Dual-Site LV Pacing in CRT Non Responders: Multicenter Randomized Trial

Study Overview
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Brief Summary
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Cardiac resynchronization therapy (CRT) is an effective treatment of heart failure (HF) refractory to optimal medical management, in presence of a depressed left ventricular (LV) ejection fraction and a wide QRS complex. It is mainly limited by a high proportion of non-responders. Attempts have been made, in small studies, to increase the number of stimulation sites in order to optimize the resynchronization therapy. V3 is a planned multicenter, randomized trial whose objective is to evaluate the clinical benefit conferred by the addition of a second endocardial or epicardial LV lead in non-responders after at least 6 months of standard biventricular stimulation. The V3 trial will examine the clinical benefit conferred by the addition of a second LV lead in non-responders compared to standard CRT.

Official Title
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Dual-Site LV Pacing in CRT Non Responders Multicenter Randomized V3 Trial

Conditions
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Heart Failure

Intervention / Treatment
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* Device: Additional Endocardial or Epicardial LV Lead
* Device: CRT-P or CRT-D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than 18 years Recipient of a CRT-P or CRT-D system for greater than 6 for standard indications, including LV ejection fraction greater than 35 percent and New York Heart Association (NYHA) functional class III or IV Optimized biventricular stimulation and medical therapy since implantation of the system Presence of sinus rhythm, or atrial fibrillation with spontaneous or induced complete atrio-ventricular block Greater than 93 percent LV stimulation since the last device interrogation, with a LV capture threshold less than 5.0 Volts/0.5 milliseconds Unchanged or worsened clinical status by CRT, according to the HF composite endpoint described by M. Packer, in absence of a reversible cause Signature of a written, informed consent to participate in the trial Exclusion Criteria: LV lead location in the great cardiac vein Life-expectancy less than 1 year due to concomitant, non-cardiovascular disorders Chronic renal dialysis Concomitant disorder which might interfere with the results of the V3 trial Blood systolic pressure greater than 180 millimeters of mercury (mmHg) or diastolic pressure greater than 95 mmHg despite optimal medical management History of stroke, myocardial infarction or unstable angina pectoris within the last 3 months Presence of correctible valvular disease Subject unable to attend follow-up at the investigative center or unable, for physical or mental reasons, to comply with the trial's procedures, or to sign the informed consent Subject is pregnant Subject participates in another research project

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: CRT With Dual Site LV Pacing<br>Cardiac resynchronization therapy with the addition of a second LV lead. Positioning of a pacing lead in a cardiac vein should be considered first. An epicardial lead will be used if the implant of an endocardial lead is impossible or previously failed. | Device: Additional Endocardial or Epicardial LV Lead<br>* Addition of a second left ventricular endocardial or epicardial lead<br>Device: CRT-P or CRT-D<br>* Implantable Cardiac Resynchronization Therapy Pacemaker (CRT-P) or Defibrillator (CRT-D) Device<br>|
| Active Comparator: Standard CRT<br>Conventional cardiac resynchronization therapy. Patients in this arm will keep their CRT system unchanged. | Device: CRT-P or CRT-D<br>* Implantable Cardiac Resynchronization Therapy Pacemaker (CRT-P) or Defibrillator (CRT-D) Device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distribution of Improved, Unchanged and Worsened Patients as Defined Per M. Packer's Clinical Composite Score | M. Packer's clinical composite score: patients were classified into 1 of 3 response groups after 12 months follow up : worsened, unchanged, or improved. Worsened : if death, hospitalization because of or associated with worsening HF, demonstrated worsening in NYHA functional class at their 12-month visit, or if investigator judges global clinical state has worsened. Improved :if they had not worsened and had demonstrated improvement in NYHA functional class, or or if investigator judges global clinical state has improved. Unchanged : if none of the previous definition applies. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distribution of Improved, Unchanged and Worsened Patients as Defined Per M. Packer's Clinical Composite Score | Distribution of improved, unchanged and worsened patients as defined per M. Packer's clinical composite score at 24 months post implantation of the second left ventricle lead in comparison to the control group M. Packer's clinical composite score: patients were classified into 1 of 3 response groups after 24 months follow up : worsened, unchanged, or improved. Worsened : if death, hospitalization because of or associated with worsening HF, demonstrated worsening in NYHA functional class at their 24-month visit, or if investigator judges global clinical state has worsened. Improved :if they had not worsened and had demonstrated improvement in NYHA functional class, or or if investigator judges global clinical state has improved. Unchanged : if none of the previous definition applies. | 24 months | 
| Rate of Adverse Events |  | 24 months | 
| Changes in 6 Minutes Hall Walk Distance Observed Between the Enrollment and the End of the Study | Changes between baseline and 24months follow up | 24 months | 
| Number of Patients With at Least One Hospitalization Related to Heart Failure Between Randomization and the End of the Study |  | 24 months | 
| Time to First Heart Failure Related Hospitalization |  | 24 months | 
| Overall Mortality |  | 24 months | 
| Changes in Echocardiographic Indexes of Left Ventricle Remodeling | Changes between baseline and 24months follow up | 24 months | 
| Changes in Quality of Life Score - Minesota Living With Heart Failure Questionnaire | Changes between baseline and 24 months follow up Minesota Living with Heart Failure Questionnaire: 21 questions - addition of scores from 1 (better) to 5 (worse) for each questions. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart failure, Cardiac resynchronization therapy, Biventricular stimulation, Multisite stimulation, Non responders