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|
| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P960040 S385/ PAS002 |
| Date Original Protocol Accepted |
07/25/2017
|
| Date Current Protocol Accepted |
08/26/2022
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| Study Name |
MANAGE-HF
|
| Device Name |
NG4 Family of Pulse Generators ICDS.
|
| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
|
| Data Source |
New Data Collection
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| Comparison Group |
Device Subjects Serve as Own Control
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| Analysis Type |
Analytical
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| Study Population |
Transit. Adolescent B (as adults) : 18-21 yrs,
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
1. To evaluate and optimize HeartLogic Heart Failure Diagnostics clinical integration and the alert management process (Phase I).
2. To evaluate Heart Logic in regards to patient outcomes of death and heart failure hospitalizations (Phase II).
|
| Study Population |
Test Device: Phases I and II: ICD and CRT-D devices with HeartLogic turned ON
Control Device: Phase II: ICD and CRT-D devices with HeartLogic alerts turned OFF
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| Sample Size |
Between 1700 and 2700 subjects will be enrolled in the study:
Phase I: Up to 200 subjects
Up to 200 subjects are required in Phase I to build critical knowledge regarding the clinical integration of HeartLogic and the alert management process.
Phase II: 1500-2500 subjects
The sample size required for Phase II of MANAGE-HF is event-driven.
Between 1500 and 2500 subjects will be enrolled in the trial to accrue the necessary number of endpoint events to sufficiently power the primary endpoint. A total of 864 endpoints events from randomized subjects in Phase II are required to sufficiently power the primary endpoint, based on the following assumptions:
Expected control group incidence of annual heart failure
hospitalization and death = 20%
One-sided Alpha = 5%
Power = 90%
Hazard Ratio = 0.8
Estimated enrollment period = 24 months
Expected Follow-up period = minimum of 24 months for last patient enrolled
Final sample size will be determined during the study using a sample size re-estimation interim analysis.
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| Key Study Endpoints |
LATITUDE NXT 5.0 System
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| Follow-up Visits and Length of Follow-up |
Follow-Up Schedule:
Enrollment Visit
Baseline Visit
Scheduled follow-up Visits
Annual Phone Calls (6, 18,30, 42 months… from baseline)
Annual In-Clinic (12,24,36,48 months…from baseline visit)
Additional Follow-up Visits
HeartLogic Alert Action Visit
Additional Subject Interactions (i.e., Not in Response to HeartLogic Alerts)
End of Study Visit
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
Phase 1: 200 subjects
Phase 2: 3886 subjects
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| Actual Number of Sites Enrolled |
Phase 1: 29 sites
Phase 2: N/A
|
| Patient Follow-up Rate |
Phase 1
Rate = 72%
191 completed the baseline visit
144 followed until the last patient enrolled completed their 12-
month visit
37 withdrawals
19 subjects died
Phase 2:
N=1458 patients were included in the analysis, of which 19 died or their device was no longer in service. These were followed for an average of 1.08 years
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| Final Safety Findings |
Phase 1 does not have s safety endpoint
Phase 2 does not have a safety endpoint
|
| Final Effect Findings |
Phase 1 does not have effectiveness endpoints
Phase 2: The observed Sensitivity was 74.5% and an adjusted Sensitivity (95% confidence interval) was 71.3% (65.4%, 76.6%). The False
Positive rate (95% confidence interval) was 1.48 (1.42, 1.59).
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| Study Strengths & Weaknesses |
Phase 1
Patients that were included in Phase I of MANAGE-HF were required to meet specific study inclusion and exclusion criteria. This included evidence of worsened heart failure prior to enrollment. In addition, patients with severe kidney impairment or short life expectancy were excluded. Thus, the results are limited to the population that was studied. Furthermore, the small sample size and lack of a control group limits the interpretation of the results.
Finally, the study was primarily conducted in the US, and results may vary in other geographies.
Phase 2:
• The pre-specified endpoints were met.
• Analysis was retrospective
- The data source for HFE was CMS claims, so there was no event or site monitoring.
- Events were not independently adjudicated.
- Some results were coarsened due to low numbers as required by CMS reporting policies.
- Only US patients are included, and results may be different in other geographies.
- Only CMS patients were included, and on average were older with more comorbidities than the patients included in the pre-market (MultiSENSE) study.
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| Recommendations for Labeling Changes |
Phase 1 - No labeling changes are recommended
Phase 2 - Labeling changes are recommended
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