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U.S. Department of Health and Human Services

522 Postmarket Surveillance Studies

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CENTER FOR DEVICES AND RADIOLOGICAL HEALTH



WELCOME TO THE 522 POSTMARKET SURVEILLANCE STUDIES WEBPAGE

 

 

 

 

            

Postmarket Surveillance Study


 
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General
Study Status Progress Adequate
522 Number / Requirement Number PS160001 / PSS001
Date Current Plan Accepted 09/15/2020
Study Name Postmarket Surveillance Study
Root Document Number P020014 
General Study Protocol Parameters
Study Design Prospective Cohort Study
Data Source New Data Collection
Comparison Group Concurrent Control
Analysis Type Descriptive
Study Population Transit. Adolescent B (as adults) : 18-21 yrs, Adult: >21
Detailed Study Protocol Parameters
Study Design Description Open-label, non-randomized, prospective observational cohort study of two cohorts of subjects who chose to undergo either hysteroscopic sterilization (Essure) or laparoscopic tubal sterilization.



Interim Data Posting



Information regarding interim study progress (such as number of study sites enrolled and number of patients enrolled) will be posted after the review of each study report as applicable. Study results will be posted at four timepoints, due to the statistical methods required for group comparisons (propensity score matching). An update will occur once enrollment into the Essure arm is completed, once all subjects have reached one-year follow-up, three-year follow-up, and after study completion.



The FDA may also post on its website or otherwise make public postmarket surveillance interim summary data or the FDA’s analyses thereof when appropriate to protect the public health, for example when interim results raise safety concerns or may otherwise impact treatment.
Study Population Description The study population includes subjects who are at least 21 years of age who have not been pregnant within the past 6 weeks.



The study population includes women who chose to undergo hysteroscopic sterilization (Essure) or laparoscopic tubal sterilization.

Sample Size On July 20, 2018, Bayer announced that Essure sales would stop in the United States after December 2018. Health care providers could implant Essure up to one year from the date the device was purchased. The planned sample size of 1,400 women per arm was no longer feasible. The FDA required study enrollment into the Essure arm to continue as long as Essure was available in the U.S. Enrollment into the laparoscopic tubal sterilization arm would stop after it reached approximately 2:1 ratio with the Essure arm.

Data Collection Main Safety Endpoints:

• Chronic lower abdominal and/or pelvic pain

• Abnormal uterine bleeding (new onset or worsening)

• Hypersensitivity and allergic reactions, and autoimmune disorders (new onset) or autoimmune- like reactions

• Invasive gynecologic surgery including Essure insert removal



Secondary Safety Endpoints:

• Other adverse events

• In the event of a device removal or event of interest, additional data collection may include bloodwork, pathology, histology, and metallurgic testing, as appropriate



Effectiveness:

• Pregnancy

Follow-up Visits and Length of Follow-up Follow-up measures include adverse event assessment, medical history including gynecological procedures, patient reported outcome (PRO) measures for chronic pelvic pain and abnormal uterine bleeding, levels of inflammatory markers and human leukocyte antigen (HLA) type, additional bloodwork for women with certain adverse events, and analysis of removed Essure devices.



60 months

Interim or Final Data Summary
Interim Safety Information As of December 31, 2019, enrollment has ended. A total of 1,128 patients have been enrolled (340 in the Essure arm and 788 in the laparoscopic tubal sterilization (LTS) arm). There were a total of 67 sites enrolled.



The data summarized below are from a planned interim analysis completed at the end of enrollment and following completion of propensity score matching. This interim analysis is based on a database lock of February 4, 2020.The study is ongoing and as of the database lock, patients are still completing 3-month, 12-month, 24-month, and 36-month follow-up visits.



A total of 1128 patients enrolled in the study at 60 investigational sites in the U.S. Of the 340 patients in the Essure group and 788 patients in the LTS group who signed informed consent and entered the screening phase, 285 and 705 patients, respectively, attended the procedure visit and, of these, 280 and 705 patients, respectively, had the procedure attempted. The patients in whom the procedure was attempted serve as the full analysis set to determine rates of events of interest. The mean (± SD) age at the time of enrollment was 33.5 (± 5.79) years. The majority of patients (80.0%) were reported as White.



A total of 94.6% (265/280) patients had successful bilateral placement of Essure after 1 or 2 placement attempts. Only patients who had successful bilateral placement and reached 3 months post-Essure placement were eligible for confirmation test. The reliance rate was 91.8% (180/196), which represents the number of patients told to rely out of the number of patients with confirmation testing attempted at the time of the interim database lock. For the LTS group, bilateral tubal occlusion was successfully achieved for 99.6% (702/705) patients.





Interim Results - Safety Endpoints (based on the propensity-score-matched (adjusted) population of 264 patients in each group, unless otherwise noted)



Chronic lower abdominal and/or pelvic pain:

The overall adjusted incidence of reported events of chronic lower abdominal and/or pelvic pain sterilization procedure was 9.1% in the Essure group and 4.5% in the LTS treatment group.



Abnormal uterine bleeding (new onset or worsening):

The overall adjusted incidence of reported events of abnormal uterine bleeding post-sterilization procedure was 16.3% in the Essure group and 10.2% in the LTS treatment group.



Hypersensitivity and allergic reactions, and autoimmune disorders (new onset) or autoimmune- like reactions:

The overall unadjudicated*, adjusted incidence of reported events of allergic/hypersensitivity type reactions post-sterilization procedure was 22.3% in the Essure group and 12.5% in the LTS group.

The overall unadjudicated*, adjusted incidence of reported events of possible newly diagnosed autoimmune disorders post-sterilization procedure was 0% in the Essure group and 1.5% subjects in the LTS group.

* These events have yet to be reviewed by a blinded independent adjudication committee to determine if events represent likely allergic/hypersensitivity reactions or autoimmune disorders. Final determination of whether or not a hypersensitivity/allergic event or an autoimmune disorder occurred will be based on the determination of the adjudication committee. Unadjudicated events include events that could have been possibly related to an inflammatory reaction, symptoms the patient believes were due to a hypersensitivity or allergic reaction, or symptoms indicating a potential autoimmune disorder, including adverse events of pelvic or lower abdominal pain.

Final Safety Findings Interim Results - Safety Endpoints continued (based on the propensity-score-matched (adjusted) population of 264 patients in each group, unless otherwise noted)



Gynecologic surgical procedures (excluding second placement attempts; including Essure removal):

The overall adjusted incidence of patients undergoing gynecologic surgical procedures after the sterilization procedure was 19.7% in the Essure group and 3.0% in the LTS group. The higher incidence in the Essure group relative to the LTS group was driven primarily by Essure removal and endometrial ablation procedures in Essure patients. The adjusted incidence of device removal was 6.8% in the Essure group and 0% in the LTS group. The adjusted incidence of endometrial ablation was 10.2% in the Essure group and 2.3% in the LTS group.



A total of 19 patients had 24 Essure removal events, as patients may have undergone more than one procedure at the time of device removal (i.e. hysterectomy AND salpingectomy). Essure removal procedures included salpingectomy (15 events), hysterectomy (5 events), salpingotomy (3 events), and cornual resection (1 event). The primary reasons for Essure removal, as assigned by the investigators, were the following: patient request (5 patients), management of adverse events related to Essure (5 patients), “Other” including management of adverse events not related to Essure (4 patients), in conjunction with other gynecologic surgery (3 patients), device failure (1 patient), and unable to rely on the device for permanent birth control and no associated adverse event (1 patient). The category of “Other” primary reasons for Essure removal included 1 patient with menorrhagia, 1 patient with a failed primary procedure, 1 patient with abnormal uterine bleeding, and 1 patient with abnormal uterine bleeding and pelvic pain.



The overall cumulative probability of device removal for any reason based on life table analysis is 14.3% at approximately 21 months after Essure placement. For the patients in the Essure group who were told they could rely on the device for permanent birth control after a satisfactory confirmation test, the cumulative probability of device removal is 11.3% at approximately 21 months after insertion. Device removals ranged from 1 day to 21 months after Essure placement.



Other adverse events:

The overall adjusted incidence of unintentional perforation of the uterus, fallopian tubes or cervix by any surgical instrument or sterilization device was 1.9% in the Essure group and 1.1% in the LTS group.

The overall adjusted incidence of expulsion (insert displaced toward the cervix or vagina and retrieved through the vagina hysteroscopically) was 0.4% in the Essure group and 0% in the LTS group.

The overall adjusted incidence of dislocation (insert displaced out of the uterus, fallopian tube, or in the intraperitoneal cavity and retrieved via laparoscopy) was 0.4% in the Essure group and 0% in the LTS group.

Final Effectiveness Findings Interim Results - Effectiveness Endpoint



Pregnancy:

One patient in the Essure group became pregnant after being told she could rely on the device for permanent birth control, and 5 patients in the LTS group became pregnant. The cumulative probability of no pregnancy based on life table analysis is 99.2% for the Essure group and 98.8% for the LTS group at approximately 21 months after insertion.

Study Strengths and Weaknesses Interim Results - Limitations



This study is not randomized and women are not blinded to their treatment group.

This study is ongoing and the results are interim. Final analyses of endpoints will not be completed until the study concludes.





  • The 522 Postmarket Surveillance Studies Program encompasses design, tracking, oversight, and review responsibilities for studies mandated under section 522 of the Federal Food, Drug and Cosmetic Act. The program helps ensure that well-designed 522 postmarket surveillance (PS) studies are conducted effectively and efficiently and in the least burdensome manner.
  • CDRH efficiently identifies the reporting status of active 522 PS studies based on study timelines incorporated in study protocols and agreed upon by the CDRH and applicants. This system represents CDRH's effort to ensure that all 522 PS commitments are fulfilled in a timely manner.
  • In addition, CDRH launched this publicly available webpage to keep all stakeholders informed of the progress of each 522 PS study. The webpage displays general information regarding each study, as well as the overall study status (based on protocol-driven timelines and adequacy of the data) and the applicant's reporting status for each submission due.

Links

Contact Information

Mandated Studies Program
Food and Drug Administration
10903 New Hampshire Ave.
Silver Spring, MD 20993-0002
Email: MandatedStudiesPrograms@fda.hhs.gov
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