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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P160048 / PAS001 |
| Date Original Protocol Accepted |
09/18/2018
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| Date Current Protocol Accepted |
03/22/2023
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| Study Name |
Post-Approval Study
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| Device Name |
EVERSENSE CONTINUOUS GLUCOSE MONITORING SYSTEM
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| Clinical Trial Number(s) |
NCT02154126 NCT02647905
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| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
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| Data Source |
New Data Collection
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| Comparison Group |
Objective Performance Criterion
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| Analysis Type |
Analytical
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| Study Population |
Transit.Adolescent B(as adults): 18 yrs < 22 yrs,
Adult: At least 22 yrs
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| Detailed Study Protocol Parameters |
| Study Objectives |
The purpose of this post-approval study (PAS) is to provide long-term safety and effectiveness of the Eversense CGM System (PMA Application P160048) in the post-market setting.
This is a prospective, multi-center study, whereby up to 400 subjects will be enrolled in the United States at up to 30 sites. The subjects will have one Sensor inserted by trained health care professionals approximately every 3 months. Sensors will be inserted in the upper arm of the subjects.
This is a new enrollment study.
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| Study Population |
Subjects may be included in the PAS if they fit the following inclusion criteria:
1. Subject has diabetes mellitus
2. Subject is greater than 18 years of age
Subjects may not be included in the PAS if they fulfill the following exclusion criteria:
1. Subject will require a planned MRI during the period of Sensor insertion
2. Subject is critically ill or hospitalized
3. Subject has a known contraindication to dexamethasone or dexamethasone acetate
4. Subjects requiring intravenous mannitol or mannitol irrigation solutions
5. Female subjects who are pregnant, planning on becoming pregnant or nursing
6. Subjects on hybrid closed loop systems or closed loop systems
7. Subjects on other CGM systems
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| Sample Size |
A total of 1400 Sensor cycles contributing to the analysis is planned.
Based on data from the PRECISE (n=81 subjects), PRECISE II (n=90 subjects), PRECISION (n=35 subjects) and PMCF (n=1686 subjects)
studies, a total of 31 events occurred that would meet the definition of the primary safety endpoint in this study. With a total of 1892 subjects, this
equates to an observed rate of approximately 1.6% with an associated 95% confidence interval of 1.1% to 2.3%. As there is variability associated with this sample, as evidenced by the confidence interval, a conservative expected rate of events for this study is 2.3%. The planned sample size of
1400 total cycles) with this expected rate should provide greater than 95% power for the test of the performance goal of 4%.
Meeting the performance goal of 4% for the planned sample size would require a worst-case observation of a rate of approximately 3% or less (i.e.,
41 or fewer events among 1400 cycles). This result will be clinically acceptable and similar to results observed in past studies.
A total of 273 enrolled subjects will achieve a total of at least 1400 Sensor cycles.
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| Key Study Endpoints |
The primary safety endpoint is the incidence of the composite of infection, secondary procedures to remove the sensor, or procedure-related adverse events of at least moderate severity.
Other safety endpoints include:
Rate of all device-related and insertion and removal procedure-related adverse events (serious and non-serious events) through 27 months post-first sensor insertion
Rate of device breakage through 27 months post-first sensor insertion
Rate of device-related and insertion and removal procedure-related serious adverse events through 27 months post-first sensor insertion
Subgroup analysis of safety endpoints based on:
o Age (<65 years vs. >65 years, minimum 40 subjects)
Diabetes type (I vs. II)
Race (non-Caucasian vs. Caucasian)
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| Follow-up Visits and Length of Follow-up |
Every 90 or 180 days (depending on whether a subject is using the 90-day or 180-day sensor) for sensor insertion/removal. Also 15 and 45 days postsensor insertion to enable documentation of any adverse events. Total duration of follow up is expected to be 24 months.
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
For P160048: 273
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| Actual Number of Sites Enrolled |
For P160048 (Adjunctive Use): 16
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| Patient Follow-up Rate |
Two hundred seventy-three (273) subjects were inserted with an initial Sensor. Of the 273, 245 subjects had a second Sensor inserted, 219 subjects had a third Sensor inserted, 210 had a fourth Sensor inserted, 191 had a fifth Sensor inserted, 145 had a sixth Sensor inserted, 124 had a seventh Sensor inserted, 111 had an eighth Sensor inserted, seven (7) had a ninth Sensor inserted, and three (3) had a tenth Sensor inserted. Ten (10) subjects participated in additional Sensor cycle(s) because of an early Sensor retirement in a previous cycle. Therefore, to achieve a total length of participation of approximately two years per protocol, a 9th and 10th Sensor was inserted.
One hundred (100) subjects discontinued their participation in the study early. Eighty-nine (89) of the 100 withdrew after removal of their last study Sensor, with the exception of three (3) subjects who withdrew prior to sensor removal and transitioned to commercial users. Eight (8) of the 100 are documented as lost to follow-up with the Sensor still in situ. Of the 92 subjects who withdrew, 27 subjects withdrew after completing the first sensor cycle, 22 after completing the second cycle, nine (9) after completing the third cycle, 11 after completing the fourth cycle, seven (7) after completing the fifth cycle, ten (10) after completing the sixth, and six (6) after completing the seventh cycle. In total, 173 subjects have completed all Sensor cycles and finished study participation.
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| Final Safety Findings |
The primary safety endpoint of the incidence of the composite of infection, secondary procedures to remove the Sensor, or procedure-related adverse events of at least moderate severity is reported in Table 13. The composite rate was 42 events out of 1,528 sensor cycles (2.75%) with a 95% upper confidence limit of 3.54%, which met the primary endpoint performance goal (p=0.0054). There were five (5) cases of infection (0.33%), 24 secondary procedures to remove the sensor (1.57%), and 15 procedure-related AEs of at least moderate severity (0.98%).
Three hundred sixty (360) adverse events (AEs) were reported during the study. All AEs have been adjudicated by CEC members. Appendix A contains the listing of all AEs adjudicated in the study. Of these events, 96 are related to the study device and/or the insertion or removal procedure, giving a rate of 6.28% per sensor insertion cycle (96 out of 1528 total sensor insertion cycles). The related adverse events (frequency, nature, and severity) are consistent with the safety profile from the clinical studies reported in the PMA application. Related adverse events for the PP population are provided and have a rate of 5.69% (72 out of 1265 sensor insertion cycles). Insertion and removal procedure-related AEs for HCPs with vs. without an MD degree are provided and did not result in a significant difference between HCP types (p=0.2908).
Of the 360 total adverse events reported, 31 events were adjudicated as serious adverse events (SAE), two (2) of which were adjudicated as related to the device, one (1) that was adjudicated as possibly related to the device, and one (1) that was adjudicated as related to the insertion/procedure and possibly related to the device. The rate of related SAEs was 0.26% (four (4) out of 1528 total sensor insertion cycles).
One hundred thirty-four (134) device malfunctions have been reported. Of those 58 are related to the Sensor and 37 are documented as Early Sensor Retirement (2.4%). The percentage of early Sensor retirements is consistent with the PRECISE II study results, wherein 91% of Sensors remained functioning through 90 days.
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| Final Effect Findings |
The primary effectiveness endpoint of Time in Range (TIR), defined as glucose values between 70 mg/dL and 180 mg/dL, at 12 months compared to the first month post-first sensor insertion is reported in Table 24. The mean TIR was 62.7% for the first month of CGM System use and 62.4% for the 12th month of CGM system use.
Sensitivity analyses for the primary effectiveness endpoint was performed using the PP analysis population and is provided. As with the entire population, the change is not statistically significant.
The additional effectiveness endpoints of average hours of use per day and change in HbA1c levels at each 6-month interval from baseline are summarized.
The Statistical Analysis Plan also specified six additional secondary endpoints, including: 1) patient satisfaction with CGM system use (CGM-SAT scale); 2) patient reported Diabetes Distress Scale (DDS); 3) success rate of insertion and removal procedures: overall and by HCP experience; 4) rate of serious adverse events based on HCP experience with the insertion/removal of Sensors; 5) HCP feedback questionnaire regarding insertion/removal; 6) residual dexamethasone level in explanted sensors.
Overall, the sponsor states that the effectiveness endpoint of the study resulted in a time in range of 62.4% at 12 months compared to 62.9% at one month post-first Sensor insertion. This demonstrates a time in range that is consistent over multiple Sensor cycles and in line with prior studies on the Eversense CGM System, which reported Time in Range from 62.3-64.5%.
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| Recommendations for Labeling Changes |
None
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