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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P020014 S041/ PAS001 |
| Date Original Protocol Accepted |
07/29/2015
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| Date Current Protocol Accepted |
04/28/2016
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| Study Name |
Post Approval Study
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| Device Name |
ESSURE SYSTEM FOR PERMANENT BIRTH CONTROL
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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 |
No Control
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| Analysis Type |
Descriptive
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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 |
This study is the continuation of the premarket study (Use of Transvaginal Ultrasound to Confirm Essure Micro-insert Placement in Women: Demonstration of Effectiveness) utilized to support P020014/S041.
The study is a prospective, multi-center, international study of women seeking permanent contraception. The objectives of the study are to evaluate the effectiveness of the Essure procedure when the TVU/hysterosalpingogram (HSG) algorithm is used for confirmation testing, evaluate the intent-to-treat reliance rate 3 months following TVU/HSG confirmation test algorithm, and evaluate subject satisfaction with the TVU confirmation test.
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| Study Population |
Women, aged 21 to 44 years of age, seeking permanent contraception
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| Sample Size |
620 patients were enrolled.
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| Key Study Endpoints |
The two co-primary endpoints of the study are to evaluate the occurrence of confirmed pregnancy among subjects relying on Essure inserts for birth control on the basis of the TVU/HSG algorithm at 1-year post-alternative contraception and to evaluate the intent-to-treat reliance rate 3 months following TVU/HSG confirmation test protocol. The secondary endpoints of the study are to evaluate subject satisfaction with TVU and to evaluate the occurrence of confirmed pregnancy at 10 years among subjects relying on Essure inserts for birth control on the basis of the TVU/HSG algorithm.
Enrollment is complete. Data to be collected will include the following:
a. Reliance rate (complete at time of approval)
b. Pregnancies and outcomes
c. Adverse Events
d. Device removal (added 2016)
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| Follow-up Visits and Length of Follow-up |
Subjects will be followed for 10 years post-device placement.
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
620 women enrolled into the study, from which 597 (96.3%) underwent an Essure placement attempt. Among the 597 women who underwent an Essure placement attempt, 582 (97.5%) achieved bilateral placement and 547 (91.6%) were told to rely on Essure for birth control following the 3-month post-placement visit.
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| Actual Number of Sites Enrolled |
20 sites were included in the study, 12 sites in the US and 8 sites outside the US.
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| Patient Follow-up Rate |
Out of all enrolled patients (620 women), 236 (n=236) women completed the study (38.1%). Out of the women who were told to rely (n=547), 236 women completed the study (43.1%). For each annual visit after approval, out of all subjects who were told to rely (n=547), the follow-up rates were:
2-year: 86.3%
3-year: 83.4%
4-year: 73.5%
5-year: 65.8%
6-year: 53.6%
7-year: 48.3%
8-year: 47.0%
9-year: 45.0%
10-year: 43.1%
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| Final Safety Findings |
There were 597 women who had an Essure procedure attempted and make up the primary safety analysis cohort.
A total 1,987 events were reported in 406/597 subjects (68.0%) from the primary safety cohort throughout the 10-year follow-up duration. There were 146 serious adverse events (SAEs) in 85 subjects.
The AEs occurring in greater than or equal to 5% of subjects were heavy menstrual bleeding (95 subjects, 15.9%), pelvic pain (60 subjects, 10.1%), dysmenorrhea (52 subjects, 8.7%), abdominal pain (34 subjects, 5.7%), urinary tract infection (34 subjects, 5.7%), arthralgia (32 subjects, 5.4%), back pain (32 subjects, 5.4%), abnormal uterine bleeding (31 subjects, 5.2%), headache (31 subjects, 5.2%), and uterine leiomyoma (30 subjects, 5.0%).
SAEs are a subset of all the reported AEs. There were 146 SAEs reported in 85 subjects. The only SAE occurring in greater than or equal to 1% of subjects was pelvic pain (9 subjects, 1.5%). Four (n=4, 0.7%) subjects died due to cardiac arrest, colon cancer, stroke, or an unknown cause. The deaths were assessed as not related to the Essure device.
None of these events represent unanticipated adverse device effects and the events are consistent with available data for Essure.
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| Final Effect Findings |
Out of the 582 women who had bilateral placement of Essure, 547 were told to rely (94%).
Overall, there were 4 pregnancies that occurred among all study subjects. In the first year, there were 3 reported pregnancies, which were reported at the time of approval. A fourth pregnancy occurred 16 months after the subject was told to rely. Overall, the study pregnancy rate was 0.78% (lower control limit 1.55%) at the end of the study.
Out of the subjects that received transvaginal ultrasound confirmation testing (n=528), 520 women were satisfied with the transvaginal ultrasound test (98.5%). Subject comfort was reported as excellent, very good, or good by 521/528 subjects (98.7%). One subject did not provide a response for subject comfort.
The study protocol was modified in early 2016 to add the capture of device removal events. The cumulative probability of device removal for all subjects for any reason at 10 years is reported as 19.5% (95% confidence interval range is 15.3-23.5%). The cumulative probability of device removal for any reason at 10 years for US subjects and OUS subjects is 20.9% (95% confidence interval range is 15.1-26.3%) and 17.6% (95% confidence interval range is 11.5-23.2%), respectively.
The study was not originally designed to collect data on device removal; as the protocol was modified during the ongoing study, some events were captured retrospectively and patient outcomes data are unavailable. Removals reported in the rate above include all removals, regardless of the reason for removal (for example, adverse event, concomitant with another gynecologic surgery, subject request). Therefore, the removal rates reported do not reflect removals due to device complications alone, which may be a lower rate.
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| Study Strengths & Weaknesses |
The study was designed to provide the pregnancy rate in women told to rely on Essure for permanent contraception after confirmation using the TVU/HSG algorithm confirmation test. The results include data from both inside the US and outside the US. One strength of the study is the long-term follow-up duration to monitor pregnancy occurrence in women told to rely on Essure for permanent contraception. A weakness of the study is the lost to follow-up rate by the end of 10 years of follow-up. The lost to follow-up rate may be in part due to COVID-19 related challenges, and other external factors.
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| Recommendations for Labeling Changes |
Not applicable. On December 31, 2018, Bayer stopped selling and distributing the Essure device in the United States. As of December 31, 2019, all unused Essure units should have been returned to Bayer so that they are no longer available for implantation. The most recent labeling from 2018 includes instructions for completing confirmation testing using TVU or HSG and the co-primary endpoint results.
This post-approval study provides information on the confirmation test methods discussed above. In this post-approval study, the findings support the information already included in the labeling.
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