Sudden Cardiac Arrest, Ventricular Arrythmia
Conditions
Keywords
Sudden Cardiac Arrest (SCA), Syncope, Non Sustained Ventricular Tachycardia (NSVT), Premature Ventricular Contractions (PVC), Left Ventricular Ejection Fraction (LVEF), Primary Prevention, Secondary Prevention, Antitachycardia pacing (ATP), shock, appropriate therapy
Brief summary
The purpose of this study is to demonstrate that primary prevention patients with one or more additional risk factors (1.5 prevention criteria: syncope/pre-syncope, non-sustained ventricular tachycardia (NSVT), frequent pre-ventricular contractions (PVCs), and low left ventricular ejection fraction (LVEF)) are at a similar risk of life-threatening ventricular arrhythmias (LTVA) when compared to secondary prevention patients, and would receive similar benefit from an implantable cardioverter defibrillator (ICD), or cardiac resynchronization therapy- defibrillator (CRT-D) implant.
Detailed description
Devices allowed in the study include any Medtronic single, dual, or triple chamber defibrillator that has received appropriate license or regulatory approval and is commercially available by Medtronic in the geography in which the implant will take place. Any market-released, commercially available lead(s) can be used in the study.
Interventions
DEVICEICD or CRT-D Device
Subjects who receive an ICD/CRT-D device implant will be implanted and follow protocol-specified programming. The programming is not investigational. Consistent programming is desirable in order to compare groups during statistical analysis.
Sponsors
Medtronic Cardiac Rhythm and Heart Failure
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has a Class I indication for implantation of an ICD according to the American College of Cardiology (ACC)/American Heart Association(AHA)/Heart Rhythm Society (HRS) or European Society of Cardiology (ESC) Guidelines * Subject (or subject's legally authorized representative) is willing and able to sign and date the Patient Informed Consent Form.
Exclusion criteria
* Subject is ≤ 18 years of age * Subject with any
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to the First Occurrence of a Ventricular Arrhythmia | Hazard ratio from study enrollment to approximately 4 years post-implant/enrollment (as reported in Statistical Analysis 1), and estimated 24 month VT-VF rate (as compared in the Outcome Measure table between Groups A and C). | Time to the first occurrence of an episode of true ventricular tachycardia or fibrillation 24 Month rates will be provided for the two groups used in the primary endpoint definition. However, the primary endpoint of hazard ratio is presented in Statistical Analysis 1 as a ratio between Groups A and C. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | Hazard ratio from study enrollment to approximately 4 years post-implant/enrollment (as reported in Statistical Analysis 1), and estimated 24 month mortality rate (as compared in the Outcome Measure table between Groups C and D). | Time to all-cause mortality |
Countries
Argentina, Belarus, Brazil, China, Colombia, Egypt, India, Malaysia, Mexico, Russia, Singapore, South Africa, South Korea, Taiwan, Tunisia, United Arab Emirates
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A: Secondary Prevention Patients- Device Implant Patients who are guideline indicated for an ICD/CRT-D for secondary prevention of sudden cardiac arrest.
These subjects receive an ICD/CRT-D implant.
ICD or CRT-D Device: Subjects who receive an ICD/CRT-D device implant will be implanted and follow protocol-specified programming. The programming is not investigational. Consistent programming is desirable in order to compare groups during statistical analysis. | 1,066 |
| Group B: Secondary Prevention Patients - no Device Implant Patients who are guideline indicated for an ICD/CRT-D for secondary prevention of sudden cardiac arrest.
These subjects choose not to receive an ICD/CRT-D implant. | 127 |
| Group C: 1.5 Prevention Patients - Device Implant Patients who are guideline indicated for an ICD/CRT-D for primary prevention of sudden cardiac arrest fall into this group if they have one of the 4 additional risk factors (syncope/pre-syncope, non-sustained ventricular tachycardia (NSVT), frequent preventricular contractions (PVCs), or low left ventricular ejection fraction (low LVEF).
These subjects receive an ICD/CRT-D implant.
ICD or CRT-D Device: Subjects who receive an ICD/CRT-D device implant will be implanted and follow protocol-specified programming. The programming is not investigational. Consistent programming is desirable in order to compare groups during statistical analysis. | 1,068 |
| Group D: 1.5 Prevention Patients - no Device Implant Patients who are guideline indicated for an ICD/CRT-D for primary prevention of sudden cardiac arrest fall into this group if they have one of the 4 additional risk factors (syncope/pre-syncope, non-sustained ventricular tachycardia (NSVT), frequent preventricular contractions (PVCs), or low left ventricular ejection fraction (low LVEF).
These subjects choose not to receive an ICD/CRT-D implant. | 845 |
| Group E: Primary, Non-1.5 Patients - Device Implant Patients who are guideline indicated for an ICD/CRT-D for primary prevention of sudden cardiac arrest fall into this group if they do NOT fall into the 1.5 prevention group. These patients do not have one of the 4 additional risk factors (syncope/pre-syncope, non-sustained ventricular tachycardia (NSVT), frequent preventricular contractions (PVCs), or low left ventricular ejection fraction (low LVEF) which would put them into the 1.5 prevention group.
These subjects receive an ICD/CRT-D implant.
ICD or CRT-D Device: Subjects who receive an ICD/CRT-D device implant will be implanted and follow protocol-specified programming. The programming is not investigational. Consistent programming is desirable in order to compare groups during statistical analysis. | 331 |
| Group F: Primary, Non-1.5 Patients - no Device Patients who are guideline indicated for an ICD/CRT-D for primary prevention of sudden cardiac arrest fall into this group if they do NOT fall into the 1.5 prevention group. These patients do not have one of the 4 additional risk factors (syncope/pre-syncope, non-sustained ventricular tachycardia (NSVT), frequent preventricular contractions (PVCs), or low left ventricular ejection fraction (low LVEF) which would put them into the 1.5 prevention group.
These subjects choose not to receive an ICD/CRT-D implant. | 452 |
| Total | 3,889 |
Baseline characteristics
| Characteristic | Group A: Secondary Prevention Patients- Device Implant | Group B: Secondary Prevention Patients - no Device Implant | Group C: 1.5 Prevention Patients - Device Implant | Group D: 1.5 Prevention Patients - no Device Implant | Group E: Primary, Non-1.5 Patients - Device Implant | Group F: Primary, Non-1.5 Patients - no Device | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 57.1 years STANDARD_DEVIATION 14.3 | 55.7 years STANDARD_DEVIATION 15.5 | 61.1 years STANDARD_DEVIATION 11.7 | 59.1 years STANDARD_DEVIATION 13.3 | 61.3 years STANDARD_DEVIATION 11.3 | 57.8 years STANDARD_DEVIATION 13.7 | 59.0 years STANDARD_DEVIATION 13.3 |
| Race/Ethnicity, Customized Race / Ethnic Origin Asian Indian | 159 Participants | 23 Participants | 115 Participants | 273 Participants | 44 Participants | 239 Participants | 853 Participants |
| Race/Ethnicity, Customized Race / Ethnic Origin Black or African | 7 Participants | 0 Participants | 8 Participants | 2 Participants | 3 Participants | 1 Participants | 21 Participants |
| Race/Ethnicity, Customized Race / Ethnic Origin Chinese | 529 Participants | 97 Participants | 595 Participants | 475 Participants | 158 Participants | 182 Participants | 2036 Participants |
| Race/Ethnicity, Customized Race / Ethnic Origin Korean | 229 Participants | 4 Participants | 158 Participants | 25 Participants | 50 Participants | 15 Participants | 481 Participants |
| Race/Ethnicity, Customized Race / Ethnic Origin Not reportable per local laws or regulations | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Race / Ethnic Origin Other Asian | 35 Participants | 1 Participants | 28 Participants | 50 Participants | 9 Participants | 5 Participants | 128 Participants |
| Race/Ethnicity, Customized Race / Ethnic Origin Other Race | 17 Participants | 0 Participants | 42 Participants | 10 Participants | 14 Participants | 5 Participants | 88 Participants |
| Race/Ethnicity, Customized Race / Ethnic Origin Subject/physician chose not to provide information | 4 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants |
| Race/Ethnicity, Customized Race / Ethnic Origin White or Caucasian | 85 Participants | 2 Participants | 119 Participants | 10 Participants | 52 Participants | 4 Participants | 272 Participants |
| Region of Enrollment Argentina | 27 participants | 0 participants | 33 participants | 1 participants | 21 participants | 0 participants | 82 participants |
| Region of Enrollment Belarus | 8 participants | 0 participants | 7 participants | 1 participants | 1 participants | 0 participants | 17 participants |
| Region of Enrollment Brazil | 9 participants | 0 participants | 6 participants | 0 participants | 0 participants | 0 participants | 15 participants |
| Region of Enrollment China | 385 participants | 85 participants | 545 participants | 359 participants | 144 participants | 136 participants | 1654 participants |
| Region of Enrollment Colombia | 11 participants | 0 participants | 25 participants | 0 participants | 6 participants | 0 participants | 42 participants |
| Region of Enrollment Egypt | 6 participants | 2 participants | 1 participants | 1 participants | 1 participants | 1 participants | 12 participants |
| Region of Enrollment India | 149 participants | 22 participants | 104 participants | 263 participants | 39 participants | 236 participants | 813 participants |
| Region of Enrollment Malaysia | 45 participants | 0 participants | 23 participants | 30 participants | 0 participants | 0 participants | 98 participants |
| Region of Enrollment Malta | 1 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 2 participants |
| Region of Enrollment Mexico | 3 participants | 0 participants | 17 participants | 9 participants | 5 participants | 4 participants | 38 participants |
| Region of Enrollment Russia | 21 participants | 0 participants | 46 participants | 0 participants | 24 participants | 0 participants | 91 participants |
| Region of Enrollment Singapore | 14 participants | 5 participants | 42 participants | 76 participants | 23 participants | 27 participants | 187 participants |
| Region of Enrollment South Africa | 5 participants | 0 participants | 9 participants | 2 participants | 3 participants | 1 participants | 20 participants |
| Region of Enrollment South Korea | 232 participants | 4 participants | 160 participants | 25 participants | 52 participants | 15 participants | 488 participants |
| Region of Enrollment Taiwan | 125 participants | 9 participants | 18 participants | 72 participants | 1 participants | 29 participants | 254 participants |
| Region of Enrollment Tunisia | 22 participants | 0 participants | 28 participants | 5 participants | 6 participants | 3 participants | 64 participants |
| Region of Enrollment United Arab Emirates | 3 participants | 0 participants | 3 participants | 1 participants | 5 participants | 0 participants | 12 participants |
| Sex: Female, Male Female | 254 Participants | 27 Participants | 253 Participants | 176 Participants | 95 Participants | 103 Participants | 908 Participants |
| Sex: Female, Male Male | 812 Participants | 100 Participants | 815 Participants | 669 Participants | 236 Participants | 349 Participants | 2981 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 33 / 371 | 0 / 18 | 24 / 220 | 24 / 173 | 3 / 76 | 4 / 71 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 88 / 371 | 0 / 18 | 72 / 220 | 37 / 173 | 20 / 76 | 10 / 71 |
Outcome results
Primary
Time to the First Occurrence of a Ventricular Arrhythmia
Time to the first occurrence of an episode of true ventricular tachycardia or fibrillation 24 Month rates will be provided for the two groups used in the primary endpoint definition. However, the primary endpoint of hazard ratio is presented in Statistical Analysis 1 as a ratio between Groups A and C.
Time frame: Hazard ratio from study enrollment to approximately 4 years post-implant/enrollment (as reported in Statistical Analysis 1), and estimated 24 month VT-VF rate (as compared in the Outcome Measure table between Groups A and C).
Population: Implanted 1.5 primary prevention and implanted secondary prevention patients. Since the primary objective is the hazard ratio of implanted 1.5 patients to implanted secondary patients, Groups B, D, E and F are not compared for this outcome. While not the primary endpoint, 24-month rates are provided to illustrate the underlying data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: Secondary Prevention Patients - Device Implant | Time to the First Occurrence of a Ventricular Arrhythmia | 32.5 Estimated 24-Month VT-VF Pct of Patients |
| Group C: 1.5 Prevention Patients - Device Implant | Time to the First Occurrence of a Ventricular Arrhythmia | 18.3 Estimated 24-Month VT-VF Pct of Patients |
Comparison: H0: Hazard ratio of Implanted 1.5 patients (Group C) to implanted secondary patients (Group A) ≤ 0.70~HA: Hazard ratio of Implanted 1.5 patients (Group C) to implanted secondary patients (Group A) \> 0.7095% CI: [0.38, 0.57]
Secondary
Mortality
Time to all-cause mortality
Time frame: Hazard ratio from study enrollment to approximately 4 years post-implant/enrollment (as reported in Statistical Analysis 1), and estimated 24 month mortality rate (as compared in the Outcome Measure table between Groups C and D).
Population: Implanted and not-implanted 1.5 primary prevention patients. Since the secondary objective is the hazard ratio of implanted 1.5 patients to not-implanted 1.5 patients, Groups A, B, E and F are not compared for this outcome. While not the secondary endpoint, 24-month rates are provided to illustrate the underlying data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: Secondary Prevention Patients - Device Implant | Mortality | 12.1 24 Mo. Mortality Rate (Pct. of Patients) |
| Group C: 1.5 Prevention Patients - Device Implant | Mortality | 18.3 24 Mo. Mortality Rate (Pct. of Patients) |
Comparison: The null hypothesis is that the hazard ratio of implanted to non-implanted 1.5 patients = 1. The alternative is that the ratio is not equal to 1.p-value: <0.000195% CI: [0.4, 0.66]Wald chi-square