Sudden Cardiac Death
Conditions
Keywords
Antitachycardia Pacing Therapy, Shock Therapy, Primary Prevention
Brief summary
The primary objective is to understand the role of antitachycardia pacing (ATP) in primary prevention patients indicated for implantable cardioverter-defibrillator (ICD) therapy and programmed according to current guidance of higher rate cut-offs and therapy delays. The time to first all-cause shock will be tested in subjects with standard therapy (ATP and shocks) compared to subjects programmed to shock only to assess equivalency.
Interventions
DEVICEArm 1 (ATP+Shock)
Subjects will be randomized and device programmed to the respective arm.
DEVICEArm 2 (shock only)
Subjects will be randomized and device programmed to the respective arm.
Sponsors
Boston Scientific Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject with a Boston Scientific transvenous ICD (de novo implant or upgrade from pacemaker to ICD) implanted because of one of the following: * Prior myocardial infarction (MI) and left ventricular ejection fraction (LVEF) ≤ 30% OR * Ischemic or non-ischemic cardiomyopathy, and LVEF ≤ 35%, and a New York Heart Association (NYHA) class II or III * Subject is age 21 or above, or is considered of legal age per given geography * Subject is willing and capable of providing informed consent * Subject is willing and capable of complying with follow-up visits as defined by this protocol
Exclusion criteria
* History of spontaneous sustained Ventricular Tachycardia (VT) (≥ 160 bpm at ≥ 30 seconds in duration) or Ventricular Fibrillation (VF) not due to a reversible cause * NYHA Class IV documented in the medical records within 90 calendar days prior to enrollment * Subject is eligible and scheduled for cardiac resynchronization (CRT) implant * Subjects with a previous subcutaneous ICD (S-ICD) * Subject with existing transvenous ICD (TV-ICD) device implanted for greater than 60 days * Subjects with coronary artery bypass graft surgery or percutaneous coronary intervention within the past 90 calendar days prior to enrollment * Subjects with documented myocardial infarction within the past 90 calendar days prior to enrollment * Subjects on the active heart transplant list * Subject who has a ventricular assist device (VAD) or is to receive a VAD * Life expectancy shorter than 18 months due to any medical condition (e.g., cancer, uremia, liver failure, etc…) * Subjects currently requiring hemodialysis * Subject who is known to pregnant or plans to become pregnant over the course of the trial * Subject is enrolled in any other concurrent clinical study, with the exception of local mandatory governmental registries and observational studies/registries, without the written approval from Boston Scientific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-Cause Shock | 5 years | The incidence of all-cause shocks in subjects programmed with shocks only will be compared with subjects programmed to standard therapy (ATP and shock) to assess equivalency. All shocks delivered by the device were adjudicated by an external committee as to whether they were appropriately or inappropriately delivered. All shocks, appropriate and inappropriate, contributed to the evaluation of this endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-Cause Shock or Death From Any Cause | 5 years | incidence of all-cause shocks or death from any cause |
| Appropriate Shock | 5 years | incidence of first appropriate shock All shocks delivered by the device were adjudicated by an external committee as to whether they were appropriately or inappropriately delivered. Appropriate shocks contributed to the evaluation of this endpoint. |
| Inappropriate Shock | 5 years | incidence of first inappropriate shock All shocks delivered by the device were adjudicated by an external committee as to whether they were appropriately or inappropriately delivered. Inappropriate shocks contributed to the evaluation of this endpoint. |
| All Cause Mortality | 5 years | incidents of all cause mortality |
Countries
Austria, Canada, Italy, Japan, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
Recruitment for participants began on 30 Sep 2016 and ended on 13 Apr 2021 when the adjudicated primary episode target had been met. Potential participants, located at medical clinics or hospitals, were eligible for the study if they were 21 years of age or older and had a Class 1 or IIA indication for primary prevention implantable cardioverter defibrillator (ICD) therapy with a low left ventricular ejection fraction. Participants were considered enrolled once consented.
Pre-assignment details
Of the 2692 participants enrolled,19 were consent ineligible and 12 were intent and therefore not randomized. 2595 participants were randomized. Consented and Ineligible: Consent signed but eligibility criteria was not met at time of enrollment • Intent: All eligibility criteria met and consent signed, but participant was not randomized due to: * no longer meeting eligibility criteria at the time of randomization * no longer willing to participate in the study
Participants by arm
| Arm | Count |
|---|---|
| ATP and Shock Once tachycardia has been detected and duration met, this group would receive antitachycardia pacing prior to shock therapy.
Arm 1 (ATP+Shock): Subjects will be randomized and device programmed to the respective arm. | 1,302 |
| Shock Only Once tachycardia has been detected and duration met, this group would receive shock therapy only.
Arm 2 (shock only): Subjects will be randomized and device programmed to the respective arm. | 1,293 |
| Total | 2,595 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 196 | 175 |
| Overall Study | Withdrawal by Subject | 337 | 307 |
Baseline characteristics
| Characteristic | ATP and Shock | Shock Only | Total |
|---|---|---|---|
| Age, Continuous | 64.0 Years STANDARD_DEVIATION 11.5 | 63.8 Years STANDARD_DEVIATION 11.1 | 63.9 Years STANDARD_DEVIATION 11.3 |
| Device Type Dual Chamber ICD | 622 Participants | 646 Participants | 1268 Participants |
| Device Type Single Chamber ICD | 678 Participants | 646 Participants | 1324 Participants |
| Diabetes | 525 Participants | 520 Participants | 1045 Participants |
| Etiology Ischemic | 757 Participants | 753 Participants | 1510 Participants |
| Etiology Non-ischemic | 545 Participants | 540 Participants | 1085 Participants |
| History of Atrial Fibrillation No History of Atrial Fibrillation | 961 Participants | 937 Participants | 1898 Participants |
| History of Atrial Fibrillation Paroxysmal Atrial Fibrillation | 176 Participants | 208 Participants | 384 Participants |
| History of Atrial Fibrillation Permanent Atrial Fibrillation | 70 Participants | 56 Participants | 126 Participants |
| History of Atrial Fibrillation Persistent Atrial Fibrillation | 95 Participants | 92 Participants | 187 Participants |
| Indication Myocardial Infarction (MI) and Ejection Fraction (EF) >/= 30% | 417 Participants | 445 Participants | 862 Participants |
| Indication New York Heart Association (NYHA) Class II/III and EF </= 35% | 876 Participants | 842 Participants | 1718 Participants |
| Indication Other | 9 Participants | 6 Participants | 15 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaksa Native | 5 Participants | 8 Participants | 13 Participants |
| Race/Ethnicity, Customized Race Asian | 209 Participants | 206 Participants | 415 Participants |
| Race/Ethnicity, Customized Race Black or African Heritage | 169 Participants | 178 Participants | 347 Participants |
| Race/Ethnicity, Customized Race Caucasian | 860 Participants | 849 Participants | 1709 Participants |
| Race/Ethnicity, Customized Race Hispanic or Latino | 39 Participants | 37 Participants | 76 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Pacific Islander | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Race Other | 3 Participants | 1 Participants | 4 Participants |
| Region of Enrollment Austria | 13 Participants | 15 Participants | 28 Participants |
| Region of Enrollment Canada | 141 Participants | 151 Participants | 292 Participants |
| Region of Enrollment Italy | 71 Participants | 71 Participants | 142 Participants |
| Region of Enrollment Japan | 65 Participants | 60 Participants | 125 Participants |
| Region of Enrollment South Korea | 123 Participants | 129 Participants | 252 Participants |
| Region of Enrollment Spain | 20 Participants | 18 Participants | 38 Participants |
| Region of Enrollment United Kingdom | 20 Participants | 17 Participants | 37 Participants |
| Region of Enrollment United States | 841 Participants | 823 Participants | 1664 Participants |
| Sex: Female, Male Female | 277 Participants | 304 Participants | 581 Participants |
| Sex: Female, Male Male | 1024 Participants | 989 Participants | 2013 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 196 / 1,302 | 175 / 1,293 |
| other Total, other adverse events | 420 / 1,302 | 448 / 1,293 |
| serious Total, serious adverse events | 633 / 1,302 | 618 / 1,293 |
Outcome results
Primary
All-Cause Shock
The incidence of all-cause shocks in subjects programmed with shocks only will be compared with subjects programmed to standard therapy (ATP and shock) to assess equivalency. All shocks delivered by the device were adjudicated by an external committee as to whether they were appropriately or inappropriately delivered. All shocks, appropriate and inappropriate, contributed to the evaluation of this endpoint.
Time frame: 5 years
Population: All randomized subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ATP and Shock | All-Cause Shock | 129 Participants |
| Shock Only | All-Cause Shock | 178 Participants |
p-value: 0.00595.9% CI: [0.57, 0.92]Log Rank
Secondary
All Cause Mortality
incidents of all cause mortality
Time frame: 5 years
Population: All randomized subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ATP and Shock | All Cause Mortality | 196 Participants |
| Shock Only | All Cause Mortality | 174 Participants |
p-value: 0.18495% CI: [0.94, 1.41]Log Rank
Secondary
All-Cause Shock or Death From Any Cause
incidence of all-cause shocks or death from any cause
Time frame: 5 years
Population: All randomized subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ATP and Shock | All-Cause Shock or Death From Any Cause | 297 Participants |
| Shock Only | All-Cause Shock or Death From Any Cause | 322 Participants |
p-value: 0.28495% CI: [0.78, 1.07]Log Rank
Secondary
Appropriate Shock
incidence of first appropriate shock All shocks delivered by the device were adjudicated by an external committee as to whether they were appropriately or inappropriately delivered. Appropriate shocks contributed to the evaluation of this endpoint.
Time frame: 5 years
Population: Randomized subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ATP and Shock | Appropriate Shock | 96 Participants |
| Shock Only | Appropriate Shock | 132 Participants |
p-value: 0.0295% CI: [0.56, 0.95]Log Rank
Secondary
Inappropriate Shock
incidence of first inappropriate shock All shocks delivered by the device were adjudicated by an external committee as to whether they were appropriately or inappropriately delivered. Inappropriate shocks contributed to the evaluation of this endpoint.
Time frame: 5 years
Population: All randomized subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ATP and Shock | Inappropriate Shock | 40 Participants |
| Shock Only | Inappropriate Shock | 62 Participants |
p-value: 0.03395% CI: [0.44, 0.97]Log Rank