Heart Failure
Conditions
Keywords
Heart failure, Cardiac resynchronization therapy, Biventricular stimulation, Multisite stimulation, Non responders
Brief summary
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.
Interventions
DEVICEAdditional Endocardial or Epicardial LV Lead
Addition of a second left ventricular endocardial or epicardial lead
DEVICECRT-P or CRT-D
Implantable Cardiac Resynchronization Therapy Pacemaker (CRT-P) or Defibrillator (CRT-D) Device
Sponsors
Medtronic
FRANCE
Medtronic Cardiac Rhythm and Heart Failure
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Distribution of Improved, Unchanged and Worsened Patients as Defined Per M. Packer's Clinical Composite Score | 12 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Adverse Events | 24 months | — |
| Changes in 6 Minutes Hall Walk Distance Observed Between the Enrollment and the End of the Study | 24 months | Changes between baseline and 24months follow up |
| Number of Patients With at Least One Hospitalization Related to Heart Failure Between Randomization and the End of the Study | 24 months | — |
| Distribution of Improved, Unchanged and Worsened Patients as Defined Per M. Packer's Clinical Composite Score | 24 months | 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. |
| Overall Mortality | 24 months | — |
| Changes in Echocardiographic Indexes of Left Ventricle Remodeling | 24 months | Changes between baseline and 24months follow up |
| Changes in Quality of Life Score - Minesota Living With Heart Failure Questionnaire | 24 months | 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. |
| Time to First Heart Failure Related Hospitalization | 24 months | — |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CRT With Dual Site LV Pacing 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.
Additional Endocardial or Epicardial LV Lead: Addition of a second left ventricular endocardial or epicardial lead
CRT-P or CRT-D: Implantable Cardiac Resynchronization Therapy Pacemaker (CRT-P) or Defibrillator (CRT-D) Device | 42 |
| Standard CRT Conventional cardiac resynchronization therapy. Patients in this arm will keep their CRT system unchanged.
CRT-P or CRT-D: Implantable Cardiac Resynchronization Therapy Pacemaker (CRT-P) or Defibrillator (CRT-D) Device | 41 |
| Total | 83 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 |
| Overall Study | Death | 17 | 17 |
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Standard CRT | Total | CRT With Dual Site LV Pacing |
|---|---|---|---|
| Age, Continuous | 72.2 years STANDARD_DEVIATION 7.9 | 71.3 years STANDARD_DEVIATION 7.8 | 70.5 years STANDARD_DEVIATION 7.7 |
| LVEDV (left ventricular end-diastolic volume) | 206 milliliter STANDARD_DEVIATION 63.9 | 213 milliliter STANDARD_DEVIATION 75.7 | 219 milliliter STANDARD_DEVIATION 85.8 |
| LVEF % (left ventricle ejection fraction) | 25.9 percent STANDARD_DEVIATION 7 | 26.4 percent STANDARD_DEVIATION 6.4 | 26.9 percent STANDARD_DEVIATION 6 |
| LVESV (left ventricular end-systolic volume) | 149 milliliter STANDARD_DEVIATION 58.7 | 151 milliliter STANDARD_DEVIATION 59.8 | 154 milliliter STANDARD_DEVIATION 61.8 |
| Paced QRS duration | 155 milliseconds STANDARD_DEVIATION 42.2 | 160 milliseconds STANDARD_DEVIATION 36.8 | 165 milliseconds STANDARD_DEVIATION 30.5 |
| Patients with ischemic heart disease | 24 participants | 46 participants | 22 participants |
| Sex: Female, Male Female | 5 Participants | 11 Participants | 6 Participants |
| Sex: Female, Male Male | 36 Participants | 72 Participants | 36 Participants |
| Time from first CRT implant | 37.8 months STANDARD_DEVIATION 23.7 | 40.6 months STANDARD_DEVIATION 26.2 | 43.5 months STANDARD_DEVIATION 28.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 38 / 42 | 34 / 41 |
| serious Total, serious adverse events | 33 / 42 | 33 / 41 |
Outcome results
Primary
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.
Time frame: 12 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CRT With Dual Site LV Pacing | Distribution of Improved, Unchanged and Worsened Patients as Defined Per M. Packer's Clinical Composite Score | Improved patients | 11 participants |
| CRT With Dual Site LV Pacing | Distribution of Improved, Unchanged and Worsened Patients as Defined Per M. Packer's Clinical Composite Score | Unchanged patients | 10 participants |
| CRT With Dual Site LV Pacing | Distribution of Improved, Unchanged and Worsened Patients as Defined Per M. Packer's Clinical Composite Score | Worsened patients | 21 participants |
| Standard CRT | Distribution of Improved, Unchanged and Worsened Patients as Defined Per M. Packer's Clinical Composite Score | Improved patients | 7 participants |
| Standard CRT | Distribution of Improved, Unchanged and Worsened Patients as Defined Per M. Packer's Clinical Composite Score | Unchanged patients | 16 participants |
| Standard CRT | Distribution of Improved, Unchanged and Worsened Patients as Defined Per M. Packer's Clinical Composite Score | Worsened patients | 17 participants |
Secondary
Changes in 6 Minutes Hall Walk Distance Observed Between the Enrollment and the End of the Study
Changes between baseline and 24months follow up
Time frame: 24 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CRT With Dual Site LV Pacing | Changes in 6 Minutes Hall Walk Distance Observed Between the Enrollment and the End of the Study | -15.1 meters | Standard Deviation 88 |
| Standard CRT | Changes in 6 Minutes Hall Walk Distance Observed Between the Enrollment and the End of the Study | 7.5 meters | Standard Deviation 96.3 |
Secondary
Changes in Echocardiographic Indexes of Left Ventricle Remodeling
Changes between baseline and 24months follow up
Time frame: 24 months
Population: Number of patients with data available for analysis of this objective
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CRT With Dual Site LV Pacing | Changes in Echocardiographic Indexes of Left Ventricle Remodeling | Changes in LVEDV | -16.4 milliliter | Standard Deviation 78.6 |
| CRT With Dual Site LV Pacing | Changes in Echocardiographic Indexes of Left Ventricle Remodeling | Changes in LVESV | -14.3 milliliter | Standard Deviation 57.6 |
| Standard CRT | Changes in Echocardiographic Indexes of Left Ventricle Remodeling | Changes in LVEDV | 7.0 milliliter | Standard Deviation 72.1 |
| Standard CRT | Changes in Echocardiographic Indexes of Left Ventricle Remodeling | Changes in LVESV | -2.0 milliliter | Standard Deviation 60.6 |
Secondary
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.
Time frame: 24 months
Population: Number of patients with data available for analysis of this objective
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CRT With Dual Site LV Pacing | Changes in Quality of Life Score - Minesota Living With Heart Failure Questionnaire | -7.33 units on a scale | Standard Deviation 23.5 |
| Standard CRT | Changes in Quality of Life Score - Minesota Living With Heart Failure Questionnaire | -7.48 units on a scale | Standard Deviation 17.2 |
Secondary
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.
Time frame: 24 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CRT With Dual Site LV Pacing | Distribution of Improved, Unchanged and Worsened Patients as Defined Per M. Packer's Clinical Composite Score | Patients improved | 8 participants |
| CRT With Dual Site LV Pacing | Distribution of Improved, Unchanged and Worsened Patients as Defined Per M. Packer's Clinical Composite Score | Patients unchanged | 8 participants |
| CRT With Dual Site LV Pacing | Distribution of Improved, Unchanged and Worsened Patients as Defined Per M. Packer's Clinical Composite Score | Patients worsened | 26 participants |
| Standard CRT | Distribution of Improved, Unchanged and Worsened Patients as Defined Per M. Packer's Clinical Composite Score | Patients improved | 3 participants |
| Standard CRT | Distribution of Improved, Unchanged and Worsened Patients as Defined Per M. Packer's Clinical Composite Score | Patients unchanged | 12 participants |
| Standard CRT | Distribution of Improved, Unchanged and Worsened Patients as Defined Per M. Packer's Clinical Composite Score | Patients worsened | 25 participants |
Secondary
Number of Patients With at Least One Hospitalization Related to Heart Failure Between Randomization and the End of the Study
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CRT With Dual Site LV Pacing | Number of Patients With at Least One Hospitalization Related to Heart Failure Between Randomization and the End of the Study | 19 participants |
| Standard CRT | Number of Patients With at Least One Hospitalization Related to Heart Failure Between Randomization and the End of the Study | 22 participants |
Secondary
Overall Mortality
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CRT With Dual Site LV Pacing | Overall Mortality | 17 participants |
| Standard CRT | Overall Mortality | 17 participants |
Secondary
Rate of Adverse Events
Time frame: 24 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CRT With Dual Site LV Pacing | Rate of Adverse Events | Patients with at least one AE | 38 participants |
| CRT With Dual Site LV Pacing | Rate of Adverse Events | Patients with at least one severe AE | 33 participants |
| Standard CRT | Rate of Adverse Events | Patients with at least one AE | 34 participants |
| Standard CRT | Rate of Adverse Events | Patients with at least one severe AE | 33 participants |
Secondary
Time to First Heart Failure Related Hospitalization
Time frame: 24 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CRT With Dual Site LV Pacing | Time to First Heart Failure Related Hospitalization | 357.6 days | Standard Error 27.17 |
| Standard CRT | Time to First Heart Failure Related Hospitalization | 402.4 days | Standard Error 41.16 |