procedure. PEA optimised configuration (PEA-CRT) is obtained, during patient's follow-up, using the Peak Endocardial Acceleration sensor features onboard the device.

Detailed Description
-----------------
The study is a prospective, multicentre, controlled and randomised clinical investigation, with two single-blinded arms. The objective of the study is to compare the clinical benefits of Cardiac Resynchronisation Therapy (CRT) optimised by automatic PEA sensor features (PEA-CRT), with those obtained by standard optimisation procedure (STD-CRT). The patient candidate for inclusion in the study has a severe chronic Heart Failure, indicated for the implantation of a Biventricular pacing system according to updated ESC guidelines (2005). All patients included in the study will be followed-up for 1 year; patient's follow-ups are scheduled during hospitalisation, at one month, 3 months, 6 months and one year after implantation.

Official Title
-----------------
Clinical Evaluation on Advanced Resynchronization

Conditions
-----------------
Heart Failure, Cardiomyopathy

Intervention / Treatment
-----------------
* Device: New Living CHF
* Device: New Living CHF


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The patient candidate for inclusion in the study must be indicated for implantation of a Biventricular pacing system, with the following clinical conditions: Severe Heart Failure (NYHA Class III or IV) Cardiomyopathy of any etiology Sinus rhythm Reduced Left-Ventricular Ejection Fraction Left-Ventricular End Diastolic Diameter greater than or equal to 30 mm/m2 (LVEDD>30 mm/m2) QRS Duration: > 150 ms or > 120 ms and documented Mechanical Dissynchrony (by ECHO) meeting two out of three of the following criteria: Aortic Pre-Ejection Delay > 140 ms Interventricular Mechanical Delay > 40 ms Delayed activation of postero-lateral Left Ventricular wall (after mitral valve opening) Optimal and stable (1 month before inclusion) pharmacological treatment, including, if tolerated, Beta Blockers, Angiotensin-Converting Enzyme (ACE) Inhibitors or ACE Inhibitor substitutes, Spironolactone, and diuretics Exclusion Criteria: Any patient who has one of the following characteristics will be excluded from the study: ICD indication (Life-threatening ventricular arrhythmias) Persistent or permanent Atrial Arrhythmia without possibility to restore sinus rhythm (spontaneous termination, anti-tachycardia pacing, pharmacological or electrical cardioversion). Patient already implanted with a conventional pacemaker device Myocardial infarction within the last three months Heart surgery, or revascularization within the last three months, or expected Heart surgery refused because of co-morbidity factors Included in transplantation list Already enrolled in other study Life expectancy less than 1 year Pregnancy Age less than 18 Forfeiture of freedom or under guardianship Not able to understand the aim of the study and its procedures Refusing to cooperate

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>PEA optimized CRT | Device: New Living CHF<br>* PEA CRT optimization<br>|
| Other: 2<br>Standard optimized CRT | Device: New Living CHF<br>* Standard optimized CRT.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint will be evaluated at 1 year (M12), in term of improved, unchanged or worsened patient's conditions, with a composite analysis of NYHA class evolution, heart-failure-related hospitalisations and Quality of Life evaluation. |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PEA-CRT optimisation is at least effective as the standard optimisation in term of efficacy of the therapy and patients' quality of life. |  | 12 months | 
| PEA is an index of the patients' clinical status and allows to predict acute HF episode in both arms. |  | 12 months | 
| Efficacy of the therapy comparing the two arms in terms of NYHA |  | 12 months | 
| Efficacy of the therapy comparing the two arms in terms of Cardiovascular mortality |  | 12 months | 
| Efficacy of the therapy comparing the two arms in terms of Heart Failure Quality Of Life (EuroQoL-5D) score |  | 12 months | 
| Efficacy of the therapy comparing the two arms in terms of BNP dosage |  | 12 months | 
| Efficacy of the therapy comparing the two arms in terms of Number and duration of heart-failure-related patient's hospitalisations, during the study period. |  | 12 months | 
| Efficacy of the therapy comparing the two arms in terms of Left Ventricular End Diastolic Diameter |  | 12 months | 
| Efficacy of the therapy comparing the two arms in terms of Left Ventricular End Systolic Diameter |  | 12 months | 
| Efficacy of the therapy comparing the two arms in terms of Left Ventricular Ejection Fraction |  | 12 months | 
| Efficacy of the therapy comparing the two arms in terms of Left Pre-Ejection Interval |  | 12 months | 
| Efficacy of the therapy comparing the two arms in terms of Right Pre-Ejection Interval |  | 12 months | 
| Efficacy of the therapy comparing the two arms in terms of Total Duration of Left Systole |  | 12 months | 
| Efficacy of the therapy comparing the two arms in terms of E velocity |  | 12 months | 
| Efficacy of the therapy comparing the two arms in terms of A velocity |  | 12 months | 
| Efficacy of the therapy comparing the two arms in terms of Ventricular spike-Mitral valve closure interval |  | 12 months | 
| Efficacy of the therapy comparing the two arms in terms of Ventricular spike-Mitral valve opening interval |  | 12 months | 
| Efficacy of the therapy comparing the two arms in terms of Mitral Valve regurgitation. |  | 12 months | 
| Time spent to achieve the CRT optimal configuration during each follow-up |  | 12 months | 
| PEA monitoring and prognostic relevance correlating the PEA diagnostic trends with the parameters used to asses the efficacy of the therapy and patients' quality of life (NYHA class, mortality, HF-hospitalisation, EuroQoL-5D score, BNP dosage, Echo |  | 12 months | 
| (LVEF) comparing the changes Left Ventricular Ejection Fraction in the two arms with an intermediate analysis at 6 months done by a Core Centre. |  | 6 and 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CRT-P, PEA, Severe Heart Failure (NYHA Class III or IV), Cardiomyopathy of any etiology, Sinus rhythm, Reduced Left-Ventricular Ejection Fraction, LVEDD>30 mm/m2, QRS Duration: > 150 ms or > 120 ms, Aortic Pre-Ejection Delay > 140 ms, Interventricular Mechanical Delay > 40 ms, Delayed activation of postero-lateral Left Ventricular wall, Optimal and stable pharmacological treatment