CRT Improved Clinical Response UK Trial

Study Overview
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Brief Summary
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The main objective of the CRICKET study is demonstrate that AV and VV optimization using SonR improves LV reverse remodeling response to CRT, compared with 'Fixed Settings' (FS) after 6 months of treatment. In this investigator-initiated, multi-centre, 2:2 factorial design, randomized, two-arm, double-blinded, cross-over, prospective trial, CRT recipients will be randomized to 'SonR' atrioventricular (AV) and ventricular-ventricular (VV) optimization or 'fixed settings'. The primary endpoint is an absolute reduction in left ventricular end-systolic volume.

Detailed Description
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This is an investigator-initiated, multi-centre, 2:2 factorial design, randomized, two-arm, double-blinded, cross-over, prospective trial Main study objectives The main objective of the CRICKET study is demonstrate that AV and VV optimization using SonR improves LV reverse remodeling response to CRT, compared with 'Fixed Settings' (FS) after 6 months of treatment. Study endpoints Primary endpoint: The primary endpoint is a reduction (absolute difference) in LVESV with SonR vs FS after 6 months of treatment. The difference intra-patient of absolute change of LVESV value will be compared between two treatments: SonR optimization vs. FS, defined as a sensed AV delay of 125 ms, VV delay of 0 ms (simultaneous). Secondary endpoints: Change in 6 MWT distance Change in NYHA class Change in quality of life Change in patient global assessment (EQ-5D) Change in Quality of life (MLWHF questionnaire) Change in LVEF AF burden Adverse Events Number of subjects Two hundred (200) patients will be enrolled. All patients will be implanted with the SonRtip bipolar atrial lead and a LivaNova (Sorin) CRT-D device offering both SonR optimization algorithm and atrio-biventricular pacing. Patients will be assigned to either the treatment or control arms, employing a 1:1 randomization with up to 100 patients in each of the 2 groups: Study Group (SonR CRT Optimization programmed AV+VV) and Control Group (Fixed Settings (FS), defined as a sensed AV delay of 125 ms, VV delay of 0 ms (simultaneous); SonR CRT Optimization programmed Off). After the first 6 months, patients will be crossed-over to the alternative arm for another 6 months. There will be no washout period. Duration of the clinical investigation The study inclusion phase is expected to last approximately 1.5 years. Follow-ups Patients will be evaluated at baseline and randomized prior to implantation to SonR optimization or FS. A further clinical assessment, ECG and echocardiography will be undertaken at 6 months. At this point, patients will be crossed over to the other arm for another 6 months. The study closes following a further clinical and echocardiographic assessment at 12 months.

Official Title
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CRT Improved Clinical Response UK Trial: A Multi-centre, Prospective, Randomized, Cross-over, Double Blind Study

Conditions
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Cardiac Failure

Intervention / Treatment
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* Other: Device programming


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible for implantation of a CRT-D device according to current NICE or ESC guidelines; In sinus rhythm; NYHA class II, III or IV Have reviewed, signed and dated an informed consent Exclusion Criteria: Inability to do a 6 min walk test. Previous implant with a pacemaker, an ICD or a CRT device (except upgrade from single chamber ICD with a fully functional defibrillation lead) not under recall or surveillance); Persistent atrial arrhythmias (or cardioversion for atrial fibrillation) within the past month; Ventricular tachyarrhythmia of transient or reversible causes such as acute myocardial infarction (MI), digitalis intoxication, drowning, electrocution, electrolyte imbalance, hypoxia or sepsis, uncorrected at the time of the enrolment; Incessant ventricular tachyarrhythmia; Unstable angina, or acute MI, Coronary Artery Bypass-Grafting (CABG), or Percutaneous Coronary Intervention (PCI) within the past 4 weeks; Correctable valvular disease that is the primary cause of heart failure; Indication for valve repair or replacement; Recent Cerebro-Vascular Accident (CVA) or Transient Ischemic Attack (TIA) (within the previous 3 months); On transplant waiting list; Previous heart transplant; 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; Unavailability for scheduled follow-up or refusal to cooperate; 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SonR optimization<br>SonRtip bipolar atrial lead and LivaNova (Sorin) CRT-D implantation with device programming: SonR CRT Optimization programmed AV+VV | Other: Device programming<br>* SonRtip bipolar atrial lead and LivaNova (Sorin) CRT-D implantation with device programming: SonR CRT Optimization programmed AV+VV<br>|
| Placebo Comparator: Fixed settings<br>SonRtip bipolar atrial lead and LivaNova (Sorin) CRT-D implantation with device programming device programming: sensed AV delay of 125 ms, VV delay of 0 ms (simultaneous); SonR CRT Optimization programmed Off). | Other: Device programming<br>* SonRtip bipolar atrial lead and LivaNova (Sorin) CRT-D implantation with device programming: SonR CRT Optimization programmed AV+VV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular end-systolic volume (LVSV) | Reduction in LVESV with SonR vs FS after 6 months of treatment | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Walking distance on 6 -minute walk test | Change in 6 MWT distance | 6 months | 
| NYHA class | Change in NYHA class | 6 months | 
| Quality of life - general (non-disease specific) | Change in quality of life, assessed using EQ-5D (section 1) | 6 months | 
| Patient global assessment | Change in patient global assessment (included in EQ-5D, section 2) | 6 months | 
| Disease-specific quality of life (heart failure) | Change in quality of life (MLWHF questionnaire) | 6 months | 
| Left ventricular ejection fraction | Change in LVEF | 6 months | 
| AF burden | AF burden according to mode-switches | 6 months | 
| System safety assessed by Adverse Events | Report all Adverse Events | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiac resynchronization therapy, optimization, heart failure, reverse left ventricular remodeling