Heart Failure
Conditions
Keywords
CRT, non responders, MultiPoint Pacing (MPP)
Brief summary
The purpose of this Clinical investigation is to assess the impact of the Multi Point Pacing (MPP) feature at 12 months in the treatment of patients not responding to standard Cardiac Resynchronization Therapy (CRT) after 6 months.
Detailed description
This study is designed as a prospective, randomized, multi-center trial. Data will be collected at enrollment, baseline, implant procedure, patient classification, 6 months and 12 months of follow-up. During the 6-month visit, the patient's response to CRT will be evaluated according to LVESV reduction. Patients with an LVESV reduction of at least 15% will be classified as responders. These patients will terminate their participation in the study and return to the center's standard practice. Patients with an LVESV reduction less than 15% will be classified as non-responders and the MPP feature will be activated according to randomization result and they will be followed until the 12-month visit.
Interventions
DEVICEMPP
All patients enrolled in the study will be implanted (according to current Guidelines) with an MPP compatible CRT device. The MPP feature will be evaluated in two study phases. Patients randomized to MPP in Phase I will have MPP programmed per the physician's discretion (no mandated MPP programming) and patients randomized to MPP in Phase II will have MPP programmed per protocol requirements (mandated MPP programming).
Sponsors
Abbott Medical Devices
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
* Meets the current ESC Guidelines or ACCF/AHA/HRS Class I or Class IIa indications for CRT implant (including upgrades from single or dual chamber ICDs) * Must be willing and able to comply with study requirements * Must indicate their understanding of the study and willingness to participate by signing an appropriate informed consent form
Exclusion criteria
* Already had a CRT device implanted * Myocardial Infarction, unstable angina within 40 days prior the enrollment * Recent cardiac revascularization (PTCA, Stent or CABG) in the 4 weeks prior to enrollment or planned for the 3 months following * Cerebrovascular Accident (CVA) or Transient Ischemic Attack (TIA) in the 3 months prior the enrollment * Primary valvular disease * Atrial Fibrillation: * Persistent AF at the time of enrollment * Permanent AF not treated with AV node ablation within 2 weeks from the CRT implant * History or incidence of Paroxysmal or Persistent AF within 30 days prior the enrollment * Unable to comply with the follow up schedule * Less than 18 years of age * Pregnant or are planning to become pregnant during the duration of the investigation * Classification of Status 1 for cardiac transplantation or consideration for transplantation over the next 12 months * Undergone a cardiac transplantation * Life expectancy \< 12 months * Currently participating in any other clinical investigation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Non-responder Patients Who Converted to Responders | Non-responder to responder conversion rate between randomization at 6 months and 12 months | The primary endpoint of this study is evaluated at 12 months after enrollment and it is defined as the percentage of non-responder patients converted to responders after 6 months of MPP feature turned ON compared to baseline, as measured by Left Ventricular End Systolic Volume (LVESV) reduction of at least 15%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Composite Score Evaluation | Baseline vs 12 Months | Packer's Clinical Composite Score evaluation between baseline and 12 months as defined below, * Worsened: the patient died because of cardiovascular reasons OR experienced a HF event OR demonstrated worsening in NYHA functional class, or had worsening of patient global assessment (PGA) score compared with the last observation * Improved: the patient survived without an HF event AND demonstrated either improvement in NYHA functional class or improvement in PGA score or both compared with the last observation * Unchanged: the patient was neither improved nor worsened |
| Reverse Left Ventricular (LV) Remodeling | Baseline vs 12 Months | Evaluation of Reverse LV remodeling, measured as changed in left ventricular end-systolic volume (LVESV) from baseline to 12 months |
| Reduction of Left Ventricular End-systolic Volume (LVESV) in Acute Phase | Baseline vs 6 Months | Reduction of LVESV between baseline and 6 Months visit |
| 6MWT Changes | Baseline vs 12 Months | Evaluation of the patient's activity status using 6 Minutes Walking Test changes from baseline to 12 months FU |
| Patient's QoL Score Changes (MLWHF) | Baseline vs 12 Months | Evaluation of patient's Quality of Life score using Minnesota Living with Heart Failure (MLWHF) Questionnaires. The MLWHF Questionnaire consists of 21 questions with a range in overall scores of 0 to 105 points (lower scores indicate better quality of life). |
| NYHA Class Changes | Baseline vs 12 Months | Evaluation of NYHA Class changes between baseline and 12 months. Increasing functional class is associated with greater risk of death or hospitalization. |
Countries
Australia, Austria, Belgium, Canada, China, Colombia, Denmark, Finland, France, Germany, Greece, India, Israel, Italy, Lebanon, Malaysia, Malta, Netherlands, Poland, Portugal, Puerto Rico, Saudi Arabia, Singapore, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
The study enrolled eligible patients with a standard CRT indication after obtaining written informed consent. The implanting physician programmed biventricular pacing (BiVP) at implant in those patients who had the quadripolar CRT system successfully implanted The implanting physician programmed the LV pacing vector, A-V delay, and V-V delay settings at their discretion until the patient's randomization at 6 months.
Pre-assignment details
For the first 6 months post-implant, all enrolled patients were followed with traditional biventricular pacing (BiVP). Only patients not responding to BiVP between baseline and 6 months (using LVESV reduction less than 15%), which is called CRT non-responders, were randomized to either MPP or continuous BiVP arm at 6 months and followed until 12 months.
Participants by arm
| Arm | Count |
|---|---|
| MPP ON MPP ON: feature is enabled after 6 months
MPP: All patients enrolled in the study will be implanted (according to current Guidelines) with an MPP compatible CRT device. The MPP feature was evaluated in two study phases. Patients randomized to MPP in Phase I had MPP programmed per the physician's discretion (no mandated MPP programming) and patients randomized to MPP in Phase II had MPP programmed per protocol requirements (mandated MPP programming). Patients from both Phases were analyzed together using as-treated analysis. | 271 |
| BiVP MPP OFF: Continuous BiVP after 6 months. Patients from both Phases were analyzed together using as-treated analysis. | 555 |
| Total | 826 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | MPP other programming | 239 | 0 |
| Overall Study | RV only pacing | 0 | 3 |
Baseline characteristics
| Characteristic | MPP ON | BiVP | Total |
|---|---|---|---|
| Age, Continuous | 68.4 years STANDARD_DEVIATION 10.3 | 68.1 years STANDARD_DEVIATION 10.6 | 68.2 years STANDARD_DEVIATION 10.5 |
| NYHA Class II | 129 Participants | 272 Participants | 401 Participants |
| NYHA Class III | 137 Participants | 268 Participants | 405 Participants |
| NYHA Class IV | 4 Participants | 13 Participants | 17 Participants |
| NYHA Class Not done | 1 Participants | 2 Participants | 3 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 45 Participants | 123 Participants | 168 Participants |
| Sex: Female, Male Male | 226 Participants | 432 Participants | 658 Participants |
| Type of Cardiomyopathy Ischemic | 147 Participants | 278 Participants | 425 Participants |
| Type of Cardiomyopathy Non-ischemic | 124 Participants | 277 Participants | 401 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 271 | 18 / 555 |
| other Total, other adverse events | 67 / 271 | 118 / 555 |
| serious Total, serious adverse events | 82 / 271 | 190 / 555 |
Outcome results
Primary
Percentage of Non-responder Patients Who Converted to Responders
The primary endpoint of this study is evaluated at 12 months after enrollment and it is defined as the percentage of non-responder patients converted to responders after 6 months of MPP feature turned ON compared to baseline, as measured by Left Ventricular End Systolic Volume (LVESV) reduction of at least 15%.
Time frame: Non-responder to responder conversion rate between randomization at 6 months and 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MPP ON | Percentage of Non-responder Patients Who Converted to Responders | 84 Participants |
| BiVP | Percentage of Non-responder Patients Who Converted to Responders | 170 Participants |
Secondary
6MWT Changes
Evaluation of the patient's activity status using 6 Minutes Walking Test changes from baseline to 12 months FU
Time frame: Baseline vs 12 Months
Population: Only subjects with 6MHWT data available at both baseline and 12 months were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MPP ON | 6MWT Changes | 41.1 meters | Standard Deviation 113.6 |
| BiVP | 6MWT Changes | 46 meters | Standard Deviation 121.1 |
Secondary
Clinical Composite Score Evaluation
Packer's Clinical Composite Score evaluation between baseline and 12 months as defined below, * Worsened: the patient died because of cardiovascular reasons OR experienced a HF event OR demonstrated worsening in NYHA functional class, or had worsening of patient global assessment (PGA) score compared with the last observation * Improved: the patient survived without an HF event AND demonstrated either improvement in NYHA functional class or improvement in PGA score or both compared with the last observation * Unchanged: the patient was neither improved nor worsened
Time frame: Baseline vs 12 Months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MPP ON | Clinical Composite Score Evaluation | Improved | 161 Participants |
| MPP ON | Clinical Composite Score Evaluation | Unchanged | 56 Participants |
| MPP ON | Clinical Composite Score Evaluation | Worsensed | 54 Participants |
| BiVP | Clinical Composite Score Evaluation | Improved | 312 Participants |
| BiVP | Clinical Composite Score Evaluation | Unchanged | 124 Participants |
| BiVP | Clinical Composite Score Evaluation | Worsensed | 119 Participants |
Secondary
NYHA Class Changes
Evaluation of NYHA Class changes between baseline and 12 months. Increasing functional class is associated with greater risk of death or hospitalization.
Time frame: Baseline vs 12 Months
Population: Only subjects with NYHA data available at both baseline and 12 months were included in this analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MPP ON | NYHA Class Changes | Improved | 125 Participants |
| MPP ON | NYHA Class Changes | Unchanged | 129 Participants |
| MPP ON | NYHA Class Changes | Worsened | 12 Participants |
| BiVP | NYHA Class Changes | Improved | 287 Participants |
| BiVP | NYHA Class Changes | Unchanged | 225 Participants |
| BiVP | NYHA Class Changes | Worsened | 20 Participants |
Secondary
Patient's QoL Score Changes (MLWHF)
Evaluation of patient's Quality of Life score using Minnesota Living with Heart Failure (MLWHF) Questionnaires. The MLWHF Questionnaire consists of 21 questions with a range in overall scores of 0 to 105 points (lower scores indicate better quality of life).
Time frame: Baseline vs 12 Months
Population: Only subjects with MLWHF data available at both baseline and 12 months were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MPP ON | Patient's QoL Score Changes (MLWHF) | -11.6 score on a scale | Standard Deviation 20 |
| BiVP | Patient's QoL Score Changes (MLWHF) | -12.2 score on a scale | Standard Deviation 21.7 |
Secondary
Reduction of Left Ventricular End-systolic Volume (LVESV) in Acute Phase
Reduction of LVESV between baseline and 6 Months visit
Time frame: Baseline vs 6 Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MPP ON | Reduction of Left Ventricular End-systolic Volume (LVESV) in Acute Phase | 2.1 percentage of LVESV change | Standard Deviation 11.2 |
| BiVP | Reduction of Left Ventricular End-systolic Volume (LVESV) in Acute Phase | 0.1 percentage of LVESV change | Standard Deviation 3.3 |
Secondary
Reverse Left Ventricular (LV) Remodeling
Evaluation of Reverse LV remodeling, measured as changed in left ventricular end-systolic volume (LVESV) from baseline to 12 months
Time frame: Baseline vs 12 Months
Population: Only subjects with LVESV data available at both baseline and 12 months were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MPP ON | Reverse Left Ventricular (LV) Remodeling | 3.0 mL | Standard Deviation 24 |
| BiVP | Reverse Left Ventricular (LV) Remodeling | 3.8 mL | Standard Deviation 23.1 |