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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P200037 / PAS001 |
| Date Original Protocol Accepted |
07/27/2021
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| Date Current Protocol Accepted |
07/27/2021
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| Study Name |
ACE-PAS
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| Device Name |
ASSURE Wearable Cardioverter Defibrillator (WCD) System
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| Clinical Trial Number(s) |
NCT03887052 NCT04132466
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| General Study Protocol Parameters |
| Study Design |
Active Surveillance
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| Data Source |
Sponsor Registry
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| Comparison Group |
Objective Performance Criterion
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| Analysis Type |
Analytical
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| Study Population |
Adult: At least 22 yrs
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| Detailed Study Protocol Parameters |
| Study Objectives |
Active surveillance study using real-world data collected in the ASSURE Registry. Outcome measures are based on analysis of ASSURE Registry data including data recorded by the ASSURE system which has been annotated by clinical experts in electrophysiology.
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| Study Population |
Adult patients prescribed the ASSURE system who have consented to participate in the ASSURE registry
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| Sample Size |
A total of 271 appropriate shock episodes for VT/VF is required to provide the desired level of statistical precision for the primary efficacy endpoint (overall shock conversion rate). It is estimated that a total of 5,179 patients will be required to provide data on 271 appropriate shock episodes.
The required sample size is based on the following assumptions:
• Performance goal of 89% for overall shock conversion rate
• Estimated ASSURE system overall shock conversion rate of 94%
• Endpoint will be met if lower bound of a 2-sided 95% exact confidence interval greater than or equal to the performance goal of 89%
The estimated number of patients required was derived from a literature review of prospective studies (6) that presented shock data for LifeVest. In these studies, 27/804 (3.36%) patients had a total of 42 appropriate shock episodes, or an average of 1.555 (42/27) shock episodes per patient. It is expected, therefore, that 174 (271/1.555) ASSURE Registry patients will account for the 271 required appropriate shock episodes. If only 3.36% of the ASSURE Registry patients will experience one or more appropriate shock episodes, a total of 5,179 (174/0.0336) patients are required to provide data on 271 appropriate shock episodes for VT/VF.
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| Key Study Endpoints |
Effectiveness
Objective: To evaluate shock effectiveness in converting ventricular tachycardia/ventricular fibrillation (VT/VF)
Primary Endpoint: Overall shock conversion rate [percent of spontaneous episodes of ventricular tachycardia/ventricular fibrillation (VT/VF) successfully converted with one or more shocks] =89.0%
Secondary Endpoint: First shock conversion rate [percent of spontaneous episodes of ventricular tachycardia/ventricular fibrillation (VT/VF) converted with a single shock] (report only)
Rationale for Effectiveness Performance Goal: The overall performance goal is based on results from LifeVest German Registry data in which the overall shock conversion rate was 94.0% for 163 appropriate shocks delivered in a population of 6,043 patients. Applying a non-inferiority margin of 5% results in a performance goal of 89%.
Safety
Objective: To evaluate the prevalence of inappropriate shocks
Primary Endpoint: Inappropriate shocks per patient-month of use [total inappropriate shocks/cumulative months of device use for all patients] = 0.0075
Secondary Endpoint: Inappropriate shock rate [percent of patients who experience at least one inappropriate shock] (report only)
Rationale for Safety Performance Goal: Based on results from two registry studies and the manufacturer reported rate which cumulatively report 0.0071 inappropriate shocks per patient month (1363 inappropriate shocks/191,743 months of cumulative wear time). The upper bound of a two-sided 95% confidence interval around 0.0071 is 0.0075.
Ancillary
Effectiveness
• Appropriate shock rate per month
• Percent of patients who experience at least one appropriate shock
• Total shocks delivered
• Shocks diverted by Alert Button press
Safety
• False Positive Shock Alarm rate
• True Positive Shock Alarm rate
• Adverse Events
Compliance
• Average Daily Usage (hours)
• Device usage in days
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| Follow-up Visits and Length of Follow-up |
The device will be used temporarily (days of use), and the data will be obtained from that period of use. No additional patient follow-up is required.
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
21,816
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| Actual Number of Sites Enrolled |
N/A since the study uses data from ASSURE Patient Registry
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| Patient Follow-up Rate |
N/A since this uses RWE
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| Final Safety Findings |
The sponsor states that sample size of 271 appropriate shock episodes for VT/VF is required to provide the desired level of statistical precision for the primary effectiveness endpoint (overall shock conversion rate).
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| Final Effect Findings |
The sponsor states the incidence rate of inappropriate shocks was 0.0065 per patient-month with an upper 95% confidence bound of 0.0073 - successfully meeting the prespecified performance goal of 0.0075. Overall, 1.3% of patients experienced inappropriate shocks, while 94% remained free from false-positive shock alarms. The overall shock conversion efficacy for spontaneous VT/VF episodes was 100%, with a lower 95% confidence bound of 98.9%, exceeding the prespecified performance goal of 89%. First-shock conversion efficacy was 97%.
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| Study Strengths & Weaknesses |
ACE-PAS was conducted as a standard of care registry and exhibits real-world performance of the ASSURE WCD in a clinical setting.
Prespecified performance goals allowed for assessment of key metrics against established, clinically meaningful benchmarks.
Large-scale study enrolling over 20,000 patients exclusively within the United States, making it the largest WCD study conducted to date. However, results may not be generalizable to populations in other geographic regions with differing healthcare systems, clinical practices, and patient demographics.
Observational study design did not include longitudinal clinical follow-up, therefore limiting insights into outcomes such as left ventricular ejection fraction improvement, implantable cardioverter defibrillator (ICD) implant, or mortality.
Study relied on device-recorded data to evaluate outcomes, which inherently lack comprehensive clinical context, such as patient-reported symptoms or standard 12-lead ECG interpretations. These data are also susceptible to transmission errors and memory corruption, and their accuracy depends on device specific detection algorithms and programming settings, which may vary among patients. To strengthen data validity, all device-detected arrhythmic episodes underwent adjudication by an electrophysiology expert panel.
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| Recommendations for Labeling Changes |
The results of the study are acceptable and should be added to the device labeling.
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