Heart Failure
Conditions
Brief summary
This IDE study is a prospective, randomized, double-blind, multi-center clinical study to evaluate the safety and efficacy of patient treatment with MPP compared to patient treatment with standard BiV pacing at 9 months. The study will be conducted at a maximum of 50 investigational centers located in the United States. A maximum of 506 subjects implanted with the Quadripolar cardiac resynchronization therapy device (CRT-D) system will be enrolled in the study.
Detailed description
All subjects will undergo a 2 dimensional Echocardiogram within the 30 days prior to implant, and again at 3, 6 and 9 months post implant. At implant, the final LV pacing configuration is programmed using any one of the 10 available pacing vectors. The paced/sensed atrioventricular (AV) and interventricular (VV) delays may be optimized as per the site's standard of care. Subjects will continue to receive BiV therapy until the 3-month follow-up visit. At the 3-month visit, responder status between Enrollment and 3 months will be assessed using the Clinical Composite Score (CCS). All subjects that are Improved using the definition outlined in the CCS will be grouped together as Responders. All subjects that are Worsened or Unchanged using the definitions outlined in the CCS will be considered as Non-responders. All subjects will undergo acute measurement of cardiac performance (e.g., Echocardiography) at various MPP combinations compared to BiV pacing. Only subjects with equal or better echocardiographic measurements (i.e., EA VTI measurements) with MPP feature on compared to BiV pacing will be randomized in a 1:1 ratio to one of the two arms - BiV arm or MPP arm. At the 9-month visit, responder status will be evaluated once again using the CCS and compared to the status at 3 months.
Interventions
DEVICEMultiPoint Pacing
Subjects are programmed to MPP between 3 and 9 months. MPP programming is stipulated by the Echocardiographic measurements (e.g. EA VTI) during an acute hemodynamic assessment at the 3-month visit in the MPP IDE study.
DEVICETraditional Biventricular Pacing
Subjects are programmed to Quadripolar BiV pacing between 3 and 9 months using any of the 10 vectors available.
Sponsors
Abbott Medical Devices
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Meets current clinical indication for implantation of a cardiac resynchronization therapy system for treatment of heart failure or life-threatening ventricular tachyarrhythmia(s) * Receiving a new CRT implant or undergoing an upgrade from an existing ICD or pacemaker implant with no prior LV lead placement * Have the ability to provide informed consent for study participation and are willing and able to comply with the prescribed follow-up tests and schedule of evaluations
Exclusion criteria
* Have had a recent Cerebrovascular Accident (CVA) or Transient Ischemic Attack (TIA) within 3 months of enrollment * Have an existing Class I recalled lead * Have a hypersensitivity to a single 1.0mg dose of dexamethasone sodium phosphate * Have a classification of Status 1 for cardiac transplantation or consideration for transplantation over the next 9 months * Have permanent atrial fibrillation (AF) * Have undergone a cardiac transplantation within 40 days of enrollment * Have had a recent myocardial infarction, unstable angina within 40 days or cardiac revascularization within 3 months of implant. * Are currently participating in a clinical investigation that includes an active treatment arm * Are pregnant or planning to become pregnant during the duration of the study * Have a life expectancy of less than 9 months due to any condition * Are less than 18 years of age
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Freedom From System-related Complications Through 9 Months Compared to an Objective Performance Criterion | Implant to 9 months | A system related complication is a complication related to the Quadripolar CRT-D device system which includes pulse generator and leads, as adjudicated by an independent Clinical Events Committee (CEC). All subjects who had an attempted implant or a successful Quadripolar system implant were included in the analysis of this safety endpoint. |
| Percentage of Non-responders With MPP Compared to Biventricular Pacing | 3 months to 9 months | The hypothesis is that the non-response rate to CRT therapy in the MPP therapy arm is not inferior to the non-response rate in the BiV arm between 3 and 9 months post-implant. Responder status was assessed using the Clinical Composite Score (CCS). A patient's CCS was classified as worsened, improved or unchanged based on the definitions below: * Worsened - patient died due to cardiovascular reasons, experienced a HF event, demonstrated worsening in NYHA class, or had worsening of PGA score compared to the last observation * Improved - patient survived without a HF event, and demonstrated either improvement in NYHA class or improvement in PGA score, or both compared to the last observation. * Unchanged - patient was neither improved nor worsened For patients who were responders at the 3-month visit, those who were Improved and Unchanged between 3 and 9 months were classified as responders, whereas those who were Worsened were grouped together as non-responders. |
Countries
United States
Participant flow
Recruitment details
The study enrolled 506 subjects at 49 investigational centers located in the U.S. A patient was considered enrolled upon signing informed consent. The first subject was enrolled on April 25, 2013. The study was double-blinded (the study subjects and the authorized personnel conducting the NYHA Class and Patient Global assessments were blinded).
Pre-assignment details
455 out of 469 subjects with an attempted implant (97% success rate) received Quadripolar BiV pacing between implant and 3 months. At 3 months, responder status was assessed per Clincial Composite Score and 1:1 randomziation was stratified by responder status. 381 patients were randomized to either BiV (n = 180) or MPP (n = 201) at 3 months.
Participants by arm
| Arm | Count |
|---|---|
| MultiPoint Pacing Arm Subjects were programmed to MPP between 3 and 9 months. MPP programming was stipulated by the Echocardiographic measurements (e.g. EA VTI) during an acute hemodynamic assessment at the 3-month visit in the MPP IDE study. | 201 |
| Biventricular Arm Subjects were programmed to Quadripolar BiV pacing between 3 and 9 months using any of the 10 vectors available. | 180 |
| Total | 381 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 6 | 7 |
| Overall Study | Hospice Admission | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Subject Non-Compliance | 1 | 0 |
| Overall Study | System Explant | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Biventricular Arm | Total | MultiPoint Pacing Arm |
|---|---|---|---|
| Age, Continuous | 68 years STANDARD_DEVIATION 10 | 68 years STANDARD_DEVIATION 10 | 67 years STANDARD_DEVIATION 10 |
| Cardiomyopathy Etiology Ischemic | 88 participants | 184 participants | 96 participants |
| Cardiomyopathy Etiology None | 1 participants | 3 participants | 2 participants |
| Cardiomyopathy Etiology Non-ischemic | 91 participants | 194 participants | 103 participants |
| Ethnicity Hispanic or Latino | 5 participants | 15 participants | 10 participants |
| Ethnicity Non-Hispanic or Latino | 175 participants | 366 participants | 191 participants |
| QRS Duration | 154 ms STANDARD_DEVIATION 20 | 156 ms STANDARD_DEVIATION 22 | 158 ms STANDARD_DEVIATION 24 |
| QRS Morphology Interventricular Conduction Delay (IVCD) | 21 participants | 53 participants | 32 participants |
| QRS Morphology Left Bundle Branch Block (LBBB) | 139 participants | 285 participants | 146 participants |
| QRS Morphology Right Bundle Branch Block (RBBB) | 20 participants | 41 participants | 21 participants |
| QRS Morphology Unknown | 0 participants | 2 participants | 2 participants |
| RACE Asian | 0 participants | 2 participants | 2 participants |
| RACE Black or African American | 16 participants | 35 participants | 19 participants |
| RACE Other | 1 participants | 5 participants | 4 participants |
| RACE White | 163 participants | 339 participants | 176 participants |
| Region of Enrollment United States | 180 participants | 381 participants | 201 participants |
| Sex: Female, Male Female | 61 Participants | 134 Participants | 73 Participants |
| Sex: Female, Male Male | 119 Participants | 247 Participants | 128 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 40 / 201 | 5 / 180 |
| serious Total, serious adverse events | 4 / 201 | 3 / 180 |
Outcome results
Primary
Freedom From System-related Complications Through 9 Months Compared to an Objective Performance Criterion
A system related complication is a complication related to the Quadripolar CRT-D device system which includes pulse generator and leads, as adjudicated by an independent Clinical Events Committee (CEC). All subjects who had an attempted implant or a successful Quadripolar system implant were included in the analysis of this safety endpoint.
Time frame: Implant to 9 months
Population: Of 469 subjects who underwent an attempted implant, 31 subjects experienced a system-related complication between implant and 9 months (13 were LV lead-related, 16 were RA/RV lead-related and 3 were Quadripolar CRT-D pulse generator related. One subject experienced more than one category of complication).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BiV/MPP Patients | Freedom From System-related Complications Through 9 Months Compared to an Objective Performance Criterion | 0.932 Event-Free Probability |
Comparison: The hypothesis is formally expressed as:~H0: Freedom from system-related complications through 9 months ≤ 75% Ha: Freedom from system-related complications through 9 months \> 75%95% CI: [0.904, 0.951]
Primary
Percentage of Non-responders With MPP Compared to Biventricular Pacing
The hypothesis is that the non-response rate to CRT therapy in the MPP therapy arm is not inferior to the non-response rate in the BiV arm between 3 and 9 months post-implant. Responder status was assessed using the Clinical Composite Score (CCS). A patient's CCS was classified as worsened, improved or unchanged based on the definitions below: * Worsened - patient died due to cardiovascular reasons, experienced a HF event, demonstrated worsening in NYHA class, or had worsening of PGA score compared to the last observation * Improved - patient survived without a HF event, and demonstrated either improvement in NYHA class or improvement in PGA score, or both compared to the last observation. * Unchanged - patient was neither improved nor worsened For patients who were responders at the 3-month visit, those who were Improved and Unchanged between 3 and 9 months were classified as responders, whereas those who were Worsened were grouped together as non-responders.
Time frame: 3 months to 9 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BiV/MPP Patients | Percentage of Non-responders With MPP Compared to Biventricular Pacing | 29.9 percentage of patients |
| Biventricular Arm | Percentage of Non-responders With MPP Compared to Biventricular Pacing | 25 percentage of patients |
Comparison: H0: (Non-responder rate in the BiV arm between 3 M randomization and 9 M) - (Non-responder rate in the MPP arm between 3 M randomization and 9 M) ≤ -0.15~Ha: (Non-responder rate in the BiV arm between 3 M randomization and 9 M) - (Non-responder rate in the MPP arm between 3 M randomization and 9 M) \> -0.15~The null hypothesis will be rejected at the 2.5% significance level if the lower one-sided 97.5% confidence bound for the difference in the proportions is above -0.15.p-value: 0.0131normal approximation for binomial dist