Heart Failure, Tachyarrhythmias, Ventricular Dysfunction
Conditions
Brief summary
The purpose of the study is two-fold. In Phase I (Protecta Clinical Study), system performance will be evaluated. In Phase II (PainFree SST), the inappropriate shock-free rate at one year of subjects implanted with a Medtronic Protecta implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy defibrillator (CRT-D) will be evaluated.
Detailed description
The PainFree SST study was a prospective, multicenter clinical trial, which was conducted in two consecutive phases. Phase I assessed safety as determined by assessment of delays in ventricular fibrillation (VF) arrhythmia detection time using new algorithms. Phase II assessed the influence of new algorithms on inappropriate and unnecessary shocks at 1 year of follow-up. Subjects enrolled in Phase I continued in Phase II of the study and data from all enrolled subjects contributed to the analysis of Phase II objectives. A sub-study of Phase II randomized secondary prevention subjects to either 18/24 NID or 30/40 NID in order to assess the safety of prolonged detection in these patients.
Interventions
DEVICEProtecta VR-ICD
Protecta single-chamber implantable cardioverter defibrillators.
DEVICEProtecta DR-ICD or CRT-D
Protecta dual-chamber implantable cardioverter defibrillators and cardiac resynchronization therapy defibrillators.
Sponsors
Medtronic Cardiac Rhythm and Heart Failure
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Patients meeting one of the following criteria can be included in Phase I of the study: * Patients indicated (per local indications) for a dual chamber implantable cardioverter defibrillator (DR-ICD)/cardiac resynchronization therapy defibrillator (CRT-D) * Patients undergoing a device replacement or upgrade to DR-ICD or CRT-D and with the protocol required leads (patients must be enrolled prior to implant) * Patients meeting one of the following criteria can be included in Phase II of the study: * Patients indicated for a DR-ICD/VR-ICD/CRT-D device and intended to receive a Protecta device * Patients undergoing a DR-ICD/VR-ICD/CRT-D device replacement or an upgrade to a Protecta DR-ICD/VR-ICD or CRT-D * Patients indicated for a DR-ICD/VR-ICD/CRT-D already implanted with a Protecta device and the protocol required leads, who have not yet been discharged after implant
Exclusion criteria
* Patients with a mechanical tricuspid heart valve * Patients enrolled or intended to participate in any concurrent drug and/or device study, which would confound the results of this trial as determined by Medtronic, during the course of this clinical study * Patients with medical conditions that preclude the testing required for all patients by the study protocol or that otherwise limit study participation required for all patients * Patients with
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Are Inappropriate Shock Free | Implant to one year post-implant | Primary objective of Phase II. Subjects implanted with a VR device will be analyzed separately from subjects implanted with a DR / CRT-D device. An inappropriate shock is a shock delivered by the defibrillator when the patient's heart rhythm was not a tachyarrhythmia, as adjudicated by the independent Episode Review Committee . |
| Percentage of Subjects With Unanticipated Severe Adverse Device Effects (Phase I) | Implant to one month post-implant | In Phase I, only DR-ICD/CRT-D devices were implanted, so that for Phase I objectives there is only 1 arm to report results for. |
| Percentage of Phase I Subjects Where the Ventricular Fibrillation (VF) Detection Time With Protecta Features on is no More Than 2 Seconds Longer Than the VF Detection Time With Protecta Features Off | At implant | In Phase I, only DR-ICD/CRT-D devices were implanted, so that for Phase I objectives there is only 1 arm to report results for. |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Secondary Prevention Subjects Who Are Syncopal Event Free | Implant to one year post-implant |
Countries
Austria, Canada, Colombia, Czechia, Denmark, Germany, India, Israel, Italy, Japan, Malaysia, Netherlands, Saudi Arabia, Slovenia, South Africa, Spain, Sweden, Switzerland, United Arab Emirates, United Kingdom, United States
Participant flow
Pre-assignment details
Twenty patients were excluded from analysis, because they did not meet the eligibility criteria; 1 patient did not sign consent, 1 patient participated in a confounding trial, 8 patients did not have an implant attempted, 5 patients failed implant, and 5 patients received a device other than the Protecta.Total enrolled=2790, total analyzed=2770
Participants by arm
| Arm | Count |
|---|---|
| DR-ICD/CRT-D Patients implanted with a dual-chamber ICD (DR-ICD) or cardiac resynchronization therapy defibrillator (CRT-D). | 2,019 |
| VR-ICD Patients implanted with a single-chamber ICD (VR-ICD). | 751 |
| Total | 2,770 |
Baseline characteristics
| Characteristic | Total | VR-ICD | DR-ICD/CRT-D |
|---|---|---|---|
| Age, Continuous | 64.8 years STANDARD_DEVIATION 12.3 | 61.9 years STANDARD_DEVIATION 12.1 | 65.9 years STANDARD_DEVIATION 12.1 |
| Heart Failure Status No Heart Failure | 354 participants | 109 participants | 245 participants |
| Heart Failure Status NYHA I | 419 participants | 187 participants | 232 participants |
| Heart Failure Status NYHA II | 1104 participants | 346 participants | 758 participants |
| Heart Failure Status NYHA III | 853 participants | 99 participants | 754 participants |
| Heart Failure Status NYHA IV | 38 participants | 8 participants | 30 participants |
| Heart Failure Status Unknown | 2 participants | 2 participants | 0 participants |
| Indication Primary Prevention | 1923 participants | 497 participants | 1426 participants |
| Indication Secondary Prevention | 847 participants | 254 participants | 593 participants |
| LVEF | 32.2 % STANDARD_DEVIATION 13.2 | 33.3 % STANDARD_DEVIATION 13.5 | 31.8 % STANDARD_DEVIATION 13 |
| QRS | 125.9 ms STANDARD_DEVIATION 33 | 107.1 ms STANDARD_DEVIATION 21.9 | 133.7 ms STANDARD_DEVIATION 33.7 |
| Region of Enrollment Austria | 58 participants | 14 participants | 44 participants |
| Region of Enrollment Canada | 264 participants | 145 participants | 119 participants |
| Region of Enrollment Colombia | 22 participants | 4 participants | 18 participants |
| Region of Enrollment Czech Republic | 63 participants | 30 participants | 33 participants |
| Region of Enrollment Denmark | 102 participants | 42 participants | 60 participants |
| Region of Enrollment Germany | 305 participants | 57 participants | 248 participants |
| Region of Enrollment India | 25 participants | 18 participants | 7 participants |
| Region of Enrollment Israel | 162 participants | 58 participants | 104 participants |
| Region of Enrollment Italy | 72 participants | 11 participants | 61 participants |
| Region of Enrollment Japan | 181 participants | 37 participants | 144 participants |
| Region of Enrollment Malaysia | 19 participants | 2 participants | 17 participants |
| Region of Enrollment Netherlands | 240 participants | 86 participants | 154 participants |
| Region of Enrollment Saudi Arabia | 164 participants | 43 participants | 121 participants |
| Region of Enrollment Slovenia | 15 participants | 0 participants | 15 participants |
| Region of Enrollment South Africa | 7 participants | 0 participants | 7 participants |
| Region of Enrollment Spain | 54 participants | 30 participants | 24 participants |
| Region of Enrollment Sweden | 20 participants | 3 participants | 17 participants |
| Region of Enrollment Switzerland | 13 participants | 0 participants | 13 participants |
| Region of Enrollment United Arab Emirates | 5 participants | 4 participants | 1 participants |
| Region of Enrollment United Kingdom | 114 participants | 11 participants | 103 participants |
| Region of Enrollment United States | 865 participants | 156 participants | 709 participants |
| Sex: Female, Male Female | 570 Participants | 140 Participants | 430 Participants |
| Sex: Female, Male Male | 2200 Participants | 611 Participants | 1589 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 452 / 2,019 | 125 / 751 |
Outcome results
Primary
Percentage of Phase I Subjects Where the Ventricular Fibrillation (VF) Detection Time With Protecta Features on is no More Than 2 Seconds Longer Than the VF Detection Time With Protecta Features Off
In Phase I, only DR-ICD/CRT-D devices were implanted, so that for Phase I objectives there is only 1 arm to report results for.
Time frame: At implant
Population: Of the 236 subjects implanted, 40 subjects / episodes were classified as not useable. In Phase I, only DR-ICD/CRT-D devices were implanted, so that for Phase I objectives there is only 1 arm to report results for.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DR-ICD/CRT-D | Percentage of Phase I Subjects Where the Ventricular Fibrillation (VF) Detection Time With Protecta Features on is no More Than 2 Seconds Longer Than the VF Detection Time With Protecta Features Off | 100 percentage of patients |
Comparison: P, the expected proportion of successes under the null hypothesis, was 95%. α, the Type I error rate, is 0.025. Power is 90%. Pa, the assumed true proportion of successes, is 99%. Based on the above assumptions, at least 173 subjects with a useable time to VF detection testing were required for this objective. Assuming a 5% rate for the potential non-adherence to the testing protocol, the required enrollment sample size was 183.p-value: <0.0001Confidence interval and hypothesis test
Primary
Percentage of Subjects Who Are Inappropriate Shock Free
Primary objective of Phase II. Subjects implanted with a VR device will be analyzed separately from subjects implanted with a DR / CRT-D device. An inappropriate shock is a shock delivered by the defibrillator when the patient's heart rhythm was not a tachyarrhythmia, as adjudicated by the independent Episode Review Committee .
Time frame: Implant to one year post-implant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DR-ICD/CRT-D | Percentage of Subjects Who Are Inappropriate Shock Free | 98.5 percentage of patients |
| VR-ICD | Percentage of Subjects Who Are Inappropriate Shock Free | 97.5 percentage of patients |
Comparison: The study was designed to include at least 1,131 patients with DR/CRT-D ICD devices in order to estimate the inappropriate shock free rate at 1 year post-implant with 1% precision.95% CI: [97.9, 99]
Comparison: This study was designed to include at least 610 patients with VR-ICD devices in order to estimate the inappropriate shock free rate at 1 year post-implant with a precision of 2%.95% CI: [96.1, 98.5]
Primary
Percentage of Subjects With Unanticipated Severe Adverse Device Effects (Phase I)
In Phase I, only DR-ICD/CRT-D devices were implanted, so that for Phase I objectives there is only 1 arm to report results for.
Time frame: Implant to one month post-implant
Population: Phase I subjects (a subset of the total number of subjects) implanted with a Protecta device with at least 30 days of follow-up or a USADE within the first 30 days post-implant are included in this analysis. One hundred subjects met the criteria above and are included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DR-ICD/CRT-D | Percentage of Subjects With Unanticipated Severe Adverse Device Effects (Phase I) | 0 percentage of patients |
Comparison: Using the one-sided one proportion Exact Test in PASS sample size software, a sample size of 76 subjects with 1-month follow-up was calculated to be required for the evaluation of this objective. To ensure adequate testing of the Protecta XT CRT-D device, the 76 subjects must have included at least 34 CRT-D subjects. Assuming an attrition rate of 10%, a sample size of 85 subjects enrolled was calculated to be required.p-value: <0.0001Exact Binomial
Secondary
Percentage of Secondary Prevention Subjects Who Are Syncopal Event Free
Time frame: Implant to one year post-implant
Population: Includes randomized secondary prevention patients from Phase II.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DR-ICD/CRT-D | Percentage of Secondary Prevention Subjects Who Are Syncopal Event Free | 96 percentage of patients |
| VR-ICD | Percentage of Secondary Prevention Subjects Who Are Syncopal Event Free | 96 percentage of patients |
Comparison: The expected syncopal event free rate was 0.984 in both programming groups. alpha, Type I error was 0.05. Power, 1-beta, was 80%. Non-inferiority margin 5% Based on the above assumptions and Farrington-Manning test, a total of 230 subjects was required. By further assuming 15% attrition rate and 5 % of crossover rate, a total of 300 subjects were needed.p-value: 0.001390% CI: [-2.7, 2.7]Farrington-Manning