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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P140003 S088/ PAS001 |
| Date Original Protocol Accepted |
08/18/2022
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| Date Current Protocol Accepted |
04/27/2023
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| Study Name |
Impella RW Surveillance of Pts using Sodium Bicarb
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| Device Name |
Impella 2.5 System, Impella CP System, Impella CP with SmartAssist System, Impella 5.0 System, Impella LD System,Impella 5.5 with SmartAssist System
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| General Study Protocol Parameters |
| Study Design |
Comprehensive/Linked/RegistryBased Surveillance
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| Data Source |
Sponsor Registry
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| Comparison Group |
Concurrent & Historical Control
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| Study Population |
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
A multicenter, observational, records review study of routine clinical care. Subjects are from post-market cohorts and new
enrollment.
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| Study Population |
Device: The study will include up to 60 sites from the US. The population enrolled in this study are all subjects who received an
Impella in which a bicarbonate-based purge solution was used. Comparator: The study will include up to 60 sites from the US. The
population enrolled in this study are all subjects who received an Impella in which a heparin-based purge solution was used.
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| Sample Size |
A sample size of 300 subjects is proposed for the study based on the following assumptions:
Event rate 6%
Target margin of error of +/- 3% (the width of 95% confidence interval of 6%)
While the sample size with the above assumptions is 275, the additional subjects ensure the target 3% margin of error for a
potentially higher event rate in the all-comers population enrolled in the study.
For Impella RP, the sample size will be the number of subjects available at the time the left-sided device population completes
enrollment, up to 30 subjects. As the use of Impella RP is an order of magnitude less than the left-sided devices, a target margin of
error is not feasible for this population.
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| Key Study Endpoints |
1. Left-sided devices (Impella 2.5, Impella CP, Impella LD, Impella 5.0 and Impella 5.5): Hierarchical composite of
stroke, transient ischemic attack (TIA), left ventricular (LV) thrombus [Time Point: Discharge]
2. Impella RP: Hierarchical composite of pulmonary thromboemboli and deep vein thrombosis (DVT) [Time Point: Discharge]
1. Bleeding, BARC greater than or equal to 3 [Time Point: Discharge]
2. For left-sided devices: Thrombotic events excluding LV thrombus, stroke and TIA [Time Point: Discharge]
3. For Impella RP: Thrombotic events excluding pulmonary thromboemboli and DVT [Time Point: Discharge]
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| Follow-up Visits and Length of Follow-up |
1. Left-sided devices (Impella 2.5, Impella CP, Impella LD, Impella 5.0 and Impella 5.5): Hierarchical composite of
stroke, transient ischemic attack (TIA), left ventricular (LV) thrombus [Time Point: Discharge]
2. Impella RP: Hierarchical composite of pulmonary thromboemboli and deep vein thrombosis (DVT) [Time Point: Discharge]
1. Bleeding, BARC =3 [Time Point: Discharge]
2. For left-sided devices: Thrombotic events excluding LV thrombus, stroke and TIA [Time Point: Discharge]
3. For Impella RP: Thrombotic events excluding pulmonary thromboemboli and DVT [Time Point: Discharge]
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
312
|
| Actual Number of Sites Enrolled |
20
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| Patient Follow-up Rate |
100%
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| Final Safety Findings |
The primary endpoint for left-sided Impella devices (Impella 2.5 System, Impella CP System, Impella LD System, Impella 5.0 System and Impella 5.5 System) was a composite of stroke, transient ischemic attack (TIA), left ventricular (LV) thrombus evaluated at discharge. Event data included all events during index hospitalization, including prior to, during and after Impella support. The composite event rate of 7.7% during the entirety of the index hospitalization fell within the expected event rate of the Impella device usage for the studied patient population. Additional descriptive endpoints included 1) BARC greater than or equal to 3 bleeding events through hospital discharge; 2) For left-sided devices, thrombotic events excluding LV thrombus, stroke, and TIA through hospital discharge; and 3) For right-sided devices, thrombotic events excluding pulmonary thromboemboli and deep vein thrombosis (DVT) through hospital discharge.
The key contributor to the composite endpoint was stroke, with 22 of the 23 composite endpoint events being stroke events (22/300; 7.33%). The remaining event was one event of left ventricular thrombus. The observed rate of stroke (7.33%) fell within with the expected stroke rate derived from literature reports.
When patients were grouped by Impella-only patients and Impella patients with other MCS (Impella + MCS), the endpoint rates were considerably lower in the Impella-only group. Specifically, the composite endpoint rate of stroke/TIA/LV thrombus was 3.1% in the Impella-only group versus 13.5% in the Impella + MCS group. Fourteen (14) out of 23 primary endpoints were reported to be unlikely or not related to the device, only two primary endpoints were found to be probably related to the device, four possibly related to the device, and relatedness of two other primary endpoints was classified as unknown. Similar to the finding seen with the primary endpoints, there is an appreciable difference in descriptive endpoint rates between Impella only and Impella + MCS sub-groups, with lower BARC greater than or equal to 3 bleeding event rates (15.4% versus 29.4%) and thrombotic event rates (3.1% versus 4.8%) seen in Impella only sub-group, with majority of the endpoints reported to be unlikely or not related to the device.
The primary endpoint for right-sided Impella devices was a composite of pulmonary thromboemboli and DVT evaluated at discharge. No patients met the primary endpoint in the right-sided cohort. No right-sided cohort patient experienced the descriptive endpoint of thrombotic events, while BARC greater than or equal to 3 bleeding was seen in 15.0% of the patients. None of the BARC greater than or equal to 3 bleeding in the right-sided cohort was reported to be definitely or probably related to the device.
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| Final Effect Findings |
The primary and descriptive endpoints of the study are described above in the “Final safety findings” section above.
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| Study Strengths & Weaknesses |
The study’s main strength was its representation of the real-world experience, representing physician preference for the use of sodium bicarbonate in the purge fluid during Impella support for a variety of challenging clinical scenarios, indications, and procedural characteristics. The study provided rigorous data on this real-world cohort.
The study’s main weaknesses were its lack of data to identify timing of the purge administration with respect to the timing of the endpoints, and lack of data to directly compare outcomes between bicarbonate and other purge fluids.
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| Recommendations for Labeling Changes |
The clinical information in the Instructions for Use should be updated to include the results of the post-approval study.
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